2024年 · 第137卷第23期

分割肝移植（SLT）是一种将完整的供体肝分割成两个解剖和功能独立的移植物，移植给两个受体的手术。SLT可有效扩大供肝来源，经过多年的探索和完善，已成为解决供肝短缺的优势手术方案。

由某些甲型禽流感病毒株（如H5N1和H7N9）引起的人感染高致病性禽流感（HPAI），导致严重的急性呼吸道疾病，死亡率很高，其中前者对鸟类具有致病性。^[1]近年来，HPAI H5在全球范围内传播，引起人类感染。首例报告的牛H5N1感染病例随后传播给人类，引起了国际社会的极大关注。根据历史流感大流行经验和病毒的生物学特性，在特定条件下，如与人和猪流感病毒重配，禽流感病毒（AIV）可能实现高效的人传人，有可能导致全球大流行。在此，我们旨在回顾人类感染H5N1禽流感的历史趋势和流行病学情况的最新发展，评估H5N1禽流感的传播风险，并为公共卫生决策提出禽流感控制建议。

Sepsis-related organ dysfunction is associated with increased morbidity and mortality. Previous studies have found that the endothelium plays crucial roles in maintaining the vascular permeability during sepsis, as well as in regulating inflammation and thrombosis. During sepsis, endothelial cells may release cytokines, chemokines, and pro-coagulant factors, as well as express adhesion molecules. In general, endothelial responses during sepsis typically inhibit bacterial transmission and coordinate leukocyte recruitment to promote bacterial clearance. However, excessive or prolonged endothelial activation can lead to impaired microcirculation, tissue hypoperfusion, and organ dysfunction. Given the structural and functional heterogeneity of endothelial cells in different organs, there are potential differences in endothelial responses by organ type, and the risk of organ damage may vary accordingly. This article reviews the endothelial response observed in sepsis and its effects on organ function, summarizes current progress in the development of therapeutic interventions targeting the endothelial response, and discusses future research directions to serve as a reference for researchers in the field.

Vascular cognitive impairment (VCI) encompasses a wide spectrum of cognitive disorders, ranging from mild cognitive impairment to vascular dementia. Its diagnosis relies on thorough clinical evaluations and neuroimaging. VCI predominately arises from vascular risk factors (VRFs) and cerebrovascular disease, either independently or in conjunction with neurodegeneration. Growing evidence underscores the prevalence of VRFs, highlighting their potential for early prediction of cognitive impairment and dementia in later life. The precise mechanisms linking vascular pathologies to cognitive deficits remain elusive. Chronic cerebrovascular pathology is the most common neuropathological feature of VCI, often interacting synergistically with neurodegenerative processes. Current research efforts are focused on developing and validating reliable biomarkers to unravel the etiology of vascular brain changes in VCI. The collaborative integration of these biomarkers into clinical practice, alongside routine incorporation into neuropathological assessments, presents a promising strategy for predicting and stratifying VCI. The cornerstone of VCI prevention remains the control of VRFs, which includes multi-domain lifestyle modifications. Identifying appropriate pharmacological approaches is also of paramount importance. In this review, we synthesize recent advancements in the field of VCI, including its definition, determinants of vascular risk, pathophysiology, neuroimaging and fluid-correlated biomarkers, predictive methodologies, and current intervention strategies. Increasingly evident is the notion that more rigorous research for VCI, which arises from a complex interplay of physiological events, is still needed to pave the way for better clinical outcomes and enhanced quality of life for affected individuals.

Liver disease involves a complex interplay of pathological processes, including inflammation, hepatocyte necrosis, and fibrosis. End-stage liver disease (ESLD), such as liver failure and decompensated cirrhosis, has a high mortality rate, and liver transplantation is the only effective treatment. However, to overcome problems such as the shortage of donor livers and complications related to immunosuppression, there is an urgent need for new treatment strategies that need to be developed for patients with ESLD. For instance, hepatocytes derived from donor livers or stem cells can be engrafted and multiplied in the liver, substituting the host hepatocytes and rebuilding the liver parenchyma. Stem cell therapy, especially mesenchymal stem cell therapy, has been widely proved to restore liver function and alleviate liver injury in patients with severe liver disease, which has contributed to the clinical application of cell therapy. In this review, we discussed the types of cells used to treat ESLD and their therapeutic mechanisms. We also summarized the progress of clinical trials around the world and provided a perspective on cell therapy.

