Volume 135 · Issue 22 · 2022

代谢紊乱，包括内分泌紊乱、肥胖症、糖尿病、脑心血管疾病，甚至癌症，是最常见和最致命的疾病，在全球范围内全因死亡率领先。^[1]例如，根据世界卫生组织的数据，二型糖尿病（T2DM）作为一种由胰岛素抵抗引起的慢性疾病，成为第九大死亡原因，2019年有150万人死亡。^[2]目前，全球约有4.22亿人患有糖尿病，其中大多数生活在中低收入国家。^[3]T2DM的高患病率与肥胖和生活方式因素（如缺乏体育锻炼）有关，尽管遗传因素与T2DM患者的亚群有关。^[4]

近年来，随着耐多药（MDR）细菌感染和慢性肺部感染患病率的增加，以吸入性抗生素为主的抗菌药物的局部应用又回到了临床实践中。用于雾化和干粉吸入器（DPI）的几种制剂已被批准用于吸入性抗感染治疗。同时，已经积累了使用经气道递送的抗微生物剂的证据和经验。然而，该领域的可用研究在研究人群、药物递送途径和剂量方面是异质性的。需要评估吸入性抗感染治疗在各种类型下呼吸道感染（LRTIs）中的疗效和安全性。而且，由于国内缺乏开发用于吸入的制剂，存在包括静脉制剂局部使用等问题。为规范成人LRTIs局部抗感染治疗的临床实践，中国胸科学会肺部感染大会发起并组织专家制定了共识文件，根据现有证据总结了呼吸道局部使用的抗菌药物及其适应症。由于高质量的证据很少，因此没有说明推荐的级别。本文为共识的执行摘要，全文发表于中国结核病与呼吸道疾病杂志.^[1]

It is controversial whether the apolipoprotein E epsilon 4 allele (APOE ε4) is a risk gene for human immunodeficiency virus (HIV)-related neurocognitive impairment. This meta-analysis aimed to summarize evidence of the associations between APOE ε4 and cognitive impairment in people living with HIV (PLWH).

Our study conducted a systematic literature search of PubMed, Web of Science, Embase, Google Scholar, and ProQuest for studies published before April 11, 2022 that evaluated associations between APOE ε4 and cognitive impairment in adult PLWH (aged ≥18 years). We calculated pooled odds ratios (ORs) of global cognitive impairment and 95% confidence intervals (CIs) and standardized mean differences (SMDs) for specific cognitive domains between APOE ε4 carriers and non-carriers. Subgroup meta-analyses were used to evaluate the result profiles across different categorical variables.

Twenty studies met the inclusion criteria, including 19 that evaluated global cognitive impairment. APOE ε4 was significantly associated with global cognitive impairment in PLWH (OR = 1.36, 95% CI = [1.05, 1.78], number of estimates [k] = 19, P = 0.02, random effects). Subgroup meta-analysis based percentage of females showed evident intergroup differences in global cognitive performance between ε4 carriers and non-carriers (P = 0.015). APOE ε4 carriers had lower cognitive test scores than non-carriers in all seven cognitive domains, including fluency (SMD = -0.51, 95% CI = [-0.76, -0.25], P < 0.001, k = 4, I²= 0%), learning (SMD = -0.52, 95% CI = [-0.75, -0.28], P < 0.001, k = 5, I² = 0%), executive function (SMD = -0.41, 95% CI= [-0.59, -0.23], P < 0.001, k= 8, I²= 0%), memory (SMD=-0.41, 95% CI= [-0.61, -0.20], P < 0.001, k= 10, I²= 36%), attention/working memory (SMD=-0.34, 95% CI= [-0.54, -0.14], P= 0.001, k= 6, I²= 0%), speed of information processing (SMD = -0.34, 95% CI = [-0.53, -0.16], P < 0.001, k = 8, I² = 0%), and motor function (SMD = -0.19, 95% CI = [-0.38, -0.01], P = 0.04, k = 7, I² = 0%).

