2007-2013年上海市HIV-1感染者毒株耐药监测

目的 了解上海市2007-2013年HIV-1感染者的原发耐药基因突变情况,掌握耐药毒株变化趋势。 方法 随机选取2007-2013年随访的常住上海未经抗病毒治疗的HIV-1感染者血浆标本1296例,进行反转录-聚合酶链反应(RT-PCR)扩增、DNA测序、亚型鉴定,并与国际HIV耐药数据库比对分析。 结果 获得1085例pol区基因片段,其中亚型分布显示,CRF01_AE 651例(60.0%),其次为CRF07_BC 253例(23.3%)、B亚型97例(8.9%)、CRF08_BC 52例(4.8%)、C亚型12例(1.1%)、CRF01_B 10例(0.9%)、F2亚型2例(0.2%)、G亚型2例(0.2%)、CRF02_AG 5例(0.5%)和CRF03_AB 1例(0.2%)。原发耐药率平均为1.4%,其中核苷类反转录酶抑制剂(NRTI)耐药相关突变率为0.3%(3/1085),非核苷类反转录酶抑制剂(NNRTI)耐药相关突变率为0.9%(9/1085),整合酶抑制剂(IN)耐药相关突变率为0.2%(2/1085)。同时发生对蛋白酶抑制剂(PIs)和NNRTIs的耐药相关突变1例。 结论 2007-2013年上海市HIV-1感染者中存在原发耐药基因变异,耐药率呈下降趋势,从2007年的4.5%下降到2013年的1.1%。耐药基因型以CRF01_AE为主,男男同性传播为主,极少数HIV感染者同时存在对2种主要治疗药物耐药,应加强CRF01_AE耐药毒株的动态监测和研究,尤其是在男男性接触人群中的变化趋势。     

上海市卢湾区人免疫缺陷病毒-1型分子流行病学和耐药监测

目的:了解上海市卢湾区2010年确认的未经抗病毒治疗HIV-1感染者亚型分布和原发性耐药的流行情况,为当前该区制定艾滋病防治策略提供科学依据。方法:随机选取确认HIV-l感染者血浆标本77份,运用反转录-聚合酶链反应(RT-PCR)扩增,进行DNA测序及系统进化树分析,同时与国际HIV耐药数据库比对,并结合流行病学资料进行分析。结果:获得45份pol区基因片段,其中亚型分布显示,CRF01_AE亚型占68.9%(31/45),CRF07_BC亚型占22.2%(10/45)、B亚型占6.7%(3/45)和C亚型为2.2%(1/45)。CRF01_AE亚型以性传播途径为主,其中男男同性接触(MSM)和异性性传播分别占为66.7%(20/30)和33.3%(10/30),在异性性传播、MSM和注射毒品中均存在CRF07_BC;B亚型均为MSM人群,C亚型为异性性接触者。本研究共发现3例耐药者,包括同时发生对核苷类反转录酶抑制剂(NRTIs)和非核苷类反转录酶抑制剂(NNRTIs)的原发耐药、只对NNRTIs的原发耐药和对整合酶抑制剂(INIs)的原发耐药各1例。测得的耐药突变位点为L74IL、V179D及V179E、E92Q和L74M。结论:上海市卢湾区2010年新确认HIV-1感染者中以CRF01_AE和CRF07_BC为主,在耐药监测中发现NRTIs、NNRTIs和INIs耐药突变株;加强对HIV-1分子流行病学和耐药的监测具有公共卫生意义。     

2011年浙江省台州地区新发现HIV-1感染者分子流行病学调查

目的 了解2011年浙江省台州地区新发现艾滋病病毒（HIV）感染者的基本情况以及不同HIV-1基因亚型的分布情况。方法 选取台州市2011年新发现未经抗病毒治疗的HIV感染者抗凝全血标本140份,提取血浆中的病毒RNA,通过RT-PCR扩增HIV-1 pol 区的蛋白酶基因全序列与反转录酶基因部分序列,使用HIV-Blast软件判定亚型。结果 2011年台州地区新发现的未经抗病毒治疗的HIV感染者男女性别比为3.24:1,感染者中92.86%为性传播感染,3.57%为注射毒品感染;共检测出5种HIV-1基因亚型,分别为CRF01_AE、CRF07_BC、CRF08_BC、B和C亚型。性传播感染人群中57.14%为CRF01_AE亚型,注射毒品人群中以CRF07_BC亚型为主。结论 台州地区艾滋病患者以性传播途径感染为主,HIV-1基因亚型呈多样性特点,CRF01_AE亚型流行于性传播感染人群,而CRF07_BC亚型流行于毒品注射感染人群。     