Chronic hepatitis B virus (HBV) infection is a global public health concern. Existing antiviral drugs, including nucleos(t)ide analogs and interferon-α, can suppress HBV replication and improve the prognosis. However, the persistence of covalently closed circular DNA (cccDNA), the integration of HBV-DNA into the host genome, and compromised immune responses impede the successful treatment of hepatitis B. While achieving a functional cure of HBV remains elusive with the current treatment methods, this is the goal of new therapeutic approaches. Therefore, developing novel antiviral drugs is necessary for achieving a functional or complete cure for chronic hepatitis B. In recent years, substantial progress has been made in drug discovery and development for HBV infection. Direct-acting antiviral agents such as entry inhibitors, capsid assembly modulators, subviral particle release inhibitors, cccDNA silencers, and RNA interference molecules have entered clinical trials. In addition, several immunomodulatory agents, including toll-like receptor agonists, therapeutic vaccines, checkpoint inhibitors, and monoclonal antibodies, are also making their way toward clinical use. In this review, we summarize the recent progress and limitations of chronic hepatitis B treatment and discuss perspectives on approaches to achieving functional cure. Although it will take some time for these new antiviral drugs to be widely used in clinical practice, combination therapy may become a preferable treatment option in the future.

Helicobacter pylori (H. pylori) infects approximately half of the population worldwide and causes chronic gastritis, peptic ulcers, and gastric cancer. Test-and-treat strategies have been recommended for the prevention of H. pylori-associated diseases. Advancements in high-throughput sequencing technologies have broadened our understanding of the complex gastrointestinal (GI) microbiota and its role in maintaining host homeostasis. Recently, an increasing number of studies have indicated that the colonization of H. pylori induces dramatic alterations in the gastric microbiota, with a predominance of H. pylori and a reduction in microbial diversity. Dysbiosis of the gut microbiome has also been observed after H. pylori infection, which may play a role in the development of colorectal cancer. However, there is concern regarding the impact of antibiotics on the gut microbiota during H. pylori eradication. In this review, we summarize the current literature concerning how H. pylori infection reshapes the GI microbiota and the underlying mechanisms, including changes in the gastric environment, immune responses, and persistent inflammation. Additionally, the impacts of H. pylori eradication on GI microbial homeostasis and the use of probiotics as adjuvant therapy are also discussed. The shifts in the GI microbiota and their crosstalk with H. pylori may provide potential targets for H. pylori-related gastric diseases and extragastric manifestations.

Efferocytosis refers to the process that phagocytes recognize and remove the apoptotic cells, which is essential for maintaining tissue homeostasis both in physiological and pathological conditions. Numerous studies have demonstrated that efferocytosis can prevent secondary necrosis and proinflammatory factor release, leading to the resolution of inflammation and tissue immunological tolerance in numerous diseases such as stroke. Stroke is a leading cause of death and morbidity for adults worldwide. Persistent inflammation triggered by the dead cells or cell debris is a major contributor to post-stroke brain damage. Effective efferocytosis might be an efficient strategy to minimize inflammation and restore brain homeostasis for neuronal regeneration and function recovery. In this review, we will discuss the phagocytes in the brain, the molecular mechanisms underlying efferocytosis, the role of efferocytosis in inflammation resolution, and the potential therapeutic applications targeting efferocytosis in stroke.

Inflammatory bowel disease (IBD) imposes a significant economic and social burden in China. We aim to assess the epidemiological trends of IBD in China, and to predict the burden in the near future.

The incidence, mortality, prevalence, and disability-adjusted life year (DALYs) of IBD from 1990 to 2021 were obtained from Global Burden of Disease Study 2021. Estimated annual percentage change (EAPC), average annual percent change, total percent change, and age-period-cohort model were used to access trends. Bayesian age-period-cohort model was utilized to predict the risk of incidence and mortality.

In 2021, IBD affected 168,077 people in China, with 24,941 new cases and 5640 deaths. The age-standardized rate (ASR) of incidence and death was 1.4 and 0.3, respectively. The incidence and prevalence in China were lower than the global and high socio-demographic index (SDI) regions, but the ASR of incidence and prevalence (EAPC: 2.93 and 2.54, respectively) had rapidly increased from 1990 to 2021. The ASR of death and DALYs had significantly decreased (EAPC: -3.05 and -2.93, respectively). Middle-aged and elderly populations faced a severe burden of incidence and prevalence, while the elderly population faced a severe mortality burden. It is projected that by 2035, the ASR of incidence will continue to rise, whereas the death rate will continue to decline.

The burden of IBD in China is serious and increasingly severe. Establishing a comprehensive disease management system in China will help better control the medical burden of IBD.

