BMC Medicine最新文献

{"title":"The efficacy of intermittent metformin plus lifestyle intervention for diabetes prevention in women with prediabetes and prior gestational diabetes: a randomized clinical, non-inferiority trial.","authors":"Fenghua Lai, Ling Pei, Changliu Xu, Huangmeng Xiao, Zeting Li, Nan Chen, Yanhong Zhou, Shuhui Liang, Yongjun Zhang, Li Ling, Yimin Wen, Shufan Yue, Yan Chen, Xiaoyu Huang, Yaping Liang, Wenxue Xiong, Wenzhan Chen, Chenxue Wang, Wanping Deng, Haitian Chen, Melissa S Putman, Liehua Liu, Shubin Hong, Hai Li, Yanbing Li, Xiaopei Cao","doi":"10.1186/s12916-026-05059-5","DOIUrl":"10.1186/s12916-026-05059-5","url":null,"abstract":"<p><strong>Background: </strong>In women with prediabetes after prior gestational diabetes mellitus (GDM), whether intermittent metformin treatment as needed is as effective as continuous use in preventing type 2 diabetes mellitus (T2DM) is unknown. We aimed to test whether an intermittent metformin treatment is non-inferior to continuous metformin strategy for prevention of T2DM in women with prediabetes after GDM.</p><p><strong>Methods: </strong>A randomized, open-label, non-inferiority trial was conducted at three centers in China. Women aged 18-45 years with prior GDM and prediabetes at 4-12 weeks postpartum were randomly assigned to receive lifestyle intervention plus intermittent or continuous metformin treatment. In the continuous group, participants were initially treated with lifestyle intervention and metformin was initiated when lifestyle intervention alone failed to maintain euglycemia and continued without interruption throughout the trial. In the intermittent group, participants were initially treated with lifestyle intervention and metformin was added when they failed to maintain euglycemia and was discontinued if the glycemic status returned to normal. The primary outcome was the difference in incidences of newly diagnosed diabetes between the two groups during the 3-year follow-up, compared against a non-inferiority margin of 10-percentage-point by following the intention-to-treat principle. Secondary outcomes included the percentage of prediabetes remission, changes from baseline in body weight, body mass index, waist circumference, fasting plasma glucose, 2-h plasma glucose, and hemoglobin A1c.</p><p><strong>Results: </strong>Among the 376 women randomized, 11.5% of women in the intermittent group and 11.1% in the continuous group developed newly diagnosed T2DM after three years (absolute risk difference 0.4% points [95% CI -6.5 to 7.4], meeting criteria for non-inferiority). None of the secondary outcomes were significantly different between the two groups. Women in the continuous group experienced higher rate of metformin-related vitamin B₁₂ deficiency (13.5% vs. 3.7%, P = 0.001).</p><p><strong>Conclusions: </strong>In postpartum women with prediabetes after GDM, a strategy of intermittent metformin as needed plus lifestyle intervention met the pre-specified 10-percentage-point non-inferiority margin for 3-year T2DM incidence compared with continuous metformin plus lifestyle intervention. The equivalence of the two metformin strategies needs to be confirmed in further trials with a narrower margin and a larger event count.</p><p><strong>Trial registration: </strong>The study was registered in the Chinese Clinical Trial Registry (ChiCTR-IOR-17012770).</p>","PeriodicalId":9188,"journal":{"name":"BMC Medicine","volume":" ","pages":""},"PeriodicalIF":8.7,"publicationDate":"2026-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13644025/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148435080","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Randomized, multicenter phase 3 study evaluating radiotherapy versus concurrent chemoradiotherapy in nasopharyngeal carcinoma patients achieving CR/PR after induction chemotherapy.","authors":"Ting Jin, Feng Jiang, Qi-Feng Jin, Yong-Hong Hua, Yong-Shi Jia, De-Xi Du, Shu-Bo Ding, Hua-Fang Su, Miao-Zhen Lu, Hui-Juan He, Xiao-Zhong Chen","doi":"10.1186/s12916-026-05064-8","DOIUrl":"10.1186/s12916-026-05064-8","url":null,"abstract":"<p><strong>Background: </strong>The present study sought to compare the clinical efficacy and safety profiles of radiotherapy (RT) and concurrent chemoradiotherapy (CCRT) in nasopharyngeal carcinoma (NPC) patients who attained complete or partial response (CR/PR) following induction chemotherapy (IC).