沈阳市新诊断HIV感染者整合酶抑制剂原发耐药分析

目的明确沈阳市新诊断的HIV-1感染者整合酶抑制剂(integrase inhibitors, InIs)耐药株的传播情况。方法回顾性收集2018年6月至2019年3月沈阳市新诊断的HIV感染者80例,扩增血浆病毒RNA的整合酶编码基因,系统进化分析病毒基因型,以Stanford HIV耐药数据库解读耐药基因突变,计算原发耐药率并分析不同亚型毒株耐药相关自然多态性。结果 80例HIV-1感染者中共检出CRF01_AE感染者51例,占63.8%;CRF07_BC感染者14例,占17.5%,B亚型感染者6例,占7.5%;其他不典型重组9例,占11.3%。2例CRF01_AE感染者检出R263K突变,1例B亚型感染者检出E138A突变,总体耐药率为3.8%。CRF01_AE感染者在整合酶耐药相关位点50、74、119、153位氨基酸具有多态性,频率分别为5.9%、2.0%、13.7%和4.0%;而CRF07_BC感染者在整合酶耐药相关位点50、74、157位上氨基酸具有多态性,频率均为7.1%。结论沈阳市新诊断HIV感染者InIs原发耐药率较低,但部分感染者在HIV整合酶耐药相关位点具有氨基酸多态性。需要加强HIV整合酶耐药监测及对我国常见HIV流行株的耐药基因型和表型研究,更好地解读HIV整合酶耐药突变的意义。     

沈阳市新诊断HIV感染者整合酶抑制剂原发耐药研究

目的 明确沈阳市新诊断的HIV-1感染者整合酶抑制剂（Integrase inhibitors, InIs）耐药株的传播情况。方法 回顾性收集2018年6月至2019年3月沈阳市新诊断的HIV感染者80例，扩增血浆病毒RNA的整合酶编码基因，系统进化分析病毒基因型，以Stanford HIV耐药数据库解读耐药基因突变，计算原发耐药率并分析不同亚型毒株耐药相关自然多态性。结果 80例HIV-1感染者中共检出CRF01_AE感染者51例，占63.8%；CRF07_BC感染者14例，占17.5%，B亚型感染者6例，占7.5%；其他不典型重组9例，占11.3%。2例CRF01_AE感染者检出R263K突变，1例B亚型感染者检出E138A突变，耐药率3.8%。CRF01_AE感染者在整合酶耐药相关位点 50、74、119、153位氨基酸具有多态性，频率分别为5.9%、2.0%、13.7%和4.0%；而CRF07_BC感染者在在整合酶耐药相关位点50、74、157位上氨基酸具有多态性，频率均为7.1%。结论 沈阳市新诊断HIV感染者InIs原发耐药率较低，但少数感染者在整合酶耐药相关位点具有氨基酸多态性。需要加强整合酶耐药监测，并加强对我国常见HIV流行株的耐药基因型及表型研究，更好地解读耐药突变的意义。     

