HIV-1耐药基因检测的研究进展

HIV-1耐药是影响艾滋病抗病毒治疗效果的主要因素。随着抗病毒疗法的普及和接受治疗者的增多,HIV-1耐药的问题日益凸显,使艾滋病治疗面临巨大的挑战。因此,了解各抗病毒药物治疗引起的HIV-1耐药突变位点并及时采用有效方法进行耐药基因检测对临床治疗具有重要指导意义。HIV-1耐药位点基因型检测方法因其快速准确的特点,目前是HIV-1耐药检测最常用也是最有前景的方法。本文对HIV-1耐药位点和耐药基因检测的研究进展做简单综述。     

HIV-1获得性耐药研究进展

HIV-1耐药性影响艾滋病的传播、治疗和预后,随着发现即治疗政策的全面推广,艾滋病治疗人数不断增加,HIV-1耐药已经成为越来越重要的公共卫生问题。HIV-1耐药包括传播性耐药和获得性耐药,传播性耐药指HIV感染者未经抗病毒治疗就发生的耐药,而获得性耐药指艾滋病病人接受抗病毒治疗后产生的耐药。本文拟从HIV-1获得性耐药现状,耐药位点分布、耐药检测方法、耐药结果解释系统和耐药产生的原因等方面进行文献整理,对我国的艾滋病抗病毒治疗和耐药监测工作有一定的参考作用。     

广西新诊断HIV/AIDS患者HIV-1整合酶区基因突变及整合酶抑制剂耐药分析

目的 了解广西新诊断HIV-1感染者整合酶抑制剂（integrase stand transfer inhibitors,INSTIs）耐药率、HIV-1整合酶区耐药相关多态性位点的突变率及影响因素。方法 使用课题组2019年10月—2020年3月收集的广西新诊断HIV/AIDS患者血液样本，提取HIV-1整合酶区RNA、巢式PCR扩增整合酶基因并测序。利用斯坦福HIV耐药数据库确定患者HIV-1整合酶区耐药突变位点并计算患者耐药率。通过序列比对分析HIV-1整合酶区耐药相关多态性突变位点，使用多因素logistic回归分析HIV-1整合酶区耐药相关多态性位点发生突变的影响因素。结果 320例HIV-1患者的HIV-1整合酶区序列中，以CRF01＿AE亚型（39.4%）为主，耐药率为2.19%，主要耐药突变位点为E92K(0.62%),次要耐药突变位点主要为E157Q(1.25%)。发生频率较高的HIV-1整合酶区耐药相关多态性位点有L74V(0.94%)、E138D(1.25%)和G163E(3.13%)。多因素logistic回归分析显示：HIV-1整合酶区耐药相关多态性突变的影响...     

江苏省HIV-1基因型抗病毒治疗失败患者耐药检测结果分析

目的了解江苏省2010—2014年HIV-1感染者抗病毒失败人群的HIV-1耐药情况,为临床抗病毒治疗提供参考。方法根据耐药检测实验室网络收集江苏省2010—2014年的HIV-1基因型耐药检测结果,对各年度相关药物耐药情况、耐药基因位点及病毒基因亚型进行统计分析。结果 2010—2014年分别纳入样本74、113、197、278、346份,其中检测出现耐药结果的比率分别为68.92%、48.67%、51.27%、52.52%和57.80%。各年度间HIV-1主要耐药药物类似,核苷类主要有3TC、ABC、DDI和FTC,非核苷类药物以EFV和NVP为主。HIV-1对蛋白酶类药物耐药差别较大,且目前使用的LPV/r的耐药率在1%以下。年度间HIV-1主要耐药位点为184、181、190及103位,其中184位突变主要引起3TC和FTC耐药,而181、190、103位突变与EFV和NVP耐药相关。HIV-1病毒基因亚型均以CRF01_AE为主,且呈上升趋势。结论江苏省HIV感染者抗病毒治疗失败人群HIV-1基因型耐药率有上升趋势,应加强对抗病毒治疗患者的耐药检测,从而及时合理调整抗病毒治疗方案。     

新疆和田地区新近诊断HIV-1人群耐药传播及亚型分布情况调查

目的了解新疆和田地区未治疗的HIV-1新诊断人群耐药传播情况及亚型分布。方法对新疆和田地区2013~2014年新诊断HIV-1感染人群随机抽样,对样本HIV-1 POL区进行亚型及耐药基因型分析,并评估新诊断人群HIV-1耐药传播水平。结果共有203个样本获得有效序列,样本中07_BC重组亚型193人,比例最大,占95.07%;C亚型5人,占2.46%;01_AE/B亚型2人,08_BC亚型3人;对HIV-1 POL区耐药基因突变位点进行分析,PR区耐药传播率为0.99%;RT区耐药传播率为2.46%。HIV-1耐药总传播率低于5%。结论新疆和田地区HIV-1新诊断人群的亚型主要是以07_BC重组亚型为主;和田地区未经抗病毒治疗新诊断HIV-I感染者中已经出现PR和RT区耐药突变株,但传播水平尚处于低流行状态,应适时开展耐药性监测。     

