Military Medical Research最新文献

{"title":"The hierarchical stratum response system of organism to microgravity during spaceflight.","authors":"Wei-Jia Sun, Rui-Kai Du, Yu-Heng Li, Guo-Hui Zhong, Jian-Wei Li, Zi-Zhong Liu, Xin-Xin Yuan, Xiao-Yan Jin, Shu-Kuan Ling, Ying-Xian Li","doi":"10.1016/j.mmr.2026.100027","DOIUrl":"10.1016/j.mmr.2026.100027","url":null,"abstract":"<p><p>With the advancement of manned spaceflight technology, significant progress has been made in the fields of aerospace medicine and space biology to address the needs of astronauts in terms of health, safety, and mission performance. The physiological and pathological changes during microgravity exposure, including perception, response, and adaptation mechanisms, are gradually being unraveled. This study aimed to systematically summarize the common features of various molecules and structures within the cell membrane, cytoplasm, and nucleus responsible for sensing microgravity. It further examined the heterogeneous responses across different tissues, organs, and cells, as well as systemic-level interactions and synergies, and proposed a novel multilevel gravity-sensing theory. Additionally, the study highlighted cutting-edge in-orbit health monitoring technologies, including rapid fluid analysis using sensitive biomarkers and non-invasive evaluation using two-photon fluorescence microscopy. Furthermore, it explored the promising applications of emerging therapeutic approaches for microgravity adaptation, including small nucleic acid drugs targeting gene regulation, exosome-based drug delivery systems, and natural small-molecule drugs aimed at combating microgravity effects.</p>","PeriodicalId":18581,"journal":{"name":"Military Medical Research","volume":"13 1","pages":"100027"},"PeriodicalIF":29.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13138232/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147840049","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":"E3 ubiquitin ligases in neurodegenerative diseases.","authors":"Duan Lu Hou, Josephine Ho, Tuchen Guan, Xiao-Xue Dong, Li Zeng, Laurie H Sanders, Yun-Cheng Wu, Eng King Tan, Zhi Dong Zhou","doi":"10.1016/j.mmr.2026.100032","DOIUrl":"10.1016/j.mmr.2026.100032","url":null,"abstract":"<p><p>Neurodegenerative diseases (NDs) are characterized by progressive neuronal loss and proteostatic failure, driven by impaired clearance of misfolded proteins via the ubiquitin-proteasome system (UPS) and autophagy. In UPS, E3 ubiquitin ligases are crucial for regulating protein ubiquitination and degradation. Mutations in E3 ligases, along with dysfunctions of specific ligases such as Parkin, the C-terminus of HSC70-interacting protein (CHIP), and tripartite motif-containing proteins, have been identified as key factors in the buildup of amyloid-β, α-synuclein, tau, trans-active response DNA-binding protein 43, and mutant huntingtin. These accumulations are associated with NDs like Parkinson's disease, Alzheimer's disease, Huntington's disease, and amyotrophic lateral sclerosis. Therapeutic strategies targeting E3 ligases, particularly proteolysis-targeting chimeras (PROTACs), are being developed for ND treatment and are currently in clinical trials. These approaches aim to enhance E3 ligase activity and promote selective protein degradation. Here, we examine how individual E3 ligases influence cell-fate decisions in NDs, showing that their substrate selection determines whether neurons survive or die. Building on this knowledge, we present an innovative therapeutic pipeline that includes ligase activators, PROTAC degraders, and miRNA switches, which are molecules designed to transition from research to clinical application.</p>","PeriodicalId":18581,"journal":{"name":"Military Medical Research","volume":"13 1","pages":"100032"},"PeriodicalIF":29.