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新纳米医学技术进行癌症早期检测和改进的治疗方法的现状和展望

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新纳米医学技术进行癌症早期检测和改进的治疗方法的现状和展望新纳米医学技术进行癌症早期检测和改进的治疗方法的现状和展望 新纳米医学技术进行癌症早期检测和改进 的治疗方法的现状和展望 aa,b作者:Dhruba J. Bharali , Shaker A. Mousa 关键字:癌症治疗 磁振荡成像(MRI) 纳米医学 纳米粒子 断层电镜扫描(PET) 量子点 目录 1.前言....................................................................................................

新纳米医学技术进行癌症早期检测和改进的治疗方法的现状和展望
新纳米医学技术进行癌症早期检测和改进的治疗方法的现状和展望 新纳米医学技术进行癌症早期检测和改进 的治疗方法的现状和展望 aa,b作者:Dhruba J. Bharali , Shaker A. Mousa 关键字:癌症治疗 磁振荡成像(MRI) 纳米医学 纳米粒子 断层电镜扫描(PET) 量子点 目录 1.前言.............................................................................................................................. 2 2.癌症治疗....................................................................................................................... 4 2.1 紫杉醇 ................................................................................................................ 5 2.2 顺铂 ................................................................................................................... 7 2.3 链霉素 ................................................................................................................ 9 2.4 氟尿嘧啶 ...........................................................................................................11 2.5 喜树碱 .............................................................................................................. 12 2.6 绿茶 ................................................................................................................. 14 2.7 甲状腺激素 ....................................................................................................... 14 3. 癌症诊断 ....................................................................................................................16 3.1 量子点 .............................................................................................................. 16 3.2 核磁共振成像 ................................................................................................... 20 3.2.1(氧化铁纳米粒子..................................................................................... 20 3.2.2(钆交联纳米粒子............................................................................................ 23 3.3(正电子发射断层扫描 ....................................................................................... 26 4.结论.............................................................................................................................29 参考文献 ........................................................................................................................30 摘要 纳米医学技术的应用,通常简称为“纳米医学”,具有维持我们 人类健康和治疗疾病的能力。我们在纳米水平的研究为我们在分子水 平上发现一些人类最复杂的疾病提供了机会,并且它在显著改善疾病 预防、诊断和治疗上也有了很显著的发展。纳米体系日新月异的进步 和新兴纳米系统技术,特别是纳米粒子的发展,对于我们进行癌症的诊断,治疗和检测有着深远的影响。纳米粒子体系通过改善的化学疗法增加药物的可溶性和稳定性而在纳米医学领域引起了强烈的关注。此外,纳米粒子通过结合在特定的肿瘤细胞表面受体,如肿瘤特异性的抗体或配体来增强纳米颗粒药物传输系统的有效性,同时它还能显著降低药物毒性。也许纳米医学上最令人兴奋的进展是肿瘤成像和载药这种多功能的纳米颗粒体系的形成。在一个相对来说很短的时期内,纳米医学已经在全球市场内占据了强有力的一部分。这篇综述提供了纳米医学的最近进展的总结,特别是在纳米颗粒和抗癌载药方面的进展。我们也讨论了各种用于癌症检测或成像的纳米探针的研究。最后,我们也会讨论这一新兴的充满活力的领域以及这一领域潜在的影响。 目录 1.前言 尽管研究者和工业界对癌症有了许多的研究,癌症仍然是美国和世界上死亡率最高的疾病之一。2007年,全世界范围内有7,021,000人死于癌症,癌症成为全球第二大杀手,死于癌症的人数占总死亡人数的12.5%。世界卫生组织估计:到2010年,癌症将成为全世界人死亡的主要原因。尽管癌症治疗在过去的几十年间有了显著的进步,但是现代癌症诊断和治疗的方法主要还是以入侵为主(比如随机活体和手术)以及粗糙的、无特异性的技术,比如像化疗和化学试剂。癌症继续成为人们致命的原因,现代治疗技术不能显著提高癌症的诊断 效果。 纳米技术应用到医药或者纳米医学领域将对普遍身体健康产生深远的影响,特别对于癌症的诊断,特异性治疗有很大的潜力。纳米的前缀在希腊文中是“侏儒”的意思。根据其形状大小,国际纳米技术协会把纳米技术定义为“在材料科学和生活现象中处于1到100纳米的粒子。”纳米粒子代表一个真正的纳米级体系,通常这个体系粒子的直径不大于1个到几百个纳米。我们可以把纳米颗粒组装到一系列的化疗药物中,并且直接标记这些载体,并把它们运送到特定的肿瘤附近,来实现高效而低毒性的治疗。此外,纳米颗粒的尺寸和表面性质修饰过后,可以阻止机体自身的调节反应,保持血液循环。这些纳米粒子的性质使得他们成为了纳米医学中研究最广泛的系统之一。早期癌症治疗的最关键的一个点在于肿瘤细胞的转移之前的诊断。如果癌症早期就被诊断出来了,大多数癌症是可以进行有效治疗的,而且患者也可以全面康复。不幸的是,癌症的早期诊断对于我们来说,仍然是一个很大的挑战,因为癌症临床上的症状在癌症发展到致命的阶段之前都很少表现出来。因此,我们急切地需要创口微小且对患者无伤害的检测和预测癌症的有效技术。为此,许多种以纳米粒子为基础的、改良的诊断成像以及靶向化疗药物技术正在开发中。靶向给药将有助于减少微创手术和放射治疗的需要,同时靶向给药更敏感的成像方法将有利于癌症的早期发现和更好的预期诊断。因此,发展的高敏感度和高特异性的以纳米粒子为基础的光学成像平台的发展会对预防、诊断和治疗癌症产生革命性的影响。 这篇综述提供了纳米医学最新进展的全面总结,特别与纳米粒子和抗癌药物运输有关。我们也讨论了各种用于癌症检测或成像的纳米探针的研究。最后,我们也会讨论这一新兴的充满活力的领域以及这一领域潜在的影响。 2.癌症治疗 大多数治疗癌症的药物是不溶于水的,而且要溶解在有机溶剂里,以便于作为可注射的溶液。这些有机溶剂有毒,而且有副作用。低分子量的抗癌药物可以迅速排泄但是治疗的表征系数很低。这就要求医院对癌症病人增加剂量,而细胞毒性和其他不良事件发生的频率也增加了。另外,化疗药物,当它们单独作用时,缺乏特异性并且会对正常组织造成重大损害,引起不良的副作用,比如骨髓被抑制、脱发和肠上皮细胞的脱落等。纳米技术和运输抗癌药物的结合为许多与传统的抗癌疗法有关的问题提供了解决 方案 气瓶 现场处置方案 .pdf气瓶 现场处置方案 .doc见习基地管理方案.doc关于群访事件的化解方案建筑工地扬尘治理专项方案下载 。纳米粒子直径通常为100纳米,它可以不溶性或难溶性药物转化为可溶的悬浮液中,这样就不需要有毒的有机溶剂。抗癌药物和纳米粒子结合,不仅可以降低细胞毒素作用,也可以增加积累在肿瘤血管的药物量,这种现象被称为渗透和保留增强作用(EPR)。Doxil? and Abraxane?是两种以纳米 技术为基础的抗癌药配方,这两种配方分别经过美国食品和药物管理局批准,用来治疗卵巢癌和乳腺。Doxil?是一种循环缓释链霉素脂质体,这种链霉素与游离链霉素相比,疗效明显加强。ABRAXANE? (Abraxis公司)是一个白蛋白结合型紫杉醇纳米颗粒配方。 ABRAXANE?配方是用来缓解由传统的紫杉醇溶剂Cremophor EL引起的过敏性反应。目前临床试验中许多以其他的纳米粒子为基础的制剂列在表1当中 。通过表面修饰或肿瘤特异性靶向模式结合被包裹和缓释的方式(即亲水性的表面改性涂料)可以增加若干倍的纳米颗粒制剂的疗效。通过这种方式,表面性能增强的纳米颗粒能够有选择性地传输给癌症位点更高剂量的药物或造影剂。下面详细地介绍被动和靶向纳米输送系统,这个系统主要用于运输一些当下使用的主要抗癌化疗药物,下面还要介绍有一定潜力的治疗癌症的药物(即绿茶提取物和甲状腺激素替代剂)。 2.1 紫杉醇 紫杉醇是至今仍在使用的最古老的化疗化合物之一。它最初是从太平洋红豆杉树和红豆杉中提取,后来由Bristol-Myers Squibb对其进行商业开发。它以Taxol?标签来出售。紫杉醇促进微管组装,并稳定微管来抵抗解聚作用,从而抑制细胞分裂。 Sharmaet等人(1996年)第一次展示了纳米微粒紫杉醇制剂的发展,他们使用聚乙烯吡咯烷酮纳米粒子合成的反向微乳液。植入黑色素瘤B16-F10细胞的C57B1 / 6小鼠与没有植入紫杉酚的小鼠相比,小鼠体内具有抗癌活性纳米粒子的肿瘤体积明显变小。既然这样的话,包含有乳酸-羟基乙酸共聚物的可生物降解的纳米粒子被广泛运用到纳米颗粒的载药系统中。Fonseca et al.等人研究表明,载有紫杉醇,直径小于200nm的PLGA纳米粒子可以通过界面沉积制备。这些PLGA纳米粒子 在第一个给药24小时内释放药物速度很快,随后进入较慢的连续释放药物阶段。体外NCI- H69的SCLC人体小肺癌细胞流活力测试表明,含紫杉醇的纳米制剂比不含紫杉醇的商业制剂对细胞的毒性低。董和丰等人口头描述了一个用PLGA/MMT制定紫杉醇的配方。使用荧光香豆素-6掺杂的的PLGA / MMT纳米粒子进行细胞摄取 分析 定性数据统计分析pdf销售业绩分析模板建筑结构震害分析销售进度分析表京东商城竞争战略分析 表明:依据不同的MMT的量,Caco-2细胞和HT-29细胞在使用PLGA / MMT比只使用PLGA的纳米粒子吸收率分别增加了57-177 ,和11-55 ,。这一配方能使药物在胃肠道停留时间(GI)更长 ,是口服紫杉醇药物的有效作用 机制 综治信访维稳工作机制反恐怖工作机制企业员工晋升机制公司员工晋升机制员工晋升机制图 。最近的一项研究表明,同样一组针对乳腺癌治疗的PLGA / MMT纳米颗粒显示出很大的潜力。连接紫杉醇的PLGA / MMT纳米粒子通过溶剂萃取/蒸发方法以及把抗人表皮生长因子受体2(HER2)抗体曲妥珠单抗结合而合成。激光共聚焦显微镜显示:在Caco-2细胞的结肠腺癌细胞和SK-BR- 3乳腺癌细胞中抗HER2 –结合PLGA /MMT纳米粒子与没有结合的纳米粒子相比,结合的纳米粒子药效吸收更好。此外,SK-BR-3细胞中,结合了抗体纳米的配方比未结合紫杉醇或或PLGA / MMT纳米粒子的配方毒效要高13倍。在另一种变化中,维生素E -TPGS乳化过,包裹紫杉醇的PLGA纳米粒子通过溶剂萃取或蒸发方法合成。这些纳米粒子刚开始表现出“爆炸性”释放效果,之后在体内再进行缓释。掺紫杉醇的维生素E- TPGS乳化的PLGA纳米粒子与商业上普遍运用的紫杉醇相比,前者在HT-29细胞中表现出卓越的细胞毒性,体内药物动力学的测量显示:紫杉醇药物与未包裹紫杉醇的药物相比,药效要好3倍。 在纳米医学中,使用不同的聚合物或者混合复合物材料合成纳米粒子是一个活跃的研究领域。根据装载药物溶解度不同,混合聚合物材料有了更多的灵活性。近来报道的混合目标聚合纳米粒子是用双组分的共聚物和包裹紫杉醇合成的。复合物的一个组成部分是聚(丙交酯) -D-α -生育酚聚乙二醇琥珀酸酯(PLA –TPGS)它们起到疏水-亲脂平衡作用,另一个部分是TPGS -COOH,TPGS -COOH有利于针对性地结合部分叶酸。混合纳米粒子与不含紫杉醇的纳米粒子相比有更好的疗效,对MCF- 7 乳腺癌细胞来说效果增加8.68,,结合了叶酸的纳米粒子把药物输送到癌细胞的效果变好,如果结合了紫杉醇的话,效果更( 24.4-31.1 ,,取决于共聚物比)。相似的结果在C6神经胶质瘤细胞也可以得到。 2.2 顺铂 顺铂是以铂类为基础的化疗药物,它于1978年被FDA批准供临床使用。从那时起,它一直是临床上使用最广泛的抗癌药物,尽管后来出现了许多新的化疗药物。它被用来治疗许多癌症,包括肉瘤、癌细胞(如小细胞肺癌和卵巢癌)、淋巴瘤、生殖细胞肿瘤。顺铂是一种能干扰有丝分裂的DNA交联剂。顺铂诱导的DNA损伤可以激活DNA修复机制,这些机制 不能修复顺铂交联而引起细胞凋亡或细胞死亡。在20世纪90年代中期, EGEA等人报道的合成烷基氰基封装顺铂的纳米颗粒并测试使用不同的表面活性剂和不同尺寸的葡聚糖包裹的纳米颗粒的包裹率(Egea等人,1994)。最大包裹率右旋糖酐70和 0.08,硫酸月桂酯钠作为稳定剂组合来实现。Avgoustakis等(2002)使用长循环PLGA-单甲氧基 - 聚(聚乙烯乙二醇)(PLGA-mPEG)纳米粒子合成了生物相容性和可生物降解的被动(无特异性的)纳米颗粒系统。 包裹顺铂的PLGA -mPEG纳米粒子作用初期能快速释放药物,然后在pH值为7.4时在体外相对缓慢地释放药物。释放动力学速度取决于PLG和-mPEG的比率,也就是说,顺铂在作用初期的释放量随着mPEG量的增加而增加。将顺铂包裹到PLGA -mPEG的纳米粒子导致BALB / cmice静脉注射的循环中停留时间增加。在体外实验结果相似, PLGA与mPEG的比例影响血液中顺铂的外形。(Avgoustakis等人,2002)。同一组的另一项研究了人前列腺癌LNCaP细胞中顺铂在PLGA -mPEG的纳米粒子与未封装的顺氯氨铂的细胞毒作用(Gryparis等人,2007)。 Barroug等人(2004)由无机纳米磷酸钙组成的顺铂的载体系统。他们对三种不同类型的磷酸钙进行了测试:次级结晶羟基磷灰石,结晶良好的羟基磷灰石,碳酸磷灰石。三个纳米粒子在体外累积释放速度相似(20天后释放70% ),但观察结晶减少速度更慢。使用无性繁殖的小鼠骨肉瘤K8细胞测试磷灰石/顺铂纳米粒子的细胞活力结果显示:细胞毒作用有一定的剂量依赖性(Barroug等人,2004)。壳聚糖及其衍生物是载药中使用最广泛的聚合物,因为它们在体内的生物相容性和生物降解性很好(Agnihotri等人,2004; Kim等人,2005年; Prabaharan ,马诺,2005年)。 Kim等人。(2008)报道了一种使用疏水性乙二醇壳聚糖( HGC )有目标地载顺氯氨铂的纳米粒子 的新方法。 用5β- cholanic酸处理乙二醇壳聚糖获得HGC- cholanic酸结合物。顺铂与包裹的疏水核心HGC纳米粒子结合在一起得到80,包裹成功率(Kim等,2008) 。此配方中的主要缺点是:与不包裹顺铂相比,包裹顺铂的细胞毒性水平很低。研究者归因于顺铂从HGC纳米粒子中释放速度较低。顺铂-HGC纳米粒子肿瘤靶向性通过使用活体动物成像和以Cy5.5标记过的顺铂-HGC纳米粒子来证明。顺铂-HGC纳米粒子聚集在肿瘤组织中的原因最有可能是因为长期循环和HGC载体的EPC效应,顺铂-HGC纳米粒子与不含顺铂的粒子相比,表现出更强的抗肿瘤效果和较低的毒性(Kim等,2008)。 2.3 链霉素 链霉素是另一种广泛地使用于治疗乳腺癌,卵巢癌,膀胱癌和肺癌化疗剂。链霉素与DNA抑制拓扑异构酶II的活性,拓扑异构酶II是DNA修复中很重要的一种酶,它可以解开DNA螺旋进行修复(Heisig,2009)。链霉素阻止了DNA再次形成双螺旋结构,从而有效地阻止复制。链霉素是一种非常有效的抗癌药物,但它有很强的副作用,副作用包括不可逆的心肌毒性和致命性充血性心脏病,因此我们限制它的使用(冯霍夫等人,1982)。使用纳米颗粒载体对链霉素进行改进是研究的热点( Jones等人,1989)。 在第一个关注链霉素纳米载体系统的研究中,对肝癌患者静脉内注射吸附到聚甲基丙烯酸酯上的链霉素纳米颗粒与不含链霉素的试剂相比,患者的血浆水平更长,总清除时间更短。(罗曼罗兰,1989)。 将polyalkylcyano丙烯酸钠纳米粒子与链霉素结合给小鼠进行静脉注射后,使其心肌毒性降低(库弗勒等人,1982年;凡尔登等人(1986),以及增加体外多药耐药的细胞流的细胞毒性(居维叶等人,1992)。简氏等人(2001)说明了利用壳聚糖纳米粒子载链霉素的可行性。链霉素结合含有葡聚糖硫酸盐的壳聚糖纳米粒子与不含链霉素的壳聚糖纳米粒子相比,有更好的细胞生长活性(简氏等人,2001)。有趣的是,在链霉素与壳聚糖在纳米粒子形成之前结合会导致活性轻度降低,这表明合成这种药物载体系统的方法是非常重要的。在另一项研究中,Mitra等(2001)发现链霉素反式结合(DEX- DXR)壳聚糖纳米粒子在BALB / c小鼠对抗J774A.1巨噬细胞移植瘤表现出更强的抗肿瘤效应。与DEX -DXR或不含链霉素的药物相比,注射了DEX- DXR壳聚糖纳米颗粒的动物表现出更高的肿瘤回归与存活时间。这些结果表明,包封链霉素的纳米颗粒不仅可以减少其副作用,还提高了治疗实体肿瘤的效果,因为它需要更长的循环时间,并且积聚在肿瘤部位的时间也更长( Mitra等,2001)。PLGA-链霉素共轭的纳米粒子也被用来作为抗癌药物。 PLGA-链霉素纳米粒子在HepG 2人肝癌细胞表现的毒性较低,但在体内,含纳米粒子药物的抗肿瘤活性的与不含链霉素的药物相差不大(Yoo等人,1999年,2000年)。包裹了聚山梨酯涂层80的PLGA 纳米粒子可以显著增加链霉素在脑组织中的量。但是,这些颗粒与不含链霉素的药物相比会引起急性肾脏中毒(Manil等, 1995),以及降低穿透人工膜的渗透率(穆勒和kreuter ,1999年)。以脂质体为基础的药物输送系统发展超过了四十年。这种方法 主要的局限性包括稳定性差,批次之间的重复性差,杀菌困难和载药量低。然而,尽管存在这些障碍,目前纳米治疗的一个成功故事是Doxil?,一种长效的聚乙二醇化脂质体链霉素。Doxil?对链霉素进行明显的改进,它是经过FDA批准用于卵巢癌的治疗的药物(斯特罗瑟马泰,2009年)。 2.4 氟尿嘧啶 氟尿嘧啶(5-FU)是嘧啶类似物,它是一种有名的抗癌药物。5-FU主要通过抑制胸苷酸合酶活性,从而阻止胸腺嘧啶脱氧核苷酸合成,胸腺嘧啶脱氧核苷酸是DNA复制必需的核苷酸。Kreuter等人在20世纪80年代中期使用聚氰基丙烯酸丁酯( PBCN )纳米粒子第一次描述了纳米粒子介导的5 - FU。PBCN结合5-FU和传统药物相比,前者在小鼠腹腔内(IP)的S180肿瘤细胞对皮下克罗克肉瘤表现出更强的细胞毒作用,PBCN标记的5-FU则能更加持久地停留在肿瘤部位(Kreuter哈特曼,1983)。此配方中的主要缺点是药物在其他器官中停留、积累的时间也很长。为了消除这种不良的副作用,Simeonova等(2003)提供了合成5-FU加载PBCN纳米粒子用来治疗皮肤损伤的不同方法( Simeonova等, 2003) 。这种配方在体外和体内的疗效有待进一步研究。 为了提高5-FU运输到肝脏的效率和减少副作用,Yu等人(2003年)使用硬脂酰化酰氯得到N1 -硬脂基-5- FU (5 - FUS),然后通过物理集聚包裹成固体脂质纳米粒子,合成5-FU。5-FuS-SLNs平均 直径为240.19纳米,载药量为20.5,。5-FuS-SLNs在体外释放药物特性可以用一个一阶药物动力学模型来解释。5-FuS-SLNs在小鼠中的分布表明,肝脏处5-FU浓度于未包裹5-FU的小鼠相比是后者的两倍。在兔上做实验,得到分布容积(Vd)的消除半衰期(T1 / 2 β)和间隙(CL)分别为0.04336 L /千克, 1.2834小时(h)和0.1632 L / h( Yu等,2003) 。这些结果表明, 5-FuS-SLNs有肝靶向性。使用的前体药物可以提高药物脂溶性为传统的胶体输送系统提供了有趣的选择。 2.5 喜树碱 Camptosar ?(盐酸伊立替康,或CPT -11 )和Hycamtin ?(拓扑替康)是两个最近被FDA批准分别用于晚期大肠癌和卵巢癌的抗癌药物。这两种药物都是首次从喜树碱( CPT)中提取的水溶性的细胞毒性生物碱。 CPT及其衍生物的作用于核酶拓扑异构酶I,它能阻止DNA链再结合,切割单链DNA重新连接,导致复制失败和最终导致细胞死亡。 CPT和CPT衍生物表现出很强的抗肿瘤活性,但其极端疏水性和内酯环的不稳定性限制了它的应用。Zhang等(2004)合成了一种亲脂性的的CPT衍生工具,他把 10 -羟基喜树碱-10 ,20-二异丁基二碳酸酯( HCPT- 1 ) ,组装成聚(己内酯-co -丙交酯的衍生物)( PCLLA )- PEG - PCLLA的三嵌段共聚物的纳米粒子。 PCLLA -PEG-PCLLA纳米粒子可以通过70-180 nm纳米沉淀而制备,并能够有效地引入羟基喜树碱-1 。在C57BL/6J小鼠静脉中注射HCPT- 1纳 米配方比未包裹HCPT- 1相比,药物停留时间更长(Zhang等,2004)。因此,以PCLLA-PEG- PCLLA三嵌段共聚物为基础的生物可降解的纳米粒子药物像亲脂性羟基喜树碱-1这种药物载体一样有前景。在另一种方法中,Min等人(2008)使用HGC纳米粒子包裹CPT,其装载效率约为80, 。疏水壳聚糖复合物是通过化学作用把5β- 半胆酸结合到亲水性乙二醇壳聚糖主链上。该复合物能够在水介质中自聚集,形成直径在280-330纳米,且能有效地包裹住疏水核心的纳米粒子。这些包裹了CPT( HGC- CPT纳米颗粒)HGC纳米粒子在对抗裸鼠体内MDA- MB231人类的乳腺癌移植瘤时显示了有效的抗癌性(民等,2008)。结合近红外( NIR )荧光团Cy5.5可以监测体内肿瘤靶向纳米粒子的特征。静脉注射CPT -HGC纳米粒子与不注射CPT相比,肿瘤和中纳米粒子会优先聚集,肿瘤生长大幅减少(民等,2008)。纳米颗粒系统的肿瘤靶向性增强可能是由于药物停留更长的时间,避开调理素作用或移除网状内皮组织系统(RES),因而导致EPR效应和抗癌活性增强。 据报道,直径100到375纳米的脂质纳米颗粒,可以将其包裹上伊立替康类似物SN-38(Williams等人,2003)。有趣的是,这个系统中的纳米颗粒制剂的疗效似乎是依赖于粒径大小。不同尺寸的纳米粒子结合SN-38注入到携带有 HT- 29人结肠胰腺移植瘤的NCR裸鼠。根据肿瘤消退的结果和小鼠生存情况来说,直径为375纳米的纳米颗粒效果最好(生存65天, 1.98毫克SN-38/小鼠 ),其次是无伊立替康(51天求生存,以9毫克伊立替康/小鼠),然后是直径为100 纳米的纳米粒子(48天生存,1.51毫克SN-38 /小鼠)。把药物与纳米颗粒结合后,SN -38的血液半衰期似乎被大大延长,可能是因为内酯环稳定性增加,从而延长了循环中的药物的活性形式的持久性。 2.6 绿茶 有大量证据表明茶叶中活性成分儿茶素类对多种癌症有抗癌疗效。 “最近的一项我们与美国威斯康星大学合作的研究表明,把绿茶儿茶酸-3-没食子酸酯(EGCG) ,即一种绿茶提取物,包裹到可生物降解的聚乳酸-聚乙二醇(PLA-PEG)纳米粒子中,可以增强肿瘤中EGCG抑制特性( Siddiqui等人,2009)。体外实验中,PLA- PEG纳米颗粒包裹EGCG与未包裹EGCG相比,前者抑制了前列腺癌细胞增长,相对于PC3和其他前列腺癌的细胞来说,使IC50值降低了。包裹EGCG纳米粒子和未包裹的纳米粒子相比,前者能更好地诱导肿瘤细胞凋亡和抑制血管生成( Siddiqui等人,2009)。更重要的是,纳米颗粒EGCG强烈抑制裸鼠体内前列腺癌细胞的致瘤性,导致前列腺肿瘤生长缓慢。这些结果强调了包裹EGCG的纳米粒子用于预防和治疗前列腺癌症的潜在能力。 2.7 甲状腺激素 甲状腺激素受体已经确定在整联蛋白αvβ3 的质膜受体上(伯格等人,2005年)。甲状腺激素在该细胞表面进行信号转导,并与血管内皮细胞和血管平滑肌细胞上的受体反应。甲状腺激素还会在肿瘤 细胞的增殖反应起到作用(Davis等人,2006年,林等人,2007)。的脱氨基T4类似物, 四碘甲腺乙酸通过阻断甲状腺激素和甲状腺激素类似物与连整蛋白结合而作为甲状腺激素受体拮抗剂而起作用(伯格等人,2005)。四碘甲腺乙酸除了能抑制人类肿瘤细胞增殖,它也能抑制血管生成,即在缺少甲状腺激素的情况下,或者通过血管内皮生长因子(VEGF)和碱性成纤维细胞生长因子(bFGF )作用(穆萨等人,2008年Rebbaa等人,2008) 。但四碘甲腺乙酸在细胞内有微弱的仿甲状腺活性( Moreno等人,2008年)。为了限制四碘甲腺乙酸接触到细胞表面的甲状腺激素受体,我们合成了纳米颗粒形式的PLGA-tetrac ,用来限制四碘甲腺乙酸进入细胞和细胞核。以此来避免仿甲状腺分子的不利影响。 在一系列的各种小鼠肿瘤异种移植模型研究中,包括人类甲状腺滤泡中,PLGA-四碘甲腺乙酸纳米粒子与未包裹PLGA-四碘甲腺乙酸的粒子相比(亚尔钦等人, 2010年a) ,对于髓癌细胞(亚尔钦等, 2010B ) 和肾细胞癌(亚尔钦等, 2009 )表现出更高的抗肿瘤生长活性。把荧光探针(Cy-3)结合到PLGA-四碘甲腺乙酸纳米粒子中,我们可以进行活细胞成像和用共聚焦显微镜监测各种细胞流的纳米粒子吸收值。如图1中所示,用Cy3标记-PLGA-四碘甲腺乙酸和Cy3-PLGA (不含四碘甲腺乙酸 )相比,前者显示出人体甲状腺滤泡状FTC- 236细胞的不同位置,原理是利用限制在细胞表面和细胞质中的四碘甲腺乙酸纳米粒子的形式并禁止它们进入细胞核。 3. 癌症诊断 因为纳米粒子独特的物理和化学性质,人们还研究了检测和监测癌症以及癌症治疗过程中作为合成支架使用的探针。使纳米粒子成为载药平台上优秀载体的共同特性,即可改变的表面性能,使得合成水溶性的可注射溶液和发展被动或主动的靶向系统,也使它们成为诊断成像平台的研究热点。使用不同的纳米技术为基础的成像方式在这一领域已经取得显著进展。 3.1 量子点 量子点是半导体纳米晶体。它们是最好的发光探针,在生物和医学领域有着巨大的发展潜力。小尺寸量子点(2-10 nm)的尺寸随光学性能改变而改变,卓越的耐光性和可修饰的表面使得量子点在光学成像上成为独一无二的探针(Bruchez等人,1998;陈聂,1998年阿克曼等人,2002; Jaiswal等人,2003 ; Alivisatos ,2004年)。镉硒(CdSe),碲化镉(CdTe)的,磷化铟(InP ),和铟砷化是生物中最使用的量子点配方。量子点根据它们的尺寸可以再发射不同的特定波长(400至1350纳米)的吸收光。量子点面临的主要挑战是如何在水溶/生理的条件下形成稳定的分散制剂,因为荧光接触到水溶液后就会熄灭。问题的解决方法在于使用不同的涂层材料。事实上,一些可以增加荧光产率的量子点涂层材料已经被发现,同时这些材料也可增强量子点表面可调性而达到目标基团直接输送到目的位点。此外,表面涂层降低了有毒材料,如镉,硒,和As 释放的毒性作用。 这些无机-有机复合纳米材料在体内已被证明能够起到有效作用,小尺寸的量子点可以畅通无阻得进入,结合靶向分子的量子点可以找到特定的“归位”肿瘤位点( Wu等人,2003; Gao等,2004; Bharali等人, 2005年; michalet等人,2005年)。与其他粒子一样,量子点可以通过各种用于靶向传输的表面分子而改变( Howarth等,2005)。量子点也有足够多的来结合化疗药物用于药物传递和体内成像以及组织工程。 Gao等人首次报道了量子点在活体动物体内用量子点来进行肿瘤的定位和活体动物成像技术(2004) 。皮下注射QD-结合前列腺癌细胞后,全身注射多功能量子点探针使癌细胞多彩荧光成像具有高灵敏性( Gao等人,2004)。一项由Bagalkot等人做的研究中( 2007年),QD - apatamer(APT)-链霉素(DOX)相结合,可用于肿瘤靶向治疗、成像和传感。这种多功能纳米粒子系统使得目标载药和通过激活量子点和癌症组织同时成像成为可能。 最近,我们使用简单的链霉亲和素生物素化学技术合成了抗前列腺特异性膜抗原(PMSA)抗体结合的聚乙二醇化的量子点(PSMA量子点)( LaRocque等人,2009)。 人们首次使用 标准 excel标准偏差excel标准偏差函数exl标准差函数国标检验抽样标准表免费下载红头文件格式标准下载 的N-羟基琥珀酰亚胺结合化学,之后抗体被结合到表面氨化的量子点上的方法生产出抗PSMA的抗体。体外融合PSMA量子点与LNCaP前列腺癌细胞(PSMA-阳性细胞系)和为结合量子点相比,PSMA量子点吸收的时间增加。我们不能监测到PMSA量子点被APC3细胞、PSMA-阴性细胞系(图2)吸收。最近证实了把四碘甲腺乙酸化学结合到聚乙二醇化量 子点上这个方法(四碘甲腺乙酸-PEG-量子点)(Bharali等,2009)。在把四碘甲腺乙酸结合到量子点上时没有量子点荧光损失。四碘甲腺乙酸 -PEG-量子点被PANC1胰腺癌细胞有效的吸收了(图3) 。重要的是用纳米配方结合的四碘甲腺乙酸保留了其抗增殖活动的能力。这些结果凸显了量子点特定位点药物传送和监测到不同癌细胞的巨大潜力。 图1 人体滤泡甲状腺癌FTC 236 细胞(A) Cy3-PLGA-腺乙酸纳米颗粒和(B) Cy3-tetrac (不含腺乙酸)共焦显微镜成像 使用近红外成像(700-1000 nm波长范围内)的量子点也有报道(Frangioni ,2003 ;普山等人,2008 ; Gao等人,2010)。NIR量子点可以增加组织渗透的深度,这样就可以在体内更为准确和灵敏地检测光子。近红外量子点也要避免自体荧光这个问题,自体荧光与动物组织中天然存在化合物的光学成像有关。 这些量子点在体内成像方面有巨大的潜力,这种技术已经运用于动物模型中的淋巴管成像(Parungo等人,2005年)。艾伦等(2010)最近一项研究说明了使用NIR量子点包裹InAs( ZnCdS )核壳进行成像的可行性。用聚乙 二醇修饰近红外量子点表面能够进行深度为200μm的肿瘤血管成像,而可见光量子点与之相比,血管造影图像效果不佳(Allen等, 2010)。 图 2 A表示LNCaP细胞中量子点和抗PSMA抗体结合的共聚焦显微成像 B 表示LNCaP细胞未结合量子点的共聚焦显微成像 C表示PC-3细胞(PSMA阴性细胞流)中结合抗PAMA的量子点的吸收 图3 A表示Pan1 细胞腺乙酸-聚乙二醇的吸收共聚焦显微成像 B表示Pan1 细胞腺乙酸-聚乙二醇和用T处理过的量子点连接 4 总之,效果十分理想的纳米器件——半导体量子点由于其独特的性能,这些性能包括高水平的发光稳定性,大小可变以及修饰物多样的性质(从可见的红外波长),能够协助进行多种诊断、治疗和作为靶向试剂。此外,近红外量子点可以最大限度地提高组织穿透力,这里能力在传统成像中被吸收和光散射所限制,近红外量子点在体内可更加准确和灵敏地检测光子。 3.2 核磁共振成像 3.2.1(氧化铁纳米粒子 从临床的角度来看,磁共振成像(MRI)是疾病诊断和监视最强大的无创性成像工具之一。近年来,纳米粒子系统提高癌症成像和MRI诊断效果明显( Sun等人,2008年b ; Shubayev等。 , 2009年Veiseh等。2010)。在纳米医学中 ,磁性纳米粒子有希望对现存的临床诊断和治疗范例产生深远影响。在大多数情况下,用于生物医学的磁性纳米粒子包括的无机纳米粒子核和在水中有良好分散性的表面涂层,( Zhang等人,2002年; Kohler等人, 2004 ;陈等人, 2008年何李,2008年) 。适宜的表面涂层也便于定位和实时监测。磁性纳米粒子在生物医学的成功应用,特别是作为MRI造影剂,归因于它优异的增强质子释放能力(约瑟夫森等人, 1988) 。超磁性氧化铁(SPIO)纳米粒子被广泛应用于肠、( Lumerin , Gastromark )脾或肝的成像中( Endorem ,菲立) ( Wang等人, 2001年, Sun等。2008B )。 Combidex ?是一种超小型supermagnetic的氧化铁( USPIO ),它是这个级别纳米粒子的代表。Combidex ?在临床试验后期用来进行淋巴结转移试验( Harisinghani等人,1997; Bonnemain,1998 )。 近年来,人们大力开发磁性纳米粒子用于靶向药物/化疗剂载药剂。人们采用的方法包括磁性药物靶向定位,以及靶向部分与纳米粒子的结合。这些类型的应用中使用最多的纳米粒子是氧化铁纳米粒 子,这些颗粒在临床前试验中取得了一定的成功实例。然而,氧化铁纳米粒子到达作用位点的深度和准确性以及相对较低的效率限制了它们的发展。近来,合成以下一代的磁性纳米粒子为基础的MRI抗药剂对改变成像范例起到明显的作用。新一代MRI抗药剂包括各种成核材料,如氧化铁,材料的包被剂和结合靶向肿瘤细胞来提高疗效和肿瘤的定位功能。 超顺磁性氧化铁纳米颗粒在临床上第一次是用在肝肿瘤成像上(默, Tombach ,1998)。超顺磁性氧化铁纳米粒子可以被Kupffer细胞吸收,Kupffer细胞是肝脏软细胞组织中的肝巨噬细胞。由于大部分肝肿瘤缺乏巨噬细胞,携带有超顺磁性氧化铁的靶向巨噬细胞加剧了健康和病变组织之间的对抗。超顺磁性氧化铁纳米粒子对T2/T2 * -加权MRI序列的负增强效应使病变组织与非增强的成像相比,更容易发现伤口,也更利于伤口的监测。微小到2-3毫米的肝肿瘤或转移病灶也能用这种技术检测到。 Ferumoxides ,是由SPIO组成的,与T10 -葡聚糖交联,120-180 nm的纳米粒子。它是欧洲第一次使用这种类型的纳米粒子造影剂作为肝脏局灶性病变检测粒子。从那时起,各种不同的尺寸和不同的涂层的氧化铁纳米颗粒被人们开发出来,其中有许多应用到市场上(柯罗等人, 2006) 。对这些磁性纳米粒子的初步毒性研究表明,现在这些粒子还没有任何有害的毒性作用。 超顺磁性纳米粒子还可以应用在对中枢神经系统(CNS)肿瘤的诊断和治疗。超顺磁性纳米粒子在这类应用中是特别有吸引力的,因 为它们可以作为血管内的造影剂和进行细胞成像。 Ferumoxtran -10 和其衍生ferumoxytol的超顺磁性纳米粒子是动物肿瘤模型中有效的MRI造影剂( Varallyay等, 2002; Neuwelt等人,2004 ;曼宁格等人,2005年)。超顺磁性纳米粒子常与靶向部分相连以提高诊断疗效。 Chlorotoxin是一种蝎子状Leiurus quinquestriatus修饰小肽。它是活体组织的神经胶质瘤细胞中一个高特异性标记物( Soroceanu等人,1998),现已运用在动物模型中肿瘤靶向(Lyons等人,2002年)。蒙等人(2007)试图增加Chlorotoxin特异性,他们把chlorotoxin、荧光标记物、荧光素异硫氰酸酯(FITC)和超顺磁性氧化铁纳米粒子结合,使肿瘤能在MRI和光学荧光中同时成像。神经胶质骨瘤细胞中FITC- chlorotoxin共轭的SPIO粒子( SPIOFC )的检测可通过MRI和电感耦合等离子体发射光谱仪定量测量实现( Meng等人,2007)。SPIOFC光学成像可以用激光扫描共聚焦显微镜实现。超顺磁性氧化铁纳米粒子与chlorotoxin粒子结合后,吸收显著增加的现象表明SPIOFC可以有效而特异地调节胶质瘤细胞, 与正常神经细胞相比,chlorotoxin更倾向于运输功能性SPIOs进入胶质瘤细胞。 Sun等人。(2008A ,B,C )发现包被聚乙二醇(PEG )和共轭chlorotoxin ( NP -PEG- CTX)的纳米氧化铁在胶质瘤内外定位时具有更高的特异性,同时也可以作为MRI增强造影剂( Sun等人,2008年c ) 。纳米粒子连接PEG官能团使得各种诊断和治疗药物与 之连接成为可能。该系统代表了可视化和靶向诊断和治疗的纳米平台的发展。NP- PEG -CTX肿瘤特异性是通过测量9 L胶质肉瘤细胞内吸收来确定的。细胞内有效性分析是通过MRI分析长有9 L胶质肉瘤移植瘤无胸腺荷瘤小鼠而实现的。 R2释放速率是通过测定造影剂的增强度来确定的( Sun等人,2008年c )。临床前和临床试验中用到的磁性纳米粒子都在表2中。 表 2 癌症成像的磁性纳米颗粒配方 3.2.2(钆交联纳米粒子 钆的配合物最常用作临床MRI造影剂。钆复合物通过在复合物附近有选择地释放水分子而增加对比度。虽然这种方法已在MRI中广泛使用,但它的灵敏度相对较低。MRI领域中纳米技术的进步使得钆灵敏度低及其相关问题得到解决。在早期的研究, Tokumitsu等(1999)证明gadopentetic酸(GD -DTPA)交联壳聚糖纳米粒子的钆中子俘 获疗法(GD –NCT)是可行的。壳聚糖分子包裹Gd的纳米粒子增加钆在体内肿瘤组织中的停留时间( Tokumitsu等人,1999)。在另一项研究中,用Gd标记的离子-6聚酰胺-胺树枝状大分子( G6 PAMAM )用于MRI 。这种MRI和近红外探测器混合探针在检测乳腺癌中取得成功。(小山等人。淋巴引流, 2007)。 Xu等人。(2007)合成了交联Gd(III)-1B4M-DTPA的G2 PAMAM树形分子用于治疗体内卵巢癌。 “树枝状高分子在MRI和光荧光中用绿色荧光标记。当这一纳米方法用于小鼠卵巢肿瘤异种移植物治疗,它能有效地定位到特异性肿瘤组织并提供足够多螯合的Gd( III )和荧光给肿瘤,使肿瘤在MRI和荧光成像中产生明显的变化(Xu等,2007) 。 使用钆树状大分子为基础的大分子(GD-G8树状分子)作为断层扫描(CT)和磁共振成像造影剂来监测对流增强传递到大脑的可行性在体外和体内得到证实,并建立了最佳剂量( Regino等人,2008)。以Gd为基础的体外CT衰减值剂(约6.0 HU /毫摩尔)是碘为基础的药剂的1.6倍,Gd -G8树枝状高分子的衰减值可以与Gd –DTPA媲美。使用23-78毫米的Gd- G8在CT和MRI下观察增强性,但是用CT和MRI划分注射部位的树枝状聚合物至少要有47毫米。在估计分布容积(Vd)时MRI比CT更敏感。浓度和有效地使用低的浓度的Gd( 小于10毫米Gd)的T1映射量可以更好地测量药物浓度和分散性( Regino等, 2008年)。 在另一种方法中, Swanson等人。(2008)使用叶酸与第五代(G5) 的聚酰胺(PAMAM)树枝状聚合物相连,以提高肿瘤过度表达的叶酸受体的选择性。这些叶酸的共轭树枝状聚合物也能与双官能螯合剂NCSDOTA共轭,然后用氯化钆处理,得到一个多功能纳米配方(Gd( III ) DOTA- G5 -FA ) 。人类KB肿瘤细胞过度表达的叶酸受体通过皮下注射到NODC .B-17 SCID小鼠来形成移植瘤。用特异性Gd -DOTA- G5- FA (?)与非特异性Gd( III ) DOTA -G5的纳米粒子处理过的小鼠肿瘤细胞,磁共振成像有明显的增强( Regino等人, 2008) 。特异性抗体纳米粒子被注射48小时后仍然能观察到信号。叶酸与树枝状聚合物结合使纳米配方的肿瘤有了特异性,使得图像增强。 在治疗恶性脑胶质瘤的主要问题是因血脑屏障造成的无效药物运输和药物在整个肿瘤组织中渗透不能成像。为了解决这些问题,沙林等。 (2009)发明了一种新的方法,即用不同尺寸的PAMAM树枝状高分子与钆-DTPA官能团表面结合。使用立体定向设备给小鼠右前左尾状核和后丘脑接种RG -2神经胶质瘤细胞。静脉注射钆和荧光结合的树枝状11.7至11.9 nm或更小的直径的大分子能有效穿过血脑屏障的毛孔并积累在原位恶性RG2胶质瘤中。直径更大的树状大分子无法穿越血脑障壁(沙林等, 2009)。在这项研究中,穿越血脑或者肿瘤障碍的纳米颗粒物理尺寸直径上限为11.7-11.9纳米或更小。这些树枝状大分子纳米配方也能延长血液的半衰期。同组更多结果表明,恶性脑瘤及周边肿瘤的血肿瘤屏障的管腔纤维糖复合物的生理状态是静脉注射的粒子的主要障碍,它与肿瘤部位无关。恶性的周边肿 瘤微血管系统和直径小于12纳米的高分子的高渗透性有利于展现这些肿瘤BTB中的糖复合物的孔。 钱永健等人最近的一项研究的结果表明用Cy5标记,Gd或两者都标记,或与活化细胞穿透肽(ACPPs)结合的G5-聚酰胺-胺(PAMAM)树枝状聚合物(约5.4 nm直径)与未结合G5 -PAMAM相比,在肿瘤组织中的吸收量要强4-15倍。,研究人员把纳米颗粒和荧光探针相结合,能够检测到残留的肿瘤和小至200微米的移位变化。此外,一旦ACPPs被激活,Gd标记的纳米颗粒能传递更高水平的Gd到肿瘤软细胞组织,足够的可视化T1加权磁共振成像,具有更大的、更持久的释放率(Olson等人, 2010)。因此,共轭树枝状高分子纳米配方产生了高标准摄取值(SUVs),并可以连接多个Gd螯合物重复物、荧光染料和其他载体用来进行双的ACPP为基础的MRI和成像。 3.3(正电子发射断层扫描 正电子发射断层扫描(PET)因不入侵的特性和患者的适应性较高,而成为医疗成像使用最广泛的工具之一,它用于诊断和监测疾病,这些疾病包括各种癌症和心脏病。