Military Medical Research最新文献

{"title":"PM2.5 as a driver of human health disorders: insights from the regulated cell death pathways.","authors":"Mohammad Amin Khalilzad, Seyyed Maysam Mousavi Shoar, Amirhosein Abbasi, Mina Shafiei Falavarjani, Mitra Khalilzad, Amirhossein Naseri, Sajad Najafi","doi":"10.1016/j.mmr.2026.100046","DOIUrl":"10.1016/j.mmr.2026.100046","url":null,"abstract":"<p><p>Fine particulate matter (PM2.5) is a prevalent environmental pollutant that has been well established as a contributor to morbidity on a global scale. An increasing body of scientific evidence suggests that PM2.5 promotes various modes of regulated cell death (RCD), including apoptosis, necroptosis, pyroptosis, PANoptosis, ferroptosis, and autophagy-dependent cell death, as well as potentially cuproptosis, across a broad spectrum of human diseases. These interconnected pathways demonstrate how exposure to pollutants induces oxidative stress, mitochondrial dysfunction, endoplasmic reticulum stress (ERS), and inflammatory responses. Alterations in lysosomal permeability serve as a critical link, connecting environmental pollutants to health conditions. Importantly, dysregulation of RCD mechanisms is associated with exposure to PM2.5 and numerous health disorders, such as cardiovascular diseases (CVDs), neurological conditions, respiratory illnesses, renal and hepatic dysfunctions, reproductive health issues, and ocular diseases. Collectively, RCD functions as a central molecular framework through which PM2.5 exposure accelerates the progression of pathological conditions. This review synthesizes recent mechanistic insights, identifies promising therapeutic candidates, and highlights critical knowledge gaps. It offers a strategic framework to guide future research endeavors aimed at mitigating the impact of PM2.5-induced RCD in human diseases. Additionally, we will identify and explore the research gaps that need to be addressed to effectively translate preclinical PM2.5 studies into clinical trials. We will also provide a comprehensive overview that both highlights these gaps and offers pathways to bridge them.</p>","PeriodicalId":18581,"journal":{"name":"Military Medical Research","volume":"13 1","pages":"100046"},"PeriodicalIF":29.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13312019/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148352571","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":"Metabolic syndrome and risk of sepsis and sepsis-related mortality: evidence from two large prospective cohort studies.","authors":"Shao-Yu Liu, Shao-Kang Xu, Jing-Li Gao, Xiao-Ke Kong, Jian Shi, Ya Miao, Yi-Ting Tang, Bin Zhao, Fang Fang, Ai-Tian Wang, Shou-Ling Wu, Jia-Qi Huang, Ben Lu","doi":"10.1016/j.mmr.2026.100031","DOIUrl":"10.1016/j.mmr.2026.100031","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Metabolic syndrome (MetS) is characterized by chronic low-grade inflammation and immune dysregulation, which may increase susceptibility to sepsis. However, epidemiologic evidence remains limited. This study aimed to evaluate the association of MetS with the risk of sepsis and sepsis-related mortality.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;This study included 359,633 participants from the UK Biobank and 152,317 participants from the Kailuan Study. MetS was defined as the presence of ≥3 metabolic abnormalities. Multivariable Cox proportional hazards models were used to estimate hazard ratios (&lt;i&gt;HRs&lt;/i&gt;) and 95% confidence intervals (CIs) for the associations of MetS with risk of sepsis and 28-day mortality following sepsis. Stratified analyses were conducted to assess potential effect modification. In the UK Biobank, we further evaluated the dose-response relationship between the number of MetS components and sepsis outcomes, explored potential mediation by inflammatory and immune biomarkers, and investigated the joint effect of MetS and lifestyle; in the Kailuan Study, we further investigated the impact of MetS evolution on sepsis risk. Sensitivity analyses were performed to evaluate the robustness of the results.