体外反搏治疗血清对培养内皮细胞基因表达的影响

目的探讨经体外反搏治疗的冠心病患者血清对血管内皮细胞基因表达的调控效应。方法分别取接受体外反搏治疗的冠心病患者1、24和36h时间点的血清，用于培养人脐静脉血管内皮细胞。用cDNA基因芯片检测3个治疗时点反搏前、后血管内皮细胞基因表达谱。结果反搏前后比较，有10个基因（核转录因子、真核转录启动因子-4、平滑肌的肌球蛋白重链、α2-肌动蛋白、微管蛋白β肽链、组织相容蛋白G、黑色素黏附分子、神经介素B受体、蛋白激酶4K2、血小板凝血酶敏感蛋白-1）的表达在3个治疗时点上出现显著改变。在1h点均为上调，在24h、36h时点均为下调。结论体外反搏治疗冠心病患者血清对血管内皮细胞的炎症反应、细胞凋亡相关基因表达有调效应，并随体外反搏治疗时间的增加早抑制其表达的趋势。     

Naturally occuring antibodies against nerve growth factor in human and rabbit sera: comparison between control and herpes simplex virus-infected patients

Antibodies against nerve growth factor (NGF) in sera were detected by enzyme-linked immunosorbent assays (ELISA), by their isolation after passage of sera through NGF immunoadsorbent columns and by their specificity to bind and immunoprecipitate mouse NGF as well as to stain by immunohistochemical methods cellular sites of NGF synthesis. Increased levels of anti-NGF antibodies were found in sera of herpes simplex virus (HSV)-infected patients but not in HSV-inoculated rabbits. As HSV latency is known to be promoted by NGF in vitro, these results may suggest that anti-NGF antibodies modulate the cytokine function of NGF and thus might play a role in HSV infection. The biological function of circulating antibodies against NGF, in general, is now open to future investigation.     

不同分级肝硬化患者血清甲状腺素水平的意义

目的探讨肝硬化患者血清中甲状腺素水平的变化与肝硬化病变程度及其临床实验室检查之间的相关性。方法用放免法测定肝硬化患者血清FT3、FT4、PC-Ⅲ、Ⅳ-C、LN及HA，并按Child—Pugh方法将肝功能分为A、B、C三级。结果随着肝硬化病变程度的加重，血清肝纤维化指标逐渐增高，甲状腺素呈下降趋势，同时血清甲状腺素水平与肝硬化的低蛋白血症、腹水及凝血酶原时间密切相关。结论肝硬化患者体内存在不同程度的甲状腺素水平紊乱，紊乱程度与肝功能受损程度有明显相关性，联合检测血清FT3、FT4、PC-Ⅲ、Ⅳ—C、LN及HA对估计肝硬化病变程度及判断预后有十分重要的临床价值。     

分泌巨噬细胞激活因子的淋巴细胞前体细胞的定量检测研究

巨噬细胞激活因子(MAF),是致敏T淋巴细胞在抗原刺激下产生的一种淋巴因子,它能激活巨噬细胞,是参与细胞免疫效应的一种重要免疫分子。因此,当机体接受抗原刺激后,若测定淋巴组织或淋巴细胞群中该种抗原特异的分泌MAF的淋巴细胞前体细胞(MAF-P)的数目,可在一定程度上反映机体的免疫反应能力。本文试图应用     

Hepatitis B virus genetic diversity and its impact on diagnostic assays

Summary.  Hepatitis B virus (HBV) circulates in blood as closely related, but genetically diverse molecules called quasispecies. During replication, HBV production may approach 10¹¹ molecules/day, although during peak activity this rate may increase 100–1000 times. Generally, DNA polymerases have excellent fidelity in reading DNA templates because they are associated with an exonuclease which removes incorrectly added nucleotides. However, the HBV-DNA polymerase lacks fidelity and proofreading function partly because exonuclease activity is either absent or deficient. Thus, the HBV genome and especially the envelope gene, is mutated with unusually high frequency. These mutations can affect more than one open reading frame because of overlapping genes. The S gene contains an exposed major hydrophilic region (residues 110–155), which encompasses the 'a' determinant that is important for inducing immunity. Nucleotide substitutions in this region are common and result in reduced binding or failure to detect hepatitis B surface antigen (HBsAg) in diagnostic assays. Adaptive immunity also depends on the recognition of HBsAg by specific antibody and variants pose a threat if they interfere with binding to antibody. Finally, genomic hypervariability allows HBV to escape selection pressures imposed by antiviral therapies, vaccines and the host immune system, and is responsible for creating genotypes, subgenotypes and subtypes.     