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13138213/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147840068","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":"Associations of Different Definitions of Prediabetes and Diabetes with All-Cause and Cause-Specific Mortality: A Nationally Representative Cohort Study.","authors":"Mei Zhang, Zixin Qiu, Yue Wang, Xiao Zhang, Shiyu Zhao, Chun Li, Zhenping Zhao, Shenhan Xiang, An Pan, Limin Wang, Maigeng Zhou, Kai Huang, Gang Liu","doi":"10.1016/j.mmr.2026.100028","DOIUrl":"10.1016/j.mmr.2026.100028","url":null,"abstract":"<p><strong>Background: </strong>The associations between different definitions of prediabetes and diabetes with mortality and life expectancy remain unclear. Clarifying these associations is essential for informing hyperglycemia management policies. We aimed to compare the prevalence of prediabetes and newly diagnosed diabetes across different glycemic indicators and diagnostic criteria, and to examine their associations with mortality and life expectancy.</p><p><strong>Methods: </strong>We analyzed data from 141,945 adults from a nationally representative cohort study in China. Cox proportional hazards regression models were used to estimate hazard ratios (HRs). Using fasting plasma glucose (FPG), 2-hour postload glucose (2hPG), and hemoglobin A1c (HbA1c) levels, prediabetes was defined according to the American Diabetes Association (ADA), World Health Organization (WHO), or International Expert Committee (IEC) criteria, and newly diagnosed diabetes according to the ADA criteria.</p><p><strong>Results: </strong>Prediabetes prevalence varied widely across glycemic indicators, ranging from 3.0% to 26.1%, while newly diagnosed diabetes prevalence ranged from 2.6% to 4.4%. Over a median follow-up of 9.0 years, a total of 6,924 deaths were documented. Compared with people with normoglycemia, prediabetes defined by FPG (either ADA or WHO criteria) was not significantly associated with increased risks of all-cause or cardiovascular disease (CVD) mortality (all <i>P</i>>0.05). In contrast, prediabetes defined by 2hPG or HbA1c (either ADA or IEC criteria) was each associated with higher risks of all-cause mortality (HRs: 1.13-1.23; all <i>P</i><0.001) and CVD mortality (HRs: 1.12-1.25; all <i>P</i><0.001). Prediabetes defined by 2hPG or HbA1c, but not FPG, was associated with 1.1-2.3 years reduction in life expectancy, with the largest loss observed for IEC HbA1c. In addition, diabetes defined by FPG, 2hPG or HbA1c was each significantly associated with higher risk of all-cause and CVD mortality (HRs: 1.25-1.51), and reduction in life expectancy (2.0-3.7 years). Furthermore, the 2hPG-based definition of prediabetes and diabetes was associated with mortality risk, independent of FPG and HbA1c levels.</p><p><strong>Conclusions: </strong>These findings suggest that reliance on FPG alone may fail to identify certain individuals at elevated mortality risk. In contrast, 2hPG and HbA1c provide additional prognostic information beyond FPG.</p>","PeriodicalId":18581,"journal":{"name":"Military Medical Research","volume":"13 1","pages":"100028"},"PeriodicalIF":29.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13127155/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147817373","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":"Bridging the lung cancer screening eligibility gap: evaluation of guideline applicability in asymptomatic patients.","authors":"Chen-Ran Wang, Ren-Da Li, Pan Wang, Xue-Si Dong, Hao Zhang, Qing-Peng Zeng, Jia-Xin Xie, Zi-Lin Luo, Xiao-Lu Chen, Ya-Di Zheng, Ji-Bin Li, Yong-Jie Xu, Fei Wang, Ni Li, Feng-Wei Tan, Jie He","doi":"10.1016/j.mmr.2026.100020","DOIUrl":"10.1016/j.mmr.2026.100020","url":null,"abstract":"<p><strong>Background: </strong>Early-onset (<50 years) and never-smoker lung cancers are increasing global concerns. The emerging trends challenge current screening guidelines, which focus on adults aged >50 years with heavy smoking histories. We applied the US Preventive Services Task Force (USPSTF) 2021 screening criteria as the primary definition of high-risk individuals eligible for lung cancer screening and assessed the potential optimization of these criteria using real-world lung cancer data in China.</p><p><strong>Methods: </strong>In this nationwide, multicenter, hospital-based observational study, we enrolled asymptomatic patients with surgically resected primary lung cancer across 26 tertiary hospitals from January 1, 2014 to December 31, 2021. Screening eligibility was classified using USPSTF 2021 criteria (aged 50-80 years, ≥20 pack-year smoking history, and ≤15 quit-years for former smokers). Temporal trends in eligibility, screening utilization, and mortality risks were assessed through joinpoint regression and Cox proportional hazards models.