Military Medical Research最新文献

{"title":"Octopus-inspired engineered bacteria with a plug-and-play surface display system achieves enhanced tumor-specific colonization and antitumor immunity.","authors":"Le-Yang Wu, Jia-Hui Qiu, Xin-Yue Qiao, Lin Li, Li-Yuan Qiao, Chen-Yang Li, Ying Sun, Shu-Hui Zhang, Zeng-Zheng Du, Xiao-Yao Chang, Cheng Cheng, Bo-Hao Wang, Yi-Han Xiao, Lin Lin, Zi-Chun Hua","doi":"10.1016/j.mmr.2026.100030","DOIUrl":"10.1016/j.mmr.2026.100030","url":null,"abstract":"<p><strong>Background: </strong>Bacteria-mediated cancer therapy leverages bacteria to modulate the tumor immune microenvironment and deliver therapeutics. However, its clinical application is limited by toxicity, off-target effects, and uncontrolled drug release. Improving tumor targeting and precise payload delivery through rational bacterial engineering is essential for increasing efficacy and safety.</p><p><strong>Methods: </strong>An attenuated <i>Salmonella</i> Δ<i>htrA</i>::<i>luxI</i>-VNP20009 strain expressing OmpA-SpyTag (AISI-ST) was constructed for the modular surface conjugation of SpyCatcherΔ (SC)-fused quadruple arginine-glycine-aspartic acid (RGD) peptides (named AISI-ST/SC-RGD×4) and for building biointerfaces for enhanced tumor adhesion via RGD-mediated integrin αvβ3 interactions. The tumor-bearing mice received intravenous injections of AISI-ST/SC-RGD×4, and their biodistribution was analyzed using bioluminescence imaging and colony-forming unit (CFU) counts. Quorum-sensing (QS)-regulated high-temperature requirement A (HtrA) and anti-programmed cell death protein 1 (anti-PD1) nanobody expression based on the <i>LuxI</i> promoter in strains was validated by Western blotting. Immune responses were assessed using flow cytometry.</p><p><strong>Results: </strong>The incubation of the fused proteins with the AISI-ST strain for 1 h was sufficient to form a stable biological interface. The quadruple RGD-modified bacteria (AISI-ST/SC-RGD×4) exhibited greater enrichment in various solid tumors and lung metastases with reduced off-target accumulation. QS induced the expression of the HtrA protein within tumors, resulting in enhanced extracellular polysaccharide-mediated immunogenicity to activate immune cells. Further expression of anti-PD1 nanobodies synergistically enhanced antitumor immunity, increasing the percentage of M1 macrophages (MACS) and CD8⁺ T cell proliferation while suppressing M2 MACS and regulatory T cells (Tregs). This approach achieves potent tumor suppression via targeted immune remodeling.</p><p><strong>Conclusions: </strong>This study presents octopus-inspired engineered bacteria with a \"plug-and-display\" system and tumor-specific drug delivery that achieves enhanced tumor targeting and potent antitumor effects. This study describes a promising strategy for the precise and safe clinical translation of bacteria-mediated cancer immunotherapy.</p>","PeriodicalId":18581,"journal":{"name":"Military Medical Research","volume":"13 1","pages":"100030"},"PeriodicalIF":29.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13138155/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147840074","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 translational preclinical strategy for chronic spinal cord injury: neuroprotective and regenerative potential of botulinum neurotoxin type A combined with muscle atrophy prevention via electrostimulation.","authors":"Valentina Mastrorilli, Siro Luvisetto, Veronica Ruggieri, Giada Raparelli, Luca Madaro, Lucia Amalia Paggi, Chiara Parisi, Francesca De Santa, Federica De Angelis, Annunziata D'Elia, Roberto Massari, Susanna Amadio, Ornella Rossetto, Valentina Vacca, Maurizia Caruso, Gianluca Sferrazza, Flaminia Pavone, Sara Marinelli","doi":"10.1016/j.mmr.2026.100049","DOIUrl":"10.1016/j.mmr.2026.100049","url":null,"abstract":"<p><strong>Background: </strong>Spinal cord injury (SCI) triggers persistent neuroinflammation, gliosis, neuronal loss, and demyelination, leading to motor deficits and neuropathic pain (NeP). Botulinum neurotoxin type A (BoNT/A) has shown anti-inflammatory and neuroprotective effects in acute SCI, but its potential in the chronic phase remains unclear. This study investigates whether combining BoNT/A with electrical muscle stimulation (EMS) enhances recovery in chronic SCI.