2025年 · 第138卷第05期

人类mpox（以前称为猴痘）在2022年出现在非洲国家以外之前，历史上很少受到关注。截至2024年9月30日，累计向世界卫生组织（WHO）报告了109,699例实验室确诊的mpox病例。^[1]自2023年5月11日世卫组织宣布mpox疫情不构成国际关注的突发公共卫生事件（全球关注卫生紧急事件）以来，已过去一年有余。然而，2024年8月14日，世卫组织宣布，刚果（金）和非洲越来越多国家的mpox热潮再次构成全球关注卫生紧急事件。尽管世卫组织提出了《2024-2027年加强预防和控制Mpox的战略框架》，但按计划在2024-2025年控制和消除Mpox似乎是一个重大挑战。^[2]此外，mpox的各种弱势人群（如儿童、孕妇和免疫抑制个体）、不良结局（如心肌炎）和医院管理策略使预防和控制工作复杂化。^[3,4,5]为了在公众中有效预防和控制mpox，了解流行趋势、Clade Ib构成的威胁以及必要的控制措施至关重要。

Ferroptosis, an iron-dependent programmed cell death process driven by reactive oxygen species-mediated lipid peroxidation, is regulated by several metabolic processes, including iron metabolism, lipid metabolism, and redox system. Macrophages are a group of innate immune cells that are widely distributed throughout the body, and play pivotal roles in maintaining metabolic balance by its phagocytic and efferocytotic effects. There is a profound association between the biological functions of macrophage and ferroptosis. Therefore, this review aims to elucidate three key aspects of the unique relationship between macrophages and ferroptosis, including macrophage metabolism and their regulation of cellular ferroptosis; ferroptotic stress that modulates functions of macrophage and promotion of inflammation; and the effects of macrophage ferroptosis and its role in diseases. Finally, we also summarize the possible mechanisms of macrophages in regulating the ferroptosis process at the global and local levels, as well as the role of ferroptosis in the macrophage-mediated inflammatory process, to provide new therapeutic insights for a variety of diseases.

The remarkable efficacy of chimeric antigen receptor (CAR) T cell therapy in hematological malignancies has provided a solid basis for the therapeutic concept, wherein specific pathogenic cell populations can be eradicated by means of targeted recognition. During the past few years, CAR-based cell therapies have been extensively investigated in preclinical and clinical research across various non-tumor diseases, with particular emphasis in the treatment of autoimmune diseases (ADs), yielding significant advancements. The recent deployment of CD19-directed CAR T cells has induced long-lasting, drug-free remission in patients with systemic lupus erythematosus (SLE) and other systemic ADs, alongside a more profound immune reconstruction of B cell repertoire compared with conventional immunosuppressive agents and B cell-targeting biologics. Despite the initial success achieved by CAR T cell therapy, it is critical to acknowledge the divergences in its application between cancer and ADs. Through examining recent clinical studies and ongoing research, we highlight the transformative potential of this therapeutic approach in the treatment of SLE, while also addressing the challenges and future directions necessary to enhance the long-term efficacy and safety of CAR-based cell therapies in clinical practice.

The combination of immune checkpoint inhibitors and chemotherapy (ICI + Chemo) shows promise in treatment of recurrent or metastatic nasopharyngeal carcinoma (RM-NPC), but some patients received limited benefit and the prognostic factors of the treatments remain unclear. Furthermore, ICIs efficacy in subsequent treatments needs further evaluation.

A systematic search on PubMed, Embase, the Cochrane Library, and major conference proceedings was conducted to identify relevant studies for meta-analysis. The study was designed to compare ICI + Chemo with chemotherapy in first-line treatment and identify efficacy predictors, and to evaluate ICIs alone in subsequent-line treatment for RM-NPC, with a focus on progression-free survival (PFS), objective response rate (ORR), and treatment-related adverse events (AEs).

