2025年 · 第138卷第02期

代谢功能障碍相关脂肪变性肝病（MASLD）是一种越来越常见的慢性肝病，全球成人患病率超过30%，截至2019年全球约有16.6亿例。^[1]代谢功能障碍相关脂肪性肝炎（MASH）是MASLD最具侵袭性的亚型之一，与心血管疾病、晚期肝纤维化的风险升高以及肝脏相关和全因发病率和死亡率增加相关。据估计，全球MASH患病率>5%，2019年报告了约3990万例病例。^[1]到2030年，肝功能失代偿、肝细胞癌和与MASH肝硬化相关的死亡的发生率预计将增加两到三倍。^[2]尽管体重减轻导致组织学改善，但分别只有25%和19%的患者MASH消退和纤维化改善。此外，实现和维持体重减轻具有挑战性，20%的患者体重反弹。^[3]瑞美替隆是一种甲状腺激素受体-β（Thr β）激动剂，是美国食品药品监督管理局（FDA）唯一批准用于伴有显著肝纤维化（≥2期）的MASH的药物；然而，有条件批准是局部的，目前不建议对肝硬化阶段的MASH进行药物治疗。^[4]因此，迫切需要有效的MASH药物。

Large language models (LLMs) such as ChatGPT, Claude, Llama, and Qwen are emerging as transformative technologies for the diagnosis and treatment of various diseases. With their exceptional long-context reasoning capabilities, LLMs are proficient in clinically relevant tasks, particularly in medical text analysis and interactive dialogue. They can enhance diagnostic accuracy by processing vast amounts of patient data and medical literature and have demonstrated their utility in diagnosing common diseases and facilitating the identification of rare diseases by recognizing subtle patterns in symptoms and test results. Building on their image-recognition abilities, multimodal LLMs (MLLMs) show promising potential for diagnosis based on radiography, chest computed tomography (CT), electrocardiography (ECG), and common pathological images. These models can also assist in treatment planning by suggesting evidence-based interventions and improving clinical decision support systems through integrated analysis of patient records. Despite these promising developments, significant challenges persist regarding the use of LLMs in medicine, including concerns regarding algorithmic bias, the potential for hallucinations, and the need for rigorous clinical validation. Ethical considerations also underscore the importance of maintaining the function of supervision in clinical practice. This paper highlights the rapid advancements in research on the diagnostic and therapeutic applications of LLMs across different medical disciplines and emphasizes the importance of policymaking, ethical supervision, and multidisciplinary collaboration in promoting more effective and safer clinical applications of LLMs. Future directions include the integration of proprietary clinical knowledge, the investigation of open-source and customized models, and the evaluation of real-time effects in clinical diagnosis and treatment practices.

This article provides an overview of the current evidence on the epidemiology, overlapping risk factors, and pathophysiology of cardiovascular disease (CVD) in patients with cancer. It explores the cardiotoxic effects of anticancer therapy and their impact on prognosis. Although cancer survival rates have improved over the last two decades, the risk of CVD has risen over time in patients with cancer. CVD and cancer share similar risk factors and a common pathophysiology involving inflammation. Many chemotherapeutic agents used to treat cancer are associated with cardiovascular complications (such as heart failure, myocardial infarction, and thrombosis). Current evidence indicates a significant burden of CVD in patients with cancer, particularly in the first year following cancer diagnosis, with elevated risk persisting beyond this period. This short- and long-term risk of CVD may vary depending on the cancer type and treatment regimen. Early identification of potential cardiovascular risk in patients with cancer, can lead to more favorable clinical and survival outcomes. Given the acute and long-term consequences, patients with cancer require increased cardiovascular care and lifestyle optimization. This article offers valuable insights into the cardiovascular burden and needs of patients with cancer. It is intended for a general medical research readership interested in the intersection of cardiology and oncology.

Vascular aging (VA) is a common etiology of various chronic diseases and represents a major public health concern. Intermittent hypoxia (IH) associated with obstructive sleep apnea-hypopnea syndrome (OSAHS) is a primary pathological and physiological driver of OSAHS-induced systemic complications. A substantial proportion of OSAHS patients, estimated to be between 40% and 80%, have comorbidities such as hypertension, heart failure, coronary artery disease, pulmonary hypertension, atrial fibrillation, aneurysm, and stroke, all of which are closely associated with VA. This review examines the molecular and cellular features common to both OSAHS and VA, highlighting decreased melatonin secretion, impaired autophagy, increased apoptosis, increased inflammation and pyroptosis, increased oxidative stress, accelerated telomere shortening, accelerated stem cell depletion, metabolic disorders, imbalanced protein homeostasis, epigenetic alterations, and dysregulated neurohormonal signaling. The accumulation and combination of these features may underlie the pathophysiological link between OSAHS and VA, but the exact mechanisms by which OSAHS affects VA may require further investigation. Taken together, these findings suggest that OSAHS may serve as a novel risk factor for VA and related vascular disorders, and that targeting these features may offer therapeutic potential to mitigate the vascular risks associated with OSAHS.

