Volume 137 · Issue 22 · 2024

人类免疫缺陷病毒（HIV）是一种适应性强、进化迅速的病毒，目前感染HIV并被诊断患有获得性免疫缺陷综合征（AIDS）的人群持续增长。尽管通过抗逆转录病毒治疗（ART）的控制，HIV感染者（PWH）的寿命得到了延长，然而，随着PWH老龄化的加剧，该人群容易出现新的并发症，包括血栓栓塞性疾病（TED）。TED已被公认为PWH中最常见的心血管疾病之一。血栓形成常引起血管阻塞、血瘀、缺血性脏器损害，导致危及生命的疾病或永久性残疾，可进一步影响PWH ART药物的选择和使用。血栓形成已经成为HIV感染者日益严重的问题，随着越来越多的人被感染，社会的负担将继续增加。因此，我们总结了HIV/TED的致病因素和治疗干预的最新进展，为深入临床研究和进一步优化合适的治疗方案提供新的思路。

移植肿瘤学是指在癌症治疗中实施移植手术，以用健康器官替换病变器官，从根本上解决癌症为核心认识。2004年初，皮肤外科医生提出了“移植肿瘤学”，最初指再一次器官移植后皮肤恶性肿瘤(DNM)。^[1]移植肿瘤学的精确概念最初是由Hibi建立的等人^[2]2014年，涵盖了三重困境（肿瘤学、免疫学和技术），并强调器官生物工程和再生医学是这些挑战的最终解决方案。萨皮索钦等人^[3]概述了移植肿瘤学的最新进展，总结了移植肿瘤学的演变、阐明、探索和扩展作为“四个E”支柱。目前，已经发表了超过250,000篇关于移植肿瘤学的文献，研究范围超出了外科手术，涵盖了肿瘤学、免疫学和其他相关学科。值得注意的是，由于肝移植（LTs）治疗肝胆恶性肿瘤的优异临床结果，移植肿瘤学的发展领域主要集中在肝移植肿瘤学上。然而，平衡潜在的临床益处和供体肝脏稀缺仍然是主要关注点。因此，目前肝移植肿瘤学的临床挑战可以总结和分类为以下五个方面：最佳候选选择标准、移植前肿瘤学管理、移植内合理的外科手术、个体化免疫抑制方案以及肿瘤复发和DNMs的临床策略。

The Acquired Immunodeficiency Syndrome Professional Group of the Society of Infectious Diseases of the Chinese Medical Association formulated the first edition of the Chinese Guidelines for the Diagnosis and Treatment of human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS) (referred to as the Guidelines) in 2005. The 2024 edition of the Guidelines has been compiled by updating the 2021 fifth edition, incorporating the latest research advancements in antiviral therapy, comprehensive management, opportunistic infections, concurrent tumors, and the prevention and intervention of HIV infection. The new edition also introduces a new section on "Incomplete immune reconstitution", proposes the concept of "HIV vulnerable populations" for the first time with recommendations for their diagnosis and treatment. This edition of the Guidelines covers 14 sections: epidemiology, pathogenic characteristics, laboratory tests, pathogenesis, clinical presentation and staging, diagnostic criteria, common opportunistic infections, antiretroviral therapy, immune reconstitution inflammatory syndrome, incomplete immune reconstitution, AIDS-related neoplasms, prevention of mother-to-child transmission and conception in serodiscordant couples, pre- and post-exposure prophylaxis, and whole-course management of HIV infection. This edition of the Guidelines aims to assist clinical physicians in making informed decisions in the diagnosis, treatment, and management of HIV/AIDS and will be periodically revised and updated based on domestic and international research progress.