</p><p><strong>Methods: </strong>This multicenter, randomized, open-label, phase 3 noninferiority trial was conducted at 7 Chinese hospitals. Patients with newly diagnosed stage III-IVb NPC who achieved CR/PR after IC were randomly allocated (1:1) to either the RT (IC + RT) group or the CCRT (IC + CCRT) group. The chemotherapy protocol was identical across the two treatment groups. The primary endpoint was progression-free survival (PFS). Secondary endpoints comprised overall survival (OS) and the incidence of adverse events. Statistical analyses were performed using the Kaplan-Meier method and log-rank test.</p><p><strong>Results: </strong>From December 2016 to May 2023, 220 eligible patients with histologically confirmed nasopharyngeal carcinoma were enrolled. The trial was terminated early due to slow accrual. Of these patients, 109 were assigned to the IC + RT group and 111 to the IC + CCRT group. The median follow-up was 57 months (range, 8-107 months). The IC + RT and IC + CCRT groups showed comparable 5-year progression-free survival rates (87.0% vs. 80.7%, P = 0.21). No significant differences were observed between the two treatment arms with respect to local relapse-free survival, regional relapse-free survival, locoregional relapse-free survival, distant metastasis-free survival, or overall survival (all P > 0.05). The IC + RT group had significantly lower incidences of grade 3-4 hematologic and gastrointestinal toxicities than the IC + CCRT group. Additionally, grade 1-2 deafness/otitis and liver dysfunction were also less frequent in the IC + RT group.</p><p><strong>Conclusions: </strong>In NPC patients achieving CR/PR after induction chemotherapy, IC + RT demonstrated a favorable safety profile compared with IC+CCRT. Although the observed survival outcomes were numerically comparable, the premature termination of the trial and insufficient statistical power preclude a definitive noninferiority claim. These hypothesis-generating findings warrant validation in future adequately powered trials.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov, NCT03015727.</p>","PeriodicalId":9188,"journal":{"name":"BMC Medicine","volume":" ","pages":""},"PeriodicalIF":8.7,"publicationDate":"2026-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13644246/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148418876","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mapping quality of primary care among 0.5 million people with multiple long-term conditions in England, 2015-2024: a retrospective cohort study using electronic health records.","authors":"Qian Gao, Meryem Cicek, Benedict Hayhoe, Geva Greenfield, Michaela Otis, Gesthimani Misirli, Azeem Majeed, Paul Aylin, Alex Bottle","doi":"10.1186/s12916-026-04964-z","DOIUrl":"10.1186/s12916-026-04964-z","url":null,"abstract":"<p><strong>Background: </strong>As the number of people with multimorbidity continues to increase, the traditional medical care model - based on single disease models - has become increasingly unsuitable to meet current challenges, leading to concerns about the quality of primary care for patients with multimorbidity. This study aimed to evaluate the quality of care for people with multimorbidity in primary care, using quality indicators identified in Electronic Health Records (EHR) data.</p><p><strong>Methods: </strong>This study used EHR from the Discover-NOW Hub for April 2015-2024, covering 95% of northwest London's population. Through review of literature and clinical guidelines, we identified eight generic and six multimorbidity-specific quality indicators (QIs) for primary care, with consideration of the availability of indicators within EHR data. The final list was derived following discussion with people with lived experience of multimorbidity and clinicians. We used heat maps to report the QI attainment levels and conducted Ordinary Least Squares and logistic regression analyses to assess sociodemographic and health-related inequalities in relation to generic and multimorbidity-specific QI.