蝮蛇抗栓酶治疗肺心病急性发作32例疗效观察

目的：探讨蝮蛇抗栓酶在治疗肺心病急性发作中的临床应用价值。方法：采用蝮蛇抗栓酶联合其它综合措施治疗肺心病急性发作３２例。结果：蝮蛇抗栓酶组３２例显效２０例,有效９例,总有效率达９０．６％,对照组总有效率仅达６５．６％。蝮蛇抗栓酶组疗效明显高于对照组（Ｐ〈０．０５）。结论：蝮蛇抗栓酶的应用为治疗肺心病提供了有效的方法。     

大肠癌新相关基因HSU17714的染色体定位研究

目的确定大肠癌新相关基因ＨＳＵ１７７１４的染色体定位。方法采用强化荧光原位杂交技术（ＦＩＳＨ）,以生物素化酪胺强化荧光原位杂交信号。结果８０．０％（１２８／１６０）的间期细胞和５９．８％（１０４／１７４）的中期分裂相可见到明显集中的ＨＳＵ１７７１４基因的杂交信号,相应荧光Ｒ带分析中,８５．１％（４０／４７）在２２号染色体上１区３带处有杂交信号。结论ＨＳＵ１７７１４基因定位于２２ｑ１３。     

p53反义RNA对肠癌细胞恶性表型的抑制作用

研究ｐ５３反义ＲＮＡ对大肠癌细胞中突变型ｐ５３致癌性的抑制效应,为肿瘤基因治疗提供新思路。方法２．１ｋｂ的人ｐ５３全长ｃＤＮＡ反向插入哺乳动物表达载体ｐＲＥＰ９,得到ｐ５３反义ＲＮＡ表达载体ｐＲＥＰ９－ｐ５３（ＡＳ）,并将其导入人肠癌细胞株ＳＷ１１１６（内源性突变型ｐ５３）,采用ＭＴＴ和ＦＣＭ方法测定ｐＲＥＰ９－ｐ５３（ＡＳ）表达的ｐ５３反义ＲＮＡ对ＳＷ１１１６细胞生长的影响。结果带有ｐＲＥＰ９－ｐ５３（ＡＳ）的ＳＷ１１１６细胞,与对照组ＳＷ１１１６细胞和带ｐＲＥＰ９空载体的ＳＷ１１１６细胞相比,由于ｐ５３反义ＲＮＡ的表达,其增殖速度显著下降,ＦＣＭ的结果也证明带ｐＲＥＰ９－ｐ５３（ＡＳ）的细胞部分受阻于Ｇ０／１期,而带ｐＲＥＰ９空载体的细胞则无明显变化。结论ｐ５３反义ＲＮＡ可以有效地抑制大肠癌细胞中突变型ｐ５３的致癌性,可用于实验性肿瘤基因治疗研究     

Dietary flavonoids, quercetin, luteolin and genistein, reduce oxidative DNA damage and lipid peroxidation and quench free radicals

Several dietary flavonoids such as quercetin, luteolin and genistein have been suggested to have cancer chemopreventive effects, although the mechanisms are not fully understood. In the present study, the effects of these flavonoids as antioxidants were investigated in the following systems: (1) production of hydrogen peroxide (H2O2) and superoxide anion (O2*-), (2) lipid peroxidation induced by FeCl2 in rat liver, and (3) formation of 8-hydroxy-2'-deoxyguanosine (8-OHdG) induced by either UV or Fenton reaction in calf thymus DNA. The results showed that quercetin and luteolin were equally potent in scavenging H2O2, with genistein having a moderate effect. Quercetin and luteolin had a potent inhibitory effect on O2*- generation by xanthine/xanthine oxidase while genistein had a moderate effect. Quercetin and luteolin were potent in inhibiting lipid peroxidation induced by FeCl2 in rat liver while genistein had a very weak inhibitory effect. All the test compounds had a potent quenching effect on 8-OHdG formation induced by UV light irradiation, with the order of effects being genistein > luteolin > quercetin. Of the test compounds, luteolin exhibited the most potent quenching effect on Fenton-induced 8-OHdG formation. The scavenging of oxygen free radicals, the inhibitory effect on lipid peroxidation and the quenching effect on 8-OHdG formation by quercetin, luteolin and genistein may, at least in part, be responsible for their anticarcinogenic effects.     