</p><p><strong>Methods: </strong>Adult mice with severe thoracic SCI (paraplegic) underwent EMS (30 min/d for 10 non-consecutive days starting 3 d post-injury) or no stimulation. Fifteen days after SCI, animals received a single intrathecal injection of BoNT/A (15 pg/5 μl) or saline. Functional recovery was assessed up to 60 d as well as in moderate and mild SCI mice. NeP onset and maintenance were evaluated. Spinal cord tissue was analysed for astrocytic and microglial morphology, neuronal and oligodendroglial survival, myelin protein expression, and <i>in vitro</i> effects on oligodendrocyte precursor cells (OPCs). The phenotype of hindlimb muscles was evaluated through morphological and gene expression analyses.</p><p><strong>Results: </strong>EMS was able to counteract muscle atrophy and fibrosis, and when combined with BoNT/A, also denervation. Moreover, the combination restored hindlimb motor function in chronic SCI, whereas BoNT/A or EMS alone were ineffective. NeP, a common comorbidity associated with SCI, was mitigated by BoNT/A treatment even when administered in the chronic phase. BoNT/A reduced astrocytic hypertrophy and excitatory synapse association and was associated with a morphology-based redistribution of microglial profiles toward a resting-like classification, decreased apoptosis, and increased neuronal and oligodendroglial survival. Myelin basic protein (MBP) expression was significantly elevated <i>in vivo</i>. <i>In vitro</i>, BoNT/A promoted OPC differentiation into myelinating oligodendrocytes, increased process complexity, and upregulated MBP, galactocerebroside C, proteolipid protein, and myelin oligodendrocyte glycoprotein under both proliferative and differentiating conditions. Cleaved synaptosomal-associated protein 25 colocalization with OPC confirmed direct BoNT/A internalization and activity.</p><p><strong>Conclusions: </strong>BoNT/A exerts neuroprotective effects in chronic SCI by reducing neuroinflammation and supporting neuronal and oligodendroglial preservation. When combined with EMS, it also promotes remyelination and improves muscle homeostasis, suggesting that early stimulation creates a permissive environment for recovery. These findings support the clinical evaluation of BoNT/A as a therapeutic strategy for chronic SCI.</p>","PeriodicalId":18581,"journal":{"name":"Military Medical Research","volume":"13 1","pages":"100049"},"PeriodicalIF":29.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13321029/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148368880","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":"Forecasting the prevalence of epilepsy in low- and middle-income countries to 2050 using a hybrid deep neural network-transformer modeling framework: insights from the Global Burden of Disease Study 2023.","authors":"Zhi-Jin Zhang, Hao-Feng Wang, Yu-Sha Cui, Shi-Nuan Lin, Han Jiao, Fan-Gang Meng, Tao Feng","doi":"10.1016/j.mmr.2026.100055","DOIUrl":"10.1016/j.mmr.2026.100055","url":null,"abstract":"<p><strong>Background: </strong>Epilepsy is a major public health challenge affecting individuals of all ages, especially in low- and middle-income countries (LMICs). Reliable prevalence projections are critical for healthcare planning and resource allocation. This study aimed to forecast the prevalence of epilepsy and its trends in LMICs by age, sex, year, and income level by 2050.</p><p><strong>Methods: </strong>Using data from the Global Burden of Disease Study (GBD) 2023, we projected the prevalence and number of idiopathic and secondary epilepsy cases in LMICs from 2024 to 2050. We developed a hybrid deep neural network (DNN)-Transformer framework that integrates Poisson regression and Autoregressive Integrated Moving Average (ARIMA) models for prevalence projection. Decomposition analysis was applied to quantify the contributions of population growth, aging, and prevalence change to the increase in epilepsy cases. Dementia-attributable epilepsy was independently projected to address secondary causes not included in GBD 2023.