</p><p><strong>Results: </strong>This study included 509,782 adult patients with multimorbidity. Attainment on generic QIs (range 23.5%-79.8%) was generally higher than multimorbidity-specific indicators (< 30%). QIs were generally stable over the past decade, but significantly reduced during the COVID-19 pandemic and fluctuated across individual QIs. Compared with healthier multimorbidity groups, those living with more comorbidities, polypharmacy and more severe frailty had higher levels of QI scores and had higher odds of uptake of individual QIs. Notably, we found socioeconomic inequalities, especially regarding ethnicity and neighbourhood deprivation, though this varied by QI.</p><p><strong>Conclusions: </strong>This study provides real-world evidence of the quality of primary care among multimorbidity patients. There was lower attainment on multimorbidity-specific QI than general indicators, with less affluent and some minority ethnic groups less likely to receive good care. Policymakers should focus on approaches to improve the support of primary care clinicians in the delivery of person-centred care for individuals with multimorbidity. Further research is needed to explore the underlying mechanisms for differential QI attainment and support primary care teams to improve the quality of care for people with multimorbidity.</p>","PeriodicalId":9188,"journal":{"name":"BMC Medicine","volume":" ","pages":""},"PeriodicalIF":8.7,"publicationDate":"2026-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13644081/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148418832","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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 exercise frequency and type with trajectories of daily activity limitations among older adults in the UK.","authors":"Hong Ding, Wen Wang","doi":"10.1186/s12916-026-05058-6","DOIUrl":"10.1186/s12916-026-05058-6","url":null,"abstract":"<p><strong>Background: </strong>Although regular exercise is widely recommended to delay functional decline, few studies have examined the joint associations of exercise frequency and type with trajectories of daily activity limitations among older adults in the UK. This study examined how exercise frequency, type, and their combination associated with population-average trajectories of daily activity limitations in UK older adults.</p><p><strong>Methods: </strong>We used data from the UK Household Longitudinal Study, including 28,419 person-wave observations of people aged 65 years and older followed across four waves between 2015 and 2023. Exercise frequency and type were assessed at baseline, and the exercise type was categorized as aerobic, resistance/strength, mind-body/balance, or no exercise, with further classification by participation frequency. Daily activity limitations were modelled as count outcomes using negative binomial generalized estimating equations to estimate population-average trajectories over time. Statistical significance was set at p < 0.05 (two-sided).</p><p><strong>Results: </strong>Compared with no exercise, participation in moderate exercise frequency was associated with a 59.1% lower rate of activities of daily living (ADL) limitations (IRR = 0.409, 95% CI: 0.355-0.472, P < 0.001) and a 59.4% lower rate of instrumental activities of daily living (IADL) limitations (IRR = 0.406, 95% CI: 0.357-0.462, P < 0.001). Aerobic exercise showed the lowest predicted limitation counts over time, followed by mind-body/balance activities. Strength-based exercise demonstrated a frequency-dependent pattern: moderate-frequency participation was associated with 62.0% lower rate of ADL limitations (IRR = 0.380, 95% CI: 0.241-0.601, P < 0.001), whereas high-frequency participation did not confer additional benefit (IRR = 1.086, 95% CI: 0.824-1.430, P = 0.560) and showed trajectories similar to those of non-exercisers.