Military Medical Research最新文献

{"title":"Identification of the lymph node metastasis atlas and optimal lymph node dissection strategy in patients with resectable lung invasive mucinous adenocarcinoma: a real-world multicenter study.","authors":"Chao Zheng, Guo-Chao Zhang, Long Zhang, Yu-Zhuo Zhang, Jia Jia, Shun Xu, Wen-Yue Zhao, Yang Liu, Meng Yue, Yue-Ping Liu, Shuang-Ping Zhang, Yi Shen, Qi-Yue Ge, Yu-Ning Han, Jing Li, Hong-Jiang Yan, Li-Yan Xue, Yu-Shun Gao, Feng-Wei Tan, Shu-Geng Gao, Qi Xue, Jie He","doi":"10.1186/s40779-025-00659-3","DOIUrl":"https://doi.org/10.1186/s40779-025-00659-3","url":null,"abstract":"<p><strong>Background: </strong>Lung invasive mucinous adenocarcinoma (LIMA) is a rare, unique, and heterogeneous subtype of lung cancer whose patterns of lymph node (LN) metastasis are unknown, and a consensus on LN dissection (LND) has not been reached. This study aimed to evaluate LN metastasis patterns in LIMAs and establish optimal LND strategies.</p><p><strong>Methods: </strong>Data about 19,596 LNs from 1474 LIMA patients collected between January 2010 and December 2021 at 8 lung cancer research centers and tertiary hospitals across China, and data from 5304 LIMA patients between 2004 and 2021 in the SEER database were analysed. Metastasis probabilities were calculated for each LN station to construct a metastasis atlas. Statistical methods, including LOWESS fitting, restricted cubic spline, Kaplan-Meier, and logistic regression analyses, were employed to identify optimal LND strategies.</p><p><strong>Results: </strong>Compared with non-mucinous adenocarcinoma patients, LIMA patients exhibited distinct clinicopathological features and a significantly lower probability of LN metastasis (4.20% vs. 7.19%, P < 0.05). Metastasis was most common in the peripheral and hilar/interlobar zones (especially stations 14 and 10), with minimal involvement in the lower zone (stations 8 and 9). A U-shaped relationship between the LN count and prognosis (including overall survival, relapse-free survival, and cancer-specific survival) was found, with 6-20 and 18 LNs as the optimal range and cut-off point, respectively. Excessive or insufficient dissection was linked to poorer outcomes. A predictive model (area under the receiver operating characteristic cure = 0.8367) revealed that patients with a probability ≥ 0.5 had a significantly greater proportion of patients with stage N1+ disease (including N1 and N2 patients) (68.09% vs. 11.63%, P < 0.001) and worse overall survival [hazard ratio (HR) = 4.00, 95% CI 2.72-5.87, P < 0.001] and relapse-free survival (HR = 5.53, 95% CI 3.97-7.71, P < 0.001). The minimum numbers of LNs for the low- (probability < 0.1), medium- (probability 0.1-0.5), and high- (probability > 0.5) risk patients were 7, 14, and 17, respectively. For those with uncertain metastatic risk, dissecting 18 LNs may be the most appropriate and robust strategy.</p><p><strong>Conclusions: </strong>This study systematically revealed the pattern of LIMA-specific LN metastasis and proposed a risk-stratified LND strategy. These recommendations balance the imperatives of accurate staging with the preservation of long-term patient prognosis, offering a practical guideline for surgical decision-making.</p>","PeriodicalId":18581,"journal":{"name":"Military Medical Research","volume":"12 1","pages":"67"},"PeriodicalIF":22.9,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145292935","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clonal hematopoiesis of indeterminate potential: a multisystem hub bridging hematopoietic dysfunction with non-hematopoietic diseases.","authors":"Jing-Lei Zhang, Shuo-Lan Tong, Qi-Qi Zhuang, Sheng-Jie Jin, Jia-Qiu Li, Jie Sun","doi":"10.1186/s40779-025-00654-8","DOIUrl":"https://doi.org/10.1186/s40779-025-00654-8","url":null,"abstract":"<p><p>Clonal hematopoiesis of indeterminate potential (CHIP), driven by leukemia-related somatic mutations in hematopoietic stem cells, previously recognized as a major risk factor for hematological malignancies, has now emerged as a potent risk factor for chronic inflammation and diverse non-hematologic diseases. CHIP-associated DNA methyltransferase 3 alpha (DNMT3A), tet methylcytosine dioxygenase 2 (TET2), and additional sex combs like 1 (ASXL1) mutations alter epigenetic programs, skew myelopoiesis, and increase proinflammatory cytokines, resulting in chronic inflammation and immune imbalance. This review integrates mechanistic insights with clinical evidence to delineate CHIP's roles in solid tumors, cardiovascular disorders, and metabolic dysregulation, with an extended discussion of renal dysfunction and neurodegenerative conditions. Furthermore, we also discuss CHIP's diagnostic and therapeutic impacts across multiple disease contexts, advocating for mutation-specific diagnostic paradigms to guide therapeutic interventions.