在嵌合抗原受体(CAR)-T细胞治疗恶性血液病引起的细胞因子释放综合征(CRS)期间，皮质类固醇的时机、剂量和使用有什么建议？

经颅磁共振引导聚焦超声（MRgFUS）是一种先进的神经调节技术，它利用磁共振成像（MRI）的力量进行引导和温度监测，并利用聚焦超声波进行无创脑调节。^[1]这种革命性的方法为治疗各种脑部疾病开辟了新的途径，包括特发性震颤（ET）、帕金森病（PD）和一些精神疾病，而不需要开放手术。^[2,3,4]然而，在标准化协议方面缺乏共识，特别是那些针对亚洲人口统计的协议。为了促进MRgFUS的标准化应用并促进临床实践中的知情决策，该领域的专家在广泛讨论后合作建立了全面的共识。共识集中在ExAblate Neuro设备（InSightec，Tirat Carmel，以色列）上，因为这些设备是目前唯一获得美国食品药品监督管理局(FDA)批准的用于脑热消融的聚焦超声(FUS)系统，并且该领域积累的大部分临床专业知识很大程度上源于它们的利用。该共识全面阐明了适应症、禁忌症、程序和临床管理。的建议表1目的加强以MRgFUS为中心的患者护理和临床方案。共识的全文见补充材料http://links.lww.com/CM9/C153.

Metabolic dysfunction-associated steatotic liver disease (MASLD), also called non-alcoholic fatty liver disease, is the most epidemic chronic liver disease worldwide. Metabolic dysfunction-associated steatohepatitis (MASH) is the critical stage of MASLD, and early diagnosis and treatment of MASH are crucial for reducing the incidence of intrahepatic and extrahepatic complications. So far, pharmacotherapeutics for the treatment of MASH are still a major challenge, because of the complexity of the pathogenesis and heterogeneity of MASH. Many agents under investigation have shown impressive therapeutic effects by targeting different key pathways, including the attenuation of steatohepatitis or fibrosis or both. It is notable that thyroid hormone receptor-β agonist, resmetirom has become the first officially approved drug for treating MASH with fibrosis. Other agents such as peroxisome proliferator-activated receptor agonists, glucagon-like peptide-1 analogs, and fibroblast growth factor 21 analogs are awaiting approval. This review focuses on the current status of drug therapy for MASH and summarizes the latest results of new medications that have completed phase 2 or 3 clinical trials, and presents the future directions and difficulties of new drug research for MASH.

Leukocyte immunoglobulin-like receptor (LILR) B4 (also known as ILT3/CD85k) is an immune checkpoint protein that is highly expressed in solid tumors and hematological malignancies and plays a significant role in the pathophysiology of cancer. LILRB4 is highly expressed in acute myeloid leukemia (AML), and this phenotype is associated with adverse patient outcomes. Its differential expression in tumors compared to normal tissues, its presence in tumor stem cells, and its multifaceted roles in tumorigenesis position it as a promising therapeutic target in AML. Currently, several immunotherapies targeting LILRB4 are undergoing clinical trials. This review summarizes advancements made in the study of LILRB4 in AML, focusing on its structure, ligands, expression, and significance in normal tissues and AML; its protumorigenic effects and mechanisms in AML; and the application of LILRB4-targeted therapies in AML. These insights highlight the potential advantages of LILRB4 as an immunotherapeutic target in the context of AML.

The triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio, a novel biomarker for metabolic syndrome (MetS), has been validated in the general population as being significantly correlated with cardiovascular disease (CVD) risk. However, its capabilities to predict CVD in people living with human immunodeficiency virus (HIV; PLWH) remain underexplored.

We conducted a retrospective cohort study of 16,081 PLWH who initiated antiretroviral therapy (ART) at the Third People’s Hospital of Shenzhen (China) from 2005 to 2022. The baseline TG/HDL-C ratio was calculated as TG (mmol/L) divided by HDL-C (mmol/L). We employed a multivariate Cox proportional hazards model to assess the association between the TG/HDL-C ratio and CVD occurrence, using Kaplan-Meier curves and log-rank tests to compare survival distributions. The increase in prediction risk upon the addition of the biomarker to the conventional risk model was examined through the assessment of changes in net reclassification improvement (NRI) and integrated discrimination improvement (IDI). Nonlinear relationships were investigated using a restricted cubic spline plot, complemented by a two-piecewise Cox proportional hazards model to analyze threshold effects.