Our meta-analysis provides significant evidence that APOE ε4 is a risk genotype for HIV-associated cognitive impairment, especially in cognitive domains of fluency, learning, executive function, and memory. Moreover, the impairment is sex specific.

PROSPERO, CRD 42021257775.

Talaromycosis（原名青霉病）是一种重要的侵袭性真菌病，由马尔尼菲塔拉菌（以前马尔尼菲青霉菌,T·马尔尼菲).^[1]世界卫生组织和食品药品监督管理局最近越来越关注这种疾病，因为它是一种被忽视的热带疾病，因为T·马尔尼菲全球感染。^[1,2]Talaromycosis是一种常见的机会性疾病，是流行地区获得性免疫缺陷综合征（AIDS）患者死亡的主要原因；此外，在人类免疫缺陷病毒（HIV）阴性个体和疫区之外，越来越多地报告了这种情况。^[3,4]在HIV阳性和HIV阴性个体中，talaromycosis的死亡率高达30%，这与晚期诊断和不及时或无效的抗真菌治疗有关。^[5]因此，早期诊断和有效的抗真菌治疗对降低死亡率至关重要。

A more comprehensive understanding of the trends of incidence, prevalence, and mortality in human immunodeficiency virus (HIV), and their complex interrelationships, may provide important evidence for decision-making related to HIV prevention and control. The variances in these indices between different population groups, genders, and ages are critical to decipher evolving patterns of the HIV epidemic in specific populations.

A secondary analysis of relevant data was conducted using data extracted from the Global Burden of Disease study of 2019. HIV/acquired immune deficiency syndrome (AIDS) incidence, prevalence, AIDS-related mortality, and mortality-to-prevalence ratio (MPR) for annual percentage change, average annual percentage change (AAPC), and corresponding 95% confidence intervals (CIs) were calculated using joinpoint regression statistical analysis.

The AAPC of HIV/AIDS incidence, prevalence, AIDS-related mortality rate, and MPR were -1.4 (95% CI: -1.6, -1.2), 4.1 (95% CI: 4.0, 4.3), 2.0 (95% CI: 1.7, 2.3), and -2.1 (95% CI: -2.3, -1.8) between 1990 and 2019 globally, and were 3.5 (95% CI: 2.2, 4.8), 6.9 (95% CI: 6.8, 7.0), 8.1 (95% CI: 7.1, 9.1), and 1.2 (95% CI: 0.1, 2.3) in China during the same period. In terms of differences in the preceding indicators by gender, we observed a similar pattern of trends for male and female genders both globally and in China during the entire study period. Each specific age group exhibits a distinct pattern in terms of incidence, prevalence, mortality rate, and MPR both globally and in China.

Prevalence and mortality rates of HIV/AIDS have increased between 1990 and 2019 globally and in China. While the incidence rate and MPR have declined globally over the past three decades, these two indicators are observed to present an increasing trend in China. There is a high HIV burden among young and middle-aged adults globally; however, the elderly have a high HIV burden in China. HIV screening at older age should be scaled up, and patients with advanced HIV disease should be provided early with additional care and health resources.

Chronic liver disease has emerged as a leading cause of non-acquired immune deficiency syndrome (AIDS)-related mortality in hepatitis C virus (HCV)/human immunodeficiency virus (HIV)-coinfected patients. The relationship between CD4 cell count and HIV-related opportunistic infections and tumors has been well characterized; however, it is unclear whether CD4 cell count is associated with HCV-related hepatic events.

This observational cohort study enrolled HCV/HIV-coinfected patients from the National Free Antiretroviral Treatment Program of China from 2004 to 2019 in Guangzhou. The primary outcome was a composite of hepatic events, including cirrhosis complications, hepatocellular carcinoma (HCC), and liver-related mortality. Kaplan-Meier survival and multivariate logistic regression analyses were performed.