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;During a median follow-up of 13.7 years, 11,040 sepsis cases were identified in the UK Biobank, whereas 5672 cases were documented in the Kailuan Study during a median follow-up of 16.4 years. After multivariable adjustment, MetS was associated with higher risks of sepsis (&lt;i&gt;HR&lt;/i&gt;=1.55, 95% CI 1.49-1.61) and 28-day mortality following sepsis (&lt;i&gt;HR&lt;/i&gt;=1.51, 95% CI 1.37-1.65) in the UK Biobank; corresponding &lt;i&gt;HRs&lt;/i&gt; were 1.32 (95% CI 1.25-1.40) and 1.49 (95% CI 1.32-1.69) in the Kailuan Study, respectively (all &lt;i&gt;P&lt;/i&gt;&lt;0.001). These associations were generally consistent across stratified analyses. Moreover, the risk of sepsis outcomes increased with the number of MetS components and was partly mediated by inflammation. Compared with individuals free of MetS, individuals with MetS and an unfavorable lifestyle had substantially higher risks of sepsis (&lt;i&gt;HR&lt;/i&gt;=1.91, 95% CI 1.81-2.00) and 28-day mortality following sepsis (&lt;i&gt;HR&lt;/i&gt;=1.84, 95% CI 1.64-2.07), whereas those with MetS but a favorable lifestyle showed only a modestly increased risk of sepsis and no excess risk of 28-day mortality (&lt;i&gt;HR&lt;/i&gt;=1.18, 95% CI 1.09-1.28 and &lt;i&gt;HR&lt;/i&gt;=1.05, 95% CI 0.88-1.27, respectively). In analyses of MetS evolution, using individuals with persistently normal metabolic status as the reference, those with a persistent MetS demonstrated the highest risks of sepsis (&lt;i&gt;HR&lt;/i&gt;=1.46, 95% CI 1.32-1.61) and 28-day mortality following sepsis (&lt;i&gt;HR&lt;/i&gt;=1.88, 95% CI 1.50-2.35), followed by individuals with progressive MetS (&lt;i&gt;HR&lt;/i&gt;=1.17, 95% CI 1.05-1.31 and &lt;i&gt;HR&lt;/i&gt;=1.36, 95% CI 1.04-1.77, respectively), whereas those who recovered from MetS did not show a significantly increased risk (&lt;i","PeriodicalId":18581,"journal":{"name":"Military Medical Research","volume":"13 1","pages":"100031"},"PeriodicalIF":29.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13138178/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147840131","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":"Real-time multicenter semantic segmentation for laparoscopic gastrectomy: development, external validation and operating room deployment of an AI navigation system.","authors":"Ke-Cheng Zhang, Di Wu, Can-Rong Lu, Zhi Qiao, Wen-Tong Xu, Feng-Lin Liu, Jing-Yu Deng, Li Yang, Lei Guo, Tian-Yu Xie","doi":"10.1016/j.mmr.2026.100040","DOIUrl":"10.1016/j.mmr.2026.100040","url":null,"abstract":"<p><strong>Background: </strong>Laparoscopic gastrectomy is technically demanding and errors often arise from limited situational awareness. Artificial intelligence (AI)-based computer vision may enhance intraoperative recognition of instruments and anatomy, but evidence for generalizable, real-time deployment remains limited.</p><p><strong>Methods: </strong>We conducted a multicenter study using laparoscopic gastrectomy videos from 4 tertiary hospitals. Data were split by institution into training, internal test, and external validation sets. A You Only Look Once version 10 (YOLOv10)-based model was developed to recognize 18 categories (11 instruments and 7 organs) and integrated into a lightweight user interface for bedside use. Mean average precision at Intersection over Union (IoU) 0.50 (mAP@50) and AP@[0.50-0.95] for boxes and masks, recall, and F1 score were calculated. The feasibility of live operating-room deployment was assessed. Surgeon cognitive workload was assessed using the National Aeronautics and Space Administration Task Load Index (NASA-TLX), and system usability was evaluated with the System Usability Scale (SUS).</p><p><strong>Results: </strong>The training set comprised 4308 frames (41,066 labels); the internal testing set, 1803 frames (17,211 labels); and the external validation set, 721 frames (6685 labels). Training performance reached box precision 0.896, recall 0.891, mAP@50 0.937, and AP@[0.50-0.95] 0.846; mask AP@[0.50-0.95] was 0.809. On the internal testing set, box AP@[0.50-0.95] was 0.670 and mask AP@[0.50-0.95] 0.642. External validation achieved box precision 0.798, recall 0.773, F1 score 0.785, mAP@50 0.832, and AP@[0.50-0.95] 0.684; mask mAP@50 was 0.836 and AP@[0.50-0.95] 0.658. High-performing classes included stapler, ultrasonic scalpel, and forceps, whereas omentum and pancreas were relatively lower. The system operated in real time during laparoscopic gastrectomy on a laptop-grade GPU, providing on-demand overlays without workflow disruption. The NASA-TLX score was 26.72±6.51, indicating low cognitive burden, and the SUS score was 78.33±5.20, demonstrating good usability.</p><p><strong>Conclusions: </strong>We present development, external validation, and live deployment of a real-time AI navigation system for laparoscopic gastrectomy across multiple centers. The model demonstrated robust detection and segmentation of instruments and organs and was feasible for bedside use. Prospective trials are warranted to evaluate effects on intraoperative safety, efficiency, and training.</p>","PeriodicalId":18581,"journal":{"name":"Military Medical Research","volume":"13 1","pages":"100040"},"PeriodicalIF":29.