天津市男男性接触人群人类免疫缺陷病毒-1感染者亚型与耐药性分析

与男性有性行为的男性(men who have sex with men,MSM)由于其特殊的高危性行为,使其成为传播AIDS的高危人群.2007年估计,我国HIV感染者和AIDS患者中,通过男男性接触传播感染的占11%[1].自1996年国内外广泛应用高效抗反转录病毒药物治疗AIDS以来,HIV耐药毒株的传播呈逐渐增高趋势,对AIDS患者药物治疗后的耐药性检测和HIV耐药病毒株流行情况的监测引起广泛关注.     

深圳市HIV感染者结核分枝杆菌初始耐药谱分析

目的分析深圳市艾滋病病毒(HIV)感染者结核分枝杆菌(MTB)对抗痨药物的耐药性,为HIV/MTB双重感染的临床治疗提供参考依据。方法收集深圳市第三人民医院2012年1月至2012年12月收治的HIV/MTB双重感染患者40例和118例单纯结核病患者的菌株材料,进行菌种分离鉴定,并行抗异烟肼(INH)、利福平(RFP)、链霉素(SM)、乙胺丁醇(EMB)、氧氟沙星(OFL)、卡那霉素(KAN)的耐药性检测。结果在抗结核药物中,HIV/MTB组初始耐药率最高的药物是INH(37.5%,15/40),而单纯结核组最高的是SM(10.2%,12/118)。在一线抗结核药物中,HIV/MTB组总初始耐药率为47.5%(19/40),明显高于单纯结核组(12.7%,15/118)。HIV/MTB组INH初始耐药率为37.5%(15/40),SM初始耐药率为27.5%(11/40),初始耐多药率为12.5%(5/40),分别与单纯结核组比较,差异均有统计学意义(P0.05)。而在二线抗结核药物中,两组初始耐药率差异无统计学意义(P0.05)。结论深圳市HIV感染者结核分枝杆菌的一线抗结核药物总初始耐药率、耐INH、耐SM、初始耐多药率高,提示临床医师应重视收集HIV感染者和当地耐结核药物资料,关注结核初始耐药问题,以便及时调整治疗方案。     

河南地区HIV/TB合并感染患者结核分枝杆菌初始耐药分析

目的了解河南地区艾滋病病毒(HIV)感染合并结核病患者结核分枝杆菌初始耐药的情况。方法选取郑州市第六人民医院2015年1月至2019年4月收治的HIV感染合并初治结核病患者80例和非HIV感染初治结核病患者163例,结核病患者的分枝杆菌培养菌型鉴定结果为结核分枝杆菌复合群,并进行药敏试验和试验结果分析。结果对一线抗结核药物初始耐药率,HIV感染合并结核病组患者异烟肼和利福平各占21.3%(17/80),非HIV感染结核病组患者链霉素占11.7%(19/163)。对一线抗结核药物总的初始耐药率分别为25.0%(20/80)和17.2%(28/163),差异无统计学意义(P0.05)。初始耐多药发生率,HIV感染合并结核病组为18.8%(15/80),非HIV感染结核病组为6.7%(11/163),差异有统计学意义(P 0.05)。HIV感染合并结核病组有1例广泛耐药患者占1.3%(1/80)。对二线抗结核药物总的初始耐药率差异无统计学意义(P0.05)。结论河南地区HIV感染合并结核病患者初始耐药中耐异烟肼、利福平比例最高,耐多药发生率比非HIV感染结核病组患者高;并出现了广泛耐药结核病患者。     