Tracheal, bronchus, and lung cancer (TBL) is a major cause of mortality and top contributor to productivity loss in large emerging economies such as the BRICS (Brazil, Russia, India, China, and South Africa). We examined the time trends of TBL mortality across the BRICS to better understand the disease burden in these countries and inform public health and healthcare resource allocation.

TBL mortality-related data between 1990 and 2019 were obtained from the Global Burden of Disease Study 2019 and analyzed using age-period-cohort models. Net drift (local drift) was used to describe the expected age-adjusted TBL mortality rate over time overall (each age group); the longitudinal age curve was used to reflect the age effect; the period rate ratios (RRs) were used to reflect the period effect; and the cohort RR was used to reflect the cohort effect.

In 2019, there were 958.3 thousand TBL deaths across the BRICS, representing 46.9% of the global TBL deaths. From 1990 to 2019, the age-standardized mortality rate (ASMR) of TBL decreased in Russia, Brazil, and South Africa while increased in China and India, with the largest reduction reported in Russia (-29.6%) and the largest increase in China (+22.4%). India showed an overall increase (+15.7%) in TBL mortality but the mortality risk decreased among individuals born after 1990 (men) and 1995 (women). Although South Africa and Brazil experienced an overall decline in TBL mortality, their recent birth cohorts, such as Brazilian individuals born after 1985 (men) and 1980 (women), and South African men born after 1995, had an increasing TBL mortality risk. China has experienced an overall increase in TBL mortality, with the mortality risk rising among individuals born after 1995 for both men and women. Russia, which had the highest TBL mortality among the BRICS countries in 1990, has demonstrated significant improvement over the past three decades.

Over the past 30 years, the BRICS accounted for an increasing proportion of global TBL mortality. TBL mortality increased in older women in all the BRICS countries except Russia. Among the recent birth cohort, the risk of TBL mortality increased in Brazil, China, and South Africa. More effective efforts are needed in the BRICS to reduce the burden of TBL and help achieve the United Nation’s Sustainable Development Goals.

在过去的几十年中，表皮功能在皮肤和皮肤外功能的调节中的关键作用已经得到了很好的证明。表皮通透性屏障功能障碍增强表皮DNA和脂质合成，以及皮肤和全身炎症。^[1,2]相反，表皮渗透性屏障功能的改善抑制了屏障破坏皮肤中的表皮脂质合成、细胞因子产生和表皮增殖。^[1,2]类似地，角质层水合(SCH)水平降低会对表皮功能产生负面影响，并增加循环中的细胞因子水平。^[3,4]相应地，表皮功能的改善除了减轻和预防炎性皮肤病如银屑病的复发之外，还降低了促炎细胞因子的循环水平。^[2,5,6]有趣的是，表皮功能的改善也减轻了老年人认知障碍的进展。^[7]综上所述，证据表明表皮功能在皮肤和皮外功能中的调节作用。因此，表皮功能的改善可以有益于整体人类健康。

肝硬化在世界范围内与高发病率、死亡率和医疗费用相关。尽管经颈静脉肝内门体分流术（TIPS）已被证明可提高肝硬化患者的生存率，但全身炎症在失代偿期肝硬化的起始和进展中至关重要。我们之前的研究表明，塞来昔布是一种具有抗炎功效的选择性环氧合酶-2抑制剂（COX-2-I），可有效改善肝纤维化。^[1]然而，很少有研究对COX-2-I治疗肝硬化进行临床探索。

血脂异常是一种代谢紊乱，在人类免疫缺陷病毒（HIV）感染者中患病率高于普通人群，它显著增加心血管疾病（CVD）的风险。^[1]HIV感染可通过持续性炎症、免疫激活和对脂质代谢的直接影响导致血脂异常。^[1]开始抗逆转录病毒治疗（ART）可加重血脂异常，通常表现为总胆固醇（TC）、低密度脂蛋白胆固醇（LDL-C）和甘油三酯（TG）浓度升高，同时高密度脂蛋白胆固醇（HDL-C）浓度降低。^[2]此外，传统风险因素会导致该人群血脂异常的发展。^[3]

致编辑：Tapinarof是一种芳香烃受体（AhR）配体，衍生自发光光杆菌.^[1]研究表明，1%tapinarof乳膏对银屑病具有很高的疗效，^[2]并已在中国和美国获批用于治疗银屑病。“产生白细胞介素(IL)-23/IL-17的辅助性T(Th17)炎症轴”在银屑病的发病机制中起主要作用。Tapinarof还抑制IL-17的表达，抑制氧化应激。^[3]在这里，我们研究了tapinarof在人和小鼠中对树突状细胞（DC）激活以及Th17和Treg分化的作用。我们还研究了tapinarof在咪喹莫特(IMQ)诱导的小鼠银屑病模型中的作用。