</p>","PeriodicalId":18581,"journal":{"name":"Military Medical Research","volume":"12 1","pages":"66"},"PeriodicalIF":22.9,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145292977","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Charting bioethical frontiers: China's human organoid guidelines in a global context.","authors":"Liang-Bin Zhou, Yi-Ting Lei, Xin-Xin Han","doi":"10.1186/s40779-025-00651-x","DOIUrl":"10.1186/s40779-025-00651-x","url":null,"abstract":"","PeriodicalId":18581,"journal":{"name":"Military Medical Research","volume":"12 1","pages":"64"},"PeriodicalIF":22.9,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12509384/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145258537","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The evolving burden of heart failure in China: a 34-year subnational analysis of trends and causes from the Global Burden of Disease Study 2023.","authors":"Xuan Yang, Zhen-Ping Zhao, Yu Shi, Gui-Yuan Han, Yan Xu, Yi-Chong Li, Mai-Geng Zhou","doi":"10.1186/s40779-025-00650-y","DOIUrl":"10.1186/s40779-025-00650-y","url":null,"abstract":"<p><strong>Background: </strong>Heart failure (HF) continues to be a public health issue in China with population aging and increasing disease drivers. The burden, spatial patterns, temporal trends, and underlying causes of HF in China at subnational levels remain inadequately understood. This study aims to assess the disease burden and causes of HF, and their regional disparities in China from 1990 to 2023.</p><p><strong>Methods: </strong>Utilizing the estimates from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2023, we assessed the prevalence and years lived with disability (YLDs) of HF and their trends in China at both national and subnational levels. Estimates were also compared by disease severity, sex, age group, cause, and region.</p><p><strong>Results: </strong>In 2023, China had an estimated 14.3 million HF cases, marking a significant 208.4% increase over the past three decades. Ischemic heart disease (IHD) has become the top cause of HF, compared with 1990, with hypertensive heart disease (HHD) at the top. Alongside chronic obstructive pulmonary disease (COPD), these three leading causes accounted for 77.4% of all HF cases. The burden of HF due to IHD and COPD exhibited distinct regional patterns and substantial disparities: regions in northern China exhibited notably higher age-standardized YLDs rates for HF due to IHD, while provinces in the western regions faced the highest burden from COPD. Six provinces with the highest tertile of YLDs rates in 2023 also experienced the most pronounced increases between 1990 and 2023.</p><p><strong>Conclusions: </strong>HF remains a significant public health challenge in China, with a marked increase in prevalence over the past three decades. The substantial regional variations highlight the need for targeted and region-specific public health strategies. Enhanced nationwide efforts should be made to reduce the geographical disparities in the burden of HF.</p>","PeriodicalId":18581,"journal":{"name":"Military Medical Research","volume":"12 1","pages":"65"},"PeriodicalIF":22.9,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12509353/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145258525","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Substantia nigra-related gene polymorphisms associated with acute antipsychotic-induced movement disorders.","authors":"Kenji Hashimoto","doi":"10.1186/s40779-025-00652-w","DOIUrl":"10.1186/s40779-025-00652-w","url":null,"abstract":"","PeriodicalId":18581,"journal":{"name":"Military Medical Research","volume":"12 