福建省MSM人群中HIV-1感染者原发性耐药基因突变研究

目的研究我省男男性行为者(MSM)中未经抗病毒治疗的人类免疫缺陷病毒(HIV)感染者的原发性基因耐药性突变发生情况,为该人群的抗病毒治疗药物选择提供依据。方法采集福建省尚未接受抗病毒治疗的MSM HIV-1感染者的外周静脉抗凝全血,分离血浆,提取血浆中HIV RNA,用RT-PCR方法扩增HIV pol区蛋白酶基因全序列与部分逆转录酶序列。所得扩增片段进行序列测定后,数据运用Contig Express拼接编辑校正后上传至斯坦福大学HIV耐药数据库进行比对,同时运用Bio-Edit和Mega等软件进行系统发生分析。结果获得50份HIV-1分离株完整的PR和RT基因序列,其中60%(30/50)为01_AE重组亚型,18%(9/50)为B亚型,20%(10/50)为07_BC重组亚型,1例08_BC重组亚型。耐药分析显示,1例发生PI(蛋白酶抑制剂)药物的主要耐药突变M46I,造成对NFV中度耐药。10例样本出现NNRTIs和NRTIS的耐药相关突变,仅1例解释为对NNRTIs的潜在低水平耐药,由V179E引起。结论福建省MSM HIV-1感染者的原发性耐药突变发生率低,有利于今后该人群抗病毒治疗工作的开展,但需加强监控该人群耐药毒株的传播。     

应用HIV-1耐药性基因型检测广东部分地区HIV耐药株

目的利用艾滋病病毒1型(HIV-1)耐药性基因型检测法,在HIV-1感染者中监测HIV-1耐药性病毒株,掌握广东省HIV-1感染者在利用抗病毒药物治疗前是否存在耐药突变及其流行情况。方法从未接受高效抗逆转录病毒联合疗法(HAART)治疗的HIV-1感染者血浆中提取病毒RNA,采用套式PCR扩增目的基因片断,并对扩增片断进行序列测定和分析。结果HIV-1耐药性基因型检测法能够从HIV-1感染者血浆病毒载量大于1 000拷贝/ml以上、CD4低于400以下的样本中扩增到目的片断。在广东省50例未治疗对象中,低中度耐药相关突变例数为2例,占4%;高度耐药相关突变例数为0;总耐药相关突变例数为2例,占4%。结论HIV-1耐药性基因型检测法能有效地监测HIV-1感染者血浆中的耐药性病毒株的存在,并且方法提供的结果准确、可靠。对广东省未接受抗病毒治疗的HIV-1感染者中耐药突变的检测表明,HIV-1感染者中存在病毒的耐药性突变,也反应了HIV毒株自然变异情况的存在。     

HIV感染孕妇耐药状况的Meta分析

目的了解艾滋病病毒(HIV)感染孕妇抗病毒药物耐药水平。方法检索3个数据库(万方、CNKI、Pubmed)并提取HIV感染孕妇耐药原始数据,根据异质性检验结果,选择模型对原始数据进行合并分析,应用R软件进行Meta分析。结果本次共纳入32篇文献研究。HIV感染孕妇抗病毒药物总耐药率为9.01%[95%可信区间(CI):6.51%～12.34%]。亚组分析,各耐药率存在地区及耐药类型差异,HIV感染孕妇传播性耐药率为7.47%(95%CI:5.24%～10.06%),获得性耐药性为22.75%(95%CI:15.36%～31.11%)。结论 HIV感染孕妇耐药率较高,应加强妊娠群体耐药监测和耐药基因个体检测,以便为孕妇提供个性化治疗方案,最大限度地发挥治疗效果。     

温州地区HIV/AIDS病人抗病毒治疗后耐药基因变异研究

目的通过调查分析温州地区已接受抗病毒治疗病人体内艾滋病病毒(HIV)毒株的耐药基因的突变发生率,为采取相应防治措施提供可靠的依据,同时指导抗病毒药物的使用。方法收集温州的11个县市区在2010-2015年接受抗病毒治疗的HIV感染者/艾滋病(AIDS)病人625例,病毒载量大于1 000拷贝/mL的70例,进行HIV蛋白酶(PR)全长和部分反转录酶(RT)基因的扩增、脱氧核糖核酸(DNA)测序、亚型鉴定,并与国际HIV耐药数据库比对分析。结果在68例获得有效序列患者中,其中亚型分布显示,CRF01_AE占52.94%(36/68),B亚型占17.65%(12/68),BC重组占25.00%(17/68),C亚型占4.41%(3/68)。抗病毒治疗患者对蛋白酶抑制剂(PI)、核苷类反转录酶抑制剂(NRTI)和非核苷类反转录酶抑制剂(NNRTI)的耐药率,分别为0.48%(3/625),7.84%(49/625)和8.32%(52/625),总耐药率为8.80%(55/625)。NRTI主要突变位点为M184V,NNRTI主要突变位点为Y181C。结论通过对抗病毒治疗病人调查发现,温州总体耐药率处于较低水平。M184V、Y181C突变位点检出率高,耐药的严重程度依次为NNRTIsNRTIsPIs。应结合实际,科学合理用药。     

