吴茱萸穴位贴敷治疗高血压病56例

目的：分析吴茱萸穴位贴敷治疗高血压病的临床疗效及安全性。方法：将56例血压控制欠佳的高血压病住院病人在维持原降压方案的基础上,加用吴茱萸穴位贴敷神阙、双侧涌泉和双侧太冲,每口1次,治疗2周,观察治疗前后的血压变化及不良反应。结果：56例中显效20例,占35．7％;有效28例,占50％;无效8例,占14．2％。平均血压下降13／8mmHg。6例出现局部皮肤瘙痒,无需特殊处理,去除药末数小时后症状消失。结论：吴茱萸穴位贴敷降压效果理想,安全性高。     

中药蜈蚣药用历史沿革及其安全性探讨

目的：对中药蜈蚣的药用历史及其安全性进行探讨。方法：查阅相关文献资料,从古文献对蜈蚣药性认识、临床毒副作用、现代毒理研究及蜈蚣的安全使用等方面进行总结阐述。结果与结论：中药蜈蚣具有悠久的药用历史,古文献中多见其有毒的记载,现代毒理学研究表明,蜈蚣具有妊娠毒性、致过敏、肝肾毒性、神经系统毒性等多方面毒性作用。服用不当可引起过敏反应、肝、肾功能损害、神经系统损害及心肌受损、消化道疾患等不良反应,临床应用过程中应对其引起足够的重视。     

Genetically engineered T cells bearing chimeric nanoconstructed receptors harboring TAG-72-specific camelid single domain antibodies as targeting agents

Despite the preclinical success of adoptive therapy with T cells bearing chimeric nanoconstructed antigen receptors (CARs), certain limitations of this therapeutic approach such as the immunogenicity of the antigen binding domain, the emergence of tumor cell escape variants and the blocking capacity of soluble antigen still remain. Here, we address these issues using a novel CAR binding moiety based on the oligoclonal camelid single domain antibodies. A unique set of 13 single domain antibodies were selected from an immunized camel phage library based on their target specificity and binding affinity. A combination of these single domain antibodies was used to generate four tumor associated glycoprotein (TAG-72)-specific CARs harboring an identical antigen binding site, but with different signaling and spacer domains. Although all four CARs were functionally active against the TAG-72 expressing tumor cells, the combination of CD3ζ, OX40, CD28 as well as the CH3–CH2–hinge–hinge domains most efficiently triggered T cell activation. Importantly, CAR mediated functions were not blocked by the soluble TAG-72 antigen at a supraphysiological concentration. Our approach may have the potential to reverse multiple tumor immune evasion mechanisms, avoid CAR immunogenicity, and overcome problems in cancer gene therapy with engineered nanoconstructs.     

Biological significance of HORMA domain containing protein 1 (HORMAD1) in epithelial ovarian carcinoma

The present study was undertaken to determine the expression and biological significance of HORMAD1 in human epithelial ovarian carcinoma. We found that a substantial proportion of human epithelial ovarian cancers expressed HORMAD1. In vitro, HORMAD1 siRNA enhanced docetaxel induced apoptosis and substantially reduced the invasive and migratory potential of ovarian cancer cells (2774). In vivo, HORMAD1 siRNA-DOPC treatment resulted in reduced tumor weight, which was further enhanced in combination with cisplatin. HORMAD1 gene silencing resulted in significantly reduced VEGF protein levels and microvessel density compared to controls. Our data suggest that HORMAD1 may be an important therapeutic target.     