诊断放射性核苷酸标记的纳米颗粒载体系统可以进一步增加PET的灵敏度,特别是用纳米粒子对癌症进行主动或被动靶向检测。在早期的研究中,放射性标记的聚(isobutylcyanoacrylate )和聚(isohexylcyanoacrylate )纳米粒子连接了DTPA被用在癌症成像上(加内姆等。1993)。尽管有报道成像有高标示性(>80 ,)和良好的等离子稳定性,对兔和人显像还 能对血液进行快速清理和高RES吸收注射的纳米粒子(60-75,)。同样,用99m鎝-葡聚糖络合物标记的聚(丁基-2 - 氰基丙烯酸酯)纳米颗粒生物分散性研究表明注射(约60 ,的注射剂量)2分钟内RES积累量显著增加。在肿瘤血管生成的抗αVβ3整合素抗体与脂质纳米粒子有选择性地结合,可传递放射性核素到肿瘤部位(Li等人, 2002年古奇奥尼等,2004)。72 h后,抗素αVβ3整合DTPA衍生物并用铟-111放射性标记的纳米粒子与未结合的纳米粒子的肿瘤相比,积累水平较高(3,)。 Bartlett等。(2007)使用PET和生物荧光素测量生物分布和生物有效性以及靶向肿瘤的(SI) RNA纳米粒子的抑制作用。这些纳米粒子包括含环糊精的聚阳离子和siRNA分子。把1 1,4,7,10 - 四氮杂环十二烷-1,4,7,10 - 四siRNA分子结合到siRNA分子5'末端,使得64Cu标记可以用于PET成像。铁传递蛋白也与siRNA纳米粒子结合用于靶向给药。携带荧光素酶的表达Neuro2A的皮下肿瘤的小鼠在注射前后可用光学成像和PET来分析以收集相关功能的生物分布数据。虽然非靶向和转针对性的siRNA纳米粒子具有相似的生物分布模式和定位肿瘤的方式。注射药物一天后,转靶向siRNA的纳米粒子与非靶向siRNA的纳米粒子相比,可降低肿瘤的荧光素酶50,活性,相(Bartlett等,2007年)。这些结果强调了靶向和非靶向肿瘤细胞内外整体的相对分布的潜在差异。这些考虑在肿瘤成像和治疗应用中结合分子的设计是很重要的。 这篇综述反复出现的主题是纳米粒子因它多功能性而在传递和 显像探针方面有许多优势。不同类型的成像探针可以组合成一个整体,用来评估纳米粒子的肿瘤靶向疗效。Cai等人。(2007)开发了用于PET和近红外荧光成像、药代动力学评估和肿瘤靶向疗效的多功能探头。 氨基量子点可用RGD肽进行修饰用于靶向运输。螯合剂1,4,7,10 - tetraazacyclodocecane-N,N’,N’’,N'''-四乙酸(DOTA) 64与RGD肽结合,后用Cu 标记用于PET成像。这种纳米颗粒体内成像( RGD肽共轭量子点)是在皮下U87MG胶质瘤动物模型(整合αvβ3阳性)进行的。这个结果表明双探头纳米技术平台可用于体内有效、可靠的成像。 另一项研究在长有Neuro2A皮下肿瘤的小鼠通过PET评估环糊精复合、含有喜树碱(称为IT -101 )并用64Cu放射性标记的纳米粒子的体内生物分布性。 IT -101用 1,4,7,10 - 四氮杂环十二烷-1,4,7 - 三乙酸配体进行化学修饰使得64Cu2 +能与纳米粒子连接。用这种纳米颗粒配方,使用PET成像可以知道各个器官的药代动力学和生物分布性以及肿瘤聚集度( Schluep等人,2009)。这种纳米粒子系统还代表了使用PET成像测量同时、非侵入性的和器官的药动学以及肿瘤分布情况。 纳伦多夫等。 (2010 )报道合成了癌症诊断和监控中多模态融合成像中有生物相容性的纳米粒子。葡聚糖包覆氧化铁纳米粒子( CLIO -47 )是结合18F同位素和远红光的荧光团而合成的。在长有皮下结肠癌CT26的BALB/c小鼠中,根据探针浓度( r2N0.99 )和空间信号的分布( r2N0.85 )可知荧光介导断层成像(FMT )和 PET有很大相关性(纳伦多夫等,2010)。注射了荧光团衍生RGD肽的小鼠,用αVβ3整合素( Integrisense ),蛋白酶传感器(宝升)和纳米状PET剂( 64Cu -CLIO - VT680 )来做靶向标记。研究人员使用多通道FMT / PET -CT测量肿瘤蛋白酶、巨噬细胞含量及整合素表达和不同肿瘤探针的定位(纳伦多夫等。2010)。因此,多通道的FMT / PET -CT融合可以无缝地整合和可视化一些重要的治疗参数。这些进步将加速新一代PET /光学分子成像剂的发展进程。 不同的成像方式的结合(如PET和可以通过使用纳米技术的光学成像)使纳米技术在临床成像方面的应用具有巨大潜力。把两种或多种成像技术与用一纳米运输系统结合,获得全面信息来提高我们对生物系统的理解。比如PET成像可以提供全身成像的信息,而光学成像能提供肿瘤微环境的有价值的分子信息。结合肿瘤靶向剂可以进一步提高治疗的灵敏度和诊断度。 4.结论 自工业革命以来,纳米技术被视为最伟大的工程进步,对当代科学和医学有潜在的影响力。尖端纳米技术在医药领域的应用以每年超过17 ,的速度增长,预计到2011年将达530亿美元( )(弗里多尼亚集团,2007年) 。据美国国家科学基金会(NSF)预测,医药行业生产的近一半产品将含有纳米组件(勒克斯研究,2006年)。纳米技术已经帮助优化了癌症的检测和治疗。 ABRAXANE是治疗转移乳腺癌的一个成功 案例 全员育人导师制案例信息技术应用案例心得信息技术教学案例综合实践活动案例我余额宝案例 ,并 把纳米药物推广到癌症治疗和化疗药物。 SPIO / USPIO纳米粒子在 对不同癌症的成像中以各种商品名而使用。根据 ClinicalTrials.gov ,它是美国和世界各地由联邦和私人资助的试 验的注册团体,现在已经有超过70个试验用纳米粒子进行癌症治疗 和成像( )。纳米技术已经开始改变疾 病治疗方法,特别是对癌症进行诊断,治疗和监控等。多功能纳米系 统可以检测肿瘤细胞,运输化疗药物并监测治疗反应,它代表了纳米 医学最让人兴奋的应用。纳米医学是治疗疾病方面的典范,从非特异 性、有毒的全身治疗到特异性、靶向检测和杀死肿瘤细胞。随着技术 不断完善,正常细胞受到的副作用影响更小,使患者有更好的医疗环 境和更长的寿命。毕竟,这是纳米医学的最终目标,而且它有望在不 久的将来成为现实。 参考文献 Agnihotri, S. 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A randomized multicenter phase II clinical trial of mitoxantrone-loaded nanoparticles in the treatment of 108 patients (英文版 ) easily blame, to prevent the broken window effect. Supervise the leading cadres to play an exemplary role, take the lead in the strict implementation of the < code > and < rule >, lead to safeguard the solemnity and authority of the party discipline, ensure that the party discipline and the laws and regulations for implementation in place. Throughout the discipline in the daily supervision and management , strengthen supervision and inspection, from the thorough investigation of violations of discipline behavior. Strengthen to key areas, key departments and key projects as well as the masses reflect the concentration of the units and departments for supervision. - strengthening supervision, discipline inspection and supervision of cadres to set an example for compliance with the < code > and < rule > is a man must be hexyl, blacksmith needs its own hardware. Discipline inspection organs as the executor of the party discipline, and supervisor of the defenders, for its supervision must be more strictly, discipline inspection and supervision of cadres to firmly establish the awareness of Party Constitution, sense of discipline and rules consciousness, politics loyalty, sense obey. Action speak Ji Ordinance to set an example of the regulations of the rule of law, strengthen supervision and accept the supervision of the firmness and consciousness, do comply with < > and < >. To firmly establish the discipline must first be disciplined, the supervisor will be subject to the supervision of "concept, and consciously safeguard and implement party compasses party, take the lead in practicing" three strict real strict, so loyal, clean, play. To be good at learning, the Constitution and the < code > as morality, politics and brought to fruition; to implement < >, do not want to, dare not, not with disciplinary ruler to supervision; to discipline a ruler, often the control inspection, and consciously in the ideological red line to draw the row Ming Good accumulation is indeed the bottom line, so that the heart has fear, said to have quit, the line has ended. Attached: indifferent to heart, calmly to the table in our life, there are many unpredictable things will happen, some good, some bad things, we cannot control is powerless to stop, but with time, you will find in life sometimes turns out to be not good, some bad things finally turned out to be a good thing, but then we muddy however did not know, this is the life teach us things. 1, life can be complex, can also be simple. Want simple life of precipitation, to have enough time to reflect, to make Become more perfect. Life is the most important thing is not to win, but the struggle; not to have conquered, but to have fought well. 2, the plain is the background of life. Live a plain life, give up on themselves is not a coward, but the wise answers; not disillusioned after the heart, such as ashes, but experience the storm after the enlightenment; not unrewarding perfunctorily, but calm attitude of life of unrestrained self-confidence. Plain living, there is no noise noisy, no earthly troubles, more did not fill in the discontent of desire, some just a calm, a calm. 3, memory of heart will not good things to erase the, life is a When no movie, pain is a beginning, the struggle is a kind of process, death is a kind of ending. Give up this giving up is the helpless, do not give up the abandoned, do not give up this giving up is ignorance, do not give up should not give up is persistent. 4, a thing figured is heaven, think impassability is hell. Since the living, to live better. Sometimes we because of too narrow-minded, too care around the chores and penny wise and pound foolish, not worth the candle. Some things to attract trouble and worry, completely depends on how we look at and deal with it. Don't always take everything back to things, and don't get into a blind alley, don't want to face, don't be narrow-minded. Poke to care, is a kind of open-minded, a free and easy. 5, I am not afraid of others behind me a knife, I afraid to look back and see stab me, is my intention to treat people; I am not afraid of the truth to tell the best friend, I'm afraid he turned to it as a joke to tell don't 6, when we are in a positive frame of mind, you will find many good things; and when we are in a negative state of mind, you will find many depressed things; life happy and worry, all is you of life attitude, optimistic, good luck; loss of sink, Eritrea company. When you are in adversity, may wish to change a point of view to think everything over to the good Think, because good mentality decided the fate of the! 7, people are tired, rest; heart tired, calm. Grow up, mature, this society read. Tired and sad, squat down, to their a hug. Because the world no one can sympathize with you, have mercy on you. You cry, tears is your own; you pain, no one can understand. Then you only tears to smile. 8, each people have youth, Each youth are a story, the life of the world never gets easier, I want what, wish the world all know, as has been the same; now want anything, for fear that others know, or like to lose the same. 9, the heart move, everything in the world is followed by birth, Rangrang, important thing is often the most difficult to open one's mouth, because words will reduce its importance; to let strangers people care about your life in the good things, the original is not easy 10, do not blame, do not laugh at who, also don't envy who. Like a person is a kind of feeling, not like a person is true. The truth is easy to explain, I feel Is unspeakable. The best travel life is that you in a strange place found a long lost touched. 11, happy life not in the bustling in, and in the peace of mind; no matter how many grievances, how uncomfortable, and ultimately to heal themselves or their own, others may got you to comfort, but never know your heart is how wanjianchuanxin. 12, ma'am, like a movie, learn to appreciate, learn to be grateful, learn tolerance, and goodness, helping others. Instead of accusing the society, as into one; and an exception is better to give than to what 13, don't envy him A sum of, don't lose your life and the life, respectively is: the former is a we experienced cannot escape in a day finally will last minute, while the latter is our persistent, we want to cherish the memory of those people and things. 14, learn to smile, learn to strong, the world you know so many people, so many people and you are, you cannot change also can't let everyone like you, so also do not want to do. Life is too short to go crazy to love to go to waste, to chase the dream to regret. 15, when temper, a blessing to go. A wounding elegant people, the key is to control their own emotions. With the mouth is the most stupid behavior. A control negative emotions than a can take a city more powerful water flow slow, language is expensive. People spent two years of time to learn to speak, but to spend a few years time to shut up. That is a kind of ability, that is a kind of wisdom. 16, life is not perfect, sometimes, growth is not a cry, not an eyeful of tears, there is no trace of emotion, there is no gleam of hope, no desire, no action, no static, there is only one kind of downward sinking feeling, sink A murky? 6? 7? 6? 7 sink? 6? 7? 6? 7 toward the bottom of the sink. 17, in some way, do not go, you will not know the other side scenery is beautiful. To you is not good, you do not mind too much, no one has an obligation to you; you learn knowledge, is you have weapons, you can start from scratch, but not unarmed; how do you treat people, does not represent how others treat you, if cannot see through this point, only inviting worry. 18, time is like a sponge in the water, as long as you are willing to squeeze, the total water is still there. Every life, after the ups and downs The best test of live, to life, survival and continuation, do not stop the struggle in the joys and sorrows of life on the road, so that different soul to bear life beat, acceptance of suffering. 19, indifferent to heart, calmly in table, elegant and comfortable life, do not take what is so important. The pursuit will be disappointed; to be alive, you will have trouble. Life is the most afraid of what all want to care about, but also what all grasp is not firm, without scenery, separated populations, such as not to desire, all docked in the fate of the end. Why is too rigid, the natural, to go stay not to live, let go of obsession, revel is 20, if the fate of the broken Hopes of sailing, please don't despair, the coast is still, if the fate of the withered petals of the beautiful, please do not sink, the spring is still, life will always be endless trouble, please don't helpless, because they are still alive, is still a dream, the sun still, we still. Lost, keep memories; to get, must work to; but the most important is good to cherish their own. 21, life, select the complex, is to choose the pain; choose a simple, is choose to be happy. The complex world like a Significance of pride. Hope is the ornate palace, outside people admiring the magnificent, living in the deep knowledge of living it to pay the price. Simple world as a simple log cabin outside ridiculed shabby, the heart is willing to go live to know the joy. Suffering and joy is their own choice. 22, learn how to use a single powerful heart, let the past be the past, let the future come. Life is really the end of the end of an eagle is flying wings, life is constantly pursuit. Don't miss to regret, don't wait for old just miss. Time to return, seize every moment, again painstakingly again tired also Those struggling to fly. 23, life could not Yimapingchuan, even flat pavement, inevitably there will be a few pieces of roadblocks. Some of the rocks around the past, while others have to move it out. Just move others put the stone is very easy, because the stone from the appearance we can discern; difficult to myself to move away the heart of stone head. Leave time to spend with her, often reflect my heart, so as to remove your heart of stone. 24, everything does not have to be demanding, come to, everything does not have to care about, over the past; failing to do not frown, laugh it laugh. Results Don't demand, do to; life is a simple, calm and peaceful. Always not to choose their own path and regret, life is like a train, the scenery and then the United States will retreat, the passage of time and encounter will eventually drifting further and further away, before is always himself. 25, everyone has a weakness, weakness is true humanity. That has no weakness, a shallow person. That people think there is no weakness, mostly false. Life has shortcomings, there are shortcomings is the real life. That no one regret, or childish or numbness or Self deception. It is in tolerance of weakness and so on to accept, people live happily. Hello, everyone! I am a party member. The title of my speech is: < study and implement the party's two laws, doing practical play highway. 2015 October 18, the Central Committee of the Communist Party of China promulgated the implementation of the < the probity of the Communist Party of China self-discipline criterion > and < Chinese Communist Party discipline and punishment regulations. We Heyuan male passers-by to respond positively to the call of the Central Committee of the party, earnestly organize the study "party two regulations", truly grasp the essence and gist, and in their respective positions, to hold the bottom line of the discipline, build a strong ideological line of defense, with the courage to play, the courage to fight tough and fearless spirit, at the crucial moment well to complete the task, with practical action to test the study and implement effect Because of discipline in the * * * * * * * * * * * story. Here, let me to cast a brick to attract jade, speak about our highway. Highway line section of the road surface transformation project, last year "towards the country seized" will be seized one of the items. To complete this arduous task, as a project management office director Comrade, keep in mind from the Communist Party membership, recognize and identify the "bottom line", strict management, and strict adherence to the quality of the project. He not only set an example, honesty and self-discipline, but also requires the management of all the members of the O.K., do not eat the construction unit one meal, do not accept the construction unit a ceremony. In this way, they didn't really dare to adhere to the principle. No comrade, constantly put on reworking an emergency meeting to Comrade Zhen to speak louder, management tube too strict. Remember in Dongguan Street, 400 meters long cement concrete surface layer, because of various reasons, the smoothness of the poor in the bottom cavity, covering film traces and car imprinting quality problems, * * * inquiries, immediately rushed to the scene to understand and verify the situation, the convening of the management office, the construction units, supervision units, construction units, construction units construction time is tight, the economic loss and other reasons to intercede ******** unmoved. He said, "now a popular word, to the discipline and rules quite in front, there are no rules Radius, you construction team not accordance with the technical specifications, quality problems, it must be to carry out rectification. Engineering quality responsibility be weightier than Mount Tai, if we manage to this matter Pavement quality quantity are placed the matter, we this time to learn two regulations have what use? Still what is the Communist Party? "Finally, in his insisted, the road after rework, to solve these problems. In the construction of the new comrades and the project all the colleagues efforts, after four months of fighting, the project the main project was finally completed and passed inspection. Thousands of miles of ice, thousands of miles Piao, this is a splendid and romantic scene. But snow for the highway, it is a disaster, a serious threat to the traffic safety. This year, a month, a century of cold wave swept from North to south, and the snow blowing to Guangdong, but also to bear the blow To * * * * the highway. In January on the evening of 23, Lianping county city temperatures dropped to minus 2 degrees, a wide range of sudden rain sleet, before and after the provincial S341 line in Jiulianshan Mountain tunnel sections of the road appeared in the snow, lead to the passing vehicles skid, traffic is blocked. In the face of the sudden natural disasters, city and county highway department immediately launched the emergency plan for disaster prevention. As the front line of the main force, Lianping Highway Bureau of all Party members and cadres to remember the Party member responsibility, braving the biting cold wind, the first time rushed to the scene, on the icy pavement of salt disposal. Because the temperature is too low, just melt water immediately freezes, addition to the ice work to increase the difficulty. To ensure In addition to the re organization of the depths of the traffic safety, road people braved the icy put reflective cones and warning signs, endure cold at minus 2,3 of Jiulianshan patrols until one in the morning. Just before dawn, Lianping Highway Bureau personnel on the icy road salt ice melting processing until ten o'clock, ice melting ice success, the road gradually returned to normal traffic. In the cold winter night, which people do not miss the warm bed, which people do not miss the warm home. However, our highway on the road to the owners of the masses can go home early, the night fighting to secure the avoidance of the road safety and smoothness, fulfill their responsibility. Xi General Secretary Every Party member cadre cautioned against said: blacksmith needs self hard "." two regulations ", is our own hard standard test, more exercise every party members and cadres of the fire. We should continue to strengthen the party two regulations, conscientiously in practical work, practical play road, the road for the development of the cause of Heyuan and struggle. In the industry domain report the situation of road traffic in recent years, in the province highway departments of the concern and support, our bureau management department based on the job, loyalty duty, best service, to further promote the highway management standardization, legal, scientific and information technology to improve the management level and service quality. This will be my last work is as follows: first, around the center, go all out to greet the seizure in 2015, "meet national examination" is my bureau work. As the highway management department, we focus on the work of the center to strengthen road renovation and management as the focal point, further optimize the service environment, improve service levels. Inspection, the inspection group and the Ministry of transport, the Bureau under the leadership of the ministries and agencies highly evaluated and fully affirmed. (a) increase road area remediation efforts. The programme of work, strengthen the organization and leadership. The timely development of the city of <*** common trunk highway area environment remediation plan >, along the road signs and markings, traffic safety facilities, on both sides of the green, advertising signs, control area illegal construction and implementation of remediation tasks to the relevant departments, clear work time of the node to ensure rectification work timely. Set up road area special rectification work leading group, implement a bureau, the Bureau of the county (District), the project road site domain environment comprehensive improvement Mechanism. To ensure that the work carried out smoothly, the bureau also organized the city road managers participated in the regulation of road region and the relevant laws and regulations of the special training. 