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13440269/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148679202","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":"Virtual medicine: medical AI in human health and diseases.","authors":"Chen Zhang, Fu-Xiao Wang, Xuan Tang, Ji-Long Li, Ning Ding, Yang Hong, Pei-Ran Song, Long Bai, Jia-Can Su","doi":"10.1016/j.mmr.2026.100012","DOIUrl":"10.1016/j.mmr.2026.100012","url":null,"abstract":"<p><p>The evolution of medicine has progressed through distinct ages: from empirical observation and evidence-based practice to the current era of precision medicine. However, traditional healthcare paradigms remain constrained by data fragmentation, scalability limits, and the overwhelming complexity of multi-omics integration. In the rapid explosion of artificial intelligence (AI), a transformative paradigm is emerging. This review introduces the concept of \"Virtual Medicine\", which is defined as a comprehensive ecosystem of AI-empowered medical practice that transcends physical limitations. This review systematically summarizes the technological foundations, historical evolution, and core applications of AI in medicine, including electronic health records (EHRs) analysis, medical imaging, multimodal diagnostics, drug discovery, precision oncology, intelligent surgery, and clinical decision support systems. It further highlights the role of medical AI in health management, public health surveillance, and healthcare delivery in resource-limited settings. Special attention is given to the transformative emergence of large language models (LLMs), such as medical large language models (MedLLM) and generative pre-trained transformer (GPT) architectures, emphasizing their potential to revolutionize virtual medical interaction, clinical reasoning, and documentation. Despite these advances, significant challenges remain regarding model transparency, data bias, fairness, and patient privacy. Overcoming these limitations necessitates standardized evaluation frameworks, interpretable algorithm designs, and strengthened privacy protections. Ultimately, these efforts aim to foster a trustworthy and equitable future for virtual medicine.</p>","PeriodicalId":18581,"journal":{"name":"Military Medical Research","volume":"13 1","pages":"100012"},"PeriodicalIF":29.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13127130/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147816646","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":"Managing acute altitude illness.","authors":"Martin Burtscher, Johannes Burtscher","doi":"10.1016/j.mmr.2026.100068","DOIUrl":"https://doi.org/10.1016/j.mmr.2026.100068","url":null,"abstract":"","PeriodicalId":18581,"journal":{"name":"Military Medical Research","volume":"13 1","pages":"100068"},"PeriodicalIF":29.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13651665/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149167094","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":"Engineering of functional auditory neurons from human induced pluripotent stem cells.","authors":"Minjin Jeong, Lucas G Vattino, Maja Djurisic, Kevin P Rose, Hiroshi Hyakusoku, Svetolik Spasic, Xiao-Jie Ma, Hiroaki Mohri, Ronna Hertzano, Anne E Takesian, Konstantina M Stankovic","doi":"10.1016/j.mmr.2026.100008","DOIUrl":"10.1016/j.mmr.2026.100008","url":null,"abstract":"<p><strong>Background: </strong>Spiral ganglion neurons (SGNs) relay auditory sensory information from the cochlea to the brain. Their loss results in permanent hearing impairment in humans due to their limited regenerative capacity. Progress in hearing restoration has been constrained by the inaccessibility of human inner ear tissue and challenges in generating functionally mature human SGN-like neurons from stem cells <i>in vitro</i>.</p><p><strong>Methods: </strong>To generate human SGN-like neurons from human induced pluripotent stem cells (hiPSCs), we recapitulated key signaling pathways involved in human inner ear development. On day (D) 11 of differentiation, nerve growth factor receptor-positive cells (precursors of pre-placodal ectoderm and neural crest) were isolated using magnetic sorting. From D18 to D25, cultures were treated with sonic hedgehogs to induce otic neural progenitors. Neuronal maturation was subsequently promoted by a cocktail of brain-derived neurotrophic factor, neurotrophin-3, and insulin-like growth factor-1, which supports SGN development. Cellular identity and functionality were assessed using single-cell RNA sequencing, immunocytochemistry, whole-cell patch-clamp electrophysiology, co-culture assays, and calcium ion (Ca²⁺) imaging.