Military Medical Research最新文献

{"title":"Immune microenvironment dynamics in pregnant patients with concomitant autoimmune diseases: mechanisms, challenges, and clinical significance.","authors":"Zi-Jun Ma, Jun Chen, Chen-Xi Yang, Shun-Ping Lin, Quan Gong, Zachary Braunstein, Ying-Ying Wei, Xiao-Quan Rao, Ji-Xin Zhong","doi":"10.1016/j.mmr.2026.100015","DOIUrl":"10.1016/j.mmr.2026.100015","url":null,"abstract":"<p><p>Throughout pregnancy, the immune microenvironment undergoes dynamic changes in patients with concomitant autoimmune diseases (AIDs). These alterations not only affect disease activity and clinical manifestations, but also play a pivotal role in sustaining maternal-fetal immune tolerance and pregnancy outcomes. Extensive preclinical studies have elucidated the mechanisms of immune regulation in normal pregnancy, whereas the dynamic immune changes in pregnancies complicated by AIDs remain poorly understood. Recent studies have revealed significant variations in immune responses to pregnancy among individuals with AIDs, which may contribute to distinct patterns of AIDs flares during this period. Despite substantial progress in immunology and reproductive medicine, comprehensive reviews addressing the dynamic changes in the immune microenvironment during pregnancy in the context of AIDs are lacking. In this review, we summarize existing knowledge and incorporate recent multidisciplinary findings, focusing on the dynamic changes in systemic immune adaptation and maternal-fetal immune interactions in the context of AIDs during pregnancy. We emphasize the clinical significance of these immune dynamics for optimizing management and therapeutic strategies. Additionally, we propose new perspectives and provide recommendations to guide future research and the development of personalized treatment approaches.</p>","PeriodicalId":18581,"journal":{"name":"Military Medical Research","volume":"13 1","pages":"100015"},"PeriodicalIF":29.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13127146/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147817421","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":"Global variations, temporal trends, and socioeconomic inequalities in the burden of malignant brain and central nervous system tumors: a population-based systematic analysis of GLOBOCAN 2024.","authors":"Shao-Yuan Lei, Yue Wu, Hong-Jun Liu, Xiao-Feng Jia, Yan-Su Guo, Rong-Shou Zheng","doi":"10.1016/j.mmr.2026.100072","DOIUrl":"10.1016/j.mmr.2026.100072","url":null,"abstract":"<p><strong>Background: </strong>Previous assessments of the burden of malignant brain and central nervous system (CNS) tumors have mainly focused on incidence and mortality rates, with less emphasis on lifetime risks. This study aimed to estimate the incidence, mortality, and lifetime risk of developing or dying from brain and CNS tumors and the impact of socioeconomic inequality across countries.</p><p><strong>Methods: </strong>Data on brain and CNS tumors were obtained from GLOBOCAN 2024 and the Cancer Incidence in Five Continents Plus (CI5plus) database, population and death data were sourced from World Population Prospects 2024. Lifetime risk estimation was conducted using the life table method adjusted for multiple primaries. We assessed trends in brain and CNS tumors incidence, lifetime risks, and histological subtypes during 2003 to 2017. The association between the human development index (HDI) and lifetime risks was assessed using generalized linear models.</p><p><strong>Results: </strong>In 2024, the age-standardized incidence and mortality rates for brain and CNS tumors were 3.37 and 2.51 per 100,000 population, respectively. The estimated global lifetime risk of developing or dying from brain and CNS tumors, from birth to death was 0.39% and 0.32%, respectively. Significant variations in lifetime risks were observed among countries and regions, as well as across different HDI levels. The lifetime risk of developing brain and CNS tumors among countries with a low, medium, high, and very high HDI was 0.16%, 0.19%, 0.45%, and 0.59%, respectively; the risks of dying from the disease in these categories were 0.14%, 0.17%, 0.34%, and 0.48%, respectively. Histological subtypes of brain and CNS tumors showed large discrepancies among age groups and countries. The most frequently diagnosed histological type was astrocytic tumors.</p><p><strong>Conclusions: </strong>We found significant heterogeneity in the incidence, mortality, and lifetime risk of brain and CNS tumors among geographic and HDI levels, which potentially reflects disparities in medical resource allocation and genetic exposures.</p>","PeriodicalId":18581,"journal":{"name":"Military Medical Research","volume":"13 1","pages":"100072"},"PeriodicalIF":29.