湛江地区献血人群HIV的基因分型及ELISA单试剂阳性者追踪检测的研究

目的了解湛江市无偿献血人群中人类免疫缺陷病毒(human immunodeficiency virus,HIV)基因分型,推测湛江市HIV病毒来源,为湛江市防控艾滋病和临床用血安全提供依据。方法从23例经湛江市CDC WB法确认的HIV无偿献血者血液中提取RNA,用RT-PCR进行gag基因扩增,并对扩增产物进行测序和序列分析。对68例ELISA单试剂阳性者献血后每2周采血1次再次检测,检测呈双试剂阳性者通过WB法确认。结果 23例阳性感染者均为HIV-1,其中12例(52.2%)为CRF01_AE重组亚型;10例(43.5%)为CRF07_BC重组亚型;1例(4.3%)为01B型。68例ELISA单试剂检测阳性者中有1例8周后确认为HIV-1 CRF01_AE重组亚型,1例10周后确认为HIV-1 CRF07_BC重组亚型,35例连续追踪6个月后依然为单试剂检测阳性,31例由于多方面的原因无法追踪,最后放弃。结论湛江地区献血人群中HIV-1亚型以CRF01_AE和CRF07_BC为主。35例单试剂阳性者可能与感染了弱病毒株或其体内病毒受体或其他病毒感染相关的基因存在变异有关,需要进一步追踪研究。     

浙江省绍兴市46例男男性行为者HIV感染基因特征分析及流行病相关因素分析

目的 了解浙江省绍兴市男男性行为者(MSM)人群中HIV-1感染者的亚型类型和特征 。方法 分析2013年1月至2014年7月本地区新确证未经抗病毒治疗的50例MSM感染者样本,采用RT-PCR和nest-PCR方法扩增HIV-1的gag和pol全长基因区,成功扩增46份样品,构建系统进化树分析基因亚型。结果 46份样品中发现CRF01_AE、CRF07_BC和B三种亚型和1株AE、BC重组亚型,各占52.17%、39.13%、6.52%和2.17%。结论 绍兴市 HIV-1感染的MSM人群中主要流行的亚型为CRF01_AE和CRF07_BC,该人群感染率高,应加强监测。     

广州市孕产妇人群HIV-1亚型分布和耐药特征分析

目的 了解广州市孕产妇人群艾滋病病毒1型（HIV-1）亚型和耐药情况。 方法 收集广州市2009 — 2014年孕产妇人群HIV-1抗体阳性样本,扩增蛋白酶（PR）和反转录酶（RT）基因序列,测序后构建系统进化树确定亚型,并与斯坦福大学HIV耐药数据库比对进行耐药分析。 结果 成功获得178份基因片段,其中10份为外籍病例;中国籍病例以CRF01_AE ［42.86%（72/168）］ 和CRF07_BC ［31.55%（53/168）］为主,外籍病例以C和CRF01_AE为主,各占30.00%（3/10）。 中、外籍病例的亚型分布差异有统计学意义（P＜0.001）。 样本总体耐药突变率为12.36%（22/178）,低度以上耐药率为5.62%（10/178）,蛋白酶抑制剂（PIs）、核苷酸反转录酶抑制剂（NRTIs）和非核苷酸反转录酶抑制剂（NNRTIs）耐药率分别为2.81%（5/178）、1.12%（2/178）和2.25%（4/178）。 耐药突变率最高的亚型为C亚型［50.00%（3/6）］。 5例外籍病例携带耐药突变,其中3例为耐药病例。 3.37%（6/178）样本被预测对单类药物呈高度耐药,未发现对多类药物呈高度耐药的样本。 结论 广州市HIV感染的孕产妇人群中有12种病毒亚型,以CRF01_AE和CRF07_BC为主,耐药突变率及耐药率低,但存在PIs或NRTIs或NNRTIs的高度耐药毒株且外籍病例具有较高耐药突变率和耐药率。      

Determination of creatine kinase isoenzyme MB activity in serum using immunological inhibition of creatine kinase M subunit activity. Activity kinetics and diagnostic significance in myocardial infarction.

This is a new method for the determination of creatine kinase isoenzyme MB activity in serum. The method uses direct activity measurement of creatine kinase B subunit activity after blocking of CK-M subunit activity by inhibiting antibodies. The test takes no longer than 15 min. The method yields an intra-serial C.V. of 2.0-12.9%, and a C.V. from day to day of 5.5%. The detection limit is 3.4 U/l creatine kinase MB. In the 95 cases with proven myocardial infarction several types of creatine kinase MB activity kinetics could be determined. The percentage of creatine kinase MB of peak CK-total is 6-25%, with a mean of 11.1%. The amount of creatine kinase MB with respect to total CK activity after reinfarction is higher than the amount after initial infarction.     