Retinal ganglion cell (RGC) death caused by acute ocular hypertension is an important characteristic of acute glaucoma. Receptor-interacting protein kinase 3 (RIPK3) that mediates necroptosis is a potential therapeutic target for RGC death. However, the current understanding of the targeting agents and mechanisms of RIPK3 in the treatment of glaucoma remains limited. Notably, artificial intelligence (AI) technologies have significantly advanced drug discovery. This study aimed to discover RIPK3 inhibitor with AI assistance.

An acute ocular hypertension model was used to simulate pathological ocular hypertension in vivo. We employed a series of AI methods, including large language and graph neural network models, to identify the target compounds of RIPK3. Subsequently, these target candidates were validated using molecular simulations (molecular docking, absorption, distribution, metabolism, excretion, and toxicity [ADMET] prediction, and molecular dynamics simulations) and biological experiments (Western blotting and fluorescence staining) in vitro and in vivo.

AI-driven drug screening techniques have the potential to greatly accelerate drug development. A compound called HG9-91-01, identified using AI methods, exerted neuroprotective effects in acute glaucoma. Our research indicates that all five candidates recommended by AI were able to protect the morphological integrity of RGC cells when exposed to hypoxia and glucose deficiency, and HG9-91-01 showed a higher cell survival rate compared to the other candidates. Furthermore, HG9-91-01 was found to protect the retinal structure and reduce the loss of retinal layers in an acute glaucoma model. It was also observed that the neuroprotective effects of HG9-91-01 were highly correlated with the inhibition of PANoptosis (apoptosis, pyroptosis, and necroptosis). Finally, we found that HG9-91-01 can regulate key proteins related to PANoptosis, indicating that this compound exerts neuroprotective effects in the retina by inhibiting the expression of proteins related to apoptosis, pyroptosis, and necroptosis.

AI-enabled drug discovery revealed that HG9-91-01 could serve as a potential treatment for acute glaucoma.

Skin cancer is a common skin disease whose incidence and mortality rates have been showing yearly increases. In this report, we update the most recent data on skin cancer as obtained from GLOBOCAN 2022.

The incidence and mortality rates of skin cancer (melanoma of skin and non-melanoma skin cancer) in GLOBOCAN 2022 were reviewed. These data were analyzed and the characteristics of incidence and mortality across five continents and top five countries and regions in each continent are presented. In addition, correlations between Human Development Index (HDI) and age-standardized incidence and mortality rates of these two skin cancers are described.

The GLOBOCAN 2022 data indicated that melanoma was the 17th most common cancer. An estimated 331,722 people were diagnosed with melanoma globally and approximately 58,667 died from this disease. For non-melanoma skin cancer, it ranks as the 5th most common cancer, and an estimated 1,234,533 people were diagnosed with non-melanoma skin cancer globally and approximately 69,416 died from this disease. The incidence of skin cancer varies across geographic regions and countries, with a predominance observed in Oceania, North America, and Europe. Australia was ranked first in terms of incidence, while incidence rates in Africa and Asia were very low. Despite these regional differences in incidence, there was little geographic variation in mortality rates. Currently, the number of deaths from non-melanoma skin cancer exceeds that of melanoma of skin. HDI was positively associated with the incidence of both types of skin cancers, with a positive correlation obtained between HDI and mortality from melanoma of skin and a negative correlation between HDI and mortality from non-melanoma skin cancer.

Skin cancer remains a major disease burden worldwide. Substantial variations are observed across countries and regions. Further research on skin cancer will be required to provide a rationale for more effective preventions and treatments of this condition.

Chronic kidney disease (CKD) is associated with common pathophysiological processes, such as inflammation and fibrosis, in both the heart and the kidney. However, the underlying molecular mechanisms that drive these processes are not yet fully understood. Therefore, this study focused on the molecular mechanism of heart and kidney injury in CKD.

We generated an microRNA (miR)-26a knockout (KO) mouse model to investigate the role of miR-26a in angiotensin (Ang)-II-induced cardiac and renal injury. We performed Ang-II modeling in wild type (WT) mice and miR-26a KO mice, with six mice in each group. In addition, Ang-II-treated AC16 cells and HK2 cells were used as in vitro models of cardiac and renal injury in the context of CKD. Histological staining, immunohistochemistry, quantitative real-time polymerase chain reaction (PCR), and Western blotting were applied to study the regulation of miR-26a on Ang-II-induced cardiac and renal injury. Immunofluorescence reporter assays were used to detect downstream genes of miR-26a, and immunoprecipitation was employed to identify the interacting protein of LIM and senescent cell antigen-like domain 1 (LIMS1). We also used an adeno-associated virus (AAV) to supplement LIMS1 and explored the specific regulatory mechanism of miR-26a on Ang-II-induced cardiac and renal injury. Dunnett’s multiple comparison and t-test were used to analyze the data.