At the median follow-up of 70 months, 213 PLWH developed CVD. Kaplan-Meier curves demonstrated a significant association between the increased risk of CVD and a higher TG/HDL-C ratio (log-rank P <0.001). The multivariate-adjusted Cox proportional hazards regression model indicated that the CVD hazard ratios (HR) (95% confidence intervals [95% CIs]) for Q2, Q3, and Q4 versus Q1 of the TG/HDL-C ratio were 2.07 (1.24, 3.45), 2.17 (1.32, 3.57), and 2.20 (1.35, 3.58), respectively (P <0.05). The consideration of the TG/HDL-C ratio in the model, which included all significant factors for CVD incidence, improved the predictive risk, as indicated by the reclassification metrics (NRI 16.43%, 95% CI 3.35%-29.52%, P = 0.014). The restriction cubic spline plot demonstrated an upward trend between the TG/HDL-C ratio and the CVD occurrence (P for nonlinear association = 0.027, P for overall significance = 0.009), with the threshold at 1.013. Significantly positive correlations between the TG/HDL-C ratio and CVD were observed below the TG/HDL-C ratio threshold with HR 5.88 (95% CI 1.58-21.88, P = 0.008), but not above the threshold with HR 1.01 (95% CI 0.88-1.15, P = 0.880).

Our study confirms the effectiveness of the TG/HDL-C ratio as a predictor of CVD risk in PLWH, which demonstrates a significant nonlinear association. These findings indicate the potential of the TG/HDL-C ratio in facilitating early prevention and treatment strategies for CVD among PLWH.

Rapid initiation of antiretroviral therapy (ART) is recommended by guidelines, however, real-world studies of same-day initiation of ART in China are limited, and an optimal treatment regimen has yet to be identified. The study aims to provide a realistic reference for rapid initiation of ART.

We retrospectively analyzed the clinical data of treatment-naïve people with human immunodeficiency virus (PWHs) who were diagnosed and prescribed same-day ART initiation from January 1, 2021 to December 31, 2022 at Chongqing Public Health Medical Center. PWHs voluntarily chose an ART regimen that divided them into two groups: National Free Antiretroviral Treatment Program (NFATP)-recommended regimens group (2 nucleoside reverse transcriptase inhibitors + non-nucleoside reverse transcriptase inhibitors/protease inhibitors) and bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) group. The primary endpoint was the virological outcome of the two groups for same-day ART initiation at 24 weeks and 48 weeks. The secondary endpoints included changes in CD4 counts, maintenance of the original ART regimen at 48 weeks, and lipid levels and renal function at 48 weeks.

A total of 255 PWHs were included in the study, including 131 (51.4%) in the NFATP group and 124 (48.6%) in the BIC/FTC/TAF group. The overall virological suppression rates at 24 weeks and 48 weeks were 78.2% (165/211) and 95.4% (207/217), respectively. At 24 weeks, the virologic suppression rate in the NFATP group was lower than that in the BIC/FTC/TAF group (65.3% [66/101] vs. 90.0% [99/110], P <0.001). The median increase in the CD4 count was 198.0 (126.0-300.0) cells/µL at 24 weeks, with 182.0 (108.0-245.0) cells/µL in the NFATP group and 219 (132.0-316.0) cells/µL in the BIC/FTC/TAF group (P = 0.035). At 48 weeks, there was no significant difference in the virological suppression rate or CD4 count between the groups. The 48-week initial ART regimen retention rates and treatment retention rates were significantly higher in the BIC/FTC/TAF group than in the NFATP group (91.1% (113/124) vs. 71.8% (94/131), 99.2% (118/119) vs. 93.0% (120/129), respectively). In terms of safety, there were no significant changes from baseline in levels of creatinine, estimated glomerular filtration rate (eGFR), or lipids in either group at 48 weeks.

ART initiation on the day of diagnosis is effective, safe, and feasible, with satisfactory rates of virologic suppression, 48-week initial ART regimen retention rates, and treatment retention rates in treatment-naïve PWHs. In our study, the early virologic suppression rate, CD4 cell counts, and treatment retention of the BIC/FTC/TAF regimens were significantly better than those of the NFATP regimens.