</p><p><strong>Results: </strong>hiPSC-derived SGN-like neurons exhibited morphological, molecular, electrophysiological, and functional characteristics of SGNs <i>in vivo</i>. Neurons acquired bipolar morphology and were wrapped by glial cells. Transcriptomic analysis revealed that SGN-like neurons were distinct from other neuronal lineages and showed similarity to type I and type II SGNs based on expression of synaptic and intrinsic excitability-related genes. Electrophysiological recordings revealed progressive hyperpolarization of resting membrane potential and emergence of overshooting action potentials, consistent with neuronal maturation. In co-culture systems, human SGN-like neurons formed functional synaptic connections with mouse cochlear hair cells and cochlear nucleus neurons, evidenced by Ca²⁺ transients and induction of the immediate early gene <i>c-Fos</i>.</p><p><strong>Conclusions: </strong>This study reports a robust and reproducible protocol for generating human SGN-like neurons from hiPSCs, providing a versatile platform for studying human auditory development, disease modeling, drug screening, and cell-based therapies for hearing restoration.</p>","PeriodicalId":18581,"journal":{"name":"Military Medical Research","volume":"13 1","pages":"100008"},"PeriodicalIF":29.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13127150/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147817435","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":"ROS-responsive drug delivery systems for chronic wound healing: advances, challenges, and translational perspectives.","authors":"Yuan Xiong, Qi-Peng Wu, Han Wang, Mohammad-Ali Shahbazi, Bo-Bin Mi","doi":"10.1016/j.mmr.2026.100019","DOIUrl":"10.1016/j.mmr.2026.100019","url":null,"abstract":"<p><p>Chronic wounds pose a substantial global health burden, due to the high incidence and recurrence rates, and associated morbidity. Excessive and sustained production of reactive oxygen species (ROS) is a hallmark of the chronic wound microenvironment, ultimately stalling the repair process. The pathological accumulation of ROS in chronic wounds has motivated the development of ROS-responsive drug delivery systems (DDS), which show considerable potential in improving wound healing outcomes. In this review, we provide a comprehensive overview of the advances in ROS-responsive DDS for chronic wound healing, summarizing the design principles, material chemistry, and underlying ROS-triggered functional mechanisms. Key translational challenges are discussed, including material biocompatibility, stability in protease- and ROS-rich wound exudates, manufacturing scalability, and regulatory considerations. Finally, we outline future perspectives, emphasizing the integration of multi-responsive functionalities, real-time ROS monitoring, and advanced biomaterial engineering to accelerate clinical translation. By aligning therapeutic release with the dynamic redox status of chronic wounds, ROS-responsive DDS holds considerable potential to redefine precision therapy for wound management.</p>","PeriodicalId":18581,"journal":{"name":"Military Medical Research","volume":"13 1","pages":"100019"},"PeriodicalIF":29.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13127131/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147817449","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":"A roadmap for heart-liver co-management in MASLD.","authors":"Xiao-Dong Zhou, Nicholas W S Chew, Ming-Hua Zheng","doi":"10.1016/j.mmr.2026.100061","DOIUrl":"https://doi.org/10.1016/j.mmr.2026.100061","url":null,"abstract":"","PeriodicalId":18581,"journal":{"name":"Military Medical Research","volume":"13 1","pages":"100061"},"PeriodicalIF":29.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13487889/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148795245","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":"RIMKLA promotes hypertension by activating PKM2 to trigger VSMC phenotype switch.","authors":"Rui Xiang, Wen-Jun Liu, Xin-Rui Zhang, Han Yan, Xin Li, Song Hou, Cheng-Qing Hu, Yun-Tao Hu, Ru-Feng Ma, Jing Li, Yu-Jing Chi, Qing-Hua Cui, Zhen-Zhen Chen, Bin Geng, Ji-Chun Yang","doi":"10.1016/j.mmr.2026.100056","DOIUrl":"10.1016/j.mmr.2026.100056","url":null,"abstract":"<p><strong>Background: </strong>Hypertension affects around one billion adults worldwide, with abnormal glucose metabolism and vascular smooth muscle cell (VSMC) phenotype switch playing crucial roles in its pathogenesis. Pyruvate kinase M2 (PKM2) is a key glycolytic enzyme, but its regulation and roles in VSMC phenotype switch and hypertension are unknown. Using the Gene Importance Calculator (GIC) to predict gene essentiality, we identified ribosomal modification protein rimK-like family member A (RIMKLA) as a highly relevant gene and explored its regulatory contributions to hypertension.