Antitumor activity and pharmacokinetics following oral administration of natural product DNA topoisomerase I inhibitors 10-hydroxycamptothecin and camptothecin in SCID mice bearing human breast cancer xenografts

The DNA topoisomerase I inhibitors, 10-hydroxycamptothecin (HCPT) and camptothecin (CPT), are indole alkaloids isolated from the Chinese tree, Camptotheca acuminata. They have been shown to have a wide spectrum of anticancer activity both in vitro and in vivo. However, their use has been limited due to their water-insolubility. The purpose of the present study was 2-fold, to determine the in vitro and in vivo activity of HCPT and CPT against human breast cancer and to determine the pharmacokinetics of the two drugs to better understand how they can best be used therapeutically. The bl vitro inhibitory effect on tumor growth was observed with breast cancer cell line MDA-MB-468. The in vivo antitumor effects were then determined using severe combined immunodeficient (SCID) mice bearing MDA-MB-468 xenografts. The tumor-bearing mice were orally administered HCPT (1, 3, 6, 9 mg/kg/day, 5 days per week) or CPT (1, 3, 6 mg/kg/day, 5 days per week) for 3 weeks. Growth of the MDA-MB-468 cells was inhibited by HCPT and CPT in vitro and in vivo in a dose-dependent manner. Complete regression of the tumor xenografts, determined by tumor measurement and microscopic examination, occurred in the groups of animals treated with doses of HCPT or CPT of 3 mg/kg/day or more. In general, HCPT was more effective and less toxic than CPT. To determine the potential mechanisms for the pharmacologic differences, the comparative pharmacokinetics of HCPT and CPT were determined in tumor-bearing SCID mice following i.v. or oral administration of H-3-HCPT or H-3-CPT. Parent drugs and their metabolites in plasma, urine, feces, and various tissues were quantified by a recently developed reversed-phase HPLC method. Significant absorption of both HCPT and CPT was observed after oral administration, with CPT having a higher bioavailability. HCPT and CPT were distributed widely into various tissues including the tumor, enterohepatic system, kidneys, and bone marrow. These studies indicate that HCPT and CPT are of potential use in treatment of breast cancer, providing the basis for the design of future human trials with these anticancer drugs.     

职业人群不健康行为生活方式与高尿酸血症的关系及高血压、血脂异常的效应修饰作用

目的 探索不健康行为生活方式与高尿酸血症的关系,以及高血压、血脂异常的效应修饰作用,为预防高尿酸血症提供理论依据。方法 采用横断面调查研究设计,基于2021年10-12月来自四川省、贵州省28个地级市和重庆市33个区（县）中国铁路成都局集团有限公司的西南职业人群队列基线数据,通过问卷调查、体格测量及实验室生化检测收集研究对象的人口学特征、行为生活方式、慢性非传染性疾病患病情况。不健康行为生活方式得分根据吸烟、饮酒、膳食模式、体力活动和低体重/超重状况进行评分,分值越高不健康行为生活方式越多。采用多因素logistic回归模型分析不健康行为生活方式评分、吸烟状况、饮酒状况等与高尿酸血症的关系,采用分层分析探索高血压等疾病对不健康行为生活方式与高尿酸血症之间关系的修饰效应。结果 共纳入11 748名研究对象,高尿酸血症患病率为34.4%。多因素logistic回归分析显示,现在吸/既往吸烟、现在饮/既往饮酒及BMI异常是高尿酸血症患病的危险因素,不健康行为生活方式对高尿酸血症患病风险呈现累积效应,随着得分的升高,高尿酸血症患病风险升高,OR值由1.64（95%CI：1.34~2.00）上升至2.89（95%CI：2.39~3.50）。分层分析结果显示,在高血压及血脂异常人群中,不健康行为生活方式对高尿酸血症患病风险影响更大。结论 多种不健康行为生活方式的共存会升高高尿酸血症患病风险,这一效应在高血压、血脂异常人群中更明显。及时纠正不健康行为生活方式,并控制高血压和血脂异常,降低患高尿酸血症的风险。     

