2024年 · 第137卷第21期

术语“急性慢性肝功能衰竭”（ACLF）最初是在近30年前提出的。^[1]ACLF不同于失代偿性肝硬化和急性肝功能衰竭，是慢性肝病背景下急性损伤导致的独立临床综合征。^[2,3]

冠状病毒疾病2019（新冠肺炎）的全球爆发始于2019年底，并持续到2024年。^[1]感染新冠肺炎的患者可能会表现出多器官受累，身体系统可能会受到不同程度的影响。许多患者在急性感染后，身体和心理症状累及多系统，并长期持续。^[2]肺康复是新冠肺炎管理中的一个关键问题。成人COVID-19患者呼吸康复的早期建议^[3]基于对严重急性呼吸综合征和中东呼吸综合征的研究和知识，结合在大流行初始阶段积累的新冠肺炎知识。然而，这些建议缺乏临床证据。因此，鉴于过去3年对新冠肺炎的进一步调查，需要一个更新的循证指南。

Recent advancements in the field of medical artificial intelligence (AI) have led to the widespread adoption of foundational and large language models. This review paper explores their applications within medical AI, introducing a novel classification framework that categorizes them as disease-specific, general-domain, and multi-modal models. The paper also addresses key challenges such as data acquisition and augmentation, including issues related to data volume, annotation, multi-modal fusion, and privacy concerns. Additionally, it discusses the evaluation, validation, limitations, and regulation of medical AI models, emphasizing their transformative potential in healthcare. The importance of continuous improvement, data security, standardized evaluations, and collaborative approaches is highlighted to ensure the responsible and effective integration of AI into clinical applications.

B7-H3 (CD276), an immune checkpoint protein of the B7 family, exhibits significant upregulation in solid tumors and hematologic malignancies, exerting a crucial role in their pathophysiology. The distinct differential expression of B7-H3 between tumors and normal tissues and its multifaceted involvement in tumor pathogenesis position it as a promising therapeutic target for tumors. In the context of acute myeloid leukemia (AML), B7-H3 is prominently overexpressed and closely associated with unfavorable prognoses, yet it has remained understudied. Despite various ongoing clinical trials demonstrating the potential efficacy of immunotherapies targeting B7-H3, the precise underlying mechanisms responsible for B7-H3-mediated proliferation and immune evasion in AML remain enigmatic. In view of this, we comprehensively outline the current research progress concerning B7-H3 in AML, encompassing in-depth discussions on its structural attributes, receptor interactions, expression profiles, and biological significance in normal tissues and AML. Moreover, we delve into the protumor effects of B7-H3 in AML, examine the intricate mechanisms that underlie its function, and discuss the emerging application of B7-H3-targeted therapy in AML treatment. By juxtaposing B7-H3 with other molecules within the B7 family, this review emphasizes the distinctive advantages of B7-H3, not only as a valuable prognostic biomarker but also as a highly promising immunotherapeutic target in AML.

Moyamoya disease (MMD) is a cerebrovascular disorder characterized by a steno-occlusive internal carotid artery and compensatory vascular network formation. Although the precise pathogenic mechanism remains elusive, genetic association studies have identified RNF213 as the principal susceptibility gene for MMD, with the single nucleotide polymorphism p.R4810K recognized as the founder variant predominantly in the Asian populations. Distinct genotype-phenotype correlations are observable in RNF213-related MMD. The clinical manifestations linked to p.R4810K bear commonalities within Asian cohort, including familial predisposition, earlier age of onset, ischemic episodes, and involvement of the posterior cerebral artery (PCA). However, despite these shared phenotypic characteristics, there is significant heterogeneity in RNF213-related MMD presentations. This diversity manifests as variations across ethnic groups, inconsistent clinical symptoms and prognosis, and occurrence of other vasculopathies involving RNF213. This heterogeneity, in conjunction with the observed low disease penetrance of RNF213 mutations, suggests that the presence of these mutations may not be sufficient to cause MMD, underscoring the potential influence of other genetic or environmental factors. Although the current research might not have fully identified these additional contributors, experimental evidence points toward the involvement of RNF213 in angiogenesis, lipid metabolism, and the immune response. Future research is required to unveil the molecular mechanisms and identify the factors that synergize with RNF213 in the pathogenesis of MMD.