</p><p><strong>Results: </strong>A total of 106,266 asymptomatic patients with lung cancer were enrolled. Among the 102,555 patients with complete age and smoking information, only 8.8% (8985/102,555) met the USPSTF 2021 eligibility criteria. The eligibility proportion declined sharply from 21.6% (350/1617) in 2014 to 6.1% (1737/28,582) in 2021, with the annual percentage change being -17.4% [95% confidence interval (CI) -19.1 to -15.9]. Patients with screening utilization, irrespective of eligibility status, demonstrated a higher proportion of stage Ia diagnoses compared with those who were not screened. Screening- ineligible group exhibited 40% lower mortality risk overall [adjusted hazard ratio (<i>HR</i>)=0.60, 95% CI 0.55-0.66], with consistent survival advantages across stage I (adjusted <i>HR</i>=0.63, 95% CI 0.54-0.74) and stage III (adjusted <i>HR</i>=0.76, 95% CI 0.64-0.90) subgroups.</p><p><strong>Conclusions: </strong>Rigid age- and smoking-based criteria overlook substantial at-risk populations in China. Implementing individualized risk stratification is essential to advance equitable lung cancer screening.</p>","PeriodicalId":18581,"journal":{"name":"Military Medical Research","volume":"13 1","pages":"100020"},"PeriodicalIF":29.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13127149/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147817410","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":"Hypoxia: a critical pathophysiological driver in respiratory inflammatory diseases.","authors":"Bing Zhong, Lan Yang, Si-Lu Sun, Hong Chen, De-Yun Wang","doi":"10.1016/j.mmr.2026.100023","DOIUrl":"10.1016/j.mmr.2026.100023","url":null,"abstract":"<p><p>Hypoxia is a central pathophysiological driver of inflammatory airway diseases, shaping disease progression largely through hypoxia-inducible factor 1α (HIF-1α) signaling. Across these disorders, hypoxia exacerbates airway inflammation through shared mechanisms. As a key signaling hub, HIF-1α disrupts epithelial barrier integrity and initiates inflammatory cascades; reprograms immune responses, promoting the activation and trafficking of eosinophils, T cells, and macrophages while reshaping cytokine profiles, to drive tissue injury; and accelerates airway remodeling, thereby worsening airflow limitation and perpetuating inflammatory cycles. Realizing effective targeted therapies will require rigorous validation of HIF-1α as a therapeutic node and the development of disease-tailored interventions aligned with distinct pathological features. In parallel, strengthened translational and clinical research on hypoxia is essential to build a robust evidence base for practice. This review synthesizes hypoxia-driven mechanisms shared across airway diseases, articulates a unifying framework for HIF-1α signaling across pathological contexts, and highlights the therapeutic implications of fundamental discoveries. By addressing the paucity of cross-disease analyses of hypoxia pathways, it provides both a conceptual foundation and a practical roadmap for developing precise and efficient targeted therapies for inflammatory respiratory diseases.</p>","PeriodicalId":18581,"journal":{"name":"Military Medical Research","volume":"13 1","pages":"100023"},"PeriodicalIF":29.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13127152/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147817475","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":"National mortality burden attributable to the unprecedented heatwave in 2022 in China.","authors":"Jian-Xiong Hu, Yu-Lin Zhuo, Guan-Hao He, Jiang-Mei Liu, Yan-Fang Guo, Tian-Tian Li, Wei-Wei Gong, Fang-Fang Zeng, Hai-Lai Duan, Rui-Lin Meng, Chun-Liang Zhou, Yi-Ze Xiao, Min Yu, Biao Huang, Mai-Geng Zhou, Wen-Jun Ma, Tao Liu","doi":"10.1186/s40779-025-00676-2","DOIUrl":"10.1186/s40779-025-00676-2","url":null,"abstract":"<p><strong>Background: </strong>In 2022, China experienced an unprecedented heatwave event, raising concerns about the health impacts of heatwaves. This study aims to understand the devastating health risk of the exceptional heatwave in 2022 by comparing heatwave-related mortality burden in 2022 with that during 2000-2021.