1","pages":"62"},"PeriodicalIF":22.9,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12490055/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145206839","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Xenopax for the treatment of steroid-refractory acute graft-versus-host disease: the RELAX study.","authors":"Le-Qing Cao, Wen-Xuan Huo, Er-Lie Jiang, Yue-Wen Fu, Xiao-Jun Xu, Ping-Chong Lei, Ming-Feng Zhao, Zhi Chen, Shu-Xia Guo, Xiao-Bing Huang, Yan-Ming Zhang, Xian-Jing Wang, Guan-Chen Bai, Feng-Bo Jin, Qing-Sheng Li, Ming-Yang Deng, Hao Zhang, Xin-Feng Wang, Xiao-Jun Huang, Xiao-Dong Mo","doi":"10.1186/s40779-025-00640-0","DOIUrl":"10.1186/s40779-025-00640-0","url":null,"abstract":"<p><strong>Background: </strong>Steroid-refractory (SR) acute graft-versus-host disease (aGVHD) is the major cause of early mortality after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Xenopax, a novel and the only available humanized interleukin-2 (IL-2) receptor antagonist, has been approved as a category 2 biological product by the National Medical Products Administration. This study aims to evaluate the efficacy, safety, and prognostic factors of xenopax treatment for SR-aGVHD in real-world settings.</p><p><strong>Methods: </strong>This was a multicenter, retrospective analysis that included SR-aGVHD patients who received xenopax at 17 hospitals across China. The data were collected from the electronic medical records in transplant databases. The primary endpoint was the 28-day overall response rate (ORR), encompassing both partial and complete responses. This study also included independent historical SR-aGVHD cohorts treated with best available treatments (BATs, n = 1009) as controls.</p><p><strong>Results: </strong>In total, 172 SR-aGVHD patients were included in this study. Xenopax was administered either as monotherapy (n = 60) or in combination with other second-line treatments (n = 112). The ORR was 64.5% [95% confidence interval (CI) 57.3-71.7%] on day 28 and 82.6% (95% CI 76.9-88.3%) at any time after xenopax treatment. The 2-year probabilities of disease-free survival, overall survival, non-relapse mortality (NRM), and relapse after xenopax treatment were 57.0% (95% CI 49.9-65.0%), 68.0% (95% CI 61.4-75.4%), 24.2% (95% CI 18.0-30.9%), and 19.0% (95% CI 12.8-25.2%), respectively. The ORR and survival were similar between patients with and without prior second-line treatments. The conditioning regimen and human leukocyte antigen disparity did not impact the efficacy of xenopax treatment. According to the multivariate analysis, the presence of grade III-IV aGVHD did not adversely affect the therapeutic response or survival. Xenopax also showed some superiority over BATs in historical cohorts.</p><p><strong>Conclusions: </strong>Our real-world findings suggest that xenopax is an effective and safe treatment for SR-aGVHD.</p>","PeriodicalId":18581,"journal":{"name":"Military Medical Research","volume":"12 1","pages":"63"},"PeriodicalIF":22.9,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12477784/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145192077","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Are metformin-based combination approaches beneficial for non-small cell lung cancer: evidence from experimental and clinical studies.","authors":"Anita Thyagarajan, Vaibhav Gajjar, Ravi P Sahu","doi":"10.1186/s40779-025-00649-5","DOIUrl":"10.1186/s40779-025-00649-5","url":null,"abstract":"<p><p>Despite having multiple treatment options, the overall outcomes, including the survival rates of non-small cell lung cancer (NSCLC) patients, remain relatively low, indicating the need to explore new approaches to achieve improved therapeutic responses. To that end, repurposed drugs such as metformin have been evaluated against many cancer types, including NSCLC. Metformin, a widely used oral hypoglycemic drug for type 2 diabetes, exhibits anticancer properties and synergy with several standards of care agents. In this review, we provide a comprehensive overview of the role and anticancer mechanisms of metformin-based combination approaches for the treatment of NSCLC. We logically discussed the experimental evidence from the in vitro and in vivo studies utilizing metformin alone, and then its combination with chemotherapeutic agents, targeted therapy, and immunotherapy. We also present clinical trials that underscore the beneficial and adverse outcomes of metformin use in combination with targeted therapy and chemotherapeutic agents, and emphasize the limitations and challenges for the treatment of diabetic and non-diabetic NSCLC patients. It appears that, regardless of the diverse anticancer mechanisms of this biguanide, the benefits may be confined to a specific patient subgroup, which opens new avenues to be explored for NSCLC treatment.