</p><p><strong>Conclusions: </strong>This study shows that exercise type and frequency jointly shape population-average trajectories of daily activity limitations in older adults. Aerobic and mind-body/balance exercises are associated with favourable functional trajectories. For resistance/strength training, moderate rather than high participation frequency appears to be associated with better functional outcomes. These findings suggest that both exercise type and frequency may be important considerations when developing exercise guidance to support functional independence in later life.</p>","PeriodicalId":9188,"journal":{"name":"BMC Medicine","volume":" ","pages":""},"PeriodicalIF":8.7,"publicationDate":"2026-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13637255/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148418695","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Functional decline in the final years of life: A multicohort study.","authors":"Junjie Lin, Mika Kivimäki, Yue Zhang, Yaguan Zhou, Xiaolin Xu","doi":"10.1186/s12916-026-05057-7","DOIUrl":"10.1186/s12916-026-05057-7","url":null,"abstract":"<p><strong>Background: </strong>Physical, cognitive, and psychological conditions are associated with an increased risk of mortality, yet few studies have characterized terminal declines in these functional domains preceding death. In this multicohort study, we examined both separate and joint trajectories of physical, cognitive, and psychological functioning during the final decade of life and assessed the role of socioeconomic status (SES).</p><p><strong>Methods: </strong>We used data from three national cohort studies: the US Health and Retirement Study, the China Health and Retirement Longitudinal Study, and the Survey of Health, Ageing and Retirement in Europe. Physical, cognitive, and psychological functioning were assessed repeatedly using measures of activities of daily living, cognitive test performance, and depressive symptoms, respectively. Mortality information was obtained from proxy respondents or national death registries. Statistical analyses included linear mixed-effects models and group-based multi-trajectory models using a backward timescale.</p><p><strong>Results: </strong>Among 79,305 participants (mean age 65.8 ± 10.3 years; 55.4% female), 12,135 (15.3%) died during the 10-year follow-up. Compared with survivors, decedents showed steeper and accelerated declines in physical (β_{death * time} -0.354, 95% confidence interval [95% CI] -0.372 to -0.336) and cognitive (β_{death * time} -0.077, 95% CI -0.092 to -0.063) functioning, and to a lesser extent in psychological functioning (β_{death * time} -0.044, 95% CI -0.061 to -0.028). In joint trajectory analyses, decedents experienced varying degrees of decline in at least one functional domain, and rapid terminal decline in physical functioning was accompanied by low and worsening cognitive and psychological functioning. In addition, higher SES was associated with lower odds of membership in adverse co-decline patterns, particularly the trajectory characterized by rapidly declining physical functioning combined with low and worsening cognitive and psychological functioning (e.g., OR _{high SES} 0.07, 95% CI 0.02 to 0.20).</p><p><strong>Conclusions: </strong>During the final decade of life, functional loss in physical and cognitive domains was more common than decline in psychological functioning. Higher SES was less likely to be associated with more unfavorable multidomain co-decline patterns.</p>","PeriodicalId":9188,"journal":{"name":"BMC Medicine","volume":" ","pages":""},"PeriodicalIF":8.7,"publicationDate":"2026-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13637263/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148418855","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparing geriatric assessment tools for predicting negative health outcomes in older adults.","authors":"Ahmad Abbadi, Francesco Innocenti, Giorgi Beridze, Emmanouil Kokoroskos, Alberto Zucchelli, Tobias Nordström, Caroline Wachtler, Laura Fratiglioni, Davide L Vetrano, Amaia Calderón-Larrañaga","doi":"10.1186/s12916-026-05008-2","DOIUrl":"10.1186/s12916-026-05008-2","url":null,"abstract":"<p><strong>Background: </strong>Amid global population aging, evidence-based geriatric assessment tools are essential for clinical decision-making and risk stratification. Despite growing interest, few studies have comprehensively compared the discriminative ability of existing tools, particularly as new tools have recently become available. In this study, we aimed to perform such a comparison across a wide range of patient-relevant health outcomes.