</p><p><strong>Methods: </strong>Internal mammary arteries from patients with hypertension and normotension, as well as arteries from angiotensin II (Ang II)-induced hypertensive mice, salt-sensitive hypertensive Dahl/SS rats, and spontaneously hypertensive rats, were analyzed in this study. Adenoviruses and adeno-associated viruses were used for ex vivo and in vivo gene overexpression. VSMC-specific RIMKLA or PKM2 knockout mice were generated using the Cre-Loxp system. Arterial tension was measured by wire myography, and blood pressure was assessed by the tail-cuff method and remote radio-telemetry. Protein-protein interactions were determined by co-immunoprecipitation with mass spectrometry. Non-targeted metabolomics, in vitro phosphorylation, adenosine triphosphate (ATP), reactive oxygen species (ROS), and cytoplasmic calcium assays were performed to identify the signaling axis involved.</p><p><strong>Results: </strong>RIMKLA expression was increased in the medial layer of the internal mammary arteries of patients with hypertension, as well as in hypertensive rat and mouse arteries. RIMKLA overexpression in the mesenteric arteries of Sprague-Dawley rats significantly increased vessel contractility. VSMC-specific RIMKLA overexpression increased arterial contractility and blood pressure in mice. VSMC-specific RIMKLA deletion attenuated Ang II-induced hypertension in mice. Mechanistically, we identified RIMKLA as a scaffold protein that binds to protein-tyrosine phosphatase 1B (PTP1B) and PKM2. RIMKLA phosphorylated PTP1B at tyrosine (Tyr)66, leading to PKM2 dephosphorylation and activation at Tyr105. Once activated, PKM2 enhanced glucose metabolism, increased ROS production, and boosted ATP secretion, driving VSMC phenotype switch. RIMKLA-induced vasoconstriction and hypertension were reversed by VSMC-specific PKM2 deletion. Additionally, a PKM2 inhibitor reduced arterial contractility and blood pressure.</p><p><strong>Conclusions: </strong>RIMKLA functioned as a scaffold protein kinase, recruiting both PTP1B and PKM2, and orchestrating PTP1B phosphorylation and its subsequent recruitment to activate PKM2. These findings position RIMKLA as a key regulator of PKM2 activation, promoting VSMC phenotype switch and contributing to hypertension.</p>","PeriodicalId":18581,"journal":{"name":"Military Medical Research","volume":"13 1","pages":"100056"},"PeriodicalIF":29.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13420487/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148631073","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":"A roadmap for medical large language models: a review of foundations, applications, and challenges.","authors":"Yu-Yang Sha, Li Yu, Ze-Hui Lin, Amandeep Kaur, Yan-Yan Lou, Shivanand S Gornale, Tian-Yu Zhang, Ling Shing Wong, Zhi-Wen Wang, Yan Yan, Xian-Bin Zhang, Rui Hong, Ka Li, Sio Kei Im, Paulo de Carvalho, Tao Tan, Ke-Feng Li","doi":"10.1016/j.mmr.2026.100050","DOIUrl":"10.1016/j.mmr.2026.100050","url":null,"abstract":"<p><p>Medical large language models (Med-LLMs) have shown considerable promise across a broad range of clinical tasks, including decision support, medical documentation, patient communication, multimodal analysis, and telemedicine. Their rapid development has generated growing interest in how large language models (LLMs) may support healthcare practice, while also raising important questions about reliability, clinical validity, and safe deployment. This review provides a structured overview of recent progress in Med-LLMs by examining their major application areas, key challenges, and emerging future directions. Current evidence shows that the clinical usefulness of Med-LLMs cannot be judged by model performance alone. Their value in practice depends on whether they are supported by reliable evidence, remain consistent with current medical knowledge, and can be integrated into clinical workflows. Important challenges remain in evaluation, safety, knowledge updating, and real-world deployment. These issues reflect a gap between performance in controlled settings and clinical practice. Future progress will require stronger clinical validation, better alignment with medical practice, and more careful deployment across different settings. The clinical impact of Med-LLMs will depend on whether they can be used as reliable tools in clinical care.</p>","PeriodicalId":18581,"journal":{"name":"Military Medical Research","volume":"13 1","pages":"100050"},"PeriodicalIF":29.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13321024/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148368509","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}