</p><p><strong>Methods: </strong>We collected daily mortality and daily maximum temperature (DMT) during 2006-2017 in 364 locations (counties/districts) of China. Heatwave was defined as an event with 2 or more consecutive days of DMT exceeding the 92.5th percentile. We employed a distributed lag nonlinear model (DLNM) and a meta-analysis to examine the heatwave-mortality association based on the data from 364 counties/districts, and then this association was used to assess the mortality burden attributable to heatwaves during 2000-2022 in 368 cities in China. A percentage change (%) indicator, comparing the 2022 mortality burden to the average value from 2000 to 2021, was further calculated to highlight the severity of heatwaves in 2022.</p><p><strong>Results: </strong>In the past 2 decades, the frequency and intensity of heatwaves in China significantly increased, with the cumulative excessive degree-day increasing to 31,626 in 2022 compared with the annual average value of 13,772 during 2000-2021 across China. In 2022, we observed 62,961 [95% confidence internal (CI) 54,945-70,413] heatwave-related deaths in China, which was much higher than the annual average [35,987 (95% CI 31,252-40,471)] attributable to heatwaves during 2000-2021. The vulnerability groups of heatwave-related mortality in 2022 primarily included patients with cardiovascular diseases [40,567 (95% CI 35,313-45,404)], females [35,876 (95% CI 31,035-41,005)], and people aged over 65 years [56,208 (95% CI 49,023-62,864)]; and greater heatwave-related mortality was found in eastern-central China. The attributable fraction (AF) of heatwave-related deaths increased from an annual average of 11.01‰ (95% CI 9.56-12.38) during 2000-2021 to 18.11‰ (95% CI 15.80-20.25) in 2022 with 64.43% increment (95% CI 38.10-93.78), and the increase rates were greater in Xizang Autonomous Region (159.77%, 95% CI 12.84-477.87) and Sichuan Province (133.64%, 95% CI 3.84-416.61).</p><p><strong>Conclusions: </strong>This study indicated that the frequency and intensity of heatwaves significantly increased in the past 2 decades in China, and the 2022 heatwaves were linked to a substantial mortality burden in China, with significant population and regional heterogeneity. Our findings underscore the need for developing comprehensive heat adaptation plans in the context of rapid aging and ongoing global warming.</p>","PeriodicalId":18581,"journal":{"name":"Military Medical Research","volume":"12 1","pages":"92"},"PeriodicalIF":29.0,"publicationDate":"2025-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12703895/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145756993","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":"National and subnational burden and causes of anemia in China from 1990 to 2023: findings from the Global Burden of Disease Study 2023.","authors":"Zheng Long, Ling-Ling Yu, Fan-Shu Yan, Pei-Pei Li, Li-Jun Wang, Mai-Geng Zhou, Bing-Xin Ji, Peng Yin","doi":"10.1186/s40779-025-00681-5","DOIUrl":"10.1186/s40779-025-00681-5","url":null,"abstract":"<p><strong>Background: </strong>Anemia is a major global health problem. There were 89% of all anemia-related disabilities in developing countries. We aim to analyze the burden of anemia and its underlying causes in China from 1990 to 2023.</p><p><strong>Methods: </strong>Utilizing the data of the 2023 Global Burden of Disease (GBD 2023) study, this study analyzed the burden of anemia in China between 1990 and 2023. Then we analyzed the number and rate of anemia attributed to 16 underlying causes for all genders and ages. Drivers of change in prevalence and years lived with disability (YLD) numbers due to anemia were explored by decomposition analysis. And locally weighted regression was used to estimate the relationship between socio-demographic index (SDI) and age-standardized prevalence rate (ASPR) and age-standardized YLD rate due to anemia.