110例人类免疫缺陷病毒感染及获得性免疫缺陷综合征患者合并血小板减少症临床分析

目的:了解人类免疫缺陷病毒感染或获得性免疫缺陷综合征(HIV/AIDS)患者合并血小板减少症的临床特点。方法:回顾性分析2009年8月至2012年12月上海市公共卫生临床中心收治的110例HIV/AIDS合并血小板减少症患者的临床资料,分析血小板减少的病因、治疗及转归。结果:110例患者中机会性感染49例(44.5%),乙型肝炎病毒和(或)丙型肝炎病毒(HBV/HCV)感染26例(23.6%),HIV相关免疫性血小板减少性紫癜(HIV-ITP)20例(18.2%),药物相关骨髓抑制7例(6.4%),AIDS相关肿瘤及其他疾病8例(7.3%)。以血小板减少为HIV/AIDS首发临床表现者10例。82.7%(91/110)的患者同时合并其他血液学异常,包括贫血(68.2%)或白细胞减少(58.2%)。81.3%的HIV-ITP患者对激素及静脉注射免疫球蛋白治疗敏感,治疗无效或复发者长期抗病毒治疗后血小板缓慢上升。结论:HIV/AIDS患者血小板减少常见病因有机会性感染、合并HBV/HCV感染、HIV-ITP、药物相关骨髓抑制等。HIV-ITP可为HIV/AIDS患者首要临床表现,其根本治疗措施为抗病毒治疗。血小板减少患者常同时合并贫血和(或)白细胞减少,多重血液学异常预示病情严重,需要积极处理原发病。     

凉山州部分彝族人群2011年HIV耐药警戒线监测研究

目的分析凉山州部分彝族人群2011年艾滋病病毒1型(HIV-I)在未治疗的感染人群中耐药毒株变异情况,为指导抗病毒治疗、评价治疗效果、合理调整治疗方案和制定应对措施提供依据。方法对129例25岁以下新确诊的HIV阳性血清样本,用In-house方法进行基因型耐药检测。共91例扩增测序成功,检测耐药传播相关的耐药突变,并分析其相关的亚型及其比例。结果 91例样本中,没有针对PR区的主要耐药性基因突变,但有7例样本存在针对RT区耐药性基因突变,4例为交叉突变(T215Y和V179E),3例为单一突变(T215Y、V179D和P225H),导致对齐多夫定(AZT)和司坦夫定(D4T)不同程度的耐药。RT区耐药株流行率为5.43%(7/129),属于中等流行水平(5%~15%)。91例样本中,CRF07-BCⅡ型所比例最大,达91.21%(83/91),B亚型仅占8.79%(8/91)。结论凉山州部分彝族人群未经抗病毒治疗的新发现HIV-1感染者中,已出现pol区耐药突变株,且传播水平达中度流行状态,需进一步加强抗病毒治疗患者的用药督导,提高其用药依从性,并持续性监测该地区抗病毒治疗人群的耐药情况。     

HIV-1耐药突变的研究进展

至2015年止,全球约有1 700万HIV/AIDS病例得到抗逆转录病毒治疗,使HIV-1死亡率和发病率迅速下降。随着抗逆转录病毒治疗向所有感染HIV者全面推进,HIV耐药突变问题对长期治疗也构成了威胁,并对全球2030年消除艾滋病这一重要公共卫生战略产生了负面影响。本综述试图从不同的经济和地理环境出发,从个体和群体水平上阐述了常用的抗逆转录病毒药物的遗传屏障、交互耐药程度、耐药突变的流行病学和耐药管理;同时本文汇总了高、中低两类国家的可传播性耐药(TDR)和获得性耐药(ADR)的流行方式,分析了两类具有重要的公共卫生意义HIV耐药突变问题,即治疗前耐药和暴露前预防性服药的耐药。此外,鉴于有效地对不同类国家的HIV病例的治疗和管理,分别分析了基因型耐药性检测和治疗实践方面的关联,这些内容对我国的艾滋病防治也具有一定的参考作用。     