致编辑：经导管主动脉瓣置换术（TAVR）在全球范围内迅速兴起，并成为治疗主动脉瓣狭窄患者的可行替代方案。肥胖是心血管疾病发展的公认风险因素，显著增加疾病负担。对主要来自西方国家的TAVR患者的研究强调了与超重或肥胖相关的风险降低，^[1,2,3]这就是所谓的“肥胖悖论”现象。然而，接受TAVR的东亚患者的体重指数（BMI）明显低于西方国家。^[4]因此，在西方国家看到的身体质量指数-死亡率关系可能不直接适用于亚洲。我们的目的是在一个中国国家队列中检查BMI与接受TAVR的患者预后结果之间的分类和剂量反应关系。

致编辑：穴位埋线（ACE）是起源于我国针灸疗法的一种传统外治法，已广泛用于治疗急慢性疾病。^[1]本单中心、随机、单盲前瞻性研究旨在探讨ACE用于开放骨科手术患者术后镇痛的有效性和安全性。该研究方案获得了上海市第四人民医院伦理委员会的批准（编号：2019112-001），并在中国临床试验注册中心注册（ChiCTR2000034008，https://www.chictr.org.cn/）。在研究入组前，从所有患者处获得了书面知情同意书。该研究包括年龄在18-80岁之间的患者，美国麻醉医师协会评分为I或II级，体重指数(BMI)在18 kg/m之间²和30kg/m²，以及2020年6月至2021年12月在同济大学医学院附属上海市第四人民医院接受全麻下开放骨科手术者。手术时间超过一个小时，但不到六个小时。知情同意书由研究人员在疼痛评估和问卷调查中获得。患有中枢神经系统疾病或精神疾病、无法控制的高血压、糖尿病、冠心病或心功能不全、严重肝肾功能不全、术前血血红蛋白<90 g/L被排除在试验之外。记录ACE矛盾治疗（如局部皮肤损伤或感染）、针灸期间晕厥史和药物或酒精滥用史，或其他临床试验的研究入组。

致编辑：我叫Ahmed Elgendi，埃及亚历山大大学肝胆外科医生。我写这封信是为了分享我在华西医院（中国成都）参加作为一带一路倡议一部分的微创肝脏外科培训项目的经验，以及它对改变我们的概念和实践产生的影响。

致编辑：小儿脊柱畸形的治疗原则是既要控制脊柱畸形，又要保持脊柱和胸部的发育和脊柱的活动度。为了实现这一目标，在过去二十年中已经引入了各种生长友好型植入物，其可分为三类，包括基于牵引的、基于压缩的和引导生长系统。本文旨在全面综述目前可用的儿童脊柱畸形生长友好型植入物，特别是近几十年来取得的进展，为临床治疗和植入物设计提供参考。

致编辑：肺癌是全球癌症相关死亡的主要原因，其中非小细胞肺癌(NSCLC)占大多数病例。^[1]光动力疗法（PDT）已用于肺癌近四十年。其相对低的风险和消融能力使其成为非小细胞肺癌有利的辅助治疗选择。由于其与其他疗法相结合的有希望的临床结果，它已被整合到肺癌的现代多学科治疗中。在此，我们全面回顾了关于PDT的现有证据，重点是肺癌的临床疗效和未来可能的发展。

致编辑：阻塞性睡眠呼吸暂停（OSA）和高血压是两种密切相关的疾病，在临床上经常共存。^[1]OSA是继发性高血压的重要原因，导致多达一半的OSA患者出现高血压。^[1]然而，OSA增加患高血压风险的潜在生物学机制仍不确定。

致编辑：增强术后恢复（ERAS）的概念因其令人印象深刻的成果和不断扩大的应用领域而引起了全世界的关注，并得到了许多政府的大力认可和支持。^[1,2]在少痛、早动、早食、安心（LEER）模式下开发加速恢复手术系统代表了一种以目标为导向的综合方法，旨在解决当前加速恢复手术实践中缺乏系统和标准化的工作流程，旨在全面标准化和系统化ERAS程序。利用LEER模式的成功，我们的团队建立了一个多学科、综合的加速康复病房，这不仅在形式和内容上创新了ERAS多学科团队（MDT），还引发了将其应用扩展到所有临床环境的新方法。^[3]这封信讨论了LEER模型应用系统的建立及其临床扩展的概念。