Substantial progress in air pollution control has brought considerable health benefits in China, but little is known about the spatio-temporal trends of economic burden from air pollution. This study aimed to explore their spatio-temporal features of disease burden from air pollution in China to provide policy recommendations for efficiently reducing the air pollution and related disease burden in an era of a growing economy.

Using the Global Burden of Disease method and willingness to pay method, we estimated fine particulate matter (PM_2.5) and/or ozone (O₃) related premature mortality and its economic burden across China, and explored their spatio-temporal trends between 2005 and 2017.

In 2017, we estimated that the premature mortality and economic burden related to the two pollutants were RMB 0.94 million (68.49 per 100,000) and 1170.31 billion yuan (1.41% of the national gross domestic product [GDP]), respectively. From 2005 to 2017, the total premature mortality was decreasing with the air quality improvement, but the economic burden was increasing along with the economic growth. And the economic growth has contributed more to the growth of economic costs than the economic burden decrease brought by the air quality improvement. The premature mortality and economic burden from O₃ in the total loss from the two pollutants was substantially lower than that of PM_2.5, but it was rapidly growing. The O₃-contribution was highest in the Yangtze River Delta region, the Fen-Wei Plain region, and some western regions. The proportion of economic burden from PM_2.5 and O₃ to GDP significantly declined from 2005 to 2017 and showed a decreasing trend pattern from northeast to southwest.

The disease burden from O₃ is lower than that of PM_2.5, the O₃-contribution has a significantly increasing trend with the growth of economy and O₃ concentration.

T-cell-mediated immunity is crucial for the effective clearance of viral infection, but the T-cell-mediated immune responses that are induced by booster doses of inactivated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines in people living with human immunodeficiency virus (PLWH) remain unclear.

Forty-five PLWH who had received antiretroviral therapy (ART) for more than two years and 29 healthy controls (HCs) at Beijing Youan Hospital were enrolled to assess the dynamic changes in T-cell responses between the day before the third vaccine dose (week 0) and 4 or 12 weeks (week 4 or week 12) after receiving the third dose of inactivated SARS-CoV-2 vaccine. Flow cytometry, enzyme-linked immunospot (ELISpot), and multiplex cytokines profiling were used to assess T-cell responses at the three timepoints in this study.

The results of the ELISpot and activation-induced marker (AIM) assays showed that SARS-CoV-2-specific T-cell responses were increased in both PLWH and HCs after the third dose of the inactivated SARS-CoV-2 vaccine, and a similar magnitude of immune response was induced against the Omicron (B.1.1.529) variant compared to the wild-type strain. In detail, spike-specific T-cell responses (measured by the ELISpot assay for interferon γ [IFN-γ] release) in both PLWH and HCs significantly increased in week 4, and the spike-specific T-cell responses in HCs were significantly stronger than those in PLWH 4 weeks after the third vaccination. In the AIM assay, spike-specific CD4⁺ T-cell responses peaked in both PLWH and HCs in week 12. Additionally, significantly higher spike-specific CD8⁺ T-cell responses were induced in PLWH than in HCs in week 12. In PLWH, the release of the cytokines interleukin-2 (IL-2), tumour necrosis factor-alpha (TNF-α), and IL-22 by peripheral blood mononuclear cells (PBMCs) that were stimulated with spike peptides increased in week 12. In addition, the levels of IL-4 and IL-5 were higher in PLWH than in HCs in week 12. Interestingly, the magnitude of SARS-CoV-2-specific T-cell responses in PLWH was negatively associated with the extent of CD8⁺ T-cell activation and exhaustion. In addition, positive correlations were observed between the magnitude of spike-specific T-cell responses (determined by measuring IFN-γ release by ELISpot) and the amounts of IL-4, IL-5, IL-2 and IL-17F.

Our findings suggested that SARS-CoV-2-specific T-cell responses could be enhanced by the booster dose of inactivated COVID-19 vaccines and further illustrate the importance of additional vaccination for PLWH.