脑小血管疾病（CSVD）是中风和痴呆的重要原因。CSVD导致高达30%的缺血性中风和80%的自发性脑实质内出血。^[1]与发达国家的数据相比，亚洲人群表现出由CSVD引起的卒中负担更重。^[2]CSVD的临床表现各不相同。我们提出了急性CSVD（aCSVD）的概念来描述具有突然发作中风症状的表型。本研究旨在引起对缺血性和出血性aCSVD的同等关注，并促进对aCSVD与非急性或隐匿性CSVD之间差异和联系的更好理解。我们关注异质性机制，并讨论治疗挑战和潜在策略。

感觉异常是临床神经病学中普遍存在的主诉，这是神经病学中一个重要但被忽视的领域。这个个体子集对临床诊断和治疗提出了实质性的挑战。因此，迫切需要关注感觉异常患者的临床诊断和治疗。

Thyroid cancer (TC) is the most common malignancy of the endocrine system. This study aimed to assess the global distribution of TC incidence and mortality in 2022, as well as to predict the burden for the year 2050.

Data from the GLOBOCAN 2022 database were used to analyze the age-standardized incidence and mortality rates of TC by sex, age group (<55 years and ≥55 years), country, world region, and level of Human Development Index (HDI) for 185 countries. The predicted incidence and mortality burden for 2050 was calculated based on demographic projections.

In 2022, an estimated 821,214 new TC cases and 47,507 TC-related deaths occurred worldwide. The age-standardized incidence rates (ASIRs) and age-standardized mortality rates (ASMRs) were higher in women (ASIR: 13.60 per 100,000; ASMR: 0.53 per 100,000) than in men (ASIR: 4.60 per 100,000; ASMR: 0.35 per 100,000). The ASIR in high HDI countries was approximately ten times higher than that in low HDI countries for both sexes, with relatively similar ASMR across regions. Among 185 countries, China had the largest number of TC cases (accounting for 56.77% of total cases) and TC-related deaths (accounting for 24.35% of global TC-related deaths), with the highest ASIR in men (13.30 per 100,000). Worldwide, approximately 64.63% of TC cases occurred in populations under 55 years old, while nearly 82.99% of TC-related deaths occurred in populations aged 55 years and above. If the rates stay the same as in 2022, it is projected that approximately 1,100,000 new TC cases and 91,000 TC-related deaths will occur in 2050, indicating a 34.15% and 89.58% increase, respectively.

TC is a highly frequent cancer worldwide with disparities across regions, genders, and age groups. Our results provide light on the worldwide TC disease burden and facilitate regionally customized prevention measures.

Lung cancer is the most common cancer and a leading cause of cancer-related deaths globally. The aim of this study was to evaluate the incidence and mortality of lung cancer worldwide in 2022 and to project the number of new cases and deaths due to lung cancer in China and the United States in 2050.

In this study, data from the GLOBCAN 2022 database were used to analyze lung cancer incidence and mortality. The current status of lung cancer incidence and deaths was described by country/region, sex, age, and the human development index (HDI), and future lung cancer incidence and deaths in China and the United States were projected for 2050.

Globally, an estimated 2,480,675 new lung cancer cases and 1,817,469 lung cancer-related deaths occurred in 2022, with age-standardized incidence rates (ASIRs) and age-standardized mortality rates (ASMRs) of 23.6/100,000 and 16.8/100,000, respectively. In China, the ASIR and ASMR for male lung cancer patients were approximately 1.7 times and 2.7 times greater than those for female lung cancer patients, respectively. The ASIR and ASMR in high-HDI countries were approximately 8.5 times and 6.5 times those in low-HDI countries, respectively. It is estimated that in 2050, there will be approximately 1120 thousand new cases and 960 thousand deaths among Chinese men, 680 thousand new cases and 450 thousand deaths among Chinese women, approximately 170 thousand new cases and 110 thousand deaths among American men, and 160 thousand new cases and 90 thousand deaths among American women.