2. Active butt joint is reported, actively strive for the support of. Local Party committee and government support is the job As a magic weapon, I am one of the Bureau of the principal leaders repeatedly attack inspection "remediation and road area to the principal leaders of the municipal report. * * *, the Secretary of municipal Party committee, mayor * *, * * *, vice mayor of many times the rate of the relevant departments directly under the responsible person in-depth National Highway G105 line, G205 line, provincial S341 line and the other highway project site, on-site office, coordination solve engineering construction and environmental comprehensive renovation in the presence of difficulties and problems. Last year, national highway along the county (District) government led organizations deploy traffic, urban management, public security, land, environmental protection, industry and commerce, highways and other related departments, to carry out to dismantle illegal construction and ground structures, cleaning up illegal standard Records label "as the main content of the road domain integrated environmental remediation activities and achieved good results. 3. Pay attention to comprehensive management, improve the effectiveness of remediation. Road construction control management has been strengthened. According to the relevant provisions of the laws and regulations of the < Highway Law > and < highway safety regulations for the protection of > and so on, county * *, * * County People's Government on highway construction control area were delineated and issue a public notice, * * County People's government also approved by the executive meeting of the government through discussion, implementation of road boundary markers of 73 million yuan of special funds input, stake setting. According to statistics, last year the city has erected building control zone peg 820, construction control area boundary markers 815 . the second is highway greening and beautification work enhance the road area remediation effectiveness. Will highway greening and beautification work as road area remediation of a key, invite garden experts to guide the design of green, the implementation of high standards for ecological landscape highway activities to create, five years, I board greening mileage of more than 900 kilometers, appropriate road greening greening rate of 100%, effectively enhance the city road greening level and grade, adds a sharp scenery line for **********. Third, rectification of illegal construction and occupation of the road has been checked. By through the town, crossing the road on many occasions to carry out concentrated rectification actions, to clear the remnants of the wall, broken Archives of highways in strict accordance with the wall of building structures and the illegal deposits, remediation along the Jeeves, Jeeves placed advertisements and vehicle maintenance, car washing and other acts, standardize and purification on both sides of the highway billboards and other non road signs, I city of national and provincial highway basic elimination of the "dirty, chaotic, poor, blocking phenomenon, highway traffic environment purification, landscaping. (2) to strengthen the management on the basic data management. The level of the archives management regulations, formulate the < file management system >, the establishment of the road, the implementation of the file manager, file collection, filing, sorting, filing, confidentiality, custody, borrow, identification pin Destroy the standardization. 2, standardized management, enhance service image (a) evaluation system to further improve in order to strengthen and standardize guidance and assessment of each county (area) bureau of highways management work, the Bureau developed a <*** City Highway Bureau highways management assessment implementation measures (Trial). To regularly check for half a year, year-end assessment and irregular random sampling combined, taking the spot road inspections, sampling sections, listening to the reports, archives data check, for each county (area) bureau of highways management work implementation of the special assessment. According to the annual comprehensive assessment appraisal score results, evaluation of outstanding, excellent compliance and Not up to the standard of four grades. And in accordance with the level of assessment, the award on behalf of dial highway management funds. Total score is above 95%, is excellent, 10 million yuan reward; total score of 90 - 94 for excellent, 8 million yuan reward; for the total score of 80 - 89 points for standard, reward 50000 yuan. On the total score is less than 79 points for non-compliance unit, circulate a notice of criticism. (II) Sheung inspection work to further standardize a is in place to ensure the inspection. National and provincial trunk highway patrol monthly not less than 20 days, State Road a week of not less than 3 times, dart a week of not less than 2 times. The second is to explore and promote the electronic patrol monitoring. City highway patrol vehicles are installed on the highway patrol vehicle monitoring system; highway law enforcement personnel are equipped with a recorder for law enforcement, on the process of supervision and law enforcement to ensure evidence has played an effective role. The third is unified and standardized inspection ledger records, inspection equipment use and management of the electronic Patrol information storage utilization. The fourth is the establishment of highway maintenance and inspections mechanism. The city's 19 country and provincial trunk highway maintenance center equipped with the CPPCC keeper, and to develop a road of the Chinese people's Political Consultative Conference tube member responsibilities. According to statistics, in 2015 (on the road. Day.... Stop the road mileage, 17 cases; clean up debris on both sides of the road 20 , demolition billboard 30, demolition chaotic scaffolding house 3, clean Lane Hawking 15.) (3) road permit work to further strengthen the implementation of administrative licensing system, strengthen the supervision and administration of the licensing. Strict implementation of the < Guangdong Province highways license implementation measures >. According to the provisions of the road approval procedures and processes to carry out road license, do according to the law, the license in accordance with the law, shall be subject to examination and approval of the. Implement the collective examination and approval, to strengthen supervision. Highways and approval of business implementation of technical review of administrative approval and separation, the audit focused on the more complex involved in the road licensing matters, collective decision-making, to improve the scientific nature of the road administrative examination and approval, reduce approval corruption risks. Second is to promote the In administrative permission of information technology to improve service quality. According to the <*** Provincial People's Government Office on Issuing 2014 improve and expand the spirit of the relevant documents of the online business hall of program of work notice > and ministries and provincial and municipal government, I realized the butt of Guangdong Province highway information network and provincial network business hall * * * branch office highways licensing examination and approval work. Simplify the licensing process, and strengthen the office system, optimize the quality of service. (4) image of the team to further enhance a is grasp Windows image.2015 years, my bureau highways licensing in the city administrative service center settings window service. According to the <** provincial highway The provisions of the administrative licensing service window management way > and < on regulating the content of the public notice >, I Bureau for damaged highway capacity compensation standard, occupied by highway repair (lost) compensation expenses standards, in accordance with the law of administrative licensing items, the communications administrative license implementation procedures into the line on the wall publicity, in the service window is equipped with all kinds of application fill in sample, administrative licensing service guide brochure, in a conspicuous place public commitment to the system and advisory telephone complaints, for the masses provides warm and thoughtful service. Second is to grasp the "Four Unifications" working in the city's highway law enforcement image. According to the Ministry of transport < to strengthen transportation administrative law enforcement image construction guidance Scheme > and the ministries of the Provincial Bureau of the relevant documents, I board in front of the June 2015 completed the identification of law enforcement, law enforcement station appearance, clothing of law enforcement, law enforcement documents "four unification". (5) the AILU nursing atmosphere further formation of my bureau attaches great importance to the propaganda work of highway management "road awareness month" into <*** City Highway Bureau 2015 road administration work points. One is around the "norms of law enforcement, improve the service" theme "road awareness month" activities carried out. According to statistics, the city's highway system were deployed highways propaganda car 60 times, staff of highways 152 people, set point consulting 6, issued and publicity Data of 8000, hanging banners 134; broadcast 60 hours / 20, update 7 inch high rod making permanent propaganda page 4; in <*** Daily > 7th edition published < highway laws and regulations publicity content >, purchased and distributed < the people's Republic of China Highway Law >, < highway Ann Quanbao supporting regulations > legal text, a total of 500 this. The second is to carry out "12.4" national legal advocacy day activities, the city road officers go deep among the masses interpretation of highway Highways Management laws, regulations and policy advocacy, analysis for illegal construction at both sides of the road, a typical case of illegal advertising management, showing public road construction and maintenance of highways The actual results of the management, the masses love protection consciousness and social awareness to further enhance the enforcement of highways. In recent years, I board in the highway management work were some beneficial explorations and the attempt, and achieved initial results, but there is still a certain gap compared with requirements of the Provincial Bureau and other brothers City, we will to implement the party's spirit of the Fifth Plenary Session of the eighth session of the opportunity, and further increase the intensity of road management work, and constantly improve the overall quality of the workforce and the ability to learn, and strive to achieve the new highway across. Today the topic of democratic life will I talk about the main to correctly treat leave turn ensure transition delicate gas is understanding, to carry out criticism and self-criticism, in-depth to find problems, profound analysis of the causes, through self analysis to find their own existence problem, to correctly understand their own, strengthen the party spirit training, to ensure that the election of smoothly and successfully completed. Below I talk about their own situation, please put forward valuable opinion. Main understanding (a) serious discipline, to create a delicate gas is in the general environment in accordance with the Central Commission for discipline inspection organs, < of Organization Department of CPC Central Committee on strengthening the election of the notice of customs supervision >, municipal < on doing a good job City Township leadership transition in the notification > and county Party Committee Organization Department of the county Party Committee Organization Department < on the convening of the correct treatment leave turn ensure transition Fengqing gas is a feature of democratic life notice > files related to the spirit of the requirements, earnestly implement the "nine is prohibited, nine shall be" the solemn discipline, I earnestly study the < Chinese Communist Party principle of honesty and self-discipline >. < Chinese Communist Party Disciplinary Regulations >, < promote leading cadre of some regulations >, < party and government leading cadres selection and appointment Regulations > and file, and a profound understanding of the nine is prohibited, a nine law "discipline essence and firmly safeguard the election of serious Ensure the unhealthy tendencies have successfully completed, and actively create a delicate gas is the election of environment, to ensure that the election, so as to further strengthen the town leadership and cadre team construction. Through the study, in-depth thinking, to a serious discipline the importance and necessity of a more profound understanding. First, it is the iron discipline. The central put forward the "nine is prohibited, nine shall be the reason for early serious general discipline, designated" high-voltage wire, "itself reflects the party committees at all levels of the reelection of attaches great importance to the objective is bright resolute attitude, the implementation of effective measures, the same candidate to fight with discipline election of wind Discipline in gas is health. Secondly, this is prevenient. From some typical cases, we can see that individual cadres election to engage in speculative hack canvassing votes, in violation of discipline, and ultimately paid a high price. The destruction of Hengyang election case and Nanchong canvassing bribery case that strengthen election discipline, serious election discipline of necessity and importance. The discipline of publicity to the public, wide report, that is, early warning, early hit precautionary needle, tell the cadres should do what shouldn't do, what to do and what not to do, and better education of cadres, warning cadres, and build a strong line of defense, to avoid the occurrence of similar problems. There is duty. Serious discipline, with a strong team is an important starting point. As the leadership of the party members and cadres, take the lead in the implementation and take the lead in upholding the election of discipline, which is a major political responsibility. Must be clear requirements, strict constraints themselves, cherish the honor, safeguard the image of the organization; promote righteousness, play an exemplary role. Especially as deputy Township, but also to give a full play to its role, always stand in the discipline of first-line maintenance. The wind Su Ji through the election of the work of the whole process. (II) serious discipline, treat correctly leave turn as a cadre of the party, whether it is in, is back, stay, turn are organization Metabolism of entrepreneurial career, need and development need. So, his first with a broad mind to treat "leave turn". The position is officer positions, power for the people service tools. Different positions of the party's cause, plays a decisive role, the same important. To ability strong, style of comrade to important positions and applause, is full of vigor and vitality and promising young cadres in leadership and cheer for their own "leave turn" and calmly face, calm place. Second is to a healthy state of mind to treat "leave turn". The personnel of metabolic, between the past and the present. Cadre new old alternant, team, push In the party constitution control strict working to career development objective need, is never the end of the historical process. Each a cadre must face up to the laws of nature to think we also took the former relay baton "go on leadership post, regardless of the current positions, positions and responsibilities have what change, can do for peace of mind and mood, such as water, in a happy mood. (3) carefully and find out the problem, correct understanding of themselves, even though they do conscientious, serious attitude, honesty in politics, but high standard < >, the control standard, especially control learning, striving for excellent activities emerge in large numbers of advanced characters, advanced deeds Static not consciously practice the "strict three real" and strengthen the party spirit accomplishment to find the gap, swing is insufficient, a clear direction, mainly manifested in the following aspects: one is the learning initiative and self-consciousness. Often busy with work as an excuse, not consciously take the initiative to spare