Scleroderma is characterized by inflammation and fibrosis, predominantly occurring in the skin and extending to various parts of the body. The pathophysiology of scleroderma is multifaceted, with the current understanding including endothelial damage, inflammatory cell infiltration, and fibroblast activation in its progression. Nonetheless, the mechanism of cellular interactions and the precise spatial distribution of these cellular events within the fibrotic tissues remain elusive, highlighting a critical gap in our comprehensive understanding of scleroderma’s pathogenesis.

In this study, we administered bleomycin intradermally to the dorsal skin of four individual murine models. Subsequently, skin tissues were harvested at predetermined intervals for comprehensive spatial transcriptomic analysis to determine the spatial dynamics influencing scleroderma pathogenesis. To validate the possible results from bioinformatic analysis, further in vitro and in vivo experiments were conducted.

Analysis of the spatial transcriptome revealed significant alterations in cell clusters during the progression of scleroderma. Gene Ontology analysis identified disruptions in lipid metabolism as the disease advanced. Pseudotime analysis provided evidence for a phenotypic transition from adipocytes to fibroblasts. In vitro studies demonstrated increased expression of Col1a1 and α-SMA as the disease progressed. These fibroblasts have been identified as key contributors to the increasing inflammation. Co-culturing TGF-β induced adipocytes with RAW264.7 cells resulted in overexpression of pro-inflammatory cytokines in the RAW264.7 cells. Both in vitro and in vivo experiments confirmed adipocyte loss and fibroblast formation, with transformed fibroblasts showing pronounced pro-inflammatory characteristics, highlighting their crucial role in the disease mechanism.

Our study showed the spatial distribution and dynamic alterations of various cell types during scleroderma progression. Crucially, we identified the transformation of adipocytes into fibroblasts as a key factor promoting disease advancement. These emergent fibroblasts intensify inflammation, indicating that research on these cell clusters could reveal key scleroderma mechanisms and guide future therapies.

致编辑：中国为人类免疫缺陷病毒（HIV）患者提供免费抗逆转录病毒治疗（ART），通常使用两种核苷类逆转录酶抑制剂（NRTIs）和一种非核苷类逆转录酶抑制剂（NNRTIs）。在过去的20年里，这种疗法显著降低了死亡率，减缓了艾滋病毒的传播。^[1,2]然而，它的耐药屏障较低，使耐药突变（DRMs）成为一个重大挑战。替诺福韦（TFV）、拉米夫定或恩曲他滨（3TC或FTC）和NNRTI（依法韦仑或奈韦拉平）方案病毒学失败后，DRM至3TC/FTC或TFV很常见。^[3]尽管如此，3TC/FTC和TFV仍包含在许多单片方案（STR）中，引发了对一线ART失败后其有效性的担忧。Bictegravir是一种与FTC和TFV艾拉酚胺（B/F/TAF）共同配制的第二代整合酶链转移抑制剂（INSTIs），可提供有效的病毒抑制、最小的药物相互作用、高耐药性屏障和优异的耐受性。^[4]B/F/TAF被推荐为HIV（PWH）患者初始治疗和转换的首选方案。^[2,5]虽然数据表明B/F/TAF对病毒学抑制的既往DRMs患者有效，但可用数据有限且具有回顾性。^[6,7,8]