Dissociable correlates of two classes of retrieval processing in prefrontal cortex

Although substantial evidence suggests that the prefrontal cortex (PFC) implements processes that are critical for accurate episodic memory judgments, the specific roles of different PFC subregions remain unclear. Here, we used event-related functional magnetic resonance imaging to distinguish between prefrontal activity related to operations that (1) influence processing of retrieval cues based on current task demands, or (2) are involved in monitoring the outputs of retrieval. Fourteen participants studied auditory words spoken by a male or female speaker and completed memory tests in which the stimuli were unstudied foil words and studied words spoken by either the same speaker at study, or the alternate speaker. On "general" test trials, participants were to determine whether each word was studied, regardless of the voice of the speaker, whereas on "specific" test trials, participants were to additionally distinguish between studied words that were spoken in the same voice or a different voice at study. Thus, on specific test trials, participants were explicitly required to attend to voice information in order to evaluate each test item. Anterior (right BA 10), dorsolateral prefrontal (right BA 46), and inferior frontal (bilateral BA 47/12) regions were more active during specific than during general trials. Activation in anterior and dorsolateral PFC was enhanced during specific test trials even in response to unstudied items, suggesting that activation in these regions was related to the differential processing of retrieval cues in the two tasks. In contrast, differences between specific and general test trials in inferior frontal regions (bilateral BA 47/12) were seen only for studied items, suggesting a role for these regions in post-retrieval monitoring processes. Results from this study are consistent with the idea that different PFC subregions implement distinct, but complementary processes that collectively support accurate episodic memory judgments.     

俯卧位通气对高海拔地区肺复张治疗无效急性呼吸窘迫综合征患者氧合的影响

目的 探讨俯卧位通气对高海拔地区肺复张术(RM)治疗无效急性呼吸窘迫综合征(ARDS)患者的治疗作用.方法 从海拔2260m的地区医院筛选RM治疗无效的41例ARDS患者[平均氧合指数( PaO2/FiO2)较RM前升高＜20％视为RM无效],依不同病因分为肺内源性ARDS组(ARDSp组)和肺外源性ARDS组(ARDSexp组),每组再按信封法随机分为俯卧位组和仰卧位组,即ARDSp俯卧位组(11例)、ARDSp仰卧位组(9例)、ARDSexp俯卧位组(10例)、ARDSexp仰卧位组(11例).在通气前及通气1、2、3、4h监测动脉血氧分压( PaO2)、PaO2/FiO2、静态顺应性(Cst)、气道阻力(Raw)的变化.结果 通气lh时,ARDSexp俯卧位组PaO2/FiO2( mm Hg,l mm Hg=0.133 kPa)即较通气前显著升高(157.4±40.6比129.3±48.7,P＜0.05),并随通气时间延长呈持续增高趋势,4h达峰值(219.1 ±41.1);且ARDSexp俯卧位组通气3h内PaO2/FiO2较其他3组显著增高,另3组间则差异无统计学意义.ARDSp俯卧位组、ARDSexp俯卧位组通气4h时PaO2/FiO2均较相应仰卧位组显著增高(208.8±39.7比127.4±47.1,219.1±41.1比124.9±50.8,均P＜0.05).4组通气前后Cst无显著改变,各组间差异也无统计学意义.ARDSp俯卧位组通气4h时Raw(cmH2O·L-1·s-1)较通气前显著降低(6.8±1.7比10.7±1.8,P＜0.05),且明显低于其他3组;其他3组各时间点Raw组内及组间比较差异均无统计学意义.结论 俯卧位通气作为ARDS机械通气重要策略之一,可以改善RM无效高原ARDS患者的氧合,为抢救患者赢得宝贵的时间.     