Fifteen trials involving 1928 patients were included. Three trials compared ICI + Chemo with chemotherapy as a first-line treatment, while 12 trials evaluated ICIs alone in subsequent-line treatment of RM-NPC patients. First-line ICI + Chemo showed superior PFS (hazard ratio [HR] = 0.52, 95% confidence interval [CI], 0.43-0.63; P <0.001) and ORR (risk ratio [RR] = 1.14, 95% CI, 1.05-1.24; P <0.001) compared to chemotherapy, without increased AEs (RR = 1.01, 95% CI, 0.99-1.03; P = 0.481). Neither programmed death-ligand 1 (PD-L1) nor other factors predicted the efficacy of ICI + Chemo vs. chemotherapy. Subsequent-line ICIs alone had a median PFS of 4.12 months (95% CI, 2.93-5.31 months), an ORR of 24% (95% CI, 20-28%), with grade 1-5/grade 3-5 AEs at 79%/14%. However, ICIs alone were associated with significantly shorter PFS (HR = 1.31, 95% CI, 1.01-1.68; P = 0.040) than chemotherapy alone.

ICI + Chemo confers superior survival benefits compared to chemotherapy in first-line RM-NPC treatment, independent of PD-L1 expression or other factors. However, ICIs alone demonstrate a manageable safety profile but do not surpass chemotherapy in efficacy for subsequent-line treatment.

心脏移植遇到了重大障碍，其中最突出的是移植后的免疫排斥。^[1]目前的抗排斥药物，包括钙调磷酸酶抑制剂（如他克莫司和环孢素）、抗代谢药（如霉酚酸酯）和皮质类固醇，^[2]有效抑制免疫反应，但有固有的局限性。长期使用这些药物会增加感染、代谢并发症和潜在器官损伤的风险。尽管它们有效，但这些药物不能确保绝对预防排斥反应，从而使接受者暴露于潜在的急性或慢性排斥反应发作。此外，它们的副作用会导致心血管问题、肾功能障碍和恶性肿瘤的易感性增加。^[3]免疫抑制方面正在进行的创新努力通过探索副作用减少的新药或替代方法来克服这些挑战。最终目标是在预防排斥反应和最小化接受心脏移植的个体长期免疫抑制治疗的固有风险之间取得微妙的平衡。

Several randomized controlled studies have suggested that the prophylactic use of proton pump inhibitors (PPIs) in intensive care unit (ICU) patients could not reduce the incidence of gastrointestinal bleeding (GIB) and may increase adverse events such as intestinal infection and pneumonia. Gut microbiota may play a critical role in the process. PPIs have been widely prescribed for GIB prophylaxis in patients with acute coronary syndrome (ACS). This study aimed to determine the short-term effects of PPI and histamine-2 receptor antagonist (H2RA) treatment on gut microbiota of ACS patients.

The study was designed as a single-blind, multicenter, three-parallel-arm, randomized controlled trial conducted at three centers in Beijing, China. We enrolled ACS patients at low-to-medium risk of GIB and randomized (2:2:1) them to either PPI (n = 40), H2RA (n = 31), or control group (n = 21). The primary outcomes were the alterations in gut microbiota after 7 days of acid suppressant therapy. Stool samples were collected at baseline and 7 days and analyzed by 16S ribosomal RNA (rRNA) gene sequencing.

There were no significant changes in the diversity of gut microbiota after the short-term use of acid suppressants, but the abundance of Fusobacterium significantly increased and that of Bifidobacterium significantly decreased, especially in PPI users. In addition, the abundance of some pathogenic bacteria, including Enterococcus and Desulfovibrio, was significantly elevated in the PPI users. The fecal microbiota of the PPI users included more arachidonic acid metabolism than that of control group.

PPIs may increase the risk of infection by adversely altering gut microbiota and elevating arachidonic acid metabolism, which may produce multiple proinflammatory mediators. For ACS patients at low-to-medium risk of GIB, sufficient caution should be paid when acid-suppressant drugs are prescribed, especially PPIs.

www.chictr.org.cn (ChiCTR2000029552).

