端粒酶hTERT和PTEN蛋白在子宫内膜样癌及子宫内膜增生中的表达及意义

目的:探讨端粒酶hTERT及PTEN蛋白在子宫内膜增生及癌变过程中的表达、意义及两者相关性。方法:所用标本包括子宫内膜单纯增生21例,复合增生18例,不典型增生20例,子宫内膜样癌39例。用免疫组化S-P法检测hTERT和PTEN表达。结果:①hTERT在子宫内膜单纯、复合、不典型增生病变和子宫内膜样癌中阳性结果分别为4/21、6/18、12/20及32/39(82.1%),前两组均为弱阳性表达,后两组多为中度和强阳性,统计分析表明不典型增生和内膜样癌中hTERT表达高于单纯和复合增生(P<0.05),不典型增生与内膜样癌两组间hTERT表达差异无显著性(P>0.05)。PTEN在子宫内膜单纯、复合、不典型增生病变和内膜样癌中表达缺失率分别为3/21、6/18、10/20及24/39(61.5%),不典型增生病变和子宫内膜样癌PTEN缺失表达率高于单纯及复合性增生(P<0.05),但不典型增生与内膜样癌两组间差异无显著性(P>0.05)。②hTERT阳性水平与PTEN的缺失表达率均与内膜样癌组织学分级有关(P<0.05),而与癌浸润深度、淋巴结转移、临床分期无相关(P>0.05)。③子宫内膜增生和内膜样癌各组中hTERT与PTEN表达不相关(P>0.05)。结论:hTERT与PTEN可作为子宫内膜样癌早期诊断和判断预后的客观指标,hTERT过表达提示端粒酶再激活,参与细胞的癌变过程,PTEN在子宫内膜癌发生发展不同阶段表达呈进行性下调或缺失,是内膜样癌发生发展的重要步骤,但两者表达之间无相关性。     

Screening workers for genetic hypersusceptibility: potential ethical, legal, and social implications from the Human Genome Project

One of the potential outcomes of the Human Genome Project will be the ability to identify individuals who are at increased risk of adverse health effects following exposure to hazardous substances in the workplace because of genetic hypersusceptibility. The ability to identify such individuals is likely to lead to the inclusion of genetic screening in worker protection programs. This technology and its applications will have a number of potential ethical, legal, and social implications. In this commentary, the authors examine five broad topics relating to the use of screening for genetic hypersusceptibility in the workplace: (1) issues of risk; (2) the rationale and legal basis for screening; (3) the privacy concerns of workers; (4) the confidentiality of test results; and (5) potential discrimination. The authors close by suggesting some guidelines for developing policies regarding genetic screening.     

Non-nucleoside HIV-1 reverse transcriptase inhibitors. Part 11: structural modulations of diaryltriazines with potent anti-HIV activity

A series of novel 6-naphthyloxy substituted DATA analogues bearing different substituents on the C-6 position of triazine ring were synthesized and evaluated for their in vitro anti-HIV activity in MT-4 cells. The results demonstrated that most of the compounds in this series are potent activity against HIV-1 with moderate to high selectivity. Among these analogues, two compounds exhibited excellent effect in inhibiting HIV-1 replication at nanomolar concentration (for compound 9h: IC(50)=9.3 nM, SI=15,385; for compound 9i: IC(50)=9.4 nM, SI=14,094), which are about 15-fold more active than nevirapine. In addition, several compounds are active against both HIV-1 and HIV-2, whose mechanism may be different from typical NNRTIs.     

两种非核苷类逆转录酶抑制剂治疗艾滋病的不良反应分析

目的 了解艾滋病患者接受两种非核苷类逆转录酶抑制剂进行抗逆转录病毒治疗发生不良反应的情况.方法 回顾性分析2015年6月至2016年6月在武汉大学中南医院就诊的126例使用依非韦伦(E-FV)和150例使用奈韦拉平(NVP)进行联合抗逆转录病毒治疗的艾滋病患者的临床资料,统计不良反应发生率.结果 EFV组的总体不良反应发生率为87.3％(110/126),高于NVP组的44.0％(66/150),差异有统计学意义(x2=55.573,P＜0.01).EFV组不良反应以头晕多梦(64.3％,81例)和皮疹(9.5％,12例)为主,NVP组以皮疹(18.0％,27例)和肝损害(16.7％,25例)为主;但EFV组患者出现精神障碍4例(其中2例自杀死亡),癫痫1例,男性乳腺增生3例,NVP组则未见.EFV组83.6％(92例)和NVP组74.2％(49例)的不良反应发生在用药的前6周内;且前者69.1％(76例)可逐渐耐受,而后者仅4.5％(3例),差异有统计学意义(x2=69.468,P＜0.01),但NVP组停药或换药后90.9％(60例)的患者不良反应消失.结论 EFV和NVP的不良反应各具特点,前者以早期轻微的神经系统症状为主,且能逐渐耐受,后者以早中期出现的皮疹和肝损害为主,常需停药或换药得以恢复.临床上对于EFV相关的精神障碍宜早期进行干预,以免发生意外.     