time to learn. Is often superior to learn what to learn what, and work closely to learn, and working relationship is not less to learn. Mainly manifested in the theoretical study is not thorough, system is not thorough, the Marxism Leninism, Mao Zedong thought, Deng Xiaoping Theory and "Three Represents" important thought, the scientific concept of development and learning, general secretary of the series of speech learning, just from the surface on learning In the less less less and not deep enough, not from the deeper study, to study, to understand, to sentiment, to use, to guide the work. The second is to investigate the research. This year their participation in the county, the county government's important meeting, the town Party work time is more, coupled with the specific affairs busy, in-depth primary research time reduced. The inspection was carried out research activities, there are surface examination, thematic research, listen to reports and discussion research, the general requirements and specific guidance, in a certain extent, affected the timely discovery and solve. Third is the level of leadership, leadership and need to be further improved. Stroke the personnel selection is positive, work coordination and cooperation can't to the best effect; in the coordination to deal with some complex problems, the approach is not enough. Especially encountered, time is tight, the task is heavy, is often the soldiers to be blocked, the water to soil cover, struggling to cope with. The global and forward-looking innovation is not enough. (4) to ensure that the transition delicate gas selected loyal to the party loyal to the people of leading cadres (recommended) for the county to provide accurate information to ensure the transition in the air, after the general election of work have a greater change. The second is balanced, promote the work in an orderly manner. In the future a period of time, the transition will be in the county under the leadership of the Extended surface. And breeding industry and the construction of key projects also in actively, they have to seriously consider, overall transition and key projects to promote. Education team members and the town, village cadres actively participate in industry cultivate the work, with outstanding achievements to accept the assessment of test of the organization and the masses of the people, in the town set up promising is a strong general business and the right atmosphere general election, do election and projects to promote the two not mistake, the promotion of two. Second, the rectification measures One is to enhance learning, awareness raising, he will continue to strengthen learning, improve the level of awareness, their own unity of thought and action to the county, township party committee of arrangements for the election. The second is correctly, strengthen discipline, own the right of transition, a matter of personal leave turn, as a town, deputy secretary of Party committee, themselves are fully aware of the only serious work, strict demands on themselves in order to not negative expectations of organizations and the masses, so that individuals can well deal with good transition in personal leave turn. Three people on the election promise as Deputy Secretary of the Party committee, in the election of my solemn commitment to Catch: if a is strictly abide by and take the lead in the implementation of the "nine is prohibited, nine" transition discipline, not to engage in cliques, not to engage in canvassing votes buying and selling, buying, and no fraud swindlers officer, do not intercede say hello, not illegal, not to run gas leak, do not interfere with changing times, accomplish strict discipline, warning, with iron discipline firmly put unhealthy trends, promote delicate gas to ensure transition in the healthy and orderly development; the second is resolutely obey organization arrangement, and resolutely to stress the party spirit, principle, discuss overall situation, correctly treat personal leave turn, the correct treatment the election results and focus on their careers, from start to finish, ensure the normal and orderly develop. For in-depth study and implement the party's eighteen, the eighth session of the fourth, the spirit of the fifth plenary session, the implementation of comprehensive strictly required, a solid grasp of the construction of Party member team, in accordance with the requirements of the county Party Committee Organization Department No. 3 (2016) Luo Zufa. According to the requirements of the < Chinese Communist Party Constitution > and the central work of education for the party members, combined with actual town, 2016 Party member education and training scheme is formulated. The guiding ideology adhere to a comprehensive study of implementing the scientific development view as guidance, in-depth study and implement the party's eighteen, the eighth session of the fourth, fifth plenary session and the General Secretary Xi Jinping series important Speech adhere to the application for promoting learning, and strive to improve our ideological and political quality of Party members; firmly establish catch a party to build pipe must be members, tube members first catch education of ideological understanding, close to the Party member's ideological and practical work, strive to build a party regular education work mechanism, promote the party members play a vanguard and exemplary role; firmly grasp the construction of ability of administration of strengthening the party, advanced nature and purity of construction of the main line, adhere to to enhanced grasp the party building work consciousness, strengthen the self construction of the party organizations as the fundamental starting point, for the town's economic and social development provided for ideological and political guarantee of the strong and powerful organization guarantee. Second, target 201 The main task of 6 years of education and training of Party members is earnestly implement the <2015 - 2018 XX County Education and training of Party members to implement views > (Luo Wei do [2015] 121) to further strengthen the work of the education and training of Party members request, to training the town, the grassroots party members and common. From 5 January 2016, through a variety of channels in a variety of forms in a planned, step by step, to focus on the organization to carry out the education and training of Party members. A party spirit idea generally enhanced. Through education and training, prompting the majority of Party members to further strengthen the ideal and faith, enhance the party concept, consciously practice the agency will socialist core value system. To further enhance the confidence of the road of socialism with Chinese characteristics, theoretical system of self-confidence and confidence. (II) Party members working ability greatly improved. Through the development of education and training, to boost the knowledge structure of Party members transformation and upgrading, improve the party to use the Marxist stand, viewpoints and methods of analysis and problem solving ability, adapt to the new situation and new tasks. (3) play an effective role of Party member model. Through the development of training and education, promote the party members in theProduction, work, learning and service to the community in give full play to the exemplary vanguard role, and actively striving to take the lead in learning to improve and take the lead in striving for success, serving the masses to take the lead and lead law-abiding, take the lead in promoting the healthy atmosphere model. (4) the building of grassroots organizations strong impetus. Through the development of education and training, the Party member troop overall quality and ability to serve the people increased, grass-roots party organization's creativity, cohesion and combat effectiveness of the improved. Contents and measures according to different type of the town, at different levels, the actual needs of the different positions of Party members, hierarchical class to carry out the education and training of Party members. Adhere to the town overall and please tutoring, please Come in and sent down the combination, to the party spirit education and ability cultivation as the center, overall constitution and discipline, the core value system, political theory, domestic and international situation in town situation, party organization construction, legal education, culture, science and technology, industrial development, management, resource management and protection, social management innovation in the aspects, to village (unit) as a unit, to all members of the organization a above rotation activities. Focus on Township and village committee cadres straight unit leading Party group secretary, activist of join or be admitted to the party, the education and training of village class mothball cadre training, efforts to strengthen the parties organization Secretary of party spirit accomplishment, do a good job of the consciousness of the party building work, enhanced the Party activist , people in rural areas to promote rural economic development of practical abilities. At the same time, through the development of the theme of practical training, autonomous learning training, make full use of the party members and cadres of modern distance education network etc., for the party members in various fields to carry out the classification of rotation, party spirit training, tobe grind quality, improve quality. Organizational Leadership (a) strengthen leadership, implement the responsibility. Town Party committee to the work of the education and training of Party members into the party building work important content, the overall responsibility of the Secretary of the Party committee, vice secretary of the lead and the implementation of specific members of the organization, the organizational Secretary of the parties to personally plan, personally deploy, supervise the implementation; the education and training of Party members to carry out into the grass-roots party Construction work responsibility system and the building of grassroots organizations special assessment, directly with the grass-roots party organizations Pingxianpingyou link, to strengthen the organization and leadership to do a good job of work to implement. (II) the overall progress, implement the plan. Ensure that the deployment, according to the arrangement of the 2016 Party member education and training plans, based on the actual needs of the party, on-demand rationing; do supervision and guidance, strengthen the supervision of the work of the education and training of Party members, guidance and services to help solve the difficulties and problems in the training; assessment, by listening to the report, information search, evaluation, etc., with emphasis on the assessment of the implementation of the plan, Party members to participate in training proportion and effect, indeed Protect task implementation. (3) the typical guide, step up publicity. Pay attention to cultivate advanced and typical, timely promotion and the typical experience of the characteristics of the practice. The work of the education and training of Party members as the focus of the grass-roots party building and the sector skills training for communication and advocacy, by setting the column, offering special journals and other forms of propaganda, to create a strong atmosphere of public opinion, promote the orderly conduct of the work and achieved certain results. In order to further implement the General Secretary Xi Jinping series of major speeches about the party's work style and clean government and anti-corruption struggle spirit and the central, province, city, County Commission for Discipline Inspection and the spirit of the plenary session, to further strengthen the awareness of the loyal party members and cadres, sense of purpose, sense of responsibility and a sense of discipline, boost the county's economic and social development. In accordance with the ensemble [of Ji Qing 2016) spirit of the document No. 3, combined with my bureau actual, make this program of activities, and a theme of learning party discipline, strict discipline, boosting Qingshen development. Second, activity time April 2016 1 - April 30, three, activity content (a) carry out party discipline learning activities. Global organization of cadres and workers to focus on learning, network learning, self-study and other forms of strengthen constitution < < the probity of the Communist Party of China self-discipline criterion "" Chinese Communist Party disciplinary Regulations >, < Xi Jinping on clean government and anti-corruption fight discusses excerpts > and other relevant information learning. Education for Party members and cadres to < code > < Regulations > as the ruler, combined with its work, measure, control and their own ideas and practical test, take the initiative to conduct Lianzheng is affirmatory consciously practice commitment, achieve the hearts of the party, Zun Jishou Confessions of readings of the Si > < confessions to carry out the hearts of the people, in the heart has the responsibility, in the heart has quit, maintain the party's advanced nature and purity. (2) to carry out special warning education activities. In the global "read < > writing experience, the concept of warning education independent micro film > reflections, prisons and courtroom free" as the main content of the special warning education activities. Use of the weekly worker will focus to watch a warning education. The < >, cadres and workers to write their feelings, reflections, and the clean publicity column posted; 4 month global organization of Party members and cadres to the eyebrow delta prison visits to detainees xianshenshuifa education of cadres and workers With low-cost combined with special method. (3) to teach a class of anti-corruption initiate cheap course. By the leaders of anti corruption and financial supervision and administration of state-owned assets of explain the profound things in a simple way to explain, so that all staff of honest business, according to the law to act in a more profound understanding, so as to enhance staff's sense of responsibility and sense of mission. (4) to promote innovation to help the family activities. To carry out the party members and cadres "motto, bright family traditions" activities for family education into harmony, filial piety, encouraging learning, goodness, thrifty, inspirational, cultivation of excellent genes to guide Party members and cadres to good tradition folk, with a good tradition being honest, with good tradition promote political winds, creating a delicate gas is the general atmosphere. Four activities (a) to strengthen leadership, careful organization. One is the establishment of the "independent warning education month" activities leading group of the state owned Financial Bureau, bureau leading Party group secretary of the leader, board members of the team to serve as deputy head. The second is making < County State Owned Financial Bureau independent warning education activities month scheme > determine promotional content, clear steps, truly understanding, measures, and put in place, ensure the effectiveness of the activities. (II) take all factors into consideration, pay attention to actual effect. According to "strict three real special education and" two studies do "activities, in based on the provisions of the action without aliasing, and creativity to carry out various forms, rich and colorful activities, and strive to Pay attention to actual effect, and resolutely prevent, going through the motions, really promote the party members and cadres from the depths of the ideological solidating abide by discipline regulations of the defence. (3) strengthening propaganda, to create atmosphere. To make full use of the column publicity, propaganda position of network, increase publicity efforts, expand warning education activities of the coverage and influence. Today, we hold the city's precise technology to poverty alleviation and project work to promote the meeting, the main purpose is to further promote the task of aiding the poor with technology roots and accelerate all kinds of scientific and technological projects. Last year, this year, the city's scientific and technological work has made remarkable achievements, such as the convening of national poverty alleviation of science and technology on the spot will, cultivate high-tech enterprises, Bashan scholar training and the introduction of scientific and technical personnel incentives, listing national agricultural science and Technology Park, science and technology incubator building. Just now, Huangli In recent years city science and technology to help the poor and science and technology project effectiveness, the main problems were analyzed, and in a period of time in the future, the city's precise technology to poverty alleviation and science and technology project work arrangements, I agree, I hope everyone to earnestly implement. Here, I stressed the three points. Learning "learning", to carry out the "learning and doing" education as the city's innovation and development of an important driving force. The Party Central Committee decided to 2016 years in all Party members to carry out learning the party constitution, party rules, a series of speech, do a qualified party member education (referred to as "learning to do"). Some time ago, I called the "learning the party constitution, party rules, a series of speech, do a qualified party member education and mobilization, the province carried out within the" two a "learning education mobilization. Municipal Party committee will soon be held a mobilization will make arrangements for the deployment. To carry out the" two a "study and education, based on" learning ", key in" do ". As the science and Technology Department of cadres and workers, to (benchmark for two pilot demonstration study through studying the party constitution of party compasses, a series of speech, not only to do a qualified party members, to do a good job of science and technology innovation. Next week, I as the city's county-level leading cadres reading class open cooperation and innovation driven study group members went to Mianyang, Meishan national innovation driven development characteristics and the province's Innovation Driven Development Zone work experience, a great harvest, feeling very deep. Mianyang, Meishan city innovation driven strength is very