Atopic dermatitis (AD) is a chronic inflammatory skin disorder impacting populations worldwide, although its clinical characteristics and patient demographics remain uncharacterized in China. The aim of this study was to investigate the demographics, comorbidities, aggravating factors, and treatments in AD patients across different age groups in China.

This cross-sectional study included Chinese AD patients from 205 hospitals spanning 30 provinces. Patients completed dermatologist-led surveys of general medical history, comorbidities, AD-related aggravating factors, and medications. Two-level mixed-ordered logistic regression was used to evaluate aggravating factors.

Overall, 16,838 respondents were included in the final analysis (aged 30.9 ± 24.1 years). The proportion of severe AD was the highest in patients with AD onset at ≥60 years (26.73%). Allergic rhinitis and hypertension were the most common atopic and metabolism-related non-atopic comorbidities, respectively. AD severity was significantly associated with chronic urticaria, food allergies, and diabetes. Aggravating factors including foods, seasonal changes, and psychological factors were also linked to AD severity. The cross-sectional survey implied that severe AD may be related to the undertreatment of effective systemic or topical interventions.

To enhance the management of AD, it is crucial to consider both aggravating factors and the increased utilization of systemic immunotherapy.

ClinicalTrials.gov, NCT05316805

Hepatitis B poses a heavy burden for children in China, however, the national studies on the distributional characteristics and health care costs of children with severe hepatitis B is still lacking. This study aimed to analyze the disease characteristics, health economic effects, and medical cost for children with severe hepatitis B in China.

Based on patient information in the Hospital Quality Monitoring System, cases with severe hepatitis B were divided into four groups according to age, and the etiology and symptoms of each group were quantified. The cost of hospitalization was calculated for cases with different disease processes, and severity of disease. The spatial aggregation of cases and the relationship with health economic factors were analyzed by Moran’s I analysis.

The total number of children discharged with hepatitis B from January 2016 to April 2022 was 1603, with an average age of 10.5 years. Liver failure cases accounted for 43.48% (697/1603) of total cases and cirrhosis cases accounted for 11.23% (180/1603). According to the grouping of disease progression, there were 1292 cases without associated complications, and the median hospitalization cost was $818.12. According to the spatial analysis, the aggregation of cases was statistically significant at the prefectural and provincial levels in 2019, 2020, and 2021 (all P <0.05). The number of severe cases was negatively correlated with gross domestic product (Moran’s I <0) and percentage of urban population (Moran’s I <0), and positively correlated with the number of pediatric beds per million population (Moran’s I >0).

The number of severe hepatitis B cases is low in areas with high gross domestic product levels and high urban population ratios, and health care costs have been declining over the years.

Approximately 40% of individuals with diabetes worldwide are at risk of developing diabetic kidney disease (DKD), which is not only the leading cause of kidney failure, but also significantly increases the risk of cardiovascular disease, causing significant societal health and financial burdens. This study aimed to describe the burden of DKD and explore its cross-country epidemiological status, predict development trends, and assess its risk factors and sociodemographic transitions.

Based on the Global Burden of Diseases (GBD) Study 2021, data on DKD due to type 1 diabetes (DKD-T1DM) and type 2 diabetes (DKD-T2DM) were analyzed by sex, age, year, and location. Numbers and age-standardized rates were used to compare the disease burden between DKD-T1DM and DKD-T2DM among locations. Decomposition analysis was used to assess the potential drivers. Locally weighted scatter plot smoothing and Frontier analysis were used to estimate sociodemographic transitions of DKD disability-adjusted life years (DALYs).