</p><p><strong>Results: </strong>From 1990 to 2023, the ASPR and age-standardized YLD rate showed a downward trend among all anemia types (P < 0.05), and the ASPR and age-standardized YLD rate of anemia in females were higher than those in males. The highest number and rate of prevalence were found in mild anemia, and the highest number and rate of YLD were found in moderate anemia. As age increased, the prevalence and YLD rate of anemia increased, with a significant increase in females aged 20-54, in particular of moderate anemia. In 2023, the highest ASPR and age-standardized YLD rate among all anemia types were in the Northwestern regions. Compared to 1990, 31 provinces, Hong Kong, and Macao exhibited declines in both the ASPR and the age-standardized YLD rate for anemia. In China, most of the prevalent cases and YLD were attributable to dietary iron deficiency in 2023. The total prevalence of anemia decreased by 46.14% [95% uncertainty interval (UI) 27.54-61.02], of which age-specific rate, population growth, and population aging accounted for -77.32%, 21.33%, and 9.84%, respectively. A negative association between SDI and the ASPR and age-standardized YLD rate of anemia was shown in China.</p><p><strong>Conclusions: </strong>From 1990 to 2023, the burden of anemia in China has decreased but remained heavy among women of childbearing age, the elderly, and in the Northwestern region. Tailored prevention and control strategies should be strengthened to reduce the burden of anemia in high-risk areas.</p>","PeriodicalId":18581,"journal":{"name":"Military Medical Research","volume":"12 1","pages":"91"},"PeriodicalIF":29.0,"publicationDate":"2025-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12703925/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145757062","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 methodological guideline for consciousness assessment via neural electrophysiological activity.","authors":"An-An Ping, Long-Zhou Guan, Yong Wang, Sheng Yang, Chao Yang, Xiao-Qing Hu, Yi-Heng Tu, He Chen, Wei-Guang Li, Xiao-Li Li","doi":"10.1186/s40779-025-00682-4","DOIUrl":"10.1186/s40779-025-00682-4","url":null,"abstract":"<p><strong>Background: </strong>Physiological, pharmacological, and pathological alterations of consciousness provide critical windows into its neural substrates. Given the inherent complexity and multidimensionality of consciousness, defining quantitative, dynamic signatures of neural activity, and translating them into clinically applicable tools remains challenge. This study aimed to build an electroencephalography (EEG)-based methodological guideline for clinical consciousness assessment.</p><p><strong>Methods: </strong>EEG signals were systematically categorized across periodic and aperiodic activity, connectivity and network topology, spatiotemporal dynamics, self-organized criticality, and transcranial magnetic stimulation (TMS)-evoked responses. These biomarkers were mapped onto a conceptual framework of consciousness, comprising wakefulness and internal/external awareness, based on their validation across clinical conditions. The discriminative efficacy of various biomarkers was then evaluated across 4 independent datasets.</p><p><strong>Results: </strong>Integrated EEG features each captured distinct yet complementary dimensions of consciousness, supporting a unified neurophysiological architecture underlying diverse alterations of consciousness. Spectral power and peak frequency tracked the loss of consciousness during propofol anesthesia and sleep. Steeper aperiodic slopes, loss of frontoparietal connectivity, disrupted small-world organization, and reduced effective dimensionality were particularly effective in distinguishing minimally conscious state (MCS) from unresponsive wakefulness syndrome (UWS). Additionally, spatiotemporal patterns exhibited consciousness-specific alterations, with both pharmacological and pathological alterations influencing specific microstate dynamics.</p><p><strong>Conclusions: </strong>Synthesizing integrated neural dynamics and multidimensional consciousness, this guideline establishes both methodological and theoretical foundations for translating neurophysiological biomarkers into clinical applications. While this work advances both conceptual clarity and practical methodology, large-scale validation across expanded clinical cohorts, experimental models, and multimodal platforms is essential to fully establish causal linkages and translational utility.