great, especially is Mianyang has become civil military integration, a comprehensive reform and innovation, our benchmarking in Mianyang, the gap is very large. Mianyang Science and technology city construction as the basis, built around the "Five" goal of building Hotbed of innovation of construction science and technology, military and civilian fusion demonstration, collecting and distributing center of scientific and technological achievements, innovative talents convergence and high technology industry concentration), vigorously promote to military and civilian fusion for the characteristics of comprehensive reform pilot innovation, and achieved remarkable results, is toward the national civil military integration innovation demonstration area, the national innovation driven development characteristics demonstration area and western economic development growth emerging great step forward. The expanding Park, stronger innovation platform; incubated enterprises, cultivate innovation; poly talent, to improve the ability of innovation; promoting fusion, highlighting the characteristics of the innovation; catch open, form innovation efforts of the experience is worth learning from. Benchmarking advanced, we have to struggling to The amount of weight is to grasp to catch the strategic innovation. To improve the target oriented system. The innovation actually placed in the core position, firmly establish the "grasping innovation development, seek innovation is to seek the future, innovation is not backward, slow innovation also will lag behind" concept, accelerate factor driven to innovation driven change. City Branch Bureau to actively seek the city management system emphasizing the innovation driven development, focus on strengthening the scientific and technological enterprise incubator construction, scientific and technological innovation platform, technology oriented small and medium-sized enterprises to cultivate, high and new technology industry output value and product evaluation. Second, we must built innovation and Entrepreneurship platform. The city will be in Pakistan and the open area to build the whole To confidence, "double center", the new industrial park for a period, the city public entrepreneurship Park Phase II, Qin Ba electricity supplier industry park for three period, incubation area of more than 50 million square meters. The county (District) to take advantage of idle assets of construction science and technology enterprise incubator, a passenger space and other new public record space, the formation of a, a, a, to create vivid situation. Third, we must foster technological innovation subject. To vigorously implement the "high and new technology enterprise doubling plan" and "science and technology oriented small and medium-sized enterprises to cultivate plan", to honor the implementation of tax incentives, financial subsidies, such as a package of policies to support, so that high technology enterprise "indomitable spirit", let the small and medium-sized enterprise "overwhelming". To increase investment in science and technology innovation. To actively seek special funds for the development of Municipal Science and technology part for cashing innovation drive the development of financial subsidy policy, transfer a portion of funds for science and technology enterprises of loan guarantees and interest subsidies. Encourage banking institutions set up science and technology branch of the franchise, push the patent pledge loan, for the small and medium sized enterprises of science and technology provide financing services tailored. Fifth, we must strengthen science and technology personnel. To attract more technology military personnel and high-end talent with technology, project, with funds to Bazhong Lingban or joint science and technology enterprises, encourage and support both inside and outside the citycomrades and the5 years of college graduates and college students to a new public space, science and technology business incubator innovation and entrepreneurship. Second, it is necessary to promote the precision technology poverty alleviation as the important content of the scientific and technological work. To build a well-off society in an all-round way by 2020 is the party's eighteen to the whole Party and the people throughout the country to make a solemn commitment. Lead the city people out of poverty to become rich go straight towards well-off, Party committees at all levels, political responsibility and mission of the times of the government's major political, technology sector is also the bounden responsibility. Municipal three tenth plenary session made < on the go all out win battle poverty alleviation and development to ensure synchronous completion of a comprehensive well-off society decided >, proposed to further promote the "five a group of" precise action to help the poor, "six precision" and "1 + 6" poverty alleviation projects, clear the "add Great science and technology achievement transformation efforts, accelerate the construction science and technology poverty demonstration village and demonstration households, give full play to the role of modern information network, for the impoverished village poor households to provide production technology, market information, policy advice, encourage scientific and technical personnel to the poor village launched a to one helping and guiding the development of income industrial projects, strengthen technical training and propaganda of popular science, highlighting grasp large breeding, family farmers, agricultural co-operatives are the backbone of the training "technical poverty alleviation mission. The city's science and technology sector must be from the political height, the assault fortified positions that help deficient up as the most important task, the most urgent work. The most arduous mission, to science and technology for precise poverty alleviation promote to speed up a well-off society in an all-round way Decision to deploy, boost the process to precise technology to poverty alleviation and the effectiveness of a well off society in an all round way. One should obey the overall situation. The city's scientific and technological system of cadres and workers, especially leading cadres, should have the political consciousness, ideological conscious action conscious, in accordance with the central, provincial and municipal deployment requirements, to strengthen the organization and leadership, reasonable arrangement of time, carefully study the deployment, to ensure poverty. There must be resolutely implement the political position and character, poverty alleviation and the attitude to be distinctive, poverty alleviation action should be strong, to politics, to understand the overall situation, re implementation, see results. To lock the target. In accordance with the provincial Party committee and the municipal Party committee, municipal government, lock 2 provincial-level General requirements for the completion of the goal of poverty alleviation poverty alleviation poverty alleviation poverty alleviation poverty alleviation poverty alleviation and Technology Demonstration County, four provincial science and technology demonstration towns, 10 provincial science and technology demonstration village and a municipal science and technology demonstration area, 2 Municipal Science and technology demonstration towns, five municipal science and technology demonstration village and the "five one" precise technology to poverty alleviation and special operations tasks, inverted duration, wall chart battle, set the time, tasks, measures, staff, given the responsibility to ensure high quality precision technology poverty alleviation task. To focus on the key. To focus on precise poverty and accurate out of poverty, detailed measures, clear job responsibilities, to develop targeted and operable precise technology to implement poverty alleviation program. Prominent precise poverty technical training, poor village informatization construction, technology oriented poverty reduction model village and demonstration households construction precision technology poverty alleviation focus, in a precise sense, precise attitude, precise style, go all out to fight the precise technology of poverty alleviation and battle. Three, it is necessary to strengthen science and technology funds supervision as an important means to enhance the quality of the project. Science and technology project fund supervision is the key to the implementation of the project of science and technology. In recent years, especially during the "Twelfth Five Year Plan" period, the system of science and technology management in the city vigorously to declare the implementation of the country and province science and technology projects, science and technology demonstration lead brought obvious effect and improve the scientific and technological innovation capability of enterprises, boosting the characteristics and advantages of industrial development, science and technology support to the economic and social leading role improved significantly. In the project management of science and technology, in addition to seriously implement the state, provincial science and technology project management rules and regulations, and the actual Bazhong, established the access system of science and technology projects, the project of science and technology commissioner system, science and technology Project credit system and scientific and technological projects honest commitment system, and the Municipal Finance Bureau jointly issued the > < Bazhong City Science and technology development funds management approach, formulated the "trilogy of seven" science and technology project implementation specification, these are worth fully affirmed. However, we should also see clearly, we in the science and technology project management still exist "account of the special accounts, earmarking system is no effective implementation and other issues. In particular, this year the Audit Commission Chengdu Tepai ban on Bazhong confidence found in the audit of science and technology business incubatorProblem has certain representativeness. The audit to us sounded the alarm, should cause everyone vigilance. Here, I will strengthen science and technology project budget supervision put forward four requirements: a strict project reporting, prevent fraud. Implementation of the project to declare the competition mechanism, the annual financial support to science and technology projects oriented society Bulletin, conditions open content, open competition to declare, open field investigation, public presentations, the public assessment of the decision, do full open and transparent, fair, accept social supervision. To those who resort to deceit or something real is not clear, suspected of defrauding, impersonator national subsidy funds, once found immediately cancel Declaration of qualification, recovery of funds subsidy and discipline in accordance with the law strictly held responsible. Second, we must innovation funds supervision. In county finance to establish science and technology project "account", the project undertaking entity in accordance with the key nodes task completion by formal invoice to apply for funding and audited by the Department of science and technology, the Ministry of finance funds, and resolutely put an end to project funds are retained, misuse and misappropriation. Third, we need to strengthen scientific and technological project supervision. Department in charge of science and technology to strengthen project inspections to check or checks, of ineffective implementation to strengthen the supervision and the existence of violations of responsibility into the project undertaker rectification. To establish a scientific and technological project, "black list" system, the Project implementation quality particularly poor recorded in the "black list", stage or permanent abolition of the applicant country, province, city science and technology project qualification. Fourth, it is necessary to carry out training funds management. Science City Bureau to the initiative to meet with the finance department, organize project unit commitment held science and technology project funds management training, of country, provincial and municipal science and technology project funds management of the relevant policies, financial acceptance specification, mid supervision points, budget review points and key contents were training system, to ensure the use of project funds safe and reasonable. Thank you all! To implement the central, provincial, city and county to make important decision about the grass-roots party construction work in the deployment, push forward the county public security organs in the work of Party building, further strengthen the party secretary of the governing party and party liability, according to < of the Organization Department of CPC Committee of Xuchang County on the issuance of the "counties as well as the authority of Party building debriefing appraisal implementation solutions" notice > requirements, according to the arrangement of the Bureau of the party work. Today, the organization held the county public security organs party secretary grasping grass-roots party construction work in the debriefing will. The implementation of this is a powerful measure to the Secretary of the party organization construction of the party,, and is learning to carry out the party's spirit of the Fifth Plenary Session of the eighth session of the, grasp the new situation of Party building work under the rules, pushing Public security party building services in the public security center of the inevitable requirement. Just now, the 3 Juzhu unit Party branch secretary of debriefing, below I on the 3 party organization work one by one review. Party branch of the Political Department Good: first, strengthen ideological and political work, pay close attention to the work of the implementation. The Political Department of the Party branch strictly in accordance with the requirements of bureau Party committee, to "strict three real special education as the main line, take effective measures, pay close attention to the ideological and political work of the implementation, strengthen the education of Party members and the police thought, improve the Police Ideological and political consciousness, make a solid foundation for public security work smooth development of health. Second, strict management team, boost the morale of the team. Strict implementation of Police Ideological Trend of periodic analysis, timely grasp the ideological situation of the personnel; strictly implement the system of check on work attendance, strengthen the daily management; cash rewards and punishments, continue to boost the morale of the team. The third is The intensification of police training, improve the police actual combat skill. Seriously and actively carry out a series of training activities and < Henan public security network, > learning activities, the majority of police in the political quality, physical quality, professional quality, policing skills improved. The fourth is to adhere to the preferential treatment from the police, the warm pool police. According to thRequirements, and actively do a good job of personnel management work, to run within the scope of the policy, help the police solve the practical difficulties, the police systemic heart into work. The fifth is strengthening propaganda, promote righteousness. Around the center of the public security work, actively do a good job in the publicity, fully display the spirit of good public security team. Six is to fulfill the responsibility of Party building, do a good job of education and management of Party member team. Sound and perfect "three class", Party of democratic appraisal, commendation and reward system, effectively enhance the branch of the creativity, cohesion and fighting capacity. Shortcomings: is ideological and political work still can not adapt to the new situation, new task, in the form of a single, innovation is not enough, lack of learning education of the appeal and study the effect of education needs to be improved, the political department to strengthen the guidance to the grass-roots units. The second is the branch of organizational life will implement the is not good enough to play an exemplary role. Traffic Police Brigade Party branch System of good practice: one is grasping the implementation of the work of Party building system, enhanced branch team cohesion, combat force. The brigade Party branch always pay close attention to the work of Party building and would not let go, conscientiously perform their duties, strict implementation of democratic life etc., to develop the branch of learning plan, all equipped with learning record the experience and experience the and organize regular inspection learning, ensures that the learning plan, implement, effect. Second is to carry out the "strict three real special education. The development of special education learning scheme, held a party branch focus on learning and the level of consultation forum, deputy director in charge of, brigade leader for the party members and the police on the lectures, deployed to carry out Ban Zicheng throughout the Yan Zhenchang Yang Shuicai to relive the oath to join the party, visit the memorial hall, learning advanced characters, micro lectures attention and learning characteristics of the activities, and to develop measures for rectification. Three is to pay attention to the party building work into the public security work. The brigade Party branch and always will be the work of Party building in 9.3 security, national civilized city re examination, the SCO security meeting, the focus of illegal investigation, "sword", "anti terrorist violence, to ensure safety", "five wave", "camp turn non bus", "detoxification", the focus of the work, in a timely manner to carry out the pre war mobilization, wartime dynamically judged, the post-war award in recognition of a series of measures Members always fighting in the first line of traffic management, all traffic police has always maintained a high state of mind, a strong impetus to the work carried out. Shortcomings: first, there is a "hand hard and soft" phenomenon. Of work of Party building under the new situation is not enough emphasis, focus on light business building, re form light effects. The second is measures are not enough effective. In particular, catch a party to build working innovation consciousness is not