The DALYs due to DKD increased markedly from 1990 to 2021, with a 74.0% (from 2,227,518 to 3,875,628) and 173.6% (from 4,122,919 to 11,278,935) increase for DKD-T1DM and DKD-T2DM, respectively. In 2030, the estimated DALYs for DKD-T1DM surpassed 4.4 million, with that of DKD-T2DM exceeding 14.6 million. Notably, middle-sociodemographic index (SDI) quintile was responsible for the most significant DALYs. Decomposition analysis revealed that population growth and aging were major drivers for the increased DKD DALYs in most regions. Interestingly, the most pronounced effect of positive DALYs change from 1990 to 2021 was presented in high-SDI quintile, while in low-SDI quintile, DALYs for DKD-T1DM and DKD-T2DM presented a decreasing trend over the past years. Frontiers analysis revealed that there was a negative association between SDI quintiles and age-standardized DALY rates (ASDRs) in DKD-T1DM and DKD-T2DM. Countries with middle-SDI shouldered disproportionately high DKD burden. Kidney dysfunction (nearly 100.0% for DKD-T1DM and DKD-T2DM), high fasting plasma glucose (70.8% for DKD-T1DM and 87.4% for DKD-T2DM), and non-optimal temperatures (low and high, 5.0% for DKD-T1DM and 5.1% for DKD-T2DM) were common risk factors for age-standardized DALYs in T1DM-DKD and T2DM-DKD. There were other specific risk factors for DKD-T2DM such as high body mass index (38.2%), high systolic blood pressure (10.2%), dietary risks (17.8%), low physical activity (6.2%), lead exposure (1.2%), and other environmental risks.

DKD markedly increased and varied significantly across regions, contributing to a substantial disease burden, especially in middle-SDI countries. The rise in DKD is primarily driven by population growth, aging, and key risk factors such as high fasting plasma glucose and kidney dysfunction, with projections suggesting continued escalation of the burden by 2030.

Preclinical studies have indicated that Angong Niuhuang Pills (ANP) reduce cerebral infarct and edema volumes. This study aimed to investigate whether ANP safely reduces cerebral infarct and edema volumes in patients with moderate to severe acute ischemic stroke.

This randomized, double-blind, placebo-controlled pilot trial included patients with acute ischemic stroke with National Institutes of Health Stroke Scale (NIHSS) scores ranging from 10 to 20 in 17 centers in China between April 2021 and July 2022. Patients were allocated within 36 h after onset via block randomization to receive ANP or placebo (3 g/day for 5 days). The primary outcomes were changes in cerebral infarct and edema volumes after 14 days of treatment. The primary safety outcome was severe adverse events (SAEs) for 90 days.

There were 57 and 60 patients finally included in the ANP and placebo groups, respectively for modified intention-to-treat analysis. The median age was 66.0 years, and the median NIHSS score at baseline was 12.0. The changes in cerebral infarct volume at day 14 were 0.3 mL and 0.4 mL in the ANP and placebo groups, respectively (median difference: -7.1 mL; interquartile range [IQR]: -18.3 to 2.3 mL, P = 0.30). The changes in cerebral edema volume of the ANP and placebo groups on day 14 were 11.4 mL and 4.0 mL, respectively (median difference: 3.0 mL, IQR: -1.3 to 9.9 mL, P = 0.15). The rates of SAE within 90 days were similar in the ANP (3/57, 5%) and placebo (7/60, 12%) groups (P = 0.36). Changes in serum mercury and arsenic concentrations were comparable. In patients with large artery atherosclerosis, ANP reduced the cerebral infarct volume at 14 days (median difference: -12.3 mL; IQR: -27.7 to -0.3 mL, P = 0.03).

ANP showed a similar safety profile to placebo and non-significant tendency to reduce cerebral infarct volume in patients with moderate-to-severe stroke. Further studies are warranted to assess the efficacy of ANP in reducing cerebral infarcts and improving clinical prognosis.

Clinicaltrials.gov, No. NCT04475328.

