冠心病痰瘀证客观指标的研究进展

通过中医学和现代医学对冠心病痰瘀证的认识及血脂、脂蛋白、血液流变学、NO、6-keto-PGF1α、TXB2微循环、冠脉造影、超声心动图等客观指标与冠心病痰瘀证相关性的研究,可心得出结论：血脂的明显升高同时伴有血液流变学异常,可作为冠心病痰瘀证的辨证参考指标。     

栝楼桂枝汤治疗脑卒中后下肢痉挛的网络药理学研究

目的 基于网络药理学研究栝楼桂枝汤治疗脑卒中后下肢痉挛的作用机制。方法 利用TCMSP数据库、SwissTarget Prediction数据平台筛选栝楼桂枝汤活性成分靶点,并借助Gephi软件构建活性成分-靶点网络,运用Genecard、DisGeNET、TTD疾病数据库筛选作用于脑卒中、下肢痉挛靶基因,应用STRING平台构建靶蛋白相互作用网络,利用ClueGO软件对靶基因进行GO功能分析,通过DAVID v6.8平台对关键靶点KEGG通路进行分析。结果 栝楼桂枝汤中黄酮类、有机酸类、皂苷类等成分作用于IL6、TNF、EGFR、ESR1、TP53、STAT3、F2等49个关键靶基因;参与横纹肌细胞增殖、骨重塑、平滑肌细胞增殖正调控、肌细胞增殖、内皮细胞增殖等14类生物过程;调控TNF、MAPK、PI3K-Akt、ALS、神经营养、5-羟色胺能神经突触等30条信号通路。结论 栝楼桂枝汤多种活性成分通过抗炎、抗氧化、神经营养及保护等药理作用,以及参与肌细胞增殖等生物过程,从中枢神经系统及外周肌肉组织双向治疗脑卒中后下肢痉挛。     

难治性精神分裂症立体定向手术治疗前后认知功能的对照

目的：应用现代立体定向手术治疗部分难治性精神分裂症50例，探讨立体定向手术对难治性精神分裂症的认知功能的改善及临床疗效。方法：采用威氏康星卡片分类测验（WCST）、韦氏成人智力测定量表观察认知功能的变化，选用简明精神病评定量表（BPRS），阳性与阴性症状量表（PANSS），临床疗效总评量表（CGI）评字疗效，由两名精神科医生手术前后评定，统一标准，评定时间分别在手术前2d和院前，手术后1，3和6mo，结果：手术后WCST的总测验次数，持续错误数，非持续错误数 均低于手术前，具有显著性差异，手术后韦氏成人智力测定智商无减低，临床疗效：临床治愈2例，显效32例，有效14例，无效2例，总有效率为96％，结论：现代立体定向手术治疗难治性精神分裂症是一种疗效明显，能改善认知功能的方法。     

调整综合目标与医疗保障制度改革接轨

医院在医疗保障制度改革出台之前,应早认识、早准备、早安排,迎接挑战,主动适应。为此,南京市第一医院1995年初起调整综合目标,探索优质、高效、低耗的改革措施,走内涵发展之路。首先是控制医疗消费过快增长,把药费、检查费控制在适当水平,从提高质量、效率上组织合理收入;其二是调整内部结构,加强管理,控制支出,降低消耗,节支堵漏,建立考核工资制和超额劳务分配制;其三是完善综合目标保证体系,从思想、组织、制度上采取措施予以保证,并强化自我约束机制和监督机制。     

Genetic effects of deoxyribonucleotide pool imbalances

In vivo DNA precursor imbalances can have profound genetic consequences in prokaryotes and eukaryotes. In vitro studies have demonstrated that DNA replication fidelity is dependent on correct balances of deoxyribonucleoside triphosphates during DNA synthesis. These findings suggest that intracellular concentrations of DNA precursors may be regulated in order to minimize the frequency of genetic change. In addition, they indicate the existence of important nonDNA targets for the induction of mutation, recombination, chromosome aberrations, etc. In this article, the genetic effects of deoxyribonueleotide pool imbalances are reviewed.     