致编辑：结核病（TB）是全球HIV感染者（PLWH）死亡的主要原因。鉴于结核病感染风险增加，建议PLWH接受结核病预防性治疗（TPT），以防止结核病活化并降低相关死亡率。然而，TPT的实施仍然薄弱，2021年全球只有21%的合格PLWH在TPT上启动，^[1]主要是由于发展中国家的执行挑战。TPT完成率低可能归因于多种原因，包括社会经济因素、个体行为（用药依从性、知识缺乏等）、抗结核药物供应链不稳定、对结核病治疗指南了解不足等。中国一直被认为是结核病高负担地区。因此，自2006年以来，国家指南中建议对HIV感染患者进行有条件的结核病预防，重点是CD4患者⁺T计数<200个细胞/µL，或潜伏性TB筛查试验呈阳性者，优选使用干扰素γ释放试验（IGRA）。自2021年以来，建议遵循世界卫生组织（世卫组织）指南实施普遍结核病预防战略。然而，在实际实践中，HIV感染者在大多数中心开始抗逆转录病毒治疗（ART）时很少接受通用TPT。然而，关于中国HIV感染者开始抗逆转录病毒疗法后活动性结核病发病率的报道很少。此外，普遍预防策略是否会使人群受益还取决于基于人群的结核病激活患病率，以及治疗费用和药物相关不良事件。因此，我们在此旨在汇编在中国北京的一个综合转诊中心开始ART的前五年PLWH活动性结核病的患病率，为HIV感染个体中更个性化的TPT提供真实世界的数据。

致编辑：颈动脉支架置入术（CAS）是颅外颈内动脉（EICA）狭窄的关键治疗方法，用于卒中二级预防。低血压是颈动脉窦球囊扩张的常见围手术期事件，可导致严重不良事件，如缺血性卒中、心肌梗死和住院时间延长（LOS）。^[1]之前的研究^[2]回顾了与CAS后低血压相关的几个因素，如年龄、冠状动脉疾病、左心房容积和斑块位置，但这些因素不容易改变。儿茶酚胺在CAS或颈动脉内膜切除术（CEA）后维持血压（BP）中起重要作用；先前的一项研究表明，CEA后，儿茶酚胺随着血压升高而升高，而CAS后，血压降低，儿茶酚胺水平无显著变化。^[3]由于研究表明肾素-血管紧张素-醛固酮系统抑制剂（RASI）药物阻断儿茶酚胺的释放，它们可能有效预防CAS后低血压。我们旨在确定RASI使用与CAS后持续性低血压之间的关系及其与儿茶酚胺水平变化的关系。

致编辑：肾细胞癌是泌尿生殖道最常见的癌症，每年在全世界导致超过170,000人死亡。对于局限性肿瘤，机器人辅助肾部分切除术（RAPN）因其众多益处而成为一种流行的选择，包括更好的人体工程学、更好的功能结果、相似的肿瘤学结果和微创性。康多手术机器人（KD-SR）是一种新型机器人手术平台，由苏州康多机器人有限公司（中国苏州）开发。最近，我们报道了与达芬奇Si手术系统（DV-SS-Si）相比，KD-SR在T1a肿瘤的手术成功率方面取得了非劣效性的结果。^[1]然而，KD-SR和DV-SS-Si的肿瘤学结果尚未比较。在这项前瞻性随机队列试验中，我们旨在比较患者报告的健康相关生活质量（HRQoL）和KD-SR的中期肿瘤学结果vs.RAPN的DV-SS-Si。

致编辑：后颅窝A组（PFA）室管膜瘤是最常见和最具侵袭性的儿科肿瘤之一，目前缺乏有效的化疗药物。^[1,2]此前，我们揭示了在PFA室管膜瘤中特别不受调节的CXorf67作为DNA同源重组（HR）修复的负调节因子，通过合成致死机制使PFA肿瘤对聚（ADP-核糖）聚合酶（PARP）抑制剂联合放疗高度敏感。^[3]然而，PFA室管膜瘤多发生在婴幼儿，电离辐射可能对他们构成很大风险。因此，对于不能或不愿意接受放疗的PFA室管膜瘤患者的治疗仍然存在迫切需求。鉴于铂类药物（顺铂和卡铂）作为DNA损伤剂，被广泛用作抗癌药物。这项研究旨在研究PARP抑制剂和DNA损伤化疗的组合是否可以有效杀死表达CXorf67的肿瘤细胞。

作者声明，在《中华医学杂志》第18期第137卷发表的文章中，^[1]在引言部分“这些癌症占全球近360万新病例和120万死亡”中发现了一个错误。应更正为“这些癌症占全球近377万新病例和135万死亡。”错误不影响文章的结果和结论。作者对由此造成的任何不便深表歉意。