</p><p><strong>Methods: </strong>This population-based prospective cohort study used data from the Swedish National study on Aging and Care in Kungsholmen (SNAC-K). We included 3,108 adults aged ≥ 60 years at baseline (2001-2004), who were followed up for up to six years. Seven tools (Health Assessment Tool [HAT], SNAC-K Frailty Index (FI) [SNACK-FI], Primary Care FI [PC-FI], Intrinsic Capacity [IC], Geriatric 8 [G8], Charlson Comorbidity Index [CCI], and Cumulative Illness Rating Scale [CIRS]) were evaluated in terms of their discriminative ability for formal care use, institutionalization, dementia, disability, injurious falls, self-rated health, quality of life, unplanned hospitalization, and mortality, using Harrell's C-index estimated from unadjusted cause-specific Cox models.</p><p><strong>Results: </strong>HAT, IC, and SNACK-FI consistently ranked among the top three performers across all outcomes. The highest C-indices were observed for institutionalization (HAT 0.93 [0.91, 0.95], IC 0.93 [0.90, 0.94], SNACK-FI 0.92 [0.89, 0.94]); 1-year mortality (HAT 0.88 [0.85, 0.91], SNACK-FI 0.87 [0.84, 0.91], IC 0.86 [0.82, 0.89]); dementia (HAT 0.87 [0.85, 0.89], IC 0.88 [0.86, 0.90], SNACK-FI 0.86 [0.83, 0.88]); and formal care use (HAT 0.83 [0.81, 0.86], IC 0.85 [0.83, 0.88], SNACK-FI 0.80 [0.77, 0.83]). Tools incorporating physical function metrics (e.g., gait speed) showed higher discriminative ability than those that omitted them. IC and SNACK-FI showed marginal and clinically negligible occasional gains over HAT ( ≤ 0.02 differences in C-index), despite greater complexity and a larger number of indicators. Guideline-endorsed tools (e.g., G8, CCI, CIRS) showed comparatively lower discrimination across outcomes.</p><p><strong>Conclusions: </strong>Contemporary geriatric assessment tools show promise. Tools incorporating physical function metrics demonstrated superior discriminative ability, suggesting these measures may be integral to geriatric prognosis and risk stratification. Given the underperformance of several established tools, reappraisal of current guideline recommendations may be warranted.</p>","PeriodicalId":9188,"journal":{"name":"BMC Medicine","volume":"24 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2026-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13348859/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148410418","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"R-MINE-containing regimen in relapsed and refractory diffuse large B-cell lymphoma: a single-arm, multicenter phase II study.","authors":"Jin-Hua Liang, Xin-Yu Zhang, Lin-Tao Bi, Wei-Wei Qin, Li-Ping Su, Jie-Ban Liu, Jia-Zhu Wu, Hua Yin, Yi-Lin Kong, Hao-Rui Shen, Jian-Yong Li, Yue Li, Li Wang, Wei Xu","doi":"10.1186/s12916-026-05051-z","DOIUrl":"10.1186/s12916-026-05051-z","url":null,"abstract":"<p><strong>Background: </strong>Improving the prognosis of patients with relapsed or refractory diffuse large B-cell lymphoma (R/R DLBCL) remains an unmet need. This multicenter, phase II study (NCT05784987) aimed to assess the efficacy and safety of a mitoxantrone hydrochloride liposome (Lipo-MIT)-based rituximab with mitoxantrone/ifosfamide/mesna/etoposide (R-MINE)-containing regimen, in which conventional mitoxantrone was replaced with Lipo-MIT, with or without a targeted agent.</p><p><strong>Methods: </strong>Patients older than 18 years with histologically confirmed R/R DLBCL were enrolled. All enrolled patients received an R-MINE-containing regimen in 21-day cycles for up to four cycles. The addition of the targeted agent (X) was individualized according to prior treatment resistance and molecular subtype. The primary endpoint was objective response rate (ORR).