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13676099/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149216522","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":"Scalable bioreactor manufacturing of iPSC-derived megakaryocytes with Proanthocyanidin A supplementation: a strategic platform for military blood supply resilience.","authors":"Rabea Dettmer, Alice Rovai, Willem Wolkers, Rainer Blasczyk, Constanca Figueiredo","doi":"10.1016/j.mmr.2026.100057","DOIUrl":"https://doi.org/10.1016/j.mmr.2026.100057","url":null,"abstract":"","PeriodicalId":18581,"journal":{"name":"Military Medical Research","volume":"13 1","pages":"100057"},"PeriodicalIF":29.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13470163/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148765332","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":"Non-invasive evaluation of muscle invasion and survival prognosis in bladder cancer using enhanced CT-based deep learning radiomics: a multi-center real-world cohort study.","authors":"Yun-Bo He, Jiao Hu, Zhi Liu, Zi-Cheng Xiao, Jin-Hui Liu, Hai-Su Liang, Wen-Zhi Deng, Zhi-Wei Li, Jun Zhang, Jia-Quan Long, Ning Gao, Bin Huang, Xi Guo, Zhen-Yu Ou, Jin-Bo Chen, Pei-Hua Liu, Min-Feng Chen, Hui-Huang Li, Rui-Zhe Wang, Xiao Guan, Shi-Yu Tong, Yang-Le Li, Wei He, Yan-Hua Zhao, Zhi-Yong Cai, Yu Gan, Cheng Zhao, Yu Cui, Yuan-Qing Dai, Yi Cai, Zhen-Yu Nie, Wei-Min Zhou, Bo-Han Zhou, Ming-Hui Hu, Ben-Yi Fan, Ding-Shan Deng, Xiong-Bing Zu","doi":"10.1016/j.mmr.2026.100001","DOIUrl":"10.1016/j.mmr.2026.100001","url":null,"abstract":"<p><strong>Background: </strong>Bladder cancer (BLCA) is a prevalent malignancy characterized by high recurrence and poor prognosis, particularly muscle-invasive bladder cancer (MIBC). Histopathology, the gold standard for assessing muscle invasion, often suffers from sampling errors and operator dependency, underscoring the need for non-invasive, accurate preoperative assessment methods. This study aimed to develop and validate a hybrid artificial intelligence (AI) model based on computed tomography (CT) radiomics and deep learning (DL) to predict MIBC and overall survival (OS) preoperatively in BLCA patients.</p><p><strong>Methods: </strong>A total of 1370 patients from 6 academic medical centers were retrospectively included. Preoperative contrast-enhanced CT scans were analyzed to extract handcrafted radiomic features using PyRadiomics and DL features using ResNet101, followed by machine learning (ML)-based modeling for prediction. A hybrid model combining radiomic and DL features was constructed and validated in internal and external cohorts. Model performance was evaluated using metrics such as the area under the curve (AUC) and Cox proportional hazards analysis for OS prediction.</p><p><strong>Results: </strong>The DL radiomics nomogram (DLRN) model demonstrated superior diagnostic performance, achieving an AUC of 0.807 in the internal validation cohort and 0.783 in the external multi-center validation cohort for predicting muscle invasion. The DLRN generated an imaging-derived risk score (DLRN score), which was subsequently incorporated as one covariate into a multivariable Cox proportional hazards model together with clinicopathological variables to evaluate OS. Using this approach, patients were effectively stratified into high- and low-risk groups for OS, showing robust generalizability across diverse clinical settings. AI-assisted diagnostics significantly improved the sensitivity and accuracy of urologists, particularly among less experienced clinicians.</p><p><strong>Conclusion: </strong>The DLRN model provides a reliable, non-invasive tool for preoperative assessment of muscle invasion and prognosis in BLCA. Addressing histopathology limitations, it offers valuable insights for personalized treatment strategies, paving the way for precision oncology in real-world clinical applications.</p>","PeriodicalId":18581,"journal":{"name":"Military Medical Research","volume":"13 1","pages":"100001"},"PeriodicalIF":29.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13273457/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148277986","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":"<i>Gadd45a</i> knockout alleviates cisplatin-induced hearing loss by inhibiting CXCL family protein expression.","authors":"Wei-Long Wang, Sheng-Yu Zou, Dan-Qi Wang, Yue Liu, Jia-Wen Li, Fang-Zi Ke, Si-Hui Wen, Bo-Wen Xu, Kun Lin, Chun-Jiang Wei, Xiao-Long Fu, Qiao-Jun Fang, Xiao-Xiang Xu, Xiong Chen, Zu-Hong He","doi":"10.1016/j.mmr.2026.100063","DOIUrl":"10.1016/j.mmr.2026.100063","url":null,"abstract":"<p><strong>Background: </strong>Cisplatin is a widely used chemotherapeutic agent, but its clinical application is limited by serious ototoxic side effects, including hearing loss, tinnitus, and vertigo. Inflammation is now recognized as a significant contributor to cisplatin-induced hearing loss, but the upstream regulators remain largely undefined. This study aimed to identify novel regulators of cisplatin-induced ototoxicity through CRISPR-Cas9 screening and to determine the role of growth arrest and DNA damage-inducible alpha (GADD45A) in cochlear inflammation and hearing loss.