Among the 793 patients, 43 developed hepatic events during a median follow-up of 6.7 years, including 35 cirrhosis complications, 13 HCC cases, and 14 cases of liver-related mortality. The 5-year and 10-year cumulative incidences of hepatic events were 4.2% and 9.3%, respectively. Patients who developed hepatic events had a less satisfactory increase in CD4 cell count, lower peak CD4 (354.5 cells/μL vs. 560.0 cells/μL, P < 0.001), and lower percentage of peak CD4 > 500 cells/μL (30.2% vs. 60.7%, P < 0.001) after the initiation of antiretroviral therapy (ART) than those who did not. The cumulative incidences of hepatic events were higher in patients with lower peak CD4 levels with adjusted odds ratios of 3.96 (95% confidence interval [CI]: 1.51-10.40), 2.25 (95% CI: 0.87-5.86), and 0.98 (95% CI: 0.35-2.74) for patients with peak CD4 at <200 cells/μL, 200-350 cells/μL, and 351 to 500 cells/μL, respectively, relative to those with peak CD4 > 500 cells/μL. Peak CD4 was negatively associated with the risk of hepatic events in a dose-response manner (P-value for trend = 0.004).

Persistently low CD4 cell counts after ART are independently associated with a high risk of hepatic events in HCV/HIV-coinfected patients, highlighting the important role of immune reconstitution in improving liver outcomes.

Ubiquitination plays an essential role in many biological processes, including viral infection, and can be reversed by deubiquitinating enzymes (DUBs). Although some studies discovered that DUBs inhibit or enhance viral infection by various mechanisms, there is lack of information on the role of DUBs in virus regulation, which needs to be further investigated.

Immunoblotting, real-time polymerase chain reaction, in vivo/in vitro deubiquitination, protein immunoprecipitation, immunofluorescence, and co-localization biological techniques were employed to examine the effect of ubiquitin-specific protease 3 (USP3) on APOBEC3G (A3G) stability and human immunodeficiency virus (HIV) replication. To analyse the relationship between USP3 and HIV disease progression, we recruited 20 HIV-infected patients to detect the levels of USP3 and A3G in peripheral blood and analysed their correlation with CD4⁺ T-cell counts. Correlation was estimated by Pearson correlation coefficients (for parametric data).

The results demonstrated that USP3 specifically inhibits HIV-1 replication in an A3G-dependent manner. Further investigation found that USP3 stabilized 90% to 95% of A3G expression by deubiquitinating Vif-mediated polyubiquitination and blocking its degradation in an enzyme-dependent manner. It also enhances the A3G messenger RNA (mRNA) level by binding to A3G mRNA and stabilizing it in an enzyme-independent manner. Moreover, USP3 expression was positively correlated with A3G expression (r= 0.5110) and CD4⁺ T-cell counts (r= 0.5083) in HIV-1-infected patients.

USP3 restricts HIV-1 viral infections by increasing the expression of the antiviral factor A3G. Therefore, USP3 may be an important target for drug development and serve as a novel therapeutic strategy against viral infections.

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.

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.

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.

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.

ChiCTR.org.cn, ChiCTR1900021195.

Single-tablet regimen (STR) provides a convenient once-daily regimen for the prevention of human immunodeficiency virus (HIV) infection. Here, we investigated the safety and tolerability of coformulated bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) as a three-drug, STR for post-exposure prophylaxis (PEP) in Chinese individuals.

This was a prospective, open-label, single-arm trial conducted in a sexually transmitted diseases and acquired immunodeficiency syndrome clinic of a tertiary hospital in Beijing, China. Adults requiring PEP were prescribed BIC/FTC/TAF one pill once a day for 28 days. Clinical and laboratory data were collected and analyzed at baseline, weeks 2, 4, 8, 12, and 24.