</p><p><strong>Results: </strong>By 2050, the age-standardized prevalence rate (ASPR) of epilepsy in LMICs was projected to reach 907.22 per 100,000 [95% uncertainty interval (UI) 731.01-1083.56], a 33.32% increase from 2023, with cases rising to 72.04 million (95% UI 57.86-86.23), a 58.68% increase. The ASPRs of idiopathic and secondary epilepsy were estimated at 323.11 and 584.10 per 100,000 in 2050, respectively, with the increase in secondary epilepsy being more than 7-fold that of idiopathic epilepsy since 2023. The ASPR of secondary epilepsy due to neonatal disorders was projected to rise by 65.76%. Model validation demonstrated good predictive performance (root mean squared error <0.001). From 2023 to 2050, the increases in idiopathic and secondary epilepsy cases were forecast to be highest in low-income countries (LICs; 76.12% and 241.50%, respectively), with growth declining as income levels increased. Population growth (21.40%) primarily drove the increase in idiopathic epilepsy cases, whereas changes in prevalence (59.89%) predominantly drove the rise in secondary epilepsy cases. Dementia-attributable secondary epilepsy was projected to reach 3.40 million cases by 2050.</p><p><strong>Conclusions: </strong>We forecast a continuous increase in the prevalence and number of epilepsy cases in LMICs through 2050, with secondary epilepsy increasing more rapidly than idiopathic epilepsy. LICs may exhibit the greatest increases over the next three decades, necessitating targeted interventions and further investigation.</p>","PeriodicalId":18581,"journal":{"name":"Military Medical Research","volume":"13 1","pages":"100055"},"PeriodicalIF":29.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13427421/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148654151","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":"Infarct volume versus NIHSS score for ischemic and bleeding risk stratification after acute ischemic stroke.","authors":"Zi-Mo Chen, Ying-Yu Jiang, Hong-Qiu Gu, Xin-Miao Zhang, Jing Jing, Jing-Lin Mo, Yong Jiang, Li-Ping Liu, Xing-Quan Zhao, Yong-Jun Wang, Zi-Xiao Li","doi":"10.1016/j.mmr.2026.100067","DOIUrl":"10.1016/j.mmr.2026.100067","url":null,"abstract":"<p><strong>Background: </strong>Whether infarct volume refines assessment of recurrent ischemic stroke (IS) and intracerebral hemorrhage (ICH) risk following acute IS beyond the National Institutes of Health Stroke Scale (NIHSS) remains uncertain. We compared their performance in ischemic-hemorrhagic risk stratification.</p><p><strong>Methods: </strong>We included 10,545 patients with acute IS from the Third China National Stroke Registry (CNSR-III) with diffusion-weighted imaging/apparent diffusion coefficient-derived infarct volume and NIHSS data. Outcomes were 90-day recurrent IS and ICH, analyzed separately. Two reciprocal Cox models were used: one with infarct volume adjusted for NIHSS, and another with NIHSS adjusted for infarct volume. Stratified analyses, restricted cubic splines, and grouped threshold analyses were exploratory. In the GOLDEN BRIDGE II study, recurrent IS and all bleeding events were assessed for external consistency.</p><p><strong>Results: </strong>In CNSR-III, larger infarct volume was independently associated with recurrent IS [hazard ratio (<i>HR</i>)=1.35, 95% confidence interval (CI) 1.25-1.47] and ICH (<i>HR</i>=2.48, 95% CI 2.11-2.91) after NIHSS adjustment, whereas NIHSS lost significance after infarct-volume adjustment (IS: <i>HR</i>=1.05, 95% CI 0.89-1.24; ICH: <i>HR</i>=1.11, 95% CI 0.78-1.58). ICH risk rose around 9.0 ml, with increased hazard at 9.0-9.9 ml (<i>HR</i>=3.61, 95% CI 1.29-10.07), while IS risk increased without a sharp rise (<i>HR</i>=1.15, 95% CI 0.98-1.35). Patients with NIHSS score ≥4 and infarct volume <9.0 ml had IS risk comparable to NIHSS score ≤3 but potentially lower ICH risk (<i>HR</i>=0.63, 95% CI 0.38-1.02). Infarct volume 9.0-17.9 ml increased ICH risk (<i>HR</i>=1.96, 95% CI 1.06-3.63). Infarct volume was <9.0 ml in 66.7% of NIHSS score 6-15 and 25.4% of NIHSS score ≥16. GOLDEN BRIDGE II confirmed principal findings, with infarct volume associated with recurrent IS (<i>HR</i>=1.37, 95% CI 1.25-1.49) and bleeding events (<i>HR</i>=1.53, 95% CI 1.31-1.78).