The immunoneuroendocrine role of melatonin

Abstract: A tight, physiological link between the pineal gland and the immune system is emerging from a series of experimental studies. This link might reflect the evolutionary connection between self-recognition and reproduction. Pinealectomy or other experimental methods which inhibit melatonin synthesis and secretion induce a state of immunodepression which is counteracted by melatonin. In general, melatonin seems to have an immunoenhancing effect that is particularly apparent in immunodepressive states. The negative effect of acute stress or immunosuppressive pharmacological treatments on various immune parameters are counteracted by melatonin. It seems important to note that one of the main targets of melatonin is the thymus, i.e., the central organ of the immune system. The clinical use of melatonin as an immunotherapeutic agent seems promising in primary and secondary immunodeficiencies as well as in cancer immunotherapy. The immunoenhancing action of melatonin seems to be mediated by T-helper cell-derived opioid peptides as well as by lymphokines and, perhaps, by pituitary hormones. Melatonin-induced-immuno-opioids (MHO) and lymphokines imply the presence of specific binding sites or melatonin receptors on cells of the immune system. On the other hand, lymphokines such as -γ-interferon and interleukin-2 as well as thymic hormones can modulate the synthesis of melatonin in the pineal gland. The pineal gland might thus be viewed as the crux of a sophisticated immunoneuroendocrine network which functions as an unconscious, diffuse sensory organ.     

Changes in connexin43, the gap junction protein of astrocytes, during development of the rat pineal gland

Abstract: The abundance of gap junctions between rat pineal astrocytes formed by connexin43 (Cx43) was studied during development. Levels and distribution of Cx43 were measured by immunoblotting and indirect immunofluorescence, respectively. The amount of Cx43 in cells located within the gland was low until about the 7th postnatal day and increased to adult values between the 14th and 21st days postpartum. Although astrocytes, recognized by their vimentin immunoreactivity, were scarce before birth, they were abundant by the 7th postnatal day suggesting that the low levels of Cx43 found at this age corresponded to a low expression of this protein. Localization of the immunoreactivity to Cx43 and vimentin showed a close correlation, indicating that mature or immature pineal astrocytes form gap junctions made of Cx43. Since Cx43 levels attained their adult values at about the time the innervation and the functional state of the gland reached maturity (2–3 weeks after birth), it is proposed that astrocyte gap junctions are involved in the function of the adult rat pineal gland.     

Response of rat pineal melatonin to calcium, magnesium, and lithium is circadian stage dependent

Abstract: Herein we documented the response of pineal melatonin production to electrolytes known to be effective on pineal function in view of a possible circadian stage dependence. We studied the release of melatonin by perifused rat pineal glands at 2 different circadian stages corresponding to the middle of the light and dark periods, i.e., respectively, 7 and 19 HALO (Hours After Light Onset, L:D = 12:12). The initial efflux rates were, as expected, much higher in the perifusates of glands removed from rats sacrificed during the dark phase than of those removed during the light phase. After 3 hr of perifusion, melatonin release reached similar levels which were found constant up to the 8th hr of perifusion, whatever the circadian stage. Perifusion of the glands with physiological concentrations for the rat of calcium (5.2 mmol/1) and magnesium (1.34 mmol/1) resulted in a stimulatory effect on the pineal glands removed from rats sacrificed in the middle of the dark period (19 HALO), whereas no effects were observed on the pineal glands removed from rats sacrificed during the light (7 HALO). Lithium (0.28 and 0.55 mmol/1) was ineffective on melatonin release in pineal glands removed 7 and 19 HALO. Our results show differences in the initial efflux rates of melatonin and in the response of perifused pineal glands to calcium and magnesium according to the circadian stage.     

Conservative management of perforated duodenal diverticulum： A case report and review of the literature

Duodenal diverticula are a relatively common condition. They are asymptomatic, unless they become complicated, with perforation being the rarest but most severe complication. Surgical treatment is the most frequently performed approach. We report the case of a patient with a perforated duodenal diverticulum, which was diagnosed early and treated conservatively with antibiotics and percutaneous drainage of secondary retroperitoneal abscesses. We suggest this method could be an acceptable option for the management of similar cases, provided that the patient is in good general condition and without septic signs.     