Compared with the control mice, miR-26a expression was significantly downregulated in both the kidney and the heart after Ang-II infusion. Our study identified LIMS1 as a novel target gene of miR-26a in both heart and kidney tissues. Downregulation of miR-26a activated the LIMS1/integrin-linked kinase (ILK) signaling pathway in the heart and kidney, which represents a common molecular mechanism underlying inflammation and fibrosis in heart and kidney tissues during CKD. Furthermore, knockout of miR-26a worsened inflammation and fibrosis in the heart and kidney by inhibiting the LIMS1/ILK signaling pathway; on the contrary, supplementation with exogenous miR-26a reversed all these changes.

Our findings suggest that miR-26a could be a promising therapeutic target for the treatment of cardiorenal injury in CKD. This is attributed to its ability to regulate the LIMS1/ILK signaling pathway, which represents a common molecular mechanism in both heart and kidney tissues.

China is one of the countries with the highest burdens of stomach cancer. The objective of this study was to analyze long-term trends in the incidence and mortality of stomach cancer in Chinese mainland from 1990 to 2019 and to make projections until 2030.

Data on stomach cancer were extracted from the Global Burden of Diseases Study 2019. Population data were extracted from the Global Burden of Diseases Study 2019 and World Population Prospects 2019. An age-period-cohort framework and decomposition analysis were used in this study.

The net drift for the incidence of stomach cancer was 0.2% (95% confidence interval [CI]: 0, 0.4%) per year for men and -1.8% (95% CI: -2.0%, -1.6%) for women. The net drift for mortality was -1.6% (95% CI: -1.8%, -1.3%) per year for men and -3.3% (95% CI: -3.5%, -3.1%) for women. In the last 10-15 years, the risk of stomach cancer occurrence and death has continued to decline for both sexes. Regarding birth cohorts, although the risk of stomach cancer death decreased in general among women and men born after 1920, the risk of occurrence increased in recent birth cohorts (men born after 1970 and women born after 1985). It is expected that the age-standardized incidence will increase among men and decrease among women, and age-standardized mortality will decrease for both sexes. The largest contributor to the projected increase in incident cases and deaths is population aging, and elderly individuals are projected to have an increased proportion of occurrence and death.

In the past three decades, the incidence of stomach cancer among men has increased in Chinese mainland, and this trend is projected to continue. Aging will be the main contributor to future increased stomach cancer occurrence and deaths. To reduce the health impact of stomach cancer, more efforts are needed.

致编辑创伤性脑损伤（TBI）在发达国家和发展中国家都是一种威胁生命的疾病和全球公共卫生问题。^[1]在过去的几十年里，与TBI相关的发病率和死亡率已经下降。然而，促成这一结果的确切机制仍不清楚。最近，研究人员已经意识到，由于脑-肠轴相互作用，中枢神经系统与肠道微生物群密切相关。^[2]许多研究将肠道微生物群及其代谢物与自闭症、抑郁症、中风和帕金森病相关联。^[3]肠道微生物组成的变化是否会影响TBI在很大程度上仍然未知。代谢组学，一种专注于推导生物流体或组织中低分子量内源性代谢物的综合分析的方法，已被用于探索多种疾病的代谢变化。然而，代谢组和TBI结果或进展之间的关系以及肠道微生物组和TBI之间的关系仍不清楚。因此，我们比较了TBI患者和健康个体的肠道微生物组和血清代谢组，以确定特定的细菌和血清代谢组差异。

致编辑：肾结石影响10-15%的成年人，大结石会导致疼痛和潜在的肾脏损伤。^[1]肾结石切开术是超过两厘米结石的主要治疗方法，以前通过开放手术进行管理，这会导致明显的疼痛、失血和长期住院。^[2]经皮肾镜取石术（PCNL）是一种微创手术，可减少疼痛，缩短恢复时间，减少并发症。然而，由于复杂的肾脏解剖结构，它需要精确的肾脏穿刺和专门的训练。^[3]

致编辑：银屑病关节炎(PsA)影响高达30%的银屑病患者，导致生活质量下降。PsA可涉及多种临床表现，包括外周性和中轴性关节炎、附着点炎、手指炎和指甲疾病。^[1]早期干预对于防止功能丧失和永久性残疾很重要；然而，PsA的诊断通常平均延迟五年。^[1]因此，鉴定可检测银屑病患者PsA的生物标志物非常重要。