致编辑心脏移植在世界范围内迅速发展，已经帮助了成千上万的终末期心脏病患者。在中国，自2015年以来，中国大陆每年的心脏移植数量稳步上升，从2015年的279例上升至2020年的557例。^[1]然而，与发达国家相比，像中国这样的发展中国家没有足够的移植体系基础，普遍面临供体器官严重短缺、器官分配体系缺失、质量控制体系缺失等三大问题。为解决上述问题，2005年至2015年间，中国政府在器官捐献、分配、医疗质量控制等方面启动了一系列改革，科学规范的移植体系得以建立。然而，很少有数据公布来评估体制改革后的现状。

致编辑：为了通过预防可改变的风险因素来促进健康，并进一步减轻心血管疾病（CVD）的负担，美国心脏协会（AHA）最近将生命的简单7（LS7）心血管健康（CVH）指标更新并修改为生命的基本8（LE8）。^[1]最近在中国和其他国家进行的一项研究报告称，较低的LE8评分与较高的动脉粥样硬化性CVD发病率和死亡风险相关。^[2]然而，CVH对急性冠心病（CHD）和卒中是否有不同的影响，更重要的是，对CVD发病阶段或进一步进展至死亡的影响仍不清楚。这些信息对于阐明CVH在一级和二级预防中的作用非常重要。

致编辑：人工智能（AI）通过实现先进的数据分析、预测建模和个性化医疗，正在彻底改变生物医学领域，推动诊断、治疗和药物发现的突破。为了实现这一目标，研究人员正试图开发基于人工智能的算法，并建立用于临床环境的模型。这一追求的主要挑战包括确保模型的准确性和一致性，并解决人工智能决策的可解释性、与现有临床工作流程的集成以及数据隐私等道德考虑因素等问题。此外，人工智能模型在于训练数据的质量和多样性——稳健的模型需要多样化和有代表性的数据集，以确保不同患者群体的可推广性，减少对大量标记数据的依赖，并保持对领域转移的弹性，从而能够适应新的和未见过的病例。尽管如此，这一领域仍在继续增长，尤其是在用于诊断疾病（如心血管疾病）的基于图像的AI模型方面。

致编辑：冠状动脉疾病（CAD）是世界范围内死亡的主要原因。有效的治疗，如经皮冠状动脉介入治疗（PCI），已经降低了CAD患者的死亡率，并使他们中的大多数过渡到心血管疾病（CVD）的慢性期。因此，对二级预防策略有很高的需求，以减少CAD的不良后果。风险评估可以量化剩余风险，识别高次要风险的患者，并促进知情的预防性治疗决策。^[1]然而，现有的次要风险评分系统，如全球急性冠状动脉事件登记（GRACE）和支架植入患者抗血小板方案不依从模式（PARIS）评分，通常涉及某些公众不熟悉的临床指标，应用于中国患者时表现不佳；因此，它限制了它们的效用，特别是作为自我评估工具。中国动脉粥样硬化性心血管疾病风险预测（China-PAR）评分是指南推荐的使用几种常规风险因素进行一级预防的实用工具。^[2]与原发性CVD相关的风险因素可能与复发事件有关，因为动脉粥样硬化的潜在病理生理学相同。此外，一级和二级心血管疾病预防共享相似的风险预防策略。^[3]因此，可以推测一级预防的风险评分扩展到二级预防。然而，China-PAR评分在CAD患者继发事件风险评估中的有效性尚不清楚。

致编辑：超过一半因心绞痛或非阻塞性冠状动脉出现心肌缺血体征而接受有创冠状动脉造影的患者（NOCA，<直径减小50%或流动储备分数>0.80)。^[1]冠状动脉微血管功能障碍（CMD）是这些患者的一个重要病理生理因素，并与不良结局相关。^[2]尽管冠状动脉反应性检测（CRT）仍然是诊断CMD的金标准，但它既有创又昂贵。负荷心脏磁共振（CMR）是一种非侵入性和有前途的替代方法，提供了诊断CMD的基本灌注参数，如心肌灌注储备指数（MPRI）和心肌灌注储备（MPR）。因此，基于目前的文献，有强有力的证据支持应激CMR在诊断CRT定义的NOCA患者CMD中的有效性。