矽肺相关蛋白的纯化,鉴定及其促成纤维细胞增殖作用

目的分离、鉴定与矽肺发生、发展过程相关的几种蛋白质,并测定其促成纤维细胞增殖的活性。方法采用高压液相色谱技术包括凝胶过滤柱层析、离子交换柱层析、反相Ｃ４高压液相色谱柱层析,分别对矽肺大鼠肺泡灌洗液（ＢＡＬＦ）、肺泡巨噬细胞冻融物（ＡＭＥ）及其条件培养液（ＡＭＣＭ）进行分离纯化,并通过Ｎ末端氨基酸序列的测定来鉴定这些蛋白质。结果（１）染尘２１天后,矽肺大鼠ＢＡＬＦ中白蛋白含量明显升高;（２）从ＢＡＬＦ、ＡＭＥ和ＡＭＣＭ中除纯化到相对分子质量为１５４００的溶菌酶外（其刺激成纤维细胞增殖的活性为１４０％）,还纯化到一种新的具有明显促成纤维细胞增殖的细胞因子（Ｆｉｂｒｏｂｌａｓｔｇｒｏｗｔｈｐｒｏｍｏｔｉｎｇｆａｃｔｏｒ,ＦＧＰＦ）,其最适作用浓度为２．０～６．０μｇ／ｍｌ。结论巨噬细胞分泌的ＦＧＰＦ和溶菌酶在矽肺纤维化过程中可能有重要作用。     

胃癌危险因素的广义相对危险度分析

应用ＧＬＩＭ软件对胃癌高发区福建省长乐市胃癌分子流行病学资料进行广义相对危险度分析,探讨代谢酶基因多态、吸烟与胃癌危险性的联系。结果表明：细胞色素Ｐ４５０２Ｅ１（ＣＹＰ２Ｅ１）、谷胱甘肽转硫酶Ｍ１（ＧＳＴＭ１）基因型和吸烟对胃癌的联合作用是一超相乘形式,偏向于相乘结构。正确识别暴露因素间交互作用的模式,对肿瘤的一级预防具有重要意义     

综合治疗对脑梗塞相关危险因素的影响

目的　探讨综合治疗对脑梗塞复发的相关危险因素的影响。方法　随机选择85 例脑梗塞伴各类危险因素患者在综合治疗前后,对他们进行血压、空腹血糖、胆固醇、甘油三酯及血液流变学等8 项指标的测定。结果　经过1 ～3 年临床观察随访,有50 % 以上高血糖、高血脂、高粘滞血症患者检验指标趋于正常,94 .3 % 的高血压得到控制与稳定,经t 检验,血液流变学4 项P 值< 0 .05 ,差异有显著意义,高血压、空腹血糖、胆固醇、甘油三酯的P 值< 0 .01 ,差异有非常显著意义。结论　综合治疗对控制相关危险因素,预防脑梗塞复发有重要临床意义     

组织全国医学文献资源共享建设全国外文生物医学期刊联合目录的研究

《组织全国医学文献资源共享建设全国外文生物医学期刊联合目录的研究》项目以全国医学文献资源共享三级网络为依托,立足于网络化发展目标,从建设地区联合目录入手,探讨通过建设全国外文生物医学期刊联合目录,发挥国家中心馆和地区中心馆的资源优势和技术优势,将共享资源由自愿参加变为各级中心馆的责任性行动,增强资源共建共享活动的生命力,开辟全国医学文献资源共享可持续发展的道路。