云南省德宏州2009年HIV-1耐药株传播水平调查

抗反转录治疗(ART)在降低HIV-1感染者并发症和艾滋病患者死亡率的同时,也促进了HIV-1耐药株的发生.耐药株有可能传播到新感染人群,从而使尚未开始治疗的HIV感染者携带HIV耐药株,导致以后的抗病毒治疗产生困难.本研究于2009年在云南省德宏州开展了HIV-1耐药警戒线调查.     

凉山彝族自治州HIV/AIDS抗病毒治疗前HIV-1耐药情况及其影响因素分析

目的 了解凉山彝族自治州（凉山州）HIV/AIDS抗病毒治疗前HIV-1耐药情况及其影响因素,为预防HIV-1耐药毒株的传播提供参考依据。方法 分别于2017年1月1日至6月30日、2018年1月1日至6月30日在凉山州开展HIV/AIDS抗病毒治疗前HIV-1耐药的横断面调查。提取获得HIV-1 pol基因区序列,根据2014年WHO耐药监测指南的推荐标准,应用HyPhy 2.2.4和Cytoscape 3.6.1软件进行HIV-1耐药毒株传播网络分析。结果 研究对象464例HIV/AIDS,HIV-1毒株为CRF07_BC亚型的占88.6%（411/464）,总的HIV-1耐药率为9.9%（46/464）,非核苷类反转录酶抑制剂（NNRTI）、核苷类反转录酶抑制剂（NRTI）和蛋白酶抑制剂（PI）耐药率分别为6.7%（31/464）、1.9%（9/464）和0.4%（2/464）;有1组HIV-1新型重组毒株URF_01BC亚型独立成簇并携带相关耐药突变位点;多因素logistic回归分析结果显示,与异性性传播人群相比,注射吸毒人群的HIV-1耐药风险较高（aOR=3.03,95% CI：1.40～6.54）。结论 凉山州HIV/AIDS抗病毒治疗前的HIV-1耐药率较高,且有新型重组毒株URF_01BC亚型携带相关耐药突变位点的成簇传播,建议加强HIV-1耐药毒株传播的预防工作。     

宁夏HIV-1感染者原发性耐药及基因变异型研究

目的 掌握本地区HIV-1 病毒耐药毒株的流行与传播情况,为有效的抗病毒治疗提供参考依据。方法 2018年3月1日-6月30日在宁夏开展HIV/AIDS抗病毒治疗前HIV-1耐药的横断面调查。提取获得HIV-1 pol基因区序列,根据2015年WHO耐药监测指南的推荐标准,采用Shafer 的耐药性突变积分表耐药评分,分值≥15判为耐药。结果 调查68例HIV/AIDS,58例巢式PCR检测获得HIV-1病毒pol区基因序列。年龄中位数为36.5岁（IQR:30～50）;男性55例(94.8%),女性3例(5.2%), Shafer 的耐药性突变积分表耐药评分,7例判为耐药,耐药率12.1%。存在4种基因亚型,分别是B亚型、CRF01_AE 亚型、CRF07_BC亚型和CRF55_01B亚型。结论 宁夏HIV-1原发性耐药率处于较高水平,应继续加强艾滋病抗病毒治疗前耐药监测。     

台州市2016-2018年新报告HIV/AIDS抗病毒治疗前HIV-1耐药及亚型流行特征分析

目的 了解台州市新报告HIV/AIDS抗病毒治疗（ART）前HIV-1耐药情况及亚型流行特点。方法 于2016年1月至2018年12月在台州市开展新报告HIV/AIDS在ART前HIV-1耐药的横断面调查,RT-PCR扩增获得HIV-1 pol基因片段并测序,提交序列至斯坦福大学耐药数据库,根据2014年WHO耐药监测指南的推荐标准,确定耐药突变位点以及HIV-1毒株对抗病毒药物的敏感性。结果 2016-2018年台州市新报告HIV/AIDS中成功获得HIV-1 pol基因区序列的研究对象806例,ART前HIV-1耐药率为2.9%（23/806）,其中,非核苷类反转录酶抑制剂（NNRTIs）、核苷类反转录酶抑制剂（NRTIs）和蛋白酶抑制剂（PIs）耐药率分别为1.9%（15/806）、0.6%（5/806）和0.0%。2016-2018年新报告HIV/AIDS在ART前HIV-1耐药率依次分别为1.6%、1.8%和4.8%。NNRTIs和NRTIs耐药突变位点以K103 N（0.7%）和M184I/V（0.5%）为主。HIV-1亚型以CRF01_AE（42.7%,344/806）、CRF07_BC（28.9%,233/806）和CRF08_BC（11.2%,90/806）为主。同性性传播者HIV-1亚型以CRF01_AE（53.3%,136/255）和CRF07_BC（32.2%,82/255）为主;异性性传播者HIV-1亚型以CRF01_AE（37.7%,203/539）、CRF07_BC（27.5%,148/539）和CRF08_BC（16.1%,87/539）为主。结论 2016-2018年台州市新报告HIV/AIDS在ART前HIV-1耐药率处于低流行状态,但存在上升趋势,需加强对HIV-1耐药型毒株的监测工作。     