</p><p><strong>Methods: </strong>To identify upstream regulators of cisplatin-induced ototoxicity, a CRISPR-Cas9-based loss-of-function screen was first performed in OC1 cells. Following the identification of <i>Gadd45a</i> as a candidate gene, its effects on cisplatin-induced cytotoxicity were evaluated using cell viability assays, flow cytometry, and TUNEL staining. Integrated transcriptomic and proteomic analyses were subsequently conducted to elucidate the downstream molecular mechanisms. Finally, the protective role of <i>Gadd45a</i> inhibition was validated <i>in vivo</i> through siRNA delivery into the posterior semicircular canal and in <i>Gadd45a</i> conditional knockout (cKO) mice.</p><p><strong>Results: </strong><i>Gadd45a</i> knockout significantly inhibited cisplatin-induced cell death in the OC1 cell line while simultaneously enhancing autophagy signaling. Transcriptomic profiling revealed a marked downregulation of the expression of C-X-C motif chemokine ligand (CXCL) family cytokines following <i>Gadd45a</i> loss, which was further supported by proteomic analysis of culture supernatants. Mechanistically, <i>Gadd45a</i> knockout specifically inhibited nuclear factor κB subunit 1 (NF-κB1) but not RELA proto-oncogene, NF-κB subunit (RELA). Immunofluorescence staining demonstrated that <i>Gadd45a</i> knockout inhibited the nuclear translocation of the NF-κB1 protein, and subsequent studies revealed that the NF-κB1 protein was degraded through the lysosomal pathway. <i>In vivo</i>, both si-<i>Gadd45a</i> injection into the semicircular canal and the knockout of <i>Gadd45a</i> effectively attenuated cisplatin-induced ototoxicity.</p><p><strong>Conclusions: </strong>This study identifies GADD45A as a key regulator of cisplatin ototoxicity and links the balance between apoptosis and autophagy with NF-κB1-CXCL-mediated inflammation. Targeted inhibition of GADD45A signaling may represent a promising therapeutic strategy to prevent hearing loss in patients receiving cisplatin chemotherapy.</p>","PeriodicalId":18581,"journal":{"name":"Military Medical Research","volume":"13 1","pages":"100063"},"PeriodicalIF":29.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13499120/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148795259","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 call for further evidence regarding the association between metabolic syndrome, sepsis, and sepsis-related death.","authors":"Shamas Mohammed","doi":"10.1016/j.mmr.2026.100069","DOIUrl":"https://doi.org/10.1016/j.mmr.2026.100069","url":null,"abstract":"","PeriodicalId":18581,"journal":{"name":"Military Medical Research","volume":"13 1","pages":"100069"},"PeriodicalIF":29.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13651663/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149166593","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":"Glycosylation as a design component of biomaterials in implant design.","authors":"Abhay Pandit","doi":"10.1016/j.mmr.2026.100070","DOIUrl":"https://doi.org/10.1016/j.mmr.2026.100070","url":null,"abstract":"<p><p>An implanted medical device is specified in detail through its bulk and surface chemistry, mechanical properties, architecture, degradation kinetics, and surface ligands, whereas the host receiving it is specified hardly at all. Much of what the host presents at that interface is glycan, and glycan-mediated recognition acts through defined receptor families, including the Siglecs, the C-type lectin receptors, the galectins, and the regulators of complement. The host glycome is not fixed. It is assembled combinatorially, varies with age, metabolic state, and inflammation, differs between recipients, and is altered systematically in disease. Those alterations are measurable before implantation and are resolved both regionally and temporally, <i>N</i>-glycosylation differing region by region within the human Parkinsonian nigrostriatum and <i>α</i>-2,6-sialylation rising from 19.5% of the <i>N</i>-glycan pool in healthy intervertebral disc to 23%-24% in degenerated tissue. This Perspective argues that glycosylation should be specified as a component of the biomaterials from which devices are built. Because a diseased glycome is typically altered in several respects at once, a design need not address all of it, and a single motif may be selected where it is quantitatively dominant, mechanistically implicated, and chemically tractable. Three propositions follow: host glycophenotype is a measurable covariate of outcome and a basis for patient stratification; glycan structure, sulfation, and presentation density are specifiable material properties, with sulfation tunable independently of backbone; the analytical methods required to control a glycan attribute are established, so that the obstacle is convention rather than capability.