There are significant differences in the incidence and mortality of lung cancer among different regions and sexes. Therefore, sex factors need to be considered in the prevention, screening, and treatment strategies of lung cancer, and the implementation of tertiary prevention measures for lung cancer, especially primary and secondary prevention, needs to be actively promoted.

Uterine fibroids (UFs), the most common tumors in women worldwide, may reduce quality of life and daily activities and even lead to adverse fertility and general health events in patients, causing significant societal health and financial burdens. The objective of this study was to evaluate the global burden through epidemiological trends and examine the potential risk factors for UFs at the national level.

Data on the incidence, prevalence, disability-adjusted life years (DALYs), age-standardized incidence rates (ASIRs), age-standardized prevalence rates (ASPRs), and age-standardized DALY rates for UFs were collected, and the associations with the Human Development Index (HDI) and fertility were evaluated. The age trends in the average annual percent change (AAPC) of the incidence and prevalence rates of UFs were evaluated by joinpoint regression analysis. The associations between lifestyle, metabolic, and socioeconomic factors and the ASIRs of UFs were examined using multivariable linear regression analysis.

The worldwide incidence and prevalence of UFs have been increasing in the past decade, with AAPCs of 0.27% in the incidence rate and 0.078% in the prevalence rate. During 2010-2019, significant increasing trends in UF ASIR were observed in 52 of 88 countries. The age-specific incidence and prevalence of UFs in most age groups showed increasing trends except for 45-54-year-old women which showed no significant trend. Ecological analysis demonstrated no relationship between the incidence of UFs and the HDI but an inverse association with fertility. The incidence of UFs was positively correlated with alcohol intake, hypertension, overweight, and obesity and negatively correlated with smoking.

With the increasing incidence and prevalence worldwide, effective targeted prevention and control of relevant risk factors at the national level should be encouraged to reduce the disease burden of UFs.

One of the significant challenges for cell therapies, such as chimeric antigen receptor (CAR)-T cell therapy, is the poor infiltration of immune cells into tumor tissues. CAR-monocytes/macrophages (CAR-M) are promising therapies because of their enrichment in the tumor microenvironment. Thus, we constructed a novel CAR-M to facilitate the infiltration of T cells and other immune cells.

The suicide gene inducible caspase-9 (iCasp9) and anti-erb-b2 receptor tyrosine kinase 2 (HER2) CAR elements were transfected into THP1 (an immortalized human monocyte cell line) by lentivirus. The suicide efficiency and specific anti-tumor efficacy were assessed using flow cytometry, inCucyte, and tumor-bearing BALB/c-nude mouse models. The activation of related signaling pathways in CAR-THP1 activation was explored by transcriptome sequencing. Finally, the synergistic therapeutic efficacy of CAR-THP1 combined with RAK cell treatment was demonstrated in tumor-bearing NOD.CB17-Prkdc^scid Il2rg^tm1/Bcgen mouse models.

We developed a novel CAR-THP1, which incorporated iCasp9, CD3ζ, and CD147 intracellular segments, based on the first-generation HER2-CAR backbone. By constructing and comparing a series of CARs with different permutations, CAR-CD3ζ-CD147-iCasp9-THP1 was selected as the optimal combination. CAR-CD3ζ-CD147-iCasp9-THP1 initiated suicide quickly and efficiently under the control of iCasp9 gene, which enabled us to achieve controlled proliferation of CAR-THP1. CAR-THP1 also exhibited robust specific anti-tumor efficacy independently of T cells in vitro and in vivo. Through transcriptional sequencing, we found that CAR-THP1 tended to differentiate into the M1 phenotype and bridged innate and adaptive immunity. A combination of CAR-THP1 and Retronectin actived killer cells (RAKs) showed better therapeutic efficiency, as the metalloproteinases (MMPs) secreted by CAR-THP1 facilitated the degradation of the dense tumor matrix. This further assisted intratumoral infiltration of T cells and augmented the anti-tumor immune response.

