Selective elimination of host cells harboring replication-competent human immunodeficiency virus reservoirs: a promising therapeutic strategy for HIV cure

Many seminal advances have been made in human immunodeficiency virus (HIV)/AIDS research over the past four decades. Treatment strategies, such as gene therapy and immunotherapy, are yielding promising results to effectively control HIV infection. Despite this, a cure for HIV/AIDS is not envisioned in the near future. A recently published academic study has raised awareness regarding a promising alternative therapeutic option for HIV/AIDS, referred to as “selective elimination of host cells capable of producing HIV” (SECH). Similar to the “shock and kill strategy,” the SECH approach requires the simultaneous administration of drugs targeting key mechanisms in specific cells to efficiently eliminate HIV replication-competent cellular reservoirs. Herein, we comprehensively review the specific mechanisms targeted by the SECH strategy. Briefly, the suggested cocktail of drugs should contain (i) latency reversal agents to promote the latency reversal process in replication-competent reservoir cells, (ii) pro-apoptotic and anti-autophagy drugs to induce death of infected cells through various pathways, and finally (iii) drugs that eliminate new cycles of infection by prevention of HIV attachment to host cells, and by HIV integrase inhibitor drugs. Finally, we discuss three major challenges that are likely to restrict the application of the SECH strategy in HIV/AIDS patients.     

尘肺并发肺结核的胸部CT表现分析

目的 探讨尘肺并发肺结核的胸部CT表现特点。方法 搜集2015年6月至2016年12月重庆市公共卫生医疗救治中心诊治的96例尘肺并发肺结核的住院患者,回顾性分析96例患者的临床及CT检查资料。对并发结核病变的发生部位、范围、形态、类型及并发其他脏器结核情况进行观察。结果 96例患者中,尘肺Ⅰ期1例,Ⅱ期23例,Ⅲ期72例。受累范围:多肺叶90例(93.8%)。发生部位:尖后段93例(96.9%),前段48例(50.0%),中叶或(和)舌段49例(51.0%),背段68例(70.8%),基底段53例(55.2%)。病变形态:斑片状影85例(88.5%),大片状影48例(50.0%),空洞64例(66.7%)[其中多发空洞占67.2%(43/64)],树芽征56例(58.3%),胸腔积液36例(37.5%),胸膜增厚72例(75.0%),纵隔淋巴结肿大85例(88.5%),纵隔淋巴结钙化58例(60.4%)。Ⅱ期尘肺患者薄壁空洞发生率为47.8%(11/23),高于Ⅲ期尘肺患者[15.3%(11/72)](χ ²=10.378,P<0.05)。Ⅲ期尘肺患者大片状影、树芽征、厚壁空洞、胸膜增厚、纵隔淋巴结肿大及钙化的发生率分别为59.7%(43/72)、69.4%(50/72)、56.9%(41/72)、83.3%(60/72)、93.1%(67/72)、69.4%(50/72),高于Ⅱ期尘肺患者[分别为21.7%(5/23)、26.1%(6/23)、8.7%(2/23)、52.2%(12/23)、78.3%(18/23)、34.8%(8/23)](χ ²值分别为10.061、13.541、14.489、9.224、4.051、8.808,P值均<0.05)。 结论 尘肺不同分期患者并发肺结核CT表现具有一定差异,以浸润灶为主,常伴有多发空洞、树芽征、胸腔积液、肺外结核等。     

结核分枝杆菌贝达喹啉和氯法齐明耐药及其交叉耐药机制研究进展

目前,全球结核病耐药现象严重,给结核病的防控工作带来了极大的困难与挑战,并亟需新型抗结核药物来阻止耐药结核病的蔓延.贝达喹啉和氯法齐明分别是世界卫生组织推荐的A组和B组核心抗结核药物,主要用于耐多药结核病的治疗且疗效较好.但近年来贝达喹啉和氯法齐明耐药的现象也时有报道,且二者存在交叉耐药的情况.本文综述了与结核分枝杆菌...     

Association of thyroid-stimulating hormone with insulin resistance and androgen parameters in women with PCOS

There is a relationship between thyroid function and insulin sensitivity and alterations in lipids and metabolic parameters. Little information is available regarding this relationship in women with polycystic ovary syndrome. However all those pathologies are also described as often affecting women with polycystic ovary syndrome. The association between thyroid-stimulating hormone <2.5 mIU/l and ≥2.5 mIU/l with insulin resistance and endocrine parameters in 103 women with polycystic ovary syndrome was studied. Clinical, metabolic and endocrine parameters were obtained and an oral glucose tolerance test was performed with calculation of insulin resistance indices. Women with thyroid-stimulating hormone ≥2.5 mIU/l had a significantly higher body mass index (P = 0.003), higher fasting insulin concentrations (P = 0.02) and altered insulin resistance indices (P = 0.007), higher total testosterone (P = 0.009) and free androgen indices (P = 0.001) and decreased sex hormone–binding globulin concentrations (P = 0.01) in comparison with women with thyroid-stimulating hormone <2.5 mIU/l. Generally, all of these parameters correlated significantly (P < 0.05) with thyroid-stimulating hormone only in women with thyroid-stimulating hormone ≥2.5 mIU/l. Women with polycystic ovary syndrome and with thyroid-stimulating hormone ≥2.5 mIU/l had significantly altered endocrine and metabolic changes.     