Digital imaging among medical facilities

The Department of Veterans Affairs (VA) in the USA operates a network of 172 medical centres which all utilize a hospital information system (HIS) which has been developed and is currently maintained by the VA. During the past several years, an image management and communication module has been developed, installed and clinically utilized at the Washington DC and Maryland VA Medical Centres. This image management and communication system, referred to as the decentralized hospital computer program (DHCP) imaging system, is fully integrated with a commercial picture archiving and communication system (PACS). The system is utilized to capture, archive, and display all images generated within the hospital including radiology, nuclear medicine, pathology, endoscopy, bronchoscopy, and dermatology, intraoperative photographs, ECG data, and a limited number of paper documents. The ultimate goal of the project is to have all patient text and image data available at any clinical workstation to any authorized user anywhere within the network of medical centres. Clinical requirements for an imaging workstation include ease of use, rapid and reliable access to the complete set of patient information, and images which are of acceptable quality to meet the requirements of the user and the subspecialty. Patient confidentiality and data security must be safeguarded at all times. Integration of the images with the remainder of the patient's database was found to be critical to the success of the project. The experience at the Washington and Maryland facilities suggests that an imaging system that is successfully integrated with a hospital information system can provide substantial clinical and economic benefits both within and among medical centres. Clinical acceptance and utilization of the system has been excellent, particularly in diagnostic radiology where DHCP Imaging has been interfaced to a commercial PAC system. Based upon this initial experience, the VA has begun to deploy the system throughout its large network of medical centres.     

Myocardial elastography at both high temporal and spatial resolution for the detection of infarcts

Myocardial elastography is a novel method for noninvasively assessing regional myocardial function, with the advantages of high spatial and temporal resolution and high signal-to-noise ratio (SNR). In this paper, in-vivo experiments were performed in anesthetized normal and infarcted mice (one day after left anterior descending coronary artery [LAD] ligation) using a high-resolution (30 MHz) ultrasound system (Vevo 770, VisualSonics Inc., Toronto, ON, Canada). Radiofrequency (RF) signals of the left ventricle (LV) in longitudinal (long-axis) view and the associated electrocardiogram (ECG) were simultaneously acquired. Using a retrospective ECG gating technique, 2-D full field-of-view RF frames were acquired at an extremely high frame rate (8 kHz) that resulted in high-quality incremental displacement and strain estimation of the myocardium. The incremental results were further accumulated to obtain the cumulative displacements and strains. Two-dimensional and M-mode displacement images and strain images (elastograms), as well as displacement and strain profiles as a function of time, were compared between normal and infarcted mice. Incremental results clearly depicted cardiac events including LV contraction, LV relaxation and isovolumetric phases in both normal and infarcted mice, and also evidently indicated reduced motion and deformation in the infarcted myocardium. The elastograms indicated that the infarcted regions underwent thinning during systole rather than thickening, as in the normal case. The cumulative elastograms were found to have higher elastographic SNR (SNR(e)) than the incremental elastograms (e.g., 10.6 vs. 4.7 in a normal myocardium, and 6.0 vs. 2.4 in an infarcted myocardium). Finally, preliminary statistical results from nine normal (m = 9) and seven infarcted (n = 7) mice indicated the capability of the cumulative strain in differentiating infracted from normal myocardia. In conclusion, myocardial elastography could provide regional strain information at simultaneously high temporal (>/=0.125 ms) and spatial ( approximately 55 microm) resolution as well as high precision ( approximately 0.05 microm displacement). This technique was thus capable of accurately characterizing normal myocardial function throughout an entire cardiac cycle, at the same high resolution, and detecting and localizing myocardial infarction in vivo.     

Clinical Pharmacokinetics of Morphine

Morphine, the most widely used mu-opioid analgesic for acute and chronic pain, is the standard against which new analgesics are measured. A thorough understanding of the pharmacokinetics of morphine is required in order to safely and effectively use this analgesic in a wide variety of patients with different levels of organ function. A MEDLINE search was conducted to identify literature published between 1966 and January 2002 relevant to the pharmacokinetics of morphine. These publications were reviewed and the literature summarized regarding unique and clinically important elements of morphine disposition relative to its parenteral administration (including intravenous, intramuscular, subcutaneous, epidural and intrathecal administration), absorption profile (immediate release, controlled release, and sublingual/buccal, and rectal administration), distribution, and its metabolism/ excretion. Special populations, including infants, elderly, and those with renal/liver failure, have a unique morphine pharmacokinetic profile that must be taken into account in order to maximize analgesic efficacy and reduce the risk of adverse events.