strong, measures and methods used in the experience of the old, old practices and effectiveness needs to be further strengthened. The third is three lesson "not very good insist, life of the party organization to carry out less often. Zhao police station Party branch Good practice: one is to strengthen the study and education. To "strict three real special education as an opportunity to take leadership lectures, seminars, individual learning, exchange of experience in various forms, the police organization learning leaders at all levels of the spirit of the important speech, < > in the constitution as well as the side of corruption cases and asked party members and the police carefully recorded study notes, writing experiences, join and pay attention to the micro lectures, according to the control requirements of inspection, enhance their own, to ensure that the learning effect. The second is to strengthen the leadership responsibility. Party branch secretary as the first responsibility of honest government, earnestly implement the" four person ", and insisted on the" important work personally Department Department, major issues personally intervene, personally key aspects of coordination, supervision of important cases personally ", Party branch members always strict demands on themselves, play an exemplary role model. Third, strengthen the service for the people. Every act of the masses for the warm reception, carefully recorded masses anti reflect each a problem, and make the resistancee bureau Party committeeHeart to answer, and constantly improve the quality of service. Combined with the "one village, one police work, police organization carefully touch row all may affect the stability of the unstable factors, resolve conflicts and disputes, and arrange for the police with daily visits, issued security leaflets, collecting sites, personnel information, promote the harmony police. Existing problems: a party branch team party affairs knowledge is not rich enough, on some of the procedural provisions are not familiar with, in a certain extent restricted the work carried out. The second is regular ideological education is not deep enough, the ideological trends of the police command is not timely and accurate. Third, there is a need to improve the management level of refinement, police standardization awareness is not strong enough, daily habit is not quite self-conscious. Since this year, bureau unit Party branch to "strict three real special education as the main line, to the service center, troop construction as the focus, adhere to the combination of ideological building of the party and the system of the party, solid to carry out the comprehensive strictly required, to further standardize the construction of the party organization, continuously improving the quality of Party members and police, continue to strengthen the party building innovation, service building execution significantly improved, has made remarkable achievements. Meeting debriefing of 3 units in the work of Party building problems in other units are also different degrees of existence to other units by the party building debriefing, draw on the experience of face the problem, replicability, careful analysis of rectification, promote the sustained and healthy development of the work of Party building units. Below, to further strengthen the county public security organs party building work stressed the views of five points. One, improve the ideological understanding, enhance the sense of political responsibility and historical mission Follow the basic construction of the party's eighteen years, Xi Jinping, general secretary: the series of important speech to the party put forward many new ideas, new judgment, the new requirements is to promote grass-roots party building work. We should thoroughly study and understand, and consciously assume responsibility. One is to grasp the party building "three questions" of the new requirements. Xi, general secretary of the party's mass line education practice summary of the General Assembly on the proposed the construction of "three questions, namely:" is not the party committees at all levels and the departments of Party committees (party) to achieve the sedulous catch a party to build is not at all levels of Party committee secretary, the Department of the party committees (party) secretary become strictly administering the party secretary? Is not at all levels and all departments of the party Forced the construction of Party committees (party) members to fulfill the responsibilities strictly responsibility? "General Secretary of the party building" three questions ", directed at the crucial point, enlightening, three mirror placed in front of everyone, let you according to a photo, see a look, want to think about the conscious of it, is the three pieces of papers placed in front of us, it is clear to judge ourselves whether in to do their duty. Building" three questions ", urge people to watch, thought-provoking, and convey a strong responsibility to ask signal. The second is to understand the building" three no "new judgment. Xi, general secretary of the party's mass line education practice summary congress pointed out that" history and reality Are accounted for in the police forces of discipline, do not do, is to stop the event tells us, not a clear responsibility to implement the responsibility, accountability, and strictly administering the party is not to ". General Secretary of the" three no ", a clear responsibility to implement the responsibility, accountability, and point out the key. The county public security organs is a team of the Communist Party as the main body, Party members and the vast majority of bureau of belonging to different units of the leadership cadres and backbone of the party members, the power and responsibility are relatively concentrated in the party's construction, must be clear responsibilities, the implementation of responsibility, accountability, or catch a party to build is an empty word. Three is to clear the" three grasping "new initiatives. The total learning book Remember that catch a party to build must grasp the responsibility system, grasping accountability must grab the responsibility person, grasping the responsibility must catch the first responsible person. Why should we let the Bureau unit Party branch secretary of the debriefing is to implement general secretary put forward "3 catch". To seize the party organization's primary responsibility, seize the key issue. Two, the full implementation of the task of ideological construction, the theory of armed tasks implementedGeneral Secretary Xi Jinping in the mass line of educational practice summary congress put forward in the new period party building thought of tasks and requirements, to strengthen the construction of the Party pointed out the direction and path. One is to strengthen theoretical study. The urgent task is to fully understand the study and implement the spirit of the fifth plenary session of the eighth session of the significance of, the organization of Party members and the police through the focus on learning, self-study and special counseling and other forms of serious in-depth learning, adhere to the first step in learning, deep layer, accurately grasp the spirit of the Third Plenary Session of the Eleventh Central Committee, and do the thinking and learning gains, use it. The second is to strengthen the party spirit temperance. Adhere to the school party constitution. Through the center of the group learning. Secretary of the party organization about lectures and other forms of learning the party constitution, enlightenment spirit, guide Bureau unit Party branch and all members of the police to firmly establish the consciousness of the party. Persist in learning advanced. Vigorously carry forward the spirit of Jiao Yulu, Yang Shuicai spirit, seriously study the advanced deeds of Comrade Yan Zhenchang, deep fine shine Dusing the police party guided, to strengthen public opinion and public servant consciousness, consciously practice the "strict three real. The third is to strengthen the party and Party discipline education. For the ideological construction of the party faces new tasks, new requirements, the emergence of many new problems, new situations, and actively take the initiative to adapt to the constantly emancipate the mind, innovative ways, making use of the Internet, micro channel, micro Bo new platform for new, enrich the content of education, improve education forms, the constant reminder education, enhance the police Party discipline in awe, guide Party members and the police do political understanding discipline about the rules of the leaders. The fourth is to strengthen the ideological and moral education. Guide the party police exemplary practice the socialist core values, cultivate good political and moral character, professional ethics, family virtue and morality, forming a strong atmosphere of moral construction. Pay attention to strengthen the positive guidance to the police party ideology, adhere to the diversification of the social ideology guided by the system of theories of socialism with Chinese characteristics, improving and perfecting the Party members and the police thought The dynamic analysis of mechanism, providing an ideological guarantee for the purity and firmness of team members. Three, fully implement the strict requirements, the management and administration of the party's responsibility to implement General Secretary Xi Jinping stressed that to implement strictly the responsibility, do a good job of Party building as the biggest achievement. Therefore, in my bureau implement comprehensive strictly required must be the party tube responsible party implemented. First, to further implement the responsibility system in Party building. To establish and improve the party building responsibility assessment mechanism, at the beginning of the year to progressively signing party builds working target responsibility book. Party organizations at all levels is mainly responsible for comrades to do a good job of Party building as the greatest achievements, adhere to the development wholeheartedly for, to concentrate its attention on the construction of the party, the party building work is included in the agenda, and business to work with the deployment, with checks, with the implementation of, true to form Party grasping, Secretary to take the lead in efforts, in charge of the leadership Specific catch, catch a, layers of implementation pattern of Party building work. Is to improve the reporting and appraising system. In accordance with the "debriefing the party building, the appraisal rating of Party building, Party building assessment test, use of cadres at request of the party", CF county Party debriefing practice, and constantly improve the annual party built debriefing appraisal system, in particular, to the year debriefing appraisal evaluation and annual comprehensive examination closely together, the party builds the job evaluation results into the leading bodies and leading cadres of the annual comprehensive assessment system, strengthen the use of dynamic management and results of debriefing appraisal work, further enhance the debriefing appraisal of scientific, effective and directive The new integration business. Three is to improve the "three class" system. "Three class" system is to improve the party's organizational life, strict party member education management system, we must do a good job in the implementation and long-term persistence. According to "the party secretary of the organization lectures", "party members and cadres micro lectures and Thematic Party Day activities, innovation" three class "form, rich" three class "content, pay attention to the work of Party building with the public security work, the formation of" the same resonance frequency, the linkage of communion "party organization life situation. At the same time, the" three class "system implementation of join or be admitted to the party organization committee debriefing appraisal of important content, strict grasp the" three class "system Real. Four, strict political discipline and political rules. Guide all Party members and the police in ideological political action always as the general secretary of the CPC Central Committee with Comrade Xi Jinping highly consistent, involved in major political principle, political stand, political views and other issues, we must be sober, stand firm. Guide the members of the civilian police to strengthen the sense of organization, determined to do the individual is subordinate to the organization, the minority is subordinate to the majority, the lower level to the higher level, and the whole party to the Central Committee. Some time ago, I held a party enlarged meeting, focus on adherence to the party's political discipline and political rules of thematic theory study, I at the meeting for the feelings to speak. I understand, party a concept of organization, can not see Party, touch not. According to the materialistic point of view, the material determines consciousness, existence determines consciousness, consciousness is the objective things in the brain to reflect, then, how to prove that the party's existence? Like the current, can not, can not be touched, but through the wire carrier, connect power supply, the electric light, the motor is running, it is proved that the current existence. Similarly, the party is by living every Party member, every Party member, speech and action of the carrier, reflecting party. Party is a whole, in order to normal operation, each party members according to their personality characteristics. Academic knowledge, professional knowledge, hobbies, physical condition, age, work experience, work experience and other comprehensive evaluation, main task of the division of labor and in jointly do a good job in party work, is mainly responsible for the Division I business, then in my division of work, in the Party committee collective discussion by, decision, foreign, on every level of members can to bureau of the party in the name and identity delivered a speech, the organization of work. In specific work, in the higher Party committees have clear provisions of the spirit, in accordance with the spirit of the documents of ranking Party committee, combined with my work of the division of labor, on behalf of the bureau Party committee put forward their views and suggestions. Since Party members according to the higher Party committees to the spirit of the document can be Bureau on behalf of the party organization of work, then the behavior has party authority and seriousness, we should respect them and be with, give support, cannot according to personal preferences, personal understanding and awareness, regardless of the occasion, in broad daylight, in meetings, especially in the lower front of, guilty of liberalism, published the higher Party committees have been expressly prohibited speech, also cannot euphemistically called the personal point of view; regardless of party image and personal image, irresponsible, gossip, just open the river, grumble, grumble about; even, sarcastic ridicule, sarcasm, oblique accusations, make people Hold the most stringent start speech, personal attacks, vent personal grudge; more even, with ulterior motives, ulterior motives; fan Yin breeze, will-o '- the wisp, deliberately and party dissension and discord, rumors spread, the spread of division, and the party and the people, the hearts of the people, the decline of morale. This kind of behavior is the party's discipline are not allowed, from my start, from the members of the Party committee member, once, who despite the party discipline, drunk, behind, the key moment, in violation of the party's political discipline, political rules and wait for the party discipline. We must strictly comply with the implementation of the central and superior party committee has clearly defined, does not allow bargaining, unconditional obedience, unconditional , does not allow a discount, or disguised discount. In addition. We want to strictly enforce the system of democratic life of the party, Party of democratic life, it is necessary to carry out criticism and self-criticism, is between the members of the Party committee of the mutual criticism, remind each other, will not do not speak, gossiping afterwards. Guide Party members and the police strictly request reporting system, regularly party members to execute the political discipline of political rules situation analysis judged and thematic summary, constantly enhance political of the political life of the party, the principle and militancy. Five, comprehensively improve the scientific level of Party building, the task of the party building To enhance the scientific level of the construction of the party is our party according to the worldly affairs, national and the new changes and new challenges of the party put forward the major issue is effective to deal with the four test ", resolve the pressing requirement of" four big risk "is the only way to maintain and develop the party's advanced natuStep is to strengthen the party's cohesion, attraction and the fighting power of the inevitable choice. Under the new situation, it is necessary to apply the law of the ruling party construction of Marxism, according to the basic requirements of maintaining the party's advanced nature, continue to study new situations, solve new problems, sum up new experience, make the party building in scientific orbit continues to advance. One to focus, efforts to lay a solid foundation. Continue to carry out the "two hit" activities, accurately grasp strictly required new rules and characteristics of the work of Party building under, deepening grass-roots increase of basic party organization and Party member quality upgrade plan. Continue to carry out the window units vanguard party post, window model building activities, and continuously Enhance the party members and the police involved in activities to create enthusiasm. Increase of Party organizations and Party members advanced typical advocacy training efforts to become a "sign", "evergreen tree". To broaden the party serving the masses channels, construction of Party members contacting and serving the masses work system, make the Party member to become truly keep in mind the purpose, advanced elements of the heart of the masses. Establish and improve incentives within the party, care, helping mechanism, we do care and love grassroots cadres, old party members, difficult