Presence of immunoreactive growth hormone and prolactin in the ovine pineal gland

Abstract: The use of antisera raised against bovine growth hormone (GH) and ovine prolactin (PRL) enabled the detection of related immunoreactive (ir) sequences of proteins in ovine pineal tissue. The isolation of PRL-like ir-material was accomplished using a 0.25 M ammonium sulphate (pH 5.5) extraction followed by ethanol precipitation, whereas the resulting 2.0 M ammonium sulphate (pH 7.0) precipitate contained a GH-like immunoreactivity. Gel chromatography of the GH-like immunoreactivity (Sephadex G-100) indicated the presence of several GH-like fragments ranging in the M_r range of 7,000 to 55,000. Analyses of the PRL-like ir-material found in pineal tissue on HPLC using a TSK 545-DEAE column led to the resolution into a single peak of immunoreactivity. A single peak of activity was also observed following chromatofocusing and hydrophobic interaction chromatography of the ir-peak from the TSK 545-DEAE column. The PRL-like ir-material inhibited the binding of [¹²⁵I]ovine PRL-S14 to anti-ovine PRL antibodies without showing an affinity for binding to anti-rat PRL or anti-bovine GH antibodies. Scatchard analysis of the binding of pineal PRL-like ir-material and pituitary ovine PRL-S14 to liver membranes from day-20 pregnant rats revealed similar affinity constants (K_a of 4.7 ± 0.2 × 10⁹ M^-1). In addition, the replication of Nb 2 Node rat lymphoma cells was stimulated by pineal PRL-like ir-material, an effect known to be specific for lactogenic hormones. The pineal PRL-like immunoreactivity appeared on sodium dodecyl sulfate polyacrylamide gels as a single major band of M_r 24,000. The functional status of PRL-and GH-like ir-material in the ovine pineal remains to be determined, but evidence is presented that the overall protein synthesis rate of the rat pineal responded to circulating concentrations of PRL.     

Microbiology of human immunodeficiency virus anorectal disease

PURPOSE: Individuals who are seropositive for the human immunodeficiency virus are at high risk for opportunistic infection and anorectal disorders. Little prospective information is available regarding anorectal pathogens in these patients. METHODS: One hundred sixty-three HIV-seropositive patients presented to the colorectal clinic between 1989 and 1992. Forty-seven (29 percent) patients were thought to have an infectious process and were prospectively studied using a standardized multiculture protocol. RESULTS: Mean age was 33 (range, 19–59) years. All were male; high-risk behavior accounted for 87 percent of HIV transmissions. Presenting complaints included anorectal pain (79 percent), pus per anum (28 percent), and blood per anum (26 percent). Examination revealed perianal tenderness (60 percent), condyloma (38 percent), perianal ulcers (38 percent), and anal fissures (34 percent). Sixty-six sets of cultures were performed; 28 patients had one set, 15 had two sets, and 4 had three sets. Thirty-two of these 47 patients (68 percent) had positive cultures including herpes (50 percent), cytomegalovirus (25 percent),Neisseria gonorrhoeae (16 percent), chlamydia (16 percent), acidfast bacilli (2 percent), and others (9 percent). Six of 32 patients with positive cultures had more than one organism cultured. Sixteen (50 percent) patients with positive cultures were treated medically, 8 (25 percent) were treated surgically and 8 (25 percent) were treated with both modalities. Sixty-one procedures were performed on 17 patients for condylomata. Eighteen patients had 20 procedures for abscesses, 50 percent of whom had positive cultures for other than common bowel flora; all improved. Fourteen patients underwent 33 procedures for perianal fistulas.Mycobacterium fortuitum was cultured from one patient who required 13 procedures for abscesses and fistulas. Forty-five (96 percent) patients were followed for an average of 12.5 months ±2.9 SEM (range, 1–94 months). Symptoms were improved or resolved in 22 of 32 (69 percent) patients with positive cultures and in 11 of 13 (84 percent) with negative cultures. CONCLUSIONS: Specific pathogens may often be identified in human immunodeficiency virus-seropositive patients with anorectal disorders if aggressively sought. Although patients without specific pathogens identified may be expected to improve with planned empiric treatment, positive identification allows more directed therapy.