致编辑：异基因造血干细胞移植（allo-HSCT）是儿童各种恶性血液病、非恶性血液病、免疫缺陷病、代谢性疾病的必要治疗手段。^[1]在完全免疫重建之前的同种异体HSCT后免疫缺陷期间，免疫系统受损的移植接受者比一般人群更易感染传染病。因此，再接种在保护儿科同种异体HSCT接受者免受疫苗可预防疾病方面起着至关重要的作用。灭活疫苗通常更安全，可以在移植后6-12个月开始给药。减毒活疫苗应在移植后至少24个月和停用免疫抑制剂后至少1年接种，因为与免疫抑制剂一起给药时存在严重疫苗诱导感染的风险。^[2,3]

致编辑：巨细胞病毒（CMV）和EB病毒（EBV）的共同再激活在单倍体相合干细胞移植（haplo-SCT）后很常见，并可导致潜在的危及生命的并发症。^[1,2]病毒特异性T淋巴细胞（VSTs）过继免疫疗法是一种关键的治疗选择，在几项临床研究中显示出控制CMV和EBV感染的有希望的结果，为70-90%的患者提供保护。^[3]多病毒特异性T细胞系提供了一种同时解决多种挑战性病毒感染的先进方法。然而，关于其长期疗效的数据有限。此外，多病毒特异性T细胞的临床试验主要集中在单一病毒再激活上，这在我们对多病毒共再激活期间VSTs有效性的理解上留下了空白。抗原竞争可能影响病毒特异性T细胞的扩增体外在产生多病毒特异性细胞系的过程中。无论体内输注细胞之间的竞争损害了过继转移的VSTs的功效仍不清楚。

致编辑：骨质疏松症的常见症状包括骨量低和骨微结构恶化，导致骨脆性和骨折。事实上，骨是由胶原纤维、脉管系统和许多特化细胞组成的复杂组织。骨中的细胞代谢和细胞行为都受细胞外基质（ECM）调节。胶原蛋白水解物作为骨骼系统中主要的ECM，通过促进成骨和血管生成在缓解骨质疏松症方面具有巨大的潜力。然而，胶原蛋白水解物的组成和结构复杂。胶原蛋白水解产物中的肽具有不同的序列和空间结构，导致不同的生物活性。^[1]此外，最近的研究主要集中在骨代谢的改变和特定基因途径的验证。基因调控机制分析尚缺乏。^[2]本工作研究了制备的胶原水解物（CH）中负责成骨和血管生成活性的关键肽序列及其分子机制。此外，还系统研究了CH对骨质疏松小鼠的保护或恢复作用以及CH对骨质疏松相关基因的调节。

致编辑：血栓性微血管病（TMA）是系统性红斑狼疮（SLE）患者中一种罕见的血液学受累，估计发病率为0.5-1.0%，包括但不限于血栓性血小板减少性紫癜（TTP）、溶血性尿毒症综合征（HUS）和其他继发性疾病。SLE-TMA起病急，预后差，表现为微血管血栓形成、血小板减少、微血管病性溶血性贫血。^[1]基于中国SLE治疗研究小组（CSTAR）注册中心，我们旨在通过一项回顾性多中心研究总结SLE-TMA患者的临床特征并探索预后危险因素。

致编辑：自身免疫性大疱性疾病(AIBD)是影响皮肤和粘膜的一组不同的自身免疫性疾病，其特征在于由靶向结构蛋白的自身抗体引起的囊泡、水疱和糜烂。AIBDs主要分为天疱疮、^[1]与抗表皮细胞表面蛋白的抗体和类天疱疮疾病，^[2]靶向表皮基底膜中的蛋白质。^[3]寻常型天疱疮（PV）是最常见的表皮内AIBD，通常影响40-60岁的个体，而大疱性类天疱疮（BP）是主要的表皮下AIBD，在老年人群中发病率增加。鉴于可用的局部和全身治疗的多样性，评估其有效性和安全性至关重要。然而，缺乏关于这些疗法的相对有效性的知识。我们的目标是通过直接比较综合关于AIBD管理的现有证据，并使用网络荟萃分析（NMA）生成治疗排名，为临床决策提供信息并优化治疗策略。