life member. In order to promote the party construction services, continue to carry out "party members and counterpart assistance" live and on-the-job Party member volunteer service activities. Second, we must strengthen management, efforts to enhance the party members Quality, and conscientiously implement < the Communist Party of China the development of Party Work Rules >, adhere to strict standards, rigorous training, strict procedures, strict regulation and control, and continuously improve the quality of Party members, optimize the structure of Party member team. Strengthening of different kinds of police, the classified management of Party members in different positions, through the implementation of target management of Party members, record management, star rating etc. ways to strengthen the education of Party members, management and service work. Adhere to the mass appraisal, solid and effective to carry out members of the public commitment, no post party post duty activities, give full play to the role of Party members. Actively introduce the Internet +, by means of information to strengthen the education and management of the party members and make full use of "Xuchang male Ann party building network "," peace of Xuchang, Communist Party members, Liancheng micro lectures and other network platform to strengthen the education and training of Party members. Three to strict requirements, efforts to improve the party's style of work. To build a first-class units, to create a first-class team, cultivate first-class style, create first-class performance as the goal, combined with learning from the advanced models, and effectively solve the police party in the party spirit, moral character, style and ability existing prominent problems; adhere to the lead austerity, oppose extravagance and waste, and oppose formalism, bureaucratism and seriously practice the "strict three real, establish a good style of work; earnestly implement the" eight insist, eight against ", advocate diligence Excited to learn and apply what they have learned, the heart of the masses, serve the people, grab get right on the job really, and to ensure the effectiveness of, hard work, thrift, the overall situation, curried, develop democracy, solidarity work, impartially and with the right of honesty in politics, life is decent, healthy interest in eight aspects of good atmosphere, promote the county public security organs party political construction has made new achievements. Fourth, it is necessary to produce battle fort effect. Party organizations at all levels to grasp the practical to the center of the public security work service key links, adhere to the completion of difficult and perilous task as the main battlefield of the work of Party building, the more encountered serious incidents, major rescue mission, a major security tasks, the more you want to play the party organization The role of core, and earnestly do a good job before the war mobilization, wartime motivation, war veteran and so, truly party members and cadres to fight to where, the life of the party organization will extend to where, the role of fighting bastion of the party organizations play where, reflecting the party building work to promote and protect the power. Comrades, in the circumstances to promote comprehensive strictly new situation, the Party Central Committee and the Party committee of a higher level of the construction of the party proposed the new, higher requirements, the work of Party building task is arduous, the glorious mission, rare opportunity. Let us to the debriefing meeting as a starting point, in the Bureau of the party's correct leadership, conscientiously study and implement the series of important speech of General Secretary Xi Jinping, spirit and the party's spirit of the Fifth Plenary Session of the eighth, thoroughly implement the comprehensive strictly required, continue to carry forward the party's fine tradition, hearten spirit, do solid work, the enterprising spirit, selfless dedication, to continue to create the county public security organs of Party building work in the new situation, to maintain social stability to ensure Successful completion of the task,re, also is aPromote public security undertakings flourish, for the construction of a beautiful and happy Xuchang county to make new and greater contributions! Carry out the party building debriefing appraisal work, implement the central and provincial Party committee, the municipal Party committee and comprehensively promote the strictly deployment requirements, implement strictly the responsibility, tamp the foundation of Party Construction of major initiatives. Public security organs as the party's absolute under the leadership of the democratic dictatorship force, as the party and the people in the hands of the "hilt" must to strengthen the work of Party building and walk in the forefront, and make an example. From just four of the Secretary of the party organization debriefing situation, the party organization of debriefing of Party building and ideological work attaches great importance to prepare more fully, in the debriefing process, say achievements do not exaggerate, speak the problem does not cover, emphasize not vanity about rectification, truly realistic. Offer as Political Bureau Director comments, targeted strong, closely with the practical assessment highlights outstanding characteristics, ask clear, point out of the results, points out the problems and points out the pressure. This is not only a debriefing meeting and Party building the responsibility to implement, today the debriefing, to do a good job of new period party building work will play a very good role in promoting. Next, according to the city bureau Party Committee on Party building work on the arrangements, Bai chief commissioned by combining city Bureau of Party building work of new requirements, borrow this opportunity to revisit four points. To improve the ideological understanding, enhance the sense of responsibility and historic mission, the party's eighteen years, Xi Jinping, general secretary Follow the construction of a series of important speech to the party put forward many new ideas, new conclusions and new requirements, the grass-roots party building work. We should thoroughly study and understand, and consciously assume responsibility. One is to grasp the party building "three questions" of the new requirements. Xi, general secretary of the last 10 August, the party's mass line education practice summary of the General Assembly on the proposed the construction of "three questions". That is: "is not the party committees at all levels and the departments of Party committees (party) to achieve the sedulous catch a party to build is not at all levels of Party committee secretary, the departments of Party committees (party) secretary become strictly administering the party secretary? Is not at all levels and all departments of Party committees (party) Forced members to fulfill the responsibilities strictly responsibility? "General Secretary of the party building" three questions ", directed at the crucial point, enlightening, three mirror placed in front of everyone, let you according to a photo, see a look, want to think the self-knowledge; is the three pieces of papers placed in front of us, it is clear to judge ourselves whether the party's construction to do their duty. Building" three questions ", urge people to watch, thought-provoking, and convey a strong responsibility to ask signal. The second is to understand the building" three no "new judgment. Xi, general secretary of the party's mass line education practice summary congress pointed out that" history and reality, especially the Are substantially more than 80% of the discipline to move tells us, clear responsibility, fulfil responsibility, accountability, and strictly administering the party is not to ". General Secretary of the" three no ", clear responsibility, fulfil responsibility, accountability, and point out the key. The city public security organs is a member of Communist Party as the main body of troops and members accounted for total number of civilian police, the Bureau of belonging to various departments of leading cadres and backbone of the party members, the power and responsibility are relatively concentrated in the party's construction, must be clear responsibilities, the implementation of responsibility, accountability, or catch of Party construction is empty. Three is to clear the" three grasping "new initiatives. Xi, general secretary of the strong , catch a party to build must grasp the responsibility system, grasping accountability must catch responsibility, grasping the responsibility must catch the first responsible person. Why should we let Jushu unit party secretary to the party organization at the next higher level debriefing is to implement general secretary put forward "3 catch". To seize the party organization is mainly responsible person, seize the key problem. Second, it is necessary to improve the work of Party building system, the system construction is to strengthen the party building work of public security is an important guarantee. To through the scientific development of the system, improve the system, execution system and make the system become a hard bound, continue to promote the public security work of Party building standardization. One is to further implement the responsibility of Party BuilSystem. It is necessary to establish and improve Party building responsibility assessment mechanism, at the beginning of the year to progressively signing party builds working target responsibility book. Party organizations at all levels is mainly responsible for comrades to do a good job of Party building as the greatest achievements, adhere to the development wholeheartedly for, to concentrate its attention on the construction of the party, the party building work is included in the important process, and business to work with the deployment, with checks, with the implementation of, true to form Party grasping, Secretary to take the lead in efforts, leaders in charge of specific grab, grab a level, layers of implementation pattern of Party building work. The second is improve the debriefing appraisal system. In accordance with the "debriefing the party building, the appraisal rating of Party building, Party building assessment test, the use of cadres at request of the party", the Secretary of the party debriefing contrast do Law, and constantly improve the annual party debriefing appraisal system, especially to the annual debriefing appraisal evaluation and annual comprehensive examination closely together, the party builds the job evaluation results into the leading bodies and leading cadres of the annual comprehensive assessment system, strengthen the use of dynamic management and results of debriefing appraisal work, further enhance the debriefing appraisal of scientific, effective and oriented. Third, improve the "three will be a lesson system." three class system is to improve the life of the party organization, strict management of Party member education system must do a good job in the implementation, insist for a long time. According to the "Secretary of the party organization lectures", "Party cadres Implementation of integrating micro lectures and theme day activities, innovation "three class" form, rich "three class" content, pay attention to the work of Party building with the public security work, the formation of "the same resonance frequency, the linkage of communion" party organization life new situation. At the same time, the "three class" of the implementation of join or be admitted to the party secretary of the organization debriefing appraisal of the important content, strict grasp the "three class" system. To strengthen the education of Party members, improve Party member of party spirit idea and political consciousness. Xi General Secretary profoundly pointed out: "firm ideal and faith are the legal team of political soul must be the ideal and belief education in political and legal team construction of the first , constantly playing firmly hold high the banner, command of the party, loyalty to the mission of the ideological foundation. "The city's public security organs is a with Communist Party members for the disciplined subject, Party members accounted for more than 80% of the total number of civilian police, bureau of belonging to different departments of leading cadres and backbone basically is a party member, do a good job in the construction of Party member team, will seize the fundamental construction of public security team. We must seize the political construction of the police as the core, adhere to the party for public security work absolute leadership this fundamental principle, put the ideal and belief of party spirit education in a more prominent position, to ensure that the Party member troop absolute loyalty, absolutely pure, absolutely reliable. To adhere to the theory of armed, serious organization And adherence to the in-depth study of the majority of Party members and the party's basic theory, especially Xi Jinping, general secretary of the series of important speech spirit, education of Party members and the party's political discipline and political rules, and consciously in accordance with the party constitution and party political life standards to regulate their own words and deeds, so that discipline, rules, listen to say hello, do in the party party, the party worry about the party, the party for the party, the party retaining the party, and always in the ideological and political action and to Xi Jinping as general secretary of the Central Committee of the party remain highly consistent, consciously do the party's loyal guards of the masses of the people caring people. To build a strong base layer organization, strengthen grass-roots party organization's cohesive force and fighting force. To strengthen the basic level party organization construction Is the key to the target is doing a good job of Party building work of the important basis and guarantee. To optimize the organizational settings. In accordance with the ease of Party members to participate in activities for Party organizations play a role in principle, reasonable norms of the party organization, Party organizations at the grassroots level full coverage, to ensure that each party members into the party organization in Party activities, organization and management, the organization of care, to accept the supervision of the organization, and actively play a role. Second, we must pay close attention to the team construction. Catch team, with the team party building is an important content and basic level party organization team with members shall complete, clear division of labor, responsibility implementation, implementation of post management. With a good team with a strong Party Secretary , to effectively strengthen the Secretary of the party organization is the Party of person of the first responsibility, sense of responsibility, the responsibility system to prevent "party construction task of Party building, Party building work and business two skins" phenomenon. Third, we need to play good battle fort action. Party organizations at all levels to effectively seize as a key link in the center of the public security work service, adhere to thedingTo the completion of difficult and perilous task as the main battlefield of the work of Party building and the encounter major emergencies and major rescue mission, a major security tasks, the more you want to play the core role of Party organizations, and earnestly do a good job in the pre war mobilization, wartime motivation, postwar entitled work truly where the battle of Party members and cadres, the party's organizational life extended to where, the role of fighting bastion of the party organizations play where, reflecting the party building work to promote and protect the power. Comrades, in the circumstances to promote comprehensive strictly new situation, do a good job of public security Party Building work as the task is arduous and glorious mission, hope everyone to firmly establish "a game of chess," thought, put down Real strictly required as the new normal organ of the party's construction, further emancipate the mind, ningxinjuli, do solid work, to maintain social stability, promote social fairness and justice, protect the people live and work, to make new and greater contributions. The accident scene of the accident treatment of XX XX, April 7 to April 11, according to traffic police detachment and the traffic police brigade of the arrangement, I had the honor to participate in the Ministry of Public Security Research Institute held high-end training class, by 5 days of training and learning, I have a deep feeling, learning a lot of new knowledge and to deal with the accident of skills, to learn and work are of great help, we will experience is summed up as follows: first, study the new knowledge, to expand the field of vision. In the research the teacher to explain, we review the < road traffic accident scene drawing >, and emphatically studied at the scene of the real record drawing standards, the graph can reflect the state and each element Full coverage regardless of size, position, give a person to live a more intuitive understanding of the next step accident treatment has a great help. At the same time, I have seen some new accident investigation equipment, such as a new generation of traffic accident scene drawing system, through training, the police can very fast rendering standard site map, data measurement, and in accordance with the Ministry of public security of the standard, and the UAV, the application of UAV camera or camera, from the fundamental solution overview accident photos. Second, on the scene photography basic requirements and accident photographic difference. The scene photography scene is the most objective real reaction. But photographs of the scene taken to ensure objective, comprehensive, timely and clear requirements, this scene photos to assurance its legal effect; the scene photography has also undergone a change by the original photography of orientation and overview of photography, Photo Center, breakdown of the photo, change for range photography, photographic overview, local camera, film element, photography of minutia, than photography, so to photographic content more refined, more specific, the as evidence of a more targeted, more accurate., on site survey extracted traces and field