基于计算生物学方法的小容量单域抗体库的构建及食品中雌二醇特异性抗体的筛选

目的构建骆驼源单域抗体实体库和虚拟库,为快速筛选检测食品中小分子污染物的特异性抗体提供新方法。方法通过基因克隆、一代测序、同源性分析的方法构建骆驼源单域抗体基因库,通过二级结构分析和同源建模的方法建立单域抗体的三维结构虚拟库,利用分子对接技术实现雌二醇特异性抗体的虚拟筛选,并以雌二醇小分子为靶标进行初步验证。结果构建的小容量单域抗体库含有2000株抗体,每一株抗体的遗传背景、蛋白质结构及抗体抗原互补决定区(CDR)的信息清晰;通过分子对接得到结合雌二醇小分子能力最高的一株抗体的半经验结合自由能绝对值为9.56;相互作用分析结果显示,单域抗体结构中和雌二醇小分子发生相互作用的主要为3个CDR区形成的loop结构,经间接ELISA验证,其和雌二醇结合的50%抑制率(IC50)值为20 ng/ml,检测限(LOD,IC10)为4.097 ng/ml。结论通过计算生物学和基因工程技术相结合的方法构建的骆驼源单域抗体库,针对食品中常见的激素类兽药雌二醇,可以筛选得到背景清晰、具有较高亲和力的特异性抗体。     

基于中医药事业管理业务域的数据集分类研究

随着我国中医药事业的飞速发展,中医药信息化发展进程也在加快,中医药事业管理业务域数据集日益丰富,分类研究基于中医药事业管理业务域数据集变得尤为重要。本研究是在相关领域专家分析研究的基础上,对中医药事业管理进行业务域信息流分析,运用线分类法与面分类法相结合的方法,将中医药事业管理的数据资源分为8个业务域,编制《中医药事业管理业务域数据集分类编码表》作为医院、大学、科研单位、企业、文化产业、中药研究中心和中医药行政主管部门等机构进行信息交换的基础,为中医药及卫生事业的战略决策提供参考。     

ZO-1不同功能片段在胃癌中表达及意义

目的探讨ZO-1不同功能结构域表达变化与胃癌侵袭转移的关系。方法制作模拟胃癌侵袭转移的组织芯片,并行免疫组化染色检测ZO-1(α-pan)、ZO-1(α+)和ZO-1(ZU5)在胃癌不同进展位点的表达。结果胃腺癌组织中ZO-1(α-pan)、ZO-1(α+)和ZO-1(ZU5)出现胞膜异位至胞质的迷离表达或不表达,并随着胃癌的侵袭,迷离表达程度加剧,当胃癌转移至淋巴结时迷离表达程度反而降低。并发现胃腺癌的迷离表达程度与组织学类型相关。结论 ZO-1(α-pan)、ZO-1(α+)和ZO-1(ZU5)胞膜异位至胞质的迷离表达或不表达,提示ZO-1的PDZ3、GUK、SH3结构域、α基序和ZU5结构域可能参与胃癌的侵袭转移及组织学结构的维持,这些结构域异常表达可能是ZO-1参与上皮-间质转化(epithelial-mesenchymal transition,EMT)或间质-上皮转化(mesenchymal-epithelial transition,MET)发生的机制之一。     

Generation and characterization of CD1d‐specific single‐domain antibodies with distinct functional features

Ligation of the CD1d antigen‐presenting molecule by monoclonal antibodies (mAbs) can trigger important biological functions. For therapeutic purposes camelid‐derived variable domain of heavy‐chain‐only antibodies (VHH) have multiple advantages over mAbs because they are small, stable and have low immunogenicity. Here, we generated 21 human CD1d‐specific VHH by immunizing Lama glama and subsequent phage display. Two clones induced maturation of dendritic cells, one clone induced early apoptosis in CD1d‐expressing B lymphoblasts and multiple myeloma cells, and another clone blocked recognition of glycolipid‐loaded CD1d by CD1d‐restricted invariant natural killer T (iNKT) cells. In contrast to reported CD1d‐specific mAbs, these CD1d‐specific VHH have the unique characteristic that they induce specific and well‐defined biological effects. This feature, combined with the above‐indicated general advantages of VHH, make the CD1d‐specific VHH generated here unique and useful tools to exploit both CD1d ligation as well as disruption of CD1d–iNKT interactions in the treatment of cancer or inflammatory disorders.