HIV-1低病毒载量患者外周血前病毒DNA优势耐药位点分析

目的 探索HIV-1低病毒载量(LVL)患者外周血HIV-1前病毒DNA是否携带优势耐药突变位点(DRMs),以及HIV-1前病毒DNA耐药检测在临床中的潜在意义.方法 采集2020年5月—2021年5月在某院门诊接受抗病毒治疗6个月以上且连续两次检测HIV-1 RNA血浆病毒载量(viral load,VL)为50～...     

Calcium intake in the elderly: validation of a dietary questionnaire

Epidemiological studies of calcium and osteoporosis have been hampered by the lack of a suitable tool for assessing calcium intake. This report describes a new frequency and amount questionnaire for measuring present and past calcium intake in the elderly. The validity of the questionnaire was tested against two commonly used standards of dietary assessment, five-day duplicate diets and seven-day weighed dietary inventories. The resulting correlation coefficients were, respectively, r = 0.76 and r = 0.69, while that for repeatability was r = 0.84. Furthermore, the questionnaire categorized subjects into thirds of the distribution of intake with almost no gross misclassification. It is suggested that the present findings may be extended to the majority of normal, healthy elderly subjects, implying wide application for the questionnaire in the assessment of calcium intake in the elderly.     

The human drama of genetics: 'hard' and 'soft' media representations of inherited breast cancer

This paper examines media coverage of 'breast cancer genetics', and explores its implications for public understanding. We present a content analysis of coverage in British newspapers and look at a variety of popular forms, including women's magazines, television soap opera and radio drama. Genetic/inherited risk receives a great deal of coverage across a wide range of media formats and outlets. Much of this attention has focused on individuals from 'high risk families' and dilemmas around prophylactic mastectomies. Through examining media coverage, combined with interviews with media personnel and their sources, we show why this story proved so attractive to the media and highlight the different production values which influence coverage. Finally, we introduce preliminary findings from focus group discussions to demonstrate how such 'human interest' framing has engaged audience attention and influenced public understandings. The paper concludes by highlighting the implications for analysing, predicting, and engaging with, media representations of science.     

Worker education in the primary prevention of occupational dermatoses

This paper reports the evaluation of a skin care education programmeconducted on a fine chemicals manufacturing site where over1,000 employees are located. Approximately 60% are involvedin chemical manufacture. Over a 12 month period production staffreceived training in prevention of occupational dermatoses linkedto a site-wide poster initiative. The incidence of new casesof occupational dermatoses fell from 0.055 (70 cases in 1,277employees) to 0.021 (27 cases in 1,277 employees) before andafter the intervention respectively (p<0.0001). After otherfactors such as chemicals handled, observer bias and changesin reporting related to socioeconomic climate were taken intoaccount it is concluded that this study demonstrates the importanceof worker education as a tool for primary prevention of disease.Training materials such as video and poster presentations maybe effectively used in the chemical manufacturing industry asan adjunct to prevention and control of exposure to substanceshazardous to the skin. Such methods may also be used in otherindustries where there are significant risks of dermatoses.     

Regional Variation in Travel-related Illness acquired in Africa,March 1997–May 2011

To understand geographic variation in travel-related illness acquired in distinct African regions, we used the GeoSentinel Surveillance Network database to analyze records for 16,893 ill travelers returning from Africa over a 14-year period. Travelers to northern Africa most commonly reported gastrointestinal illnesses and dog bites. Febrile illnesses were more common in travelers returning from sub-Saharan countries. Eleven travelers died, 9 of malaria; these deaths occurred mainly among male business travelers to sub-Saharan Africa. The profile of illness varied substantially by region: malaria predominated in travelers returning from Central and Western Africa; schistosomiasis, strongyloidiasis, and dengue from Eastern and Western Africa; and loaisis from Central Africa. There were few reports of vaccine-preventable infections, HIV infection, and tuberculosis. Geographic profiling of illness acquired during travel to Africa guides targeted pretravel advice, expedites diagnosis in ill returning travelers, and may influence destination choices in tourism.     