exploration process traces are extracted by the problems and errors. Trace on the scene of the discovery and extraction as a matter of So the scene investigation is an important part of the process, on the analysis of the cause of the accident and the accident are very important role, through the teacher's explanation and analysis them as an expert, from the perspective of identification of traces of the scene points extraction and pointed out the direction for under our own exploration site to extract traces, at the same time, through the teacher's explanation, accidents will produce certain traces, which requires us in the scene of the accident investigation of careful, and not missing any useful to our trace on the scene. On advanced equipment of traffic accident identification, genetic analysis of the role of. I feel the deepest is now home Car safety air bag with something called the airbag module. This is known as "black box" car equipment, has a record of when the speed, whether to take braking, take a few braking and other data, recording, has a very large role for analyzing the cause of the incident, next serious accidents must pay attention to extract such equipment; and escape accidents are common in the general video surveillance on the blurred image, wLicense plate number; shellac, fiber identification, etc. with advanced equipment can make the identification, with the advanced equipment, technical backing, feeling the impartial handling of the each accident and escape detection accident confidence. On the scene of the accident protection. The teacher from three aspects to explain the road traffic accident and law enforcement duty site safety protection: 1, from the level of laws and regulations, Ministry of public security, proceeding from the actual conditions promulgated on the rules and regulations to strictly enforced, which requires each of us a police starting from their own point of view, for their own safety, must not omit any link, don't be afraid of trouble, this is Lists are not qualified for you alone are responsible for the unit is responsible for the family is responsible for; 2. Strengthen on-site protection facilities of the configuration and use, the first to buy and configuration of safety protection equipment, if equipment, but also about what door? Then is another question, equipment, how to use, the teacher of Tianjin accident lesson, because a lot of equipment, is not put into use, resulting in our police due to the lack of timely reminder of the accident, causing us to a number of police casualties; 3, the device is put into use, but also strengthen individual protection skills and teamwork training. In a word, We want to use qualified equipment and abide by laws and regulations, strengthen training of personal skills and teamwork and ensure its own security in the field staff. Through the study of five days of training, an increase of knowledge, learning the something new, strengthen the unit and brother of business flow, also found their own shortcomings, the next step I want to share of Wuxi advanced concepts and colleagues, common learning and common progress, makes the traffic police brigade accident treatment work more on the floor! In recent years, XX city always adhere to a hand grasping the building, a hand grasp the management, and actively explore new mode of Biogas Service, strive to innovate new mechanism for ecological compensation, pay attention to enhance the image of the new energy team, cohesion to create a new bright spot of circular agriculture, biogas in scientific management, comprehensive utilization and achieved certain results. First, the cultivation of new business entities, to explore new mode of follow-up services XX city has been built biogas 11 million households, biogas digesters is "treasure pool, biogas replaced the coal and firewood, become a clean, economic life energy, biogas pool instead of the old cesspool, become to improve the sanitary conditions of important possessions. With the maintenance quantity is increasing year by year, firedamp follow-up service into the long-standing problem. To do a good job of Biogas Service, polish up the brand of "XX model and we guide biogas mechanic established biogas cooperation, energy service companies, such as the model of market main body. Through market service, breakthrough in the past by the government construction, maintenance, a pack in the end of the narrow concept, establish the" who benefits, who management "the correct concept. The main body of the new take innovative service mode, expand service content and other measures, developing biogas service, centralized gas supply pipeline construction and gas charging operation and other aspects of comprehensive management. It not only solves the problem of farm household biogas, and change the follow-up services, but also increases the income of service team. The cultivation of new subjects, to consolidate and improve the service system, the effective establishment of a long-term mechanism of biogas services, to achieve the standardization of the follow-up services, intensive and professional. Two, the introduction of international carbon trading, innovative new mechanism for ecological compensation XX City Xiang Bai Guo centripetal rich is an ordinary farmers biogas, biogas his home with very good results, he is carbon fund project of farmers, this year, the winner of the Netherlands government to pay him thehich can identifyInspired by the introduction of $23, he used this carbon trading income to buy a new gas stove. This is XX household biogas clean development mechanism project is the United Nations first successfully registered household biogas carbon fund project. The project of 4330 household biogas pool, each year to reduce carbon emissions in 7298 tons, carbon emissions trading income of 10 million US dollars, equivalent to RMB 65 million yuan, carbon trading income subsidies to build pool farmer for biogas digesters follow-up maintenance provides ongoing capital investment in carbon fund project, XX City, the implementation of the "gas rewards" project, "whether the normal ignition, gas pressure size, pig herds head number Indicators will biogas digester using effect is good, medium and poor to refine the management and posting the use of farm household biogas, biogas use good farmers reward. Ecological compensation project implementation, increase the income of farmers, mobilize the enthusiasm of farmers, increase rate of the use of biogas, at this stage for the implementation of the voluntary emission reduction projects to provide a reference. Three, establish an advanced service model, highlighting the new image of the energy team Repeatedly since the technology of biogas digesters "third built seven in charge, not good will be" a year, two years, three years four years keep frogs. To catch the follow-up service, to catch the team XX City in strengthening the team building process, the emergence of a number of service models and technical experts. Dragon and Phoenix Town Agricultural Service Center of Yuan Liang, is a typical representative. He from 2005 years engaged in gas, ten years as one day, always keep the people of noble sentiment, conscientiously perform their duties conscientiously serve the masses. His advanced deeds of people's daily, the farmer daily, Hubei Daily and other media reported that 2015 was named the provincial labor Model, by the Deputy Secretary of the provincial Party committee Zhang Changer as the new era of Shi Chuanxiang, Yuan Liang with his dedication to the cause of the gas, won the majority of people good reputation. Vigorously promote the typical deeds, strengthen the play. Incentive motivation, the city "for everyone to learn advanced, all vying for the advanced, everyone catch up with and surpass the advanced" has become so rampant, the team has the typical, post a pacesetter, set up the city's rural energy team for the good image of the civil service. Four, to promote the development of circular agriculture, build a comprehensive utilization of a new bright spot Table, an important role in the profound understanding of the ecological "XX" from the ecological agriculture, XX city to biogas development of ecological agriculture, always adhere to the construction of biogas energy line overall circulation agriculture demonstration, in accordance with the "gas into people's homes, free installation, according to the charges, comprehensive utilization" principle, vigorously carry out the centralized gas supply, recycling for the purpose of biogas engineering construction. One is to carry out multi demonstration. The dragon and Phoenix Town, Tun Xiang Bai Guo Xiang, the construction of the biogas engineering as a link to the "pig - biogas - vegetable", "pig - biogas - tea", "pig - biogas - fruit" cycle of agricultural demonstration base, through a variety of experiments and demonstrations, summarize test result And promotion of demonstration experience. The second is to enhance the quality. The city in biogas production and utilization, research and development of "high yield biogas fermentation device and selenium enriched biogas fertilizer production method" is State Intellectual Property Office of the grant of the patent right, to enhance the level of technology of the city of Biogas fertilizer use. The third is to expand the use of the area. According to local conditions, due to implement the strategy, the follow-up services of biogas and biogas comprehensive utilization of organic combination, to solve the "planting no biogas pool", "biogas pool or not in the labor force", practical problems such as "labor without cultivation", let biogas fertilizer was in circulation and utilization. The next step, XX city will in accordance with the provincial, state energy deployment, and further increase the efforts to the construction of biogas project, to accelerate rural biogas to the scale of development, comprehensive utilization and scientific management in the direction of transformation and upgrading, promote the sustainable development of biogas in rural areas. In recent years, under the support and guidance of the provincial rural energy office, the county completed a total of household biogas pool nearly 7 million households, large-scale biogas project 4, small and medium-sized biogas project in 141, rural service outlets 211, subsidies for solar water heater 2340, biomass stove 2300 units, for the development of green agriculture, improve the people's quality of life play great role. In particular, we succeed in biogas purification, high value utilization based on, to further expand the scale, to open up the market, standardized management, to promote the transformation and upgrading of rural biogas project made some active exploration. Our approach to report as follows: One, scale development, play the economic and social benefits of high quality of methane utilization Biogas high-quality exploit inspired new rural of our country's energy market, for installation of gas pipeline engineering of new rural residential demand. Since last year the province's rural biogas high quality using after the spot, we based on the basis, to expand the scale, an ample supply of gas source, to ensure that farmers with adequate quality of bio gas. One is to expand the size of the original base. Last year held a spot of Qianfeng county and in the province of rural energy office, county government support, in the original 30 acres of the project on the basis of, to ratify the new 10 acres of land, according to large scale biogas centralized gas supply engineering construction requirements, invest 100 million yuan to build a 3000m3 volume of anaerobic fermentation tank, the implementation of technical innovation, using carbon steel output pipeline, building to gas 10000m3 above the new holder, and complete the related projects, assurance that have been developed to farmers with the supply of gas, 2016 Spring Festival peak gas during. There have been no interruption in supply, the user of ten Satisfaction. Second is to actively open up new bases. This year, we through the comprehensive deployment of the county government, related to the integration of sector funds, in Pu Zhen Zhang Zhuang Songlin farm, the port town of gold farming cooperatives, plans to build two 2000m3 volume fermentor, copy forward mode, solve environmental pollution, fruit trees fertilizer, life problems with gas. We will also under the support of relevant departments, the forward mode is launched county public security, with conditions in other counties, willingness of biogas engineering base, to assist in the construction of gas compression purification equipment and production and marketing integration mode. At present, Qianfeng company has been declared a biogas purification, compression and canning 10 a number of utility Technology patents, 2 invention patents, has applied for a registered trademark of the striker, and with the equipment manufacturers to improve the equipment stereotypes and production and business license related work. File, identity to access to a wide range of measures to implement a decentralized, and third, we will steadily develop the market, we forward the company together to form a team, the public security county, Nanping, lotus pond gate three town residential area development, joint concentrated propaganda, further mobilize and organize farmers to base inspection, to the user, enhance the perceptual knowledge, so that the majority of users of biomass gas from ignorance, doubt, and the safe, convenient, economical and practical advantages of convinced, blown away. At the same time, begin to rural area market development, Meng Zhen Jin Gang Cun Zha Kou Zhen De Yi Village pilot, the biomass gas supply farmers, let old people's lives improve grades. Popular support, this year, has added 2382 users. In the commercial sector, has also developed more than 10 food and beverage industry users, the amount of gas is equivalent to 500 civilian gas consumption. Two, make an inventory of the stock, to play the role of high quality of the use of Biogas Rectification has been built in the biogas project, the use of mobile integrated compression purification equipment, the nearest gas recovery, the nearest distribution, improve the use of the original biogas project effect, give full play to the role of high quality and revitalize thProvince's rural marsh gas with high quality use after the spot, we organized a special group, on the basis of a full range of investigation and research, and forward the company together on the county's three large and medium-sized anaerobic fermentation tank be renovated and through technical transformation to restore gas production capacity, building integrated mobile compression purified gas recovery equipment, gas recovery at the price of one yuan per cubic meter by striker company recovery. Both sides have certain economic benefits, not only start the utilization of waste fermentation tank, but also saves the cost of new fermentation tank, achieve a win-win results. Transformation of concentrated residential above at the same time, we also the county nearly 20 100m3 volume fermentation tank, technological transformation, the use of forward the company's equipment, so that to make full use of the conditions are ripe for the District, we use small equipment for purification of direct supply, the use of the user directly with clean and high quality raw material gas, deeply welcome. For example, we in Zhang Tian Si Zhen Chang Chun Cun residential area gas investment less than 20 million yuan, to more than 100 users for the natural gas. Through the entire old buildings and building new, one or two years to cover the whole county, and truly let the rural biogas upgrading work implemented, resulting in greater social benefits and economic benefits. Three, comprehensive utilization, to play the key role of biogas project to boost green agriculture Consumptive striker in my county is planting, livestock and poultry, aquatic County, according to statistics, the county pig herds 57 million head, poultry kept caged 9.7 million, large-scale farms and farming district more than 1000, animal manure and sewage emissions 20 million tons, aquaculture and environmental protection pressure. In the county government's support, we have more channels to raise funds, the biogas project near the base of the five towns more than 20 a livestock and poultry farm manure renovation to achieve separation of dry and wet, and each farm road repair, the company and the aquaculture field signed agreement, the implementation of paid service. On the one hand, to solve the environmental pollution problems, to ensure that the livestock and poultry breeding The healthy development of the industry, on the other hand, to ensure the Qianfeng company production of biomass gas raw materials, can effectively reduce the cost. In the treatment of biogas slurry and residue, we equip the a full automatic drip injection and spraying fertilization system, biogas slurry destined for the vegetable fruit base, through the pipe network, the use of automation in process of sprinkler irrigation and achieve small investment, big gains in effect. Combined with biogas centralized supply through the establishment of biogas households, biogas comprehensive utilization demonstration area, fan out from point to area, to expand the scale, give full play to the commercial, biogas fertilizer fertilize the soil effect. Comprehensive utilization of agricultural structure adjustment to construction of biogas as a link, promote aquaculture, driven by planting industry development, and vigorously promote the "pig - Marsh - fruit, pig - Marsh - food, pig - Marsh - Fish" green mode, to create eco brand, organic brand. Over the past two years, we met with Xing Long ecological farm, Dorian vegetable cooperatives and Jin Gang grape base jointly invested more than 30 million, to build three "three natural ponds" comprehensive utilization project pilot, the economic benefit is obvious, vegetable growers of identity And praise. Although we have done some work on the use of biogas in high quality, but according to industry standards and market operation requirements there are many procedures need to complete, we urge the department pay more to give guidance and support, to ensure that rural biogas high-quality use of standardization, scale, standardization and rapidly to the province, and strive to promote the country.e stock.
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