</p>","PeriodicalId":18581,"journal":{"name":"Military Medical Research","volume":"13 1","pages":"100070"},"PeriodicalIF":29.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13651666/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149169733","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":"Engineered exosomes for diabetic foot ulcers: lessons learned, challenges remain.","authors":"Hyun-Do Jung","doi":"10.1016/j.mmr.2026.100022","DOIUrl":"10.1016/j.mmr.2026.100022","url":null,"abstract":"","PeriodicalId":18581,"journal":{"name":"Military Medical Research","volume":"13 1","pages":"100022"},"PeriodicalIF":29.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13127148/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147817323","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":"From nerve to bone: a tale of autonomic nervous system, bone cells, and beyond.","authors":"Wei-Jun Huang, Yong-Kang Hu, Heng-Zhen Li, Wen-Hao Lu, Guang Yang, Bing-Zhou Ji, Wen-Feng Xiao, Yu-Sheng Li","doi":"10.1016/j.mmr.2026.100051","DOIUrl":"10.1016/j.mmr.2026.100051","url":null,"abstract":"<p><p>Bone is a multifunctional organ essential for structural support, protection, hematopoiesis, and endocrine regulation. Emerging research increasingly highlights the pivotal role of the nervous system in bone metabolism, repair, and musculoskeletal disease progression, particularly the autonomic nervous system (ANS), which precisely regulates bone tissue cells via sympathetic and parasympathetic pathways. The ANS regulates the activity of mesenchymal stem cells (MSCs), osteoblasts, osteoclasts, chondrocytes, and nucleus pulposus cells (NPCs) via neurotransmitters such as norepinephrine (NE), acetylcholine (ACh), neuropeptide Y (NPY), and vasoactive intestinal peptide (VIP), thereby modulating core pathological processes in bone-related disorders including osteoporosis (OP), osteoarthritis (OA), intervertebral disc degeneration (IVDD), and traumatic fractures. Targeted neuromodulation is emerging as a promising therapeutic strategy for musculoskeletal disorders. This review aims to summarize the regulatory roles of the ANS in bone cell metabolism and bone-related pathologies and to evaluate current ANS-bone axis-based interventions to promote skeletal health and alleviate the burden of musculoskeletal diseases.</p>","PeriodicalId":18581,"journal":{"name":"Military Medical Research","volume":"13 1","pages":"100051"},"PeriodicalIF":29.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13330628/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148391318","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 roles, mechanisms, and therapeutic implications of glucocorticoids in glucose and lipid metabolism.","authors":"Qiu-Yu Xu, Jie Zhang, Xin-Jian Wan, Ling Wu, Ji-Chun Yang, Yan Lu","doi":"10.1016/j.mmr.2026.100037","DOIUrl":"10.1016/j.mmr.2026.100037","url":null,"abstract":"<p><p>Glucocorticoids (GCs), steroid hormones synthesized and secreted by the adrenal cortex, have been the subject of intensive scientific investigation for over eight decades due to their critical roles in physiological and pathological processes. The systemic secretion, bioavailability, and tissue-specific concentrations of GCs are strictly orchestrated by the hypothalamic-pituitary-adrenal axis, serum corticosteroid-binding globulin levels, and the enzymatic activation of 11β-hydroxysteroid dehydrogenase type 1 and 2 (11β-HSD1 and 11β-HSD2). As pivotal metabolic messengers, GCs signal through binding to glucocorticoid receptors (GR) to maintain metabolic homeostasis by modulating the transcriptional landscape of genes central to glucose and lipid metabolism. Any imbalance in GC levels, whether excess or deficiency, leads to the development of diverse metabolic disorders. Elucidating the underlying mechanisms of this metabolic regulation remains a primary objective of contemporary research. This review summarizes landmark discoveries and focuses on the metabolic impact and dysfunction of glucocorticoids, aiming to establish a robust foundation for the development of optimized therapeutic interventions for patients with metabolic diseases.</p>","PeriodicalId":18581,"journal":{"name":"Military Medical Research","volume":"13 1","pages":"100037"},"PeriodicalIF":29.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13200049/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148032656","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}