CAR-THP1 might be effective against HER2-positive tumor cells and has great potential for combination therapy with other immune cells.

Renal ischemia-reperfusion (R-I/R) injury is the most prevalent cause of acute kidney injury, with high mortality and poor prognosis. However, the underlying pathological mechanisms are not yet fully understood. Therefore, this study aimed to investigate the role of N-myc downstream-regulated gene 2 (Ndrg2) in R-I/R injury.

We examined the expression of Ndrg2 in the kidney under normal physiological conditions and after R-I/R injury by immunofluorescence staining, real-time polymerase chain reaction, and western blotting. We then detected R-I/R injury in Ndrg2-deficient (Ndrg2^-/-) mice and wild type (Ndrg2^+/+) littermates in vivo, and detected oxygen and glucose deprivation and reperfusion (OGD-R) injury in HK-2 cells. We further conducted transcriptomic sequencing to investigate the role of Ndrg2 in R-I/R injury and detected levels of oxidative stress and mitochondrial damage by dihydroethidium staining, biochemical assays, and western blot. Finally, we measured the levels of mitophagy in Ndrg2^+/+ and Ndrg2^-/- mice after R-I/R injury or HK-2 cells in OGD-R injury.

Ndrg2 was primarily expressed in renal proximal tubules and its expression was significantly decreased 24 h after R-I/R injury. Ndrg2^-/- mice exhibited significantly attenuated R-I/R injury compared to Ndrg2^+/+ mice. Transcriptomics profiling showed that Ndrg2 deficiency induced perturbations of multiple signaling pathways, downregulated inflammatory responses and oxidative stress, and increased autophagy following R-I/R injury. Further studies revealed that Ndrg2 deficiency reduced oxidative stress and mitochondrial damage. Notably, Ndrg2 deficiency significantly activated phosphatase and tensin homologue on chromosome ten-induced putative kinase 1 (PINK1)/Parkin-mediated mitophagy. The downregulation of NDRG2 expression significantly increased cell viability after OGD-R injury, increased the expression of heme oxygenase-1, decreased the expression of nicotinamide adenine dinucleotide phosphate oxidase 4, and increased the expression of the PINK1/Parkin pathway.

Ndrg2 deficiency might become a therapy target for R-I/R injury by decreasing oxidative stress, maintaining mitochondrial homeostasis, and activating PINK1/Parkin-mediated mitophagy.

对于局部晚期胃癌（LAGC）患者，在新辅助期加入程序性细胞死亡蛋白1（PD-1）抑制剂可显著提高围手术期化疗的有效性。然而，很大比例的程序性死亡-配体1联合阳性评分（PD-L1 CPS）的患者<1或微卫星稳定（MSS）状态可能仍不会受益。抗血管生成剂阿帕替尼可以促进血管正常化，这由神经/胶质抗原2(NG2)标记的周细胞与血小板内皮细胞粘附分子(CD31)标记的内皮细胞的比率指示，^[1]并与PD-1抑制剂协同作用，提高化疗和免疫治疗的疗效。然而，基线NG2的预测值⁺/CD31⁺免疫治疗的比例尚未确定。基于我们初步研究的积极结果【补充表1，http：//links.lww.com/CM9/C151】，在cT3/4 LAGC患者中使用三联围手术期FLOT化疗联合信迪利单抗和阿帕替尼进行了一项II期试验，该试验旨在与先前涉及FLOT化疗的研究相比，在不增加毒性风险的情况下提高治疗效果。此外，我们还检查了基线NG2的潜力⁺/CD31⁺比率作为该强化治疗方案的预测标志物。