致编辑：高度近视（HM）的患病率在全球范围内一直在增加，尤其是在中国年轻人中。^[1]大多数关于近视个体的眼部生物特征参数的早期研究主要集中在患有白内障的儿童、青少年和老年人身上，缺乏对患有HM的年轻人的眼部生物特征参数的研究。此外，HM患者的眼部生物特征参数和眼轴长度（AL）之间的关系尚不清楚。^[2,3]因此，了解中国年轻HM患者的眼部生物特征及其与AL的相关性至关重要。

致编辑：为了降低肾移植术后急性排斥反应（AR）的风险，免疫抑制诱导治疗已被普遍应用于围手术期。目前，兔抗胸腺细胞球蛋白（rATG）和巴利昔单抗是用于肾移植的两种主要诱导剂。在成人肾移植中，rATG诱导的AR发生率通常低于巴利昔单抗。^[1]儿童的免疫系统与成人不同。在小儿肾移植中，哪种诱导治疗对预防早期AR更有效，是一个值得回答的重要临床问题。由于该领域的报道较少，且不同年龄儿童的免疫系统存在差异，我们现对中国多中心队列数据进行了总体和年龄分层分析，以比较rATG和巴利昔单抗诱导治疗组在儿科已故供体肾移植中的AR率和其他结局。

致编辑：超声心动图是诊断和预测心血管疾病的有价值的工具；然而，它有一定的局限性，例如依赖于运算符和具有复杂的多维性质，这可能使解释具有挑战性。人工智能（AI）擅长分析和处理大型、复杂和多维数据。它可以自动分析和整合来自多个来源的信息，以建立预测模型。这可以提高超声心动图在医疗保健中的效率，从而能够改进心脏病的检测、诊断和管理。这项研究强调了机器学习（ML）结合超声心动图在心血管预测模型开发中的临床应用，为改善患者护理提供了见解。

致编辑：近年来，转移性激素敏感性前列腺癌（mHSPC）的治疗经历了快速发展。多西他赛（DOC）或雄激素受体靶向剂（ARTA）和雄激素剥夺疗法（ADT）是最常用的全身疗法。

致编辑：由于眼附件淋巴瘤（OAL）和特发性眼眶炎症（IOI）相似的临床症状和影像学特征，区分它们是具有挑战性的。先前的研究表明，基于磁共振成像（MRI）的放射学特征可以为区分OAL和IOI提供有价值的见解。然而，这些影像学发现的诊断准确性很大程度上依赖于主观解释，导致不一致且有时有争议的结论。基于MRI的放射组学与机器学习（ML）的集成有望以更客观的方式提供定量特征，从而进一步建立诊断模型并提高诊断准确性。

致编辑：创伤后应激障碍（PTSD）是一种严重的创伤后精神障碍，与恐惧记忆密切相关。^[1]目前的治疗如选择性5-羟色胺再摄取抑制剂具有有限的有效性和副作用，需要新的非侵入性方法。PTSD通常与抑郁症同时发生，两者都与炎症系统破坏有关，患者的促炎细胞因子增加。^[2,3]经皮耳迷走神经刺激（taVNS）显示出通过减少神经炎症来治疗抑郁症的前景。^[4]taVNS结合了耳针（一种传统中医技术）和神经解剖学，针对迷走神经的耳支影响丘脑和海马等大脑区域。本研究假设taVNS可能通过调节炎症反应来降低恐惧条件小鼠的恐惧记忆。我们利用恐惧调节小鼠模型来评估对冷冻行为的影响，并量化血清和大脑区域内的炎症标志物，包括皮质酮、白细胞介素-10（IL-10）和白细胞介素-1 β（IL-1 β）。

致编辑：术后器官损伤和并发症是围手术期发病率和死亡率的主要原因。尽管许多回顾性研究揭示了术中低血压与围手术期器官损伤之间的关联，^[1]关于严格血压管理和临床结局的前瞻性随机试验结果不一致。^[2,3,4]手术引起的压力也可能引起器官损伤。右美托咪定已被证实可减弱应激介质的过度表达；然而，围手术期右美托咪定是否能改善临床结局仍不确定。^[5,6]因此，这项2 × 2析因随机试验旨在研究联合/不联合右美托咪定的靶向血压管理是否可以最大限度地减少非心脏大手术后中高危患者30天内主要器官损伤和并发症的发生。

作者声明，在通信“慢性肺病继发肺动脉高压中的肥胖悖论”中，^[1]发表在卷。137，第18期，第2260-2262页中华医学杂志，作者贡献应更正为“吴长伟和吴文辉对本工作贡献相等”。作者对由此造成的任何不便深表歉意。