Of 112 participants enrolled in the study, 109 (97.3%) were male and the mean age was 30 ± 8 years. PEP completion was 96.4% (95% confidence interval: 91.1-99.0%). Two participants stopped PEP after 2 days because the source partner was identified as HIV uninfected. One participant was excluded due to hepatitis B virus infection according to the exclusion criteria. One discontinued due to the participant’s decision. No participant acquired HIV through week 24. Adherence was 98.9% (standard deviation [SD]: 3.3%) by self-reporting and 98.5% (SD: 3.5%) by pill count. Only five participants experienced mild clinical adverse events attributed to the study drug (including headache, diarrhea, and nausea) and four participants had elevated serum creatinine (grade 1).

A once daily, STR of BIC/FTC/TAF used as PEP was safe and well-tolerated with a high rate of completion and adherence in Chinese. BIC/FTC/TAF may be a good option for PEP.

ChiCTR.org.cn, ChiCTR2100048080

Understanding the characteristics of newly diagnosed primary human deficiency virus-1 (HIV-1) infection in the context of the post-antiretroviral therapy era and HIV drug prophylaxis is essential for achieving the new target of 95-95-95-95 by 2025. This study reported the characteristics of newly diagnosed primary HIV-1 infection in Shenzhen.

This is a real-world retrospective study. Eighty-seven newly diagnosed primary HIV-1-infected patients were recruited from January 2021 to March 2022 at the Third People’s Hospital of Shenzhen. Demographic, epidemiological, diagnostic, drug resistance, and medical data were described and analyzed.

Overall, 96.6% (84/87) of the newly identified primary HIV-1-infected patients were male, including 88.5% (77/87) men have sex with men (MSM), with a median age of 29.0 years (Q₁-Q₃: 24.0-34.0 years); of these, 85.1% (74/87) reported high-risk sexual behaviors with casual partners. The rate of condom usage was only 28.7% (25/87). The overall rate of pre-exposure prophylaxis (PrEP) and post-exposure prophylaxis (PEP) was 8.0% (7/87, including 4 PrEP and 3 PEP cases) around the potential exposure, although 41.4% of the patients had prior awareness of such interventions. Moreover, only 19.5% (17/87) had previously used PrEP or PEP. Of those, 58.8% (10/17) of the patients obtained drugs from the internet, and only 35.3% (6/17) reported good compliance. A total of 54.0% (47/87) of subjects were diagnosed by the HIV nucleic acid test. Acute retroviral syndrome appeared in 54.0% (47/87) of patients. The prevalence of transmitted drug resistance (TDR) mutation was 33.9% (19/56), including 6 (10.7%) against nucleoside reverse transcriptase inhibitor (NRTI) plus non-nucleoside reverse transcriptase inhibitor (NNRTI), 8 (14.3%) against NNRTI, and 5 (8.9%) against protease inhibitor (PI) only.

Owing to the low utilization rate and incorrect usage of PrEP and PEP, massive efforts are needed to promote HIV-preventive strategies in the MSM population. The extremely high prevalence of TDR mutation in this population implies the need for future pretreatment drug resistance surveillance.

在全球范围内，儿童食物过敏的患病率估计约为4%至10%。^[1]食物过敏通常在过敏三月的早期开始，牛奶过敏（CMA）是婴儿和儿童最常见的食物过敏原之一。在欧洲，经挑战证实的CMA的总体发病率为0.54%，在美国，总体患病率为0.4%，儿科患病率为1.9%。^[2,3,4]在中国，经口服食物激发（OFC）确认的CMA在各个城市的患病率为0.83%至3.5%。^[5]双盲安慰剂对照食物激发在临床实践中没有广泛应用，因为其过程复杂，接受测试的患者有过敏反应的风险。过敏原特异性IgE（sIgE）通常被用作食物过敏的关键评估方法。