Pharmacogenetics of non-nucleoside reverse transcriptase inhibitors (NNRTIs) in resource-limited settings: Influence on antiretroviral therapy response and concomitant anti-tubercular,antimalarial and contraceptive treatments

The burden of human immunodeficiency virus (HIV) is mainly concentrated to resources-limited countries where the response to available antiretroviral therapy is often limited by the occurrence of toxicity or by the emergence of HIV drug resistance. Efavirenz and nevirapine are the antiretroviral drugs most prescribed in resources-limited countries as part of antiretroviral combination therapy. Their metabolism and conjugation are largely influenced by enzymatic genetic polymorphisms. The genetic variability of their metabolism could be associated to different metabolic phenotypes causing reduced patients' adherence because of toxicity or drug–drug interactions with concomitant therapies. The purpose of this review is to summarize published evidence on pharmacogenetic and pharmacokinetic aspects related to efavirenz and nevirapine, the influence of concomitant anti-tubercular, anti-malarial or contraceptive treatments, and the impact of human genetic variation and drug–drug interaction on the virologic and immunologic response to antiretroviral therapy in resources-limited countries.     

RT—PCR检测胃癌患者外周血中细胞角蛋白20mRNA及其意义

目的检测胃癌患者外周血中细胞角蛋白20（CK20）mRNA的表达情况，并探讨其存在的临床意义。方法应用逆转录-聚合酶链反应（RT—PCR）检测56例胃癌（胃癌组）、18例良性胃病（良性胃病组）、20例正常献血者（对照组）外周血中CK20 mRNA的表达情况。结果对照组及良性胃病组外周血中CK20 mRNA均为阴性表达，胃癌组外周血中阳性表达率为35．7％。胃癌组外周血中CK20 mRNA的阳性表达率在不同肿瘤组织学类型、TNM分期之间差异有统计学意义（P〈0．05），在不同肿瘤部位及患者性别之间差异无统计学意义（P均〉0．05）。结论胃癌患者外周血中CK20 mRNA的阳性表达可作为肿瘤细胞血行播散的标志，有助于胃癌预后的判断。     

Synthesis and in vitro anti-HIV evaluation of a new series of 6-arylmethyl-substituted S-DABOs as potential non-nucleoside HIV-1 reverse transcriptase inhibitors

A series of new 5-alkyl-2-benzylsulfanylpyrimidin-4(3H)-ones (5a-y) bearing different substituted arylmethyl moieties at the C-6 position of the pyrimidine core have been synthesized and evaluated for their in vitro activities against HIV-1 and HIV-2 in MT-4 cell cultures. The majority of the title compounds showed moderate to good activities against HIV-1 with an IC(50) range from 6.67 microM to 0.12 microM. Among them, 6-(3,5-dimethylbenzyl) analogue 5q exhibited the most potent anti-HIV-1 activity (IC(50)=0.12 microM, SI>2642), which was about 40-fold more active than the reference compounds 1-[(2-hydroxyethoxy)methyl]-6-(phenylsulfanyl)thymine (HEPT) and 2',3'-dideoxyinosine (DDI). The structure-activity relationships (SARs) of these new congeners were further discussed.     

RT-PCR检测胃癌患者外周血中细胞角蛋白20 mRNA及其意义

目的检测胃癌患者外周血中细胞角蛋白20(CK20)mRNA的表达情况,并探讨其存在的临床意义。方法应用逆转录-聚合酶链反应(RT-PCR)检测56例胃癌(胃癌组)、18例良性胃病(良性胃病组)、20例正常献血者(对照组)外周血中CK20mRNA的表达情况。结果对照组及良性胃病组外周血中CK20mRNA均为阴性表达,胃癌组外周血中阳性表达率为35.7%。胃癌组外周血中CK20mRNA的阳性表达率在不同肿瘤组织学类型、TNM分期之间差异有统计学意义(P<0.05),在不同肿瘤部位及患者性别之间差异无统计学意义(P均>0.05)。结论胃癌患者外周血中CK20mRNA的阳性表达可作为肿瘤细胞血行播散的标志,有助于胃癌预后的判断。     

Hereditary anaemias: genetic basis, clinical features, diagnosis, and treatment

The hereditary anaemias present a major genetic health problem that contributes considerably to childhood mortality and morbidity in many developing countries. This article summarizes recent scientific and technical advances in knowledge concerning the genes involved and their interaction to produce major haemoglobinopathies, the clinical pictures of these conditions, and their diagnostic criteria. Though there is no definitive cure, supportive treatment for the haemoglobinopathies has improved significantly, offering better quality of life and improved survival, and should be attempted for all such patients. For sickle cell disease, this comprises a simple set of rules that should be incorporated into existing medical care, whereas for thalassaemia, a regimen of intensive blood transfusion and regular subcutaneous infusion of deferoxamine is recommended. This treatment is stressful and probably too expensive to be applied in many developing countries until the birth rate of patients needing it can be sufficiently reduced by community control programmes.