利培酮合并氯氮平与单用利培酮治疗精神分裂症对照观察

目的：评价利培酮合并氯氮平治疗精神分裂症的疗效和副作用。方法：将40例精神分裂症病人按序贯法随机分配到利培酮合并氯氮平组（20例）,单用利培酮组（20例）,治疗8例,用简明精神病量表（BPRS）评定疗效,用副反应量表（TESS）评定副反应。结果：利培酮合并氯氮平组与单用利培酮组之间疗效无显著性差异,在缺乏活力因子方面,两组间有差异,利培酮合并氯氮组的副反应有活动减少、嗜睡、便秘、唾液增多、心动过速等,单用利培酮组的副反应主要是锥体外系反应。结论：利培酮合并中小剂量的氯氮平,有助于预防或减少锥体外系反应,而其它副反应并不因合并用药而加重。     

HIV感染者原发性中枢神经系统弥漫大B细胞淋巴瘤1例

报告1例HIV感染者原发性中枢神经系统弥漫大B细胞淋巴瘤.患者女,31岁,无明显诱因出现额部持续性隐痛1个月,伴视物模糊、纳差、恶心、呕吐.右侧枕部占位组织病理检查显示弥漫浸润的小-中等大小圆形或椭圆形细胞,伴广泛坏死,胞质丰富淡染,核质细腻,可见核仁,核膜清晰,核分裂易见.患者3年前确诊抗HIV抗体阳性,未进行规范高...     

世界卫生组织耐药结核病治疗整合指南(2020年版)解读

1993年结核病被世界卫生组织宣布为"全球公共卫生紧急事件"。在复杂和严峻的大背景下,世界卫生组织发布了耐药结核病治疗整合指南(2020年版),相信有助于加速推动终止结核病策略的进程,扭转当前耐药结核病防治的被动局面。本文分别从异烟肼耐药结核病、含贝达喹啉全口服短程方案治疗耐多药结核病(MDR-TB)和利福平耐药结核病...     

恩度联合顺铂治疗非小细胞肺癌恶性胸腔积液近远期疗效

目的探讨恩度联合顺铂治疗非小细胞肺癌恶性胸腔积液近期与远期疗效。方法临床入选42例非小细胞肺癌恶性胸腔积液患者,按照随机数字方法分成两组,每组21例。对照组采用顺铂40mg胸腔内注入,每周1次,连续3周;研究组患者胸腔内注入恩度30mg,每周2次,同时在胸腔内注入顺铂40mg,每周1次,连续3周。观察两组患者的近期与远期疗效以及毒副作用。结果研究组胸水改善总有效率、生活质量改善率、生存时间、1年生存率、2年生存率较对照组明显增高（P〈0．05）。两组患者在胃肠道反应、发热、乏力、白血病减少、血小板减少、肝肾功能损害、心电图改变等方面的毒副反应均无统计学差异（P〉0．05）。结论恩度联合顺铂治疗非小细胞肺癌恶性胸腔积液能够更好地减少胸腔积液,改善生活质量,延长生存期。     

中药品质一致性评价探索

目的：针对目前中药品质评价存在的诸多问题,建立适合中药产业化发展的一致性评价体系。方 法：基于中药自身的特殊性,结合当前中药品质评价的先进技术手段,通过构建中药品质一致性评价体系,为探 索新的品质评价方法寻求突破口。结果：提出了一种新的中药品质评价模式,即通过采用“性状评价+化学评 价+生物评价”三者相结合,建立统一评价模式,将各项指标性成分有效完整结合起来,实现对中药品质的整体 一致性评价。结论：该探索为保证中药品质的一致性评价提供一定借鉴与思考。     

Synergistic sulfonamides plus clindamycin as an alternative therapeutic regimen for HIV-associated Toxoplasma encephalitis: a randomized controlled trial

Background:The preferred therapeutic regimen for Toxoplasma encephalitis (TE) is a combination of pyrimethamine and sulfadiazine, and trimethoprim-sulfamethoxazole (TMP-SMX) plus azithromycin is the widespread alternative therapeutic regimen. The synergistic sulfonamides tablet contains TMP, sulfadiazine, and SMX and hypothetically could be used for TE treatment. This study aimed to compare the efficacy and safety of synergistic sulfonamides plus clindamycin (regimen B) with TMP-SMX plus azithromycin (regimen A) for the treatment of human immunodeficiency virus (HIV) associated TE.Methods:This was an open-labeled, multi-center randomized controlled trial recruited from 11 centers. Each recruited patient was randomly assigned to receive regimen A or regimen B for at least 6 weeks. The overall response was evaluated by assessment of the clinical response of TE-associated clinical features and the radiological response of TE-associated radiological findings. The overall response rate, clinical response rate, radiological response rate, and adverse events were assessed at 2, 6, and 12 weeks. Death events were compared between the two regimens at 6, 12, and 24 weeks.Results:A total of 91 acquired immunodeficiency syndrome (AIDS)/TE patients were included in the final analysis (44 in regimen A vs. 47 in regimen B). The overall response rate, which refers to the combined clinical and radiological response, was 18.2% (8/44) for regimen A and 21.3% (10/47) for regimen B at week 6. The results of clinical response showed that, in comparison with regimen A, regimen B may perform better with regards to its effect on the relief of clinical manifestations (50.0% [22/44] vs. 70.2% [33/47], P = 0.049). However, no significant differences in radiological response, mortality events, and adverse events were found between the two regimens at week 6.Conclusions:Synergistic sulfonamides plus clindamycin, as a novel treatment regimen, showed no significantly different efficacy and comparable safety in comparison with the TMP-SMX plus azithromycin regimen. In addition, the regimen containing synergistic sulfonamides may exhibit advantages in terms of clinical symptom alleviation.Trial Registration:ChiCTR.org.cn, ChiCTR1900021195.