慢性乙型肝炎病毒（HBV）感染是一个重大的全球公共卫生问题。每年约有887,000人死于HBV感染相关疾病，其中肝硬化和肝细胞癌（HCC）是主要的死亡原因。^[1]及时的抗病毒治疗大大降低了肝硬化和HCC的风险。然而，不幸的是，在那些有资格接受抗病毒治疗的患者中，只有25%的诊所环境患者和12%的社区环境患者获得了及时的抗病毒治疗。^[2]因此，识别需要抗病毒治疗的慢性HBV感染患者的可靠方法是必要的，特别是在社区中使用。

报告表明，全球约有3770万人感染了人类免疫缺陷病毒（HIV），^[1]10%至28%的艾滋病毒感染者（PLWH）同时感染乙型肝炎病毒（HBV）。^[2]HIV和HBV共有的传播途径可以解释HIV/HBV合并感染比例相对较高的原因，^[3]这是对全球公共卫生的重大挑战。在中国，PLWH的乙型肝炎表面抗原（HBsAg）患病率估计为13.7%。^[4]

致编辑：随着抗逆转录病毒治疗（ART）方案的最新进展，许多患者可能会从转换药物中受益。新型组合药物elvitegravir/cobicistat/恩曲他滨/替诺福韦（E/C/F/TAF）已在中国获批用于人类免疫缺陷病毒/获得性免疫缺陷综合征（HIV/AID[PLWHA]）感染者，也已纳入医保范围。这种单片方案为许多PLWHA提供了方便的、每日一次的治疗选择。E/C/F/TAF显示可增加ART依从性，降低耐药性和病毒学失败的风险。^[1,2,3,4]然而，另一项研究显示，在未接受治疗和有经验的成人中，与基于替诺福韦（TDF）的治疗相比，基于替诺福韦阿拉酚胺（TAF）的治疗患者的几种脂质参数水平更高。^[5]2019年，在我们的抗病毒治疗中心进行了E/C/F/TAF的IV期临床研究，使我们能够探索转换后12个月随访期间的病毒学和免疫学反应。我们还探讨了PLWHA患者肾功能、肝功能和血脂参数的变化。

致编辑：即使出现了高效抗逆转录病毒疗法，人类免疫缺陷病毒1型（HIV-1）仍然是世界范围内严重的公共卫生问题。抗逆转录病毒疗法（ART）的广泛使用，一方面显著提高了HIV-1感染者的预期寿命；另一方面，也不可避免地带来了一个难题——病毒抗药性。病毒耐药性是进化上的常见现象，特别是在依从性差和药物水平次优的患者中。通过采用病毒敏感的ART方案，可以避免在经历过治疗的患者中出现病毒耐药性而导致的病毒抑制失败。然而，在传播过程中获得的病毒耐药性，称为“传播的耐药性”，可能是消除HIV-1感染的主要障碍。因为在未经治疗或新诊断的HIV-1患者中进行的基因型耐药性测试不如在经历过治疗的患者中广泛实施。HIV-1中的传播耐药突变（TDRMs）对当前ART方案和暴露前预防（PrEP）的疗效构成严重威胁。更好地了解当地TDRM的患病率可以为临床和政府层面的决策提供有价值的数据。

致编辑：计算机断层扫描（CT）已被用于高危人群的肺癌筛查，随后肺癌相关死亡率降低。^[1]然而，它也导致外周肺结节（PPNs）的发现显著增加，这需要进一步的诊断。常规支气管镜检查用于从腔内途径对肺组织进行活检，以确保微创。然而，由于支气管镜的直径相对较大，到达肺的外围是具有挑战性的，这限制了支气管镜对PPNs的诊断价值。尽管已经开发了各种先进的支气管镜技术来改善PPN诊断，但合并诊断率仅为70%，^[2]这表明诊断准确性仍然可以提高。机器人辅助支气管镜检查系统可能是解决这些限制的替代解决方案。离子^TMsystem（Intuitive Surgical，Inc.，Sunnyvale，CA，USA）是一种机器人辅助支气管镜检查平台，使用形状传感技术，显著提高了定位和穿刺小PPN的能力。^[3]然而，很少有研究评估该系统在中国人群中的使用情况。