</p><p><strong>Conclusions: </strong>Infarct volume better characterizes post-stroke ischemic-hemorrhagic risk than NIHSS. Prospective validation is required before using infarct volume to guide antiplatelet selection.</p>","PeriodicalId":18581,"journal":{"name":"Military Medical Research","volume":"13 1","pages":"100067"},"PeriodicalIF":29.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13597881/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149039840","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":"Chinese expert consensus on wound repair of venous leg ulcers (2025 edition).","authors":"Pi-Hong Zhang, Xiao-Bing Fu, Yue-Sheng Huang","doi":"10.1016/j.mmr.2026.100058","DOIUrl":"10.1016/j.mmr.2026.100058","url":null,"abstract":"<p><p>Venous leg ulcers (VLUs) result from a multifactorial interplay of etiological factors, posing significant challenges in clinical management. Effective treatment requires a comprehensive assessment to identify the underlying pathophysiological mechanisms, followed by the implementation of an individualized, multidisciplinary approach that integrates the expertise of vascular surgeons, wound care specialists, and other pertinent healthcare professionals. Although both domestic and international vascular surgery societies, as well as other relevant specialties, have issued consensus statements on the diagnosis and treatment of VLUs or clinical guidelines for managing chronic lower extremity venous diseases, there remains a notable gap in systematic guidance specifically focused on wound repair for VLUs. In particular, standardized protocols for surgical wound repair are either lacking or insufficiently detailed in these documents. With the establishment and advancement of wound repair as a specialized field in China, Chinese experts have accumulated substantial clinical experience in the diagnosis and management of VLU-related wound healing. To standardize the surgical repair of VLUs and improve both therapeutic outcomes and patients' quality of life, the Wound Repair Professional Committee of the Chinese Medical Doctor Association convened a panel of multidisciplinary experts for extensive deliberations. Based on a synthesis of current international and domestic evidence and clinical practice, the committee reached consensus on evidence-based recommendations for key issues in VLU wound management, including debridement techniques, indications, timing, and approaches to wound repair for VLUs. This consensus is intended to serve as a practical reference for clinicians involved in the care of patients with VLUs.</p>","PeriodicalId":18581,"journal":{"name":"Military Medical Research","volume":"13 1","pages":"100058"},"PeriodicalIF":29.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13452334/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148697814","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":"Crosstalk in the brain tumor microenvironment: mechanisms, therapeutic strategies, and clinical advances.","authors":"Gui-Long Tanzhu, Liu Chen, Jiao-Yang Ning, Gang Xiao, Su Wen, Ce Wang, Hao Wen, Ke-Qin Zhang, Jie Yang, Mu-Yuan Jia, Hai-Bin Deng, Thomas Michael Marti, Paul R Lockman, Rong-Rong Zhou","doi":"10.1016/j.mmr.2026.100047","DOIUrl":"10.1016/j.mmr.2026.100047","url":null,"abstract":"<p><p>Brain tumors, including primary intracranial tumors and brain metastases (BrMs), represent a major threat to human health and are associated with extremely poor prognoses. The brain tumor microenvironment (BTME) is a complex ecosystem composed of various elements, including tumor cells, immune cells, neurons, the vascular system, the extracellular matrix, and cytokines. These elements not only coexist spatially but are also functionally connected, interacting through intricate networks that collectively influence tumor initiation, progression, and therapeutic efficacy. In recent years, the application of novel technologies such as single-cell and spatial transcriptomics has uncovered complex cellular heterogeneity and spatial organization within the BTME. This review comprehensively summarizes the key components and functions of the BTME in tumor development and therapy, the mechanisms underlying intercellular interactions, with an emphasis on their clinical potential and challenges.