</p>","PeriodicalId":18581,"journal":{"name":"Military Medical Research","volume":"12 1","pages":"61"},"PeriodicalIF":22.9,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12455790/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145124944","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dual character of surface engineering on SN38 prodrug nano-assemblies: divergent effects on in vitro and in vivo behavior.","authors":"Ya-Qiao Li, Zhi-Yu Kuang, Bao-Yuan Zhang, Yan-Zhong Hao, Ling-Xiao Li, Jing-Xuan Zhang, Ya-Fan Xiao, Bo-Wen Zhang, Xian-Bao Shi, Xiao-Hui Pu, Zhong-Gui He, Bing-Jun Sun","doi":"10.1186/s40779-025-00648-6","DOIUrl":"10.1186/s40779-025-00648-6","url":null,"abstract":"<p><strong>Background: </strong>Surface engineering has emerged as a promising strategy to enhance the performance of nanomedicines. In particular, the PEGylation levels for chemotherapy drug 7-Ethyl-10-hydroxycamptothecin (SN38) prodrug nanoparticles (NPs) play a crucial role in determining their stability, drug release kinetics, cytotoxicity, cellular uptake, in vivo pharmacokinetics, biodistribution, and antitumor efficacy. The study aims to investigate the surface engineering for chemotherapy drugs, providing new solutions for improving their in vivo delivery.</p><p><strong>Methods: </strong>We systematically evaluated the effects of different PEGylation levels on NPs (W_DSPE-mPEG2k/W_prodrug; 0%, 5%, 20%, 40%, 60%, 80%, 100%, 150%, and 200% NPs) incorporated on SN38 prodrug NPs via surface engineering. Drug release was measured using high-performance liquid chromatography (HPLC), while cytotoxicity was assessed via the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Cellular uptake was accurately quantified using liquid chromatography-mass spectrometry (LC-MS). The in vivo pharmacokinetics of the NPs were evaluated in Sprague-Dawley rats, and the biodistribution and antitumor efficacy were assessed using a CT26 colon tumor-bearing BALB/c mice model. Additionally, we examined intestinal toxicity to evaluate the safety profile.</p><p><strong>Results: </strong>All the different PEGylation levels of SN38 prodrug NPs exhibited high drug loading (> 25%) but distinct behaviors depending on the PEGylation level. Low PEGylation (20%) led to poor colloidal stability, reduced cellular uptake, and rapid clearance by the mononuclear phagocyte system (MPS), resulting in unfavorable pharmacokinetics. Moderate PEGylation (80%) improved in vitro stability and uptake but remained insufficient to prevent rapid clearance in vivo. In contrast, high PEGylation (150%) significantly enhanced pharmacokinetic profiles, prolonged circulation, and increased tumor accumulation. The 150% NPs also showed superior antitumor efficacy without triggering anti-polyethylene glycol (PEG) immune responses or accelerated blood clearance (ABC) effects. Although high PEGylation slightly reduced cellular uptake, it conferred essential stability for systemic delivery, improving in vivo therapeutic outcomes.</p><p><strong>Conclusions: </strong>The high PEGylation (150% NPs) exhibited the best antitumor effect and the lowest degree of intestinal toxicity. Our findings underscore the critical impact of PEGylation level on enhancing the performance and safety of SN38 prodrug NPs.</p>","PeriodicalId":18581,"journal":{"name":"Military Medical Research","volume":"12 1","pages":"60"},"PeriodicalIF":22.9,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12452009/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145113676","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Camouflaged membrane-bridged radionuclide/Mn single-atom enzymes target lipid metabolism disruption to evoke antitumor immunity.","authors":"Meng-Die Yang, Chun-Yan Zhu, Gang Yang, Xiao-Yi Zhang, Yi Zhu, Miao Chen, Jia-Jia Zhang, Ling Bai, Shan-Shan Qin, Chao Ma, Fei Yu, Kun Zhang","doi":"10.1186/s40779-025-00647-7","DOIUrl":"10.1186/s40779-025-00647-7","url":null,"abstract":"<p><strong>Background: </strong>Lipid metabolic reprogramming has been increasingly recognized as a key factor contributing to tumor immune evasion, therapeutic resistance, and plasticity, which collectively compromise the efficacy of targeted radionuclide therapy (TRT). Overcoming the immunosuppressive and hypoxic tumor microenvironment (TME) while interfering with tumor lipid metabolism may offer a promising strategy to potentiate TRT outcomes.