银屑病关节炎(PsA)是一种慢性全身性炎性疾病，影响外周和中轴关节、附着点、皮肤和指甲。它严重降低了生活质量和心理社会功能。尽管肿瘤坏死因子抑制剂（TNFi）显著改善了PsA的患者结局，但仍有显著的未满足需求。

致编辑：在2019冠状病毒病（COVID-19）大流行期间，严重急性呼吸综合征冠状病毒2（新型冠状病毒）的奥密克戎变种在全球传播。专家一致认为，奥密克戎变异株致病性较低，潜伏期较短，更容易引起上呼吸道感染。经综合考虑，中国国家卫生健康委员会已于2022年12月26日将COVID-19的术语由“新型冠状病毒肺炎”更名为“新型冠状病毒感染”，并于2023年1月8日将管理由A级降为B级。^[1]尽管此次调整是近三年来疫情防控政策最重大的战略性转变，但新型冠状病毒并未完全消失，一些国家正经历多波感染增加。监测新冠肺炎的影响和预防和控制策略的有效性仍然是公共卫生的优先事项。

致编辑：全身性轻链(AL)淀粉样变性是一种罕见且致命的疾病，全世界每年每百万人中约有10人受到影响，其特征是由危险的浆细胞或B细胞克隆产生的错误折叠、聚集的免疫球蛋白轻链。由于非特异性症状，AL淀粉样变性的诊断经常面临障碍。由于对AL淀粉样变性的更深入了解和治疗进展，患者的总生存期（OS）在全球范围内显著改善。^[1,2]然而，有关中国情况的数据仍然有限，特别是自新型治疗药物于2017年底被纳入国家医疗保险报销清单（NMIRL）以来，系统性轻链被列入第一份发布的国家罕见病清单，以及中国国家卫生健康委员会于2018年成立了肿瘤多学科团队（MDT）。因此，在中国西部开展了一项多中心、回顾性、真实世界研究（AMY4002），报告了2018年前后中国AL淀粉样变性患者的临床基线、治疗模式和结局。

致编辑：胃肠道间质瘤（GISTs）是胃肠道最常见的间叶肿瘤。胃肠道间质瘤多发生在40-60岁左右患者的胃或小肠，对化疗或放疗不敏感。分别约有10%和85%的成人和儿童胃肠道间质瘤患者不携带任何一种突变成套工具或者PDGFRA，从而定义为试剂盒/PDGFRA野生型。^[1]根据琥珀酸脱氢酶亚基B（SDHB）免疫组化（IHC）染色，试剂盒/PDGFRA野生型GIST（WT-GIST）可分为两组：琥珀酸脱氢酶（SDH）缺陷型GIST，其特征在于缺乏SDHB表达和SDH亚基突变（SDHX，即。SDHA,SDHB,SDHC，和SDHD），尤其是SDHA和表突变SDHC甲基化；和SDH非缺陷型GIST，其特征在于缺乏SDHX突变和其他基因的突变，主要涉及RAS信号通路【补充图1，http：//links.lww.com/CM9/C138】。

致编辑：原发性肝癌是我国最常见的恶性肿瘤之一。2020年，中国报告了410038例肝癌新发病例和391152例肝癌死亡病例，这使得肝癌成为中国第二大常见癌症相关死亡原因；在这些癌症中，肝细胞癌（HCC）占85-90%。^[1]HCC对中国人民的生命健康构成重大威胁。

致编辑：自2021年11月以来，奥密克戎的出现引起了全球的关注。在奥密克戎菌株中，奥密克戎XBB.1.5是最近发现的。它携带缺失和30多个突变，改变了严重急性呼吸综合征冠状病毒-2（新型冠状病毒）的生物学特征，以增强传播性和免疫逃逸能力。^[1]人类免疫缺陷病毒(PLWH)患者以获得性分化簇(CD)4为特征⁺T细胞缺乏，进展为严重冠状病毒疾病的风险较高2019（新冠肺炎）。^[2]疫苗是预防新型冠状病毒感染的最具保护性的工具。^[3]然而，加强疫苗接种在PLWH中诱导针对奥密克戎XBB.1.5的中和抗体（NAb）产生的程度尚不清楚。