Self-reported health problems among Swedish miners one year after unemployment

Unemployment is considered to be a public health concern sincedeterioration in the health of the unemployed is often anticipated.However, for some groups, such as miners, unemployment mightimprove health due to a cessation of potentially harmful occupationalexposures. This study evaluates the health of 79 miners in oneSwedish iron-ore mine, and 226 age-matched controls from thegeneral population, during one year after the closure of themine. The participants received a questionnaire regarding medicalhistory and subjective symptoms at the beginning of the studyperiod, and after one year. Statistically significant negativeeffects on self-reported health attributable to unemploymentwere not found, although neuropsychiatric symptoms were morecommon among the unemployed miners. The miners reported a statisticallysignificant improvement in grip force (p=0.031). They had asignificantly higher prevalence of symptoms associated withmining related exposures when compared with the population controls;pain in the upper extremities [relative risk (RR)=2.27, 95%confidence interval (Cl)=1.44–3.59), back pain (RR=1.84;Cl=1.237–2.75), vasospastic disease of the fingers (RR=2.05;Cl=1.18–3.57) and obstructive respiratory symptoms (attacksof dyspnea and wheezing: RR=3.67; Cl=1.167–11.6).     

Excès de cas humains et animaux de tularémie en France au cours de l’hiver 2007–2008 : émergence ou phénomène isolé ?

Context

Tularemia is a zoonosis affecting humans and hares in France. We describe the results of surveillance in both species, in 2007 and 2008.

Methods

Human tularemia cases are mandatorily notifiable in France since 2003. In hares, surveillance relies on volunteer hunter associations in all districts of the country. Data from mandatory reports and volunteer surveillance in 2007/2008 were analyzed and compared with previous results.

Results

In 2007/2008, 144 cases were reported in humans and 117 cases in hares. This was a 100% increase compared to previous years. Human cases differed from those of previous years only by the frequency of contact with breeding animals. Human cases without any documented risk exposure were also more frequent.

Conclusion

An increase of tularemia cases occurred in 2007/2008 in both species. Complementary studies are needed to identify the species reservoir in France to understand the causes of this peak of cases.     

深圳公立医院管理体制改革制度设计

深圳公立医院管理体制改革实行政事分开、管办分开,在理事会架构下按法定机构模式组建市医管中心,落实公立医院运营管理自主权.作者从当前公立医院管理体制的弊端入手,介绍了深圳市进行公立医院管理体制改革的基本思路及改革方案设计的主要举措,深入剖析了的改革方案的特点,并对改革效果进行了预测.     

Effects of nitrogen dioxide on red blood cells of rats: Changes in components of red cell membranes during in vivo exposure to NO2

Red cell membranes, prepared from red blood cells of rats exposed to 4, 10, or 20 ppm nitrogen dioxide (NO₂) for 1 to 10 days, were examined for evidence of changes in membrane components. Appreciable changes were not found in contents of phospholipid and cholesterol during exposure to 10 ppm NO₂. By contrast, protein content altered with the time of exposure. Moreover, changes in protein composition were observed by employing sodium dodecyl sulfate — polyacrylamide gel electrophoresis. Twenty-four-hour exposure to NO₂ at the concentration above 10 ppm resulted in a marked increase in the percentage of lysophosphatidylethanolamine (LysoPE) to the total phospholipids. The prolonged exposure to 10 ppm NO₂ gave rise to a further increase in LysoPE, whereas the percentage of phosphatidylethanolamine (PE) showed a gradual decrease. A 1-day exposure to 4.0 ppm NO₂ also caused an increase in sialic acid content and decreases in those of PE and hexose. In addition to contents of these components the percentage of LysoPE increased 5 days after exposure and the elevated values were maintained up to the end of exposure period. These results demonstrate that red blood cells in circulation exhibit different membrane properties in terms of lipid and carbohydrate composition during 10 days of exposure to 4.0 ppm NO₂.     

The design of hazard risk assessment matrices for ranking occupational health risks and their application in mining and minerals processing

Two hazard risk assessment matrices for the ranking of occupational health risks are described. The qualitative matrix uses qualitative measures of probability and consequence to determine risk assessment codes for hazard-disease combinations. A walk-through survey of an underground metalliferous mine and concentrator is used to demonstrate how the qualitative matrix can be applied to determine priorities for the control of occupational health hazards. The semi-quantitative matrix uses attributable risk as a quantitative measure of probability and uses qualitative measures of consequence. A practical application of this matrix is the determination of occupational health priorities using existing epidemiological studies. Calculated attributable risks from epidemiological studies of hazard-disease combinations in mining and minerals processing are used as examples. These historic response data do not reflect the risks associated with current exposures. A method using current exposure data, known exposure-response relationships and the semi-quantitative matrix is proposed for more accurate and current risk rankings.