中草药醛糖还原酶抑制剂筛选模型的建立

目的：通过观察中药知母对醛糖还原酶活性的抑制作用，建立一种适用于筛选中草药醛糖还原酶抑制剂的模型。方法：大鼠12只随机分成3组：空白对照组、知母组、阳性药物组，分别给予生理盐水、知母水提液、依帕司他水溶液灌胃。采用“通法”给药方案制备含药血清，部分血清经过丙酮预处理。将知母水提液和含药（知母）血清分别加人体外建立的以DL-甘油醛为底物、NADPH为辅酶的醛糖还原酶活性测定体系。结果：丙酮处理过的空白血清较未处理的空白血清对酶活性的影响更小；知母水提液对醛糖还原酶抑制率达99％，含药（知母）血清对醛糖还原酶抑制率达67％。结论：运用血清药理学实验方法建立的筛选模型能有效、可靠的进行中草药醛糖还原酶抑制剂的筛选。     

联合应用SSH和cDNA表达谱芯片筛选肝星状细胞早期活化的相关基因

目的利用抑制消减杂交(suppressionsubtractivehybridization,SSH)和cDNA表达谱芯片筛选早期活化的肝星状细胞(hepaticstellatecell,HSC)和大鼠正常肝脏组织、轻度肝纤维化组织、重度肝纤维化组织中差异表达的基因。方法从SSH构建的大鼠轻度肝纤维化、重度肝纤维化2个差异cDNA文库中挑选1000条上调显著的基因,与正常大鼠4136条基因克隆制作成一张芯片,筛选早期活化的肝星状细胞相关基因。结果获得与HSC早期活化相关的上调基因有202条,下调基因有80条,其中血清和糖皮质激素调节蛋白激酶(serumandglucocorticoidsensitivekinase,SGK)在正常大鼠基因克隆和2周及8周SSH上调差异基因中均呈上调信号。结论联合应用SSH和cDNA表达谱芯片是筛选和鉴定不同样本中差异表达基因的快速、经济和有效的方法;SGK可能作为多种细胞信号传导通路和细胞磷酸化级联反应的一个功能性交汇点,参与了肝星状细胞的早期活化和信号传导。     

Progression-free interval in ovarian cancer and predictive value of an ex vivo chemoresponse assay

The study objective was to determine the effectiveness of a phenotypic chemoresponse assay in predicting response to chemotherapy measured by progression-free interval (PFI) in a retrospective series of ovarian cancer patients whose tumor specimens had been tested with the ChemoFx assay. A statistically significant correlation between assay prediction of response and PFI was observed in 256 cases with an exact or partial match between drug(s) assayed and received. In 135 cases with an exact match, the hazard ratio for progression of the resistant group was 2.9 (confidence interval [CI]: 1.4-6.3; P < 0.01) compared to the sensitive group and 1.7 (CI: 1.2-2.5) for the intermediate compared to the sensitive group. The median PFI for patients treated with drugs assayed as resistant was 9 months, 14 months for those with drugs assayed as intermediately sensitive, and PFI had not been achieved for those with drugs assayed as sensitive. These data indicate that the ChemoFx assay is predictive of PFI in ovarian cancer. As the majority of ovarian cancers display different degrees of response to different chemotherapy agents ex vivo, the incorporation of assay information into treatment selection has the potential to improve clinical outcomes in ovarian cancer patients.     

血清瘦素在男生青春发育期的动态观察

目的 探讨血清瘦素在男生青春期发育中的作用。方法 健康男生170名，调查首次遗精时间，测定血清瘦素、睾酮、促卵泡成熟激素、黄体生成激素水平，采用多元Logistic回归模型分析男生青春期发育的影响因素；同时，连续两年观察，分析血清瘦素在青春期的动态变化。结果 末次研究已遗精组血清瘦素、睾酮、促卵泡成熟激素、黄体生成激素水平均明显高于未遗精组。多因素分析显示血清瘦素、睾酮、促卵泡成熟激素、体重为男生青春期发育的独立影响因素。初次资料分析，遗精前组血清瘦素、睾酮明显高于未遗精组。结论 血清瘦素、睾酮、促卵泡成熟激素、体重为男生青春期发育的独立影响因素，男生遗精前期血清瘦素、睾酮已有明显改变。