致编辑黑色素瘤是一种高度侵袭性的恶性肿瘤，其发病率与社会发展水平有关，发达国家的发病率高于发展中国家。^[1]中国人口众多，在过去30年中经历了大幅的经济增长和城市化，人口老龄化日益严重。

致编辑：食管狭窄可以是良性的，也可以是恶性的。良性狭窄通常由食管反流、放射治疗、腐蚀性摄入或早期食管肿瘤内镜粘膜下剥离（ESD）或内镜粘膜切除术后的手术吻合引起。恶性狭窄是由晚期癌症引起的。食管狭窄常导致吞咽困难、营养不良、误吸和呼吸衰竭，使保守治疗具有挑战性。支架植入是缓解吞咽困难、控制狭窄相关并发症和改善患者生活质量的主要选择。

致编辑：心包交感神经副神经节瘤少见，可危及生命。它表现为症状，如难治性高血压、心悸和其他激素相关的表现。本研究介绍了一例起源于纵隔的3型副神经节瘤的独特病例，伴有多模态影像学表现，包括计算机断层扫描(CT)扫描，¹⁸F-氟脱氧葡萄糖正电子发射断层扫描/CT（¹⁸F-FDG PET/CT），⁶⁸Ga-DOTA-1-Nal3-奥曲肽正电子发射断层扫描/CT（⁶⁸Ga-DOTANOC PET/CT)，以及¹⁸F-氟二羟基苯丙氨酸正电子发射断层扫描/CT（¹⁸F-FDOPA PET/CT)。

致编辑：痛风性关节炎是一种自身炎症性疾病，表现出快速发作的临床症状，但通常在7-10天内自发消退。在急性痛风炎症反应中，尿酸单钠（MSU）晶体被巨噬细胞膜上的Toll样受体（TLRs）识别为损伤相关的分子模式。随后，TLR-NF-κ-B抑制剂α（I κ B α）/核因子κ B（NF-κ B）途径被激活，产生许多炎症因子、中性粒细胞趋化因子和组织蛋白酶并参与核苷酸结合寡聚化结构域受体蛋白3（NLRP3）炎症小体的组装。^[1]NLRP3炎症小体由NLRP3、凋亡相关斑点样蛋白（ASC）和胱天蛋白酶-1组成。NLRP3炎症小体和NF-κ B途径之间的协同作用通过激活白细胞介素(IL)-1 β和IL-18的成熟、诱导上睑下垂和释放大量促炎介质在痛风炎症中起着至关重要的作用。研究表明，增加的抗炎介质，如转化生长因子β 1（TGF-β 1）和IL-10参与急性炎症自发缓解。^[2]诱饵受体3(DcR3)是炎症和免疫应答的重要调节因子。DCR3通过与DR3竞争结合TL1A，阻断人肿瘤坏死因子相关配体1A(TL1A)/死亡受体3(DR3)轴而发挥抗炎作用。TL1A/DR3/DcR3轴是一种新的免疫途径，参与几种自身炎性疾病的发病机制。^[3]然而，目前尚不清楚TL1A/DR3/DcR3轴是否参与痛风性关节炎的发生、进展和自发缓解。在这里，我们测量了急性痛风（AG）或临界间痛风（IG）患者中DcR3、TL1A和DR3的表达水平。随后，我们使用用DcR3特异性小干扰RNA（si-DcR3）或DcR3过表达质粒（pcDNA-DcR3）转染的THP-1细胞来确定DcR3在MSU诱导的痛风炎症中的功能。

作者声明，在第136卷第22期发表的文章中中华医学杂志,^[1]在“实时定量PCR（qPCR）验证”章节中发现错误。引物序列小韦荣氏菌被错误地粘贴为16S rRNA引物序列。校正的引物序列应如下：