</p>","PeriodicalId":18581,"journal":{"name":"Military Medical Research","volume":"13 1","pages":"100047"},"PeriodicalIF":29.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13310652/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148352567","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":"Downregulation of FTO aggravates osteoarthritis with obesity by erasing m⁶A methylation of PDP2.","authors":"Xu-Ying Sun, Jing-Yue Su, Xin Chen, Yi-Xin Yang, Sheng-Wu Yang, Chun-Wu Zhang, Yu-Sheng Li, Jian Xu, Zhen-Han Deng","doi":"10.1016/j.mmr.2026.100054","DOIUrl":"10.1016/j.mmr.2026.100054","url":null,"abstract":"<p><strong>Background: </strong>Osteoarthritis (OA) is currently the most common age-related degenerative joint disease, but there remains a lack of disease-modifying therapy for OA treatment. This study aimed to elucidate the critical roles and underlying mechanism of the fat mass and obesity associated gene (FTO) in OA pathogenesis induced by high fat diet (HFD) and HFD coupled with destabilized medial meniscus (DMM) surgery, and to ascertain the synergistic action of the two in OA pathogenesis.</p><p><strong>Methods: </strong>Mouse models were established using solely HFD feeding and combined HFD feeding and DMM surgery. Primary mouse chondrocytes were treated with palmitic acid (PA) and interleukin-1β (IL-1β) to simulate lipotoxicity and inflammation. FTO expression was modulated via genetic, adenoviral, or pharmacological methods. Downstream pyruvate dehydrogenase phosphatases 2 (PDP2) and YTH N⁶-methyladenosine RNA binding protein 2 (YTHDF2) were similarly manipulated by siRNA or overexpression plasmids; adenovirus-mediated knockdown/overexpression of <i>Pdp2</i> was applied <i>in vivo</i>. Mechanistic studies included RNA sequencing (RNA-Seq) and methylated RNA immunoprecipitation sequencing (MeRIP-Seq).</p><p><strong>Results: </strong>The results revealed reduced FTO expression in the cartilage of both obese OA patients and mouse models. Genetically, adenovirus-induced or pharmacologically-induced FTO inhibition exacerbated OA progression in HFD-fed and HFD+DMM mice. Mechanistically, <i>Fto</i> knockdown downregulated the PDP2 level in an m⁶A-dependent manner via YTHDF2. <i>Pdp2</i> knockdown exacerbated OA progression in HFD-fed and HFD+DMM mice, whereas PDP2 overexpression markedly alleviated cartilage degeneration. Moreover, YTHDF2 overexpression reversed the role of <i>Fto</i> knockdown in lipid deposition and cartilage degeneration.</p><p><strong>Conclusions: </strong>Our study identifies that downregulation of FTO exerts a pivotal effect on OA with obesity. FTO drives disease progression by regulating PDP2 activity, and YTHDF2 mediates the m⁶A modification of FTO to PDP2. Targeting the FTO/YTHDF2/PDP2 axis offers promising therapeutic potential for OA treatment.</p>","PeriodicalId":18581,"journal":{"name":"Military Medical Research","volume":"13 1","pages":"100054"},"PeriodicalIF":29.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13400393/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148592544","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 RCT to mechanistic study: ATRA reverses myofibroblast activation by reprogramming glucose metabolism via HIC1 and PCK1/2 to attenuate hypertrophic scar formation.","authors":"Zi-Chao Li, Yi-Fu Zhu, Ya-Juan Song, Zhi-Jun Tan, Bin Liu, Yan Jiang, Hou-An Xiao, Dong-Mei Zu, Tong Wang, Yi Shi, Yan Jiao, Xue-Yong Li, Xing-Bo Xu, Lei Shang, Zhou Yu, Bao-Qiang Song","doi":"10.1016/j.mmr.2026.100021","DOIUrl":"10.1016/j.mmr.2026.100021","url":null,"abstract":"<p><strong>Background: </strong>Abnormal glucose metabolism often contributes to myofibroblast activation and the pathogenesis of skin fibrotic diseases. All-trans retinoic acid (ATRA), the active component of tretinoin cream, can regulate glucose metabolism and activate myofibroblasts. Importantly, investigating the potential of ATRA to inhibit myofibroblast activation by modulating glucose metabolism could reveal the translational significance of ATRA in attenuating hypertrophic scar (HS) formation.