</p><p><strong>Methods: </strong>In this report, a radiopharmaceutical with multienzymatic catalysis activities is developed, wherein tumor cell membrane-coated manganese single-atom nanozymes (Mn/SAE@M) as supports deliver iodine-131 (¹³¹I) to the tumor. The Mn/SAE nanozyme core was synthesized in situ within hollow mesoporous zeolitic imidazolate frame-8 (ZIF-8) nanoparticles, then coated with homologous tumor cell membranes for targeted delivery and subsequently labeled with ¹³¹I using the Chloramine-T method. A series of in vitro and in vivo experiments was performed in non-small cell lung cancer (NSCLC) models to evaluate therapeutic efficacy and immune activation.</p><p><strong>Results: </strong>¹³¹I-Mn/SAE@M exhibited efficient tumor targeting and internalization mediated by membrane camouflage. Within the TME, the radiopharmaceuticals initiated abundant oxygen (O₂) release through catalase (CAT)-like catalysis, thereby mitigating a hypoxic microenvironment. In particular, it produced and enriched more reactive oxygen species (ROS) through oxidase (OXD)-, peroxidase (POD)-, and glutathione oxidase (GSHOx)-like catalytic processes. Importantly, ¹³¹I-Mn/SAE@M activated the cGAS-STING pathway, interfered with the lipid metabolic homeostasis of tumor cells, and induced ferroptosis, which is unraveled to take responsibility for the potentiated antitumor immunity. In bilateral NSCLC tumor-bearing mice, the treatment suppressed both the first and the second tumors, indicating the generation of systemic antitumor immune responses and immunological memory.</p><p><strong>Conclusions: </strong>Such SAE-based radiopharmaceuticals provide a candidate platform to elevate TRT efficiency, and the proof-of-concept rationale of disrupting lipid metabolic homeostasis through multienzyme-mimicking cascade reactions also provides a general avenue to improve TRT and synergistically magnify antitumor immunity.</p>","PeriodicalId":18581,"journal":{"name":"Military Medical Research","volume":"12 1","pages":"59"},"PeriodicalIF":22.9,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12447611/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145086383","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ALDH2 in autophagy and cell death: molecular mechanisms and implications for diseases.","authors":"Yu Duan, Ze-Chen Shan, Jiao-Jiao Pang, Yu-Guo Chen","doi":"10.1186/s40779-025-00646-8","DOIUrl":"10.1186/s40779-025-00646-8","url":null,"abstract":"<p><p>Aldehyde dehydrogenase (ALDH) 2, a mitochondrial enzyme, is the main acetaldehyde dehydrogenase involved in the scavenging of alcohol-derived acetaldehyde and endogenous aldehydes. The ALDH2^rs671 mutation affects 560 million East Asians and is closely related to an increased risk of various human diseases. In addition to its well-known function in detoxifying alcohol-derived acetaldehyde and endogenous aldehydes, ALDH2 is implicated in human health through its regulation of autophagic machinery and multiple cell death pathways (e.g., apoptosis, necroptosis, pyroptosis, ferroptosis, and NETosis). This review summarizes the current knowledge of ALDH2 and the regulatory mechanism through which ALDH2 regulates autophagy and cell death. In addition, we outline the potential role of ALDH2 in the regulation of autophagy and cell death during the occurrence and progression of human diseases, aiming to provide a novel theoretical framework for human disease treatment.</p>","PeriodicalId":18581,"journal":{"name":"Military Medical Research","volume":"12 1","pages":"58"},"PeriodicalIF":22.9,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12445042/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145086396","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}