致编者：吉罗维氏肺孢子虫（P.jirovecii）肺炎（PJP）是一种机会性感染，通常发生在免疫抑制患者中。由于使用免疫抑制治疗，实体器官移植（SOT）接受者PJP的发病率很高。近年来，宏基因组下一代测序（mNGS）越来越多地用于传染病的诊断。在此，我们报告了10例由mNGS诊断的PJP病例，并比较了mNGS与常规实验室方法的诊断价值。

致编辑：在中国，结直肠癌（CRC）在癌症发病率中排名第三，在癌症相关死亡中排名第五。^[1]大多数结直肠癌起源于腺瘤性息肉。结肠镜检查可以早期发现和切除息肉，预防结直肠癌。然而，常规结肠镜检查的息肉漏诊率可能超过40%。^[2]用于检测息肉的新型内窥镜装置在过去几十年中取得了一些进展，^[3]但是仍然依赖于运营商并且需要额外的成本。因此，近年来出现了人工智能（AI）辅助的息肉检测系统。本研究旨在以临床前方式评估我们新开发的人工智能辅助结肠镜息肉检测系统的有效性。

致编辑：股骨旋转对齐不仅会影响髌骨跟踪并改变峰值接触力，还会决定部件的屈曲间隙。^[1]如果外旋角度过大，会导致屈膝时内侧隔室松动；如果角度太小，会导致内侧隔室变窄。一系列研究发现，股骨假体对齐不良导致全膝关节置换术（TKA）后的不良结局，如较低的膝关节协会评分、屈曲不稳定、聚乙烯过早磨损、部件过早松动和持续的膝关节疼痛。引入新的骨标志有助于股骨旋转对位，减少TKA中股骨旋转对位不良引起的不良影响。内侧滑车上的表面，在本研究中被命名为内侧滑车上表面（MTSS），被发现可能平行于手术经髁轴（sTEA），该轴通常被用作TKA中股骨旋转对齐的参考轴。因此，由于其特殊的解剖位置，MTSS可用作TKA中的参考表面。MTSS内侧边界靠近股骨干轴线，远端紧邻内侧滑车上缘。MTSS在TKA中的具体位置如所示图1A.

致编辑：关于肱骨干中远端骨折切开复位内固定（ORIF）和微创钢板接骨术（MIPO）的益处，文献中存在争议。^[1]ORIF具有解剖复位、固定牢固、对肘、肩关节功能影响小等优点。然而，它也有一些缺点，包括需要大切口和更多的软组织解剖，中断骨折部位的血液供应，导致愈合困难和骨不愈合的风险增加，以及医源性桡神经损伤的高风险。相比之下，MIPO治疗肱骨干中远端骨折具有软组织解剖少、避免桡神经暴露、医源性桡神经麻痹风险低等优点。本研究旨在比较MIPO和常规ORIF治疗肱骨干中远端骨折的中期安全性和有效性。

致编辑：作为泌尿科医生最有力的工具之一，输尿管支架常用于结石、梗阻、输尿管损伤和肾移植等疾病，并在3天至4周后用可视化仪器取出。最初，硬性膀胱镜检查（RC）最常用于支架取出，但由于其不灵活和直径大，RC经常导致疼痛和对患者的潜在损害，如血尿、疼痛和下尿路症状，尤其是对男性。

致编辑1866年，蒙特加扎第一个提出了冷冻人类精液库的建议。^[1]1981年，中国第一家人类精子库在中信湘雅医院成功建立。在之前的四十年间，从1981年到2020年，中国大陆有27个人类精子库。人类精子库为中国大陆需要长期保存生育能力的男性提供精子冷冻保存服务。