</p><p><strong>Methods: </strong>We first conducted a multicenter, double-blind, randomized controlled trial (RCT) to compare the effects of tretinoin cream with those of the first-line medication, silicone gel. In the mechanistic study, the characteristics of glucose metabolic reprogramming and the activation of hypertrophic scar fibroblasts (HSFs) after ATRA treatment were identified through multi-omics profiling, complemented by glucose metabolism assays and functional validations. Besides, genetic overexpression targeting the potential downstream molecules of ATRA, including hypermethylated in cancer 1 (HIC1), phosphoenolpyruvate carboxykinase (PCK)1, and PCK2, was conducted <i>in vitro</i> in HSFs and <i>in vivo</i> in skin fibroblasts of Col1a2-CreER mice.</p><p><strong>Results: </strong>Our RCT demonstrated that tretinoin cream is non-inferior to silicone gel in preventing HS formation, with the absolute risk difference of incidence rates [-8.65% 90% two-sided confidence interval (CI) -23.03 to 5.74] and in decreasing scar thickness [(2856.20±211.83) μm vs. (1664.57±273.50) μm], attributing to the reduction in HSF proliferation and the proportion of myofibroblasts. Moreover, tretinoin cream effectively mitigated HS formation in both mice and rabbits without impeding normal wound healing. Mechanistically, HSFs underwent glucose reprogramming, characterized by increased aerobic glycolysis, which facilitated the transition of HSFs to myofibroblasts and their proliferation. However, ATRA upregulated HIC1, PCK1, and PCK2 expression through retinoic acid receptor alpha (RARα) activation, thereby inhibiting the fibrotic phenotypes of HSFs by suppressing aerobic glycolysis and facilitating gluconeogenesis. The fibroblast-specific overexpression of HIC1, PCK1, or PCK2 in Col1a2-CreER mice significantly reduced myofibroblast activation and hypertrophic scarring.</p><p><strong>Conclusions: </strong>Our study not only substantiated that topical tretinoin cream could serve as an effective strategy to prevent HSs in clinical settings, but also established ATRA as a regulator of glucose metabolism. Importantly, ATRA/RARα-mediated glucose reprogramming was identified as a potential therapeutic target for attenuating HS formation.</p><p><strong>Trial registration: </strong>ChiCTR, ChiCTR2500097242. Registered on 14 Feb, 2025. Available from https://www.chictr.org.cn/bin/project/edit?pid=220146.</p>","PeriodicalId":18581,"journal":{"name":"Military Medical Research","volume":"13 1","pages":"100021"},"PeriodicalIF":29.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13138214/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147840076","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 expanding landscape of regulated cell death.","authors":"Dao-Lin Tang, Rui Kang","doi":"10.1016/j.mmr.2026.100060","DOIUrl":"https://doi.org/10.1016/j.mmr.2026.100060","url":null,"abstract":"","PeriodicalId":18581,"journal":{"name":"Military Medical Research","volume":"13 1","pages":"100060"},"PeriodicalIF":29.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13476493/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148765921","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":"Lean body mass mediates the sex dimorphism in cardiac and large arterial elastances.","authors":"Xin-Yu Liu, Mei-Han Guo, David Montero","doi":"10.1016/j.mmr.2026.100016","DOIUrl":"10.1016/j.mmr.2026.100016","url":null,"abstract":"","PeriodicalId":18581,"journal":{"name":"Military Medical Research","volume":"13 1","pages":"100016"},"PeriodicalIF":29.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13127128/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147817451","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}