综合指标与岗位工资结合管理方法初探

介绍了西安医科大学第一附属医院以医院分级管理和工资制度改革为契机，试行综合指标与岗位工资相结合的管理方法，即把医院分级管理的综合目标进行分解，与职工的岗位工资挂钩，通过量化考核，评出分值，然后根据分值计算职工每月的工资和岗位津贴，从分配上体现出多劳多得、工作质量好、服务优者多得的原则。     

Thioredoxin reductase as a novel molecular target for cancer therapy

Tumor cell proliferation, de-differentiation, and progression depend on a complex combination of altered cell cycle regulation, excessive growth factor pathway activation, and decreased apoptosis. The understanding of these complex mechanisms should lead to the identification of potential targets for therapeutic intervention. Redox-sensitive signaling factors also regulate multiple cellular processes including proliferation, cell cycle, and pro-survival signaling cascades, suggesting their potential as molecular targets for anticancer agents. These observations suggest that redox-sensitive signaling factors may be potential novel molecular markers. We hypothesized that thioredoxin reductase-1 (TR), a component of several redox-regulated pathways, may represent a potential molecular target candidate in response to agents that induce oxidative stress. There have been numerous biological studies over the last decade investigating the cell biological, biochemical, and genetic properties of TR both in culture and in in vivo models. In addition, using a series of permanent cell lines that express either a wild-type TR or a dominant mutant TR gene or a chemical agent that inhibits TR we demonstrated that TR meets most criteria that would identify a molecular target. Based on these results we believe TR is a potential molecular target and discuss potential clinical possibilities.     

New approaches to blockade of alpha4-integrins, proven therapeutic targets in chronic inflammation

The recruitment of leukocytes into tissue is a pivotal step in inflammation. alpha4-Integrins are adhesion receptors on circulating leukocytes that mediate attachment to the endothelium and facilitate their migration into the inflamed tissue. This multistep process is mediated by the interaction of alpha4-integrins with their counter receptors VCAM-1 and MadCAM-1 that are expressed on endothelial cells. alpha4-Integrins act as both adhesive and signaling receptors. Paxillin, a signaling adaptor molecule, binds directly to the alpha4 cytoplasmic tail and its binding is important for cell migration. Blocking the adhesive functions of alpha4-integrins has been shown to be an effective therapeutic approach in the treatment of autoimmune diseases, but also carries the risk of defects in development, hematopoiesis and immune surveillance. Interfering with alpha4 signaling by inhibiting the alpha4-paxillin interaction decreases alpha4-mediated cell migration and adhesion to VCAM-1 and MadCAM under shear flow. These in vitro effects are accompanied by a selective impairment of leukocyte migration into inflammatory sites when the alpha4-paxillin interaction is blocked in vivo. Thus, blockade of alpha4-integrin signaling may offer a novel strategy for interfering with the functions of these receptors in pathological events while sparing important physiological functions.     

The haemolytic plaque reduction technique to measure cytotoxicity with hybridoma cells as a target

The use of hybridoma cells as targets to measure cell-mediated cytotoxicity has been established. The ability of target hybridoma cells to form haemolytic plaques has been used as an indicator of target viability and therefore, cytotoxicity has been detected by plaque reduction (PR). Allogeneic responses, spontaneous cytotoxic responses and anti-hapten responses have been measured by the PR assay. Compared with the standard [51Cr]chromate release assay, small numbers of target cells (400 or less) can be used in the PR assay and this results in a greatly enhanced sensitivity in detecting small amounts of cytotoxicity. The ability to construct a range of hybridoma targets with the appropriate cell surface determinants presents a new approach, of general applicability, to the sensitive detection of cytotoxic lymphocytes.     

New approaches for male fertility control: HE6 as an example of a putative target

Reversible contraceptive methods for males are still not available. During the last few years several marketing studies have clearly shown that men and women would welcome a situation where men could assume responsibility for family planning. Schering AG and Organon are currently collaborating to develop a hormonal method for male fertility control based on the combination of etonogestrel as gestagenic component and testosterone undecanoate.

To further optimize male contraceptives in terms of improved efficiency, rapid onset, reversibility, fewer side effects and a convenient method of application, a search for innovative non-hormonal approaches was started. During the last few years, numerous proteins were identified which play a specific role in male fertility. These proteins have first to fulfil a set of indication-specific criteria before a drug discovery process can be initiated. The most important criteria for a putative target protein are tissue-selective expression, crucial biological function in fertility, drugable properties and feasibility of assay development for high-throughput-screening and lead optimization.

The G-protein-coupled receptor HE6 was selected as target and the above selection criteria were applied. HE6 displays a preferred epididymis-specific expression pattern and belongs to the superfamily of GPCRs, which are well known to be drugable with small molecules. A knockout mouse was generated which revealed an infertility phenotype with the onset occurring 6 weeks after initiation of spermatogenesis at the latest. Surprisingly, no epididymis-specific phenotype was observed. Instead, the reabsorption of testicular fluid along the efferent ducts was strongly affected. No further obvious side effects were observed in male or female mice. This study with HE6 exemplifies how targets for male contraception have to be validated before drug development can start.