</p>","PeriodicalId":18581,"journal":{"name":"Military Medical Research","volume":"12 1","pages":"90"},"PeriodicalIF":29.0,"publicationDate":"2025-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12699880/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145742700","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":"Risk factor control in relation to mortality and life expectancy among people with type 2 diabetes: results from 3 nationwide cohort studies.","authors":"Zi-Xin Qiu, Frank Qian, Yan-Bo Zhang, Jun Liu, Ting-Ting Geng, Rui Li, Pang Yao, Oscar H Franco, Eric B Rimm, JoAnn E Manson, An Pan, Mai-Geng Zhou, Kai Huang, Gang Liu","doi":"10.1186/s40779-025-00674-4","DOIUrl":"10.1186/s40779-025-00674-4","url":null,"abstract":"<p><strong>Background: </strong>Type 2 diabetes (T2D) is a global epidemic that reduces life expectancy. Evidence is limited on the benefits of achieving multiple guideline-recommended targets and cross-country differences. This study aimed to quantify the associations of risk factor control with mortality and life expectancy among individuals with T2D using nationwide cohorts from China, the USA, and the UK.</p><p><strong>Methods: </strong>We included 46,351 adults with T2D at baseline from China Chronic Disease and Risk Factors Surveillance (CCDRFS; 2013, follow-up until 2021), USA National Health and Nutrition Examination Survey (USA NHANES; 1999-2018, follow-up until 2019), and UK Biobank (2006-2010, follow-up until 2022). Patients with T2D were matched to controls without T2D using propensity score matching based on key demographic factors. Cox regression estimated mortality associated with lifestyle and metabolic factors outside target ranges [physical inactivity, smoking, unhealthy diet, elevated hemoglobin A1c (HbA1c), dyslipidemia, high blood pressure].</p><p><strong>Results: </strong>Only a small proportion of participants achieved ≥ 5 combined targets: 16.0% in CCDRFS, 9.9% in USA NHANES, and 6.8% in UK Biobank. During 470,369 person-years of follow-up, 7650 deaths (16.5%) occurred among individuals with T2D, and 9349 deaths (10.2%) occurred among controls over 965,249 person-years. At age 50, individuals with ≤ 1 risk factor outside the target lived 6-9 years longer than those with ≥ 5, and their life expectancy was comparable to that of controls without T2D. The association was independent of genetic predisposition to shorter lifespan in the UK Biobank. Additionally, individuals with T2D who failed to achieve optimal metabolic control but maintained a healthy lifestyle had a longer life expectancy compared with those who achieved optimal metabolic control but had an unhealthy lifestyle across all cohorts, with life expectancy gains ranging from 1.5 to 3.4 years depending on sex and cohort. Among individuals with T2D, healthy lifestyle behaviors (physical activity, non-smoking, a healthy diet) and HbA1c control contributed most to gains in life expectancy. Variations in multiple risk factor control and their associations with all-cause mortality were observed across different population subgroups.</p><p><strong>Conclusions: </strong>Achievement of guideline targets for multiple risk factors was low among individuals with T2D in China, the USA, and the UK. Comprehensive management of multiple risk factors, particularly lifestyle factors, was associated with a substantial reduction in the life expectancy gap between those with and without T2D, underscoring the importance of guideline-based care and individualized management.</p>","PeriodicalId":18581,"journal":{"name":"Military Medical Research","volume":"12 1","pages":"89"},"PeriodicalIF":29.0,"publicationDate":"2025-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12679727/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145687639","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 promise of cardiomyocyte computational models for drug safety.","authors":"Lei Wang, Blanca Rodriguez","doi":"10.1186/s40779-025-00675-3","DOIUrl":"10.1186/s40779-025-00675-3","url":null,"abstract":"","PeriodicalId":18581,"journal":{"name":"Military Medical Research","volume":"12 1","pages":"88"},"PeriodicalIF":22.9,"publicationDate":"2025-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12679758/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145687615","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}