</p><p><strong>Results: </strong>From March 27, 2023, to July 10, 2025, 60 patients were enrolled. Of the 55 efficacy-evaluable patients, the ORR was 76.4% (95% confidence interval [CI]: 63.0%-86.8%), and the complete response rate was 52.7% (95% CI: 38.8%-66.3%). With the median follow-up of 13.9 months, the median PFS was 17.5 months (95% CI: 10.8-24.2), and the estimated PFS rate at 1 year was 58.5%. The median OS was not reached, with an estimated 1-year OS rate of 84.0%. Late relapse after the last-line therapy was identified as the only independent predictor for ORR, with an ORR of 86.4%. Grade ≥ 3 treatment-related adverse events (TRAEs) occurred in 46.7% of patients, with neutropenia (33.3%) being the most common. No serious TRAEs or TRAE-related deaths occurred.</p><p><strong>Conclusions: </strong>The Lipo-MIT-based R-MINE-containing regimen showed encouraging efficacy and a manageable safety profile in R/R DLBCL, warranting further validation.</p><p><strong>Clinical trial registration: </strong>This trial is registered with ClinicalTrials.gov (NCT05784987). URL https//clinicaltrials.gov/study/NCT05784987.</p>","PeriodicalId":9188,"journal":{"name":"BMC Medicine","volume":" ","pages":""},"PeriodicalIF":8.7,"publicationDate":"2026-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13637323/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148418853","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting ADGRG1 in cancer-associated adipocytes reprograms the immunosuppressive microenvironment and enhances immunotherapy responsiveness in triple-negative breast cancer models.","authors":"Ziling Zhou, Hanyi Zhong, Han Wang, Shoutang Wang, Nan Zhang, Zheng Wang, Renhong Huang, Kunwei Shen","doi":"10.1186/s12916-026-05049-7","DOIUrl":"10.1186/s12916-026-05049-7","url":null,"abstract":"<p><strong>Background: </strong>The adipocyte-rich microenvironment of the breast plays a crucial role in tumor progression, yet the functional heterogeneity of cancer-associated adipocytes (CAAs) and their specific mechanisms in driving immunosuppressive microenvironment and therapy resistance remain inadequately characterized.</p><p><strong>Methods: </strong>We performed an integrated analysis of single-nucleus RNA sequencing (snRNA-seq) data from human adipose tissue and bulk transcriptomic data from the TCGA-BRCA and METABRIC cohorts. A prognostic signature was developed based on transcriptional features of CAA subpopulations. Functional roles of the key gene ADGRG1 were investigated through in vitro co-culture systems and in vivo breast cancer models using genetic knockdown/overexpression and pharmacological inhibition.</p><p><strong>Results: </strong>snRNA-seq revealed a distinct CAA subpopulation enriched in aggressive contexts, labeled as HAD7. The HAD7-based signature stratified patients into high- and low-score groups, with the high-score group exhibiting poor survival and an immunosuppressive microenvironment. ADGRG1 was identified as a core driver. In vitro, ADGRG1 in CAAs promoted cancer cell migration, invasion, and epithelial mesenchymal transition. In vivo, adipocyte-specific ADGRG1 enhanced tumor growth, metastasis, and impaired anti-tumor immunity. Mechanistically, ADGRG1 activated a CXCL8-AKT/mTOR signaling axis. Crucially, pharmacological inhibition of ADGRG1 synergized with anti-PD-1 therapy, effectively suppressing tumor growth and metastasis by reversing immunosuppressive microenvironment.</p><p><strong>Conclusions: </strong>Our study identifies ADGRG1 as a master regulator of a pro-tumorigenic CAA subpopulation. Targeting the ADGRG1-CXCL8-AKT/mTOR axis represents a promising stromal-targeting strategy to overcome immunotherapy resistance in breast cancer.</p>","PeriodicalId":9188,"journal":{"name":"BMC Medicine","volume":" ","pages":""},"PeriodicalIF":8.7,"publicationDate":"2026-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13637322/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148418819","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development and validation of a novel multimodal deep neural network model based on CBC digit parameters and scattergrams for rapid hematolymphoid malignancy classification: a multicenter cohort study.","authors":"Hongyan Liao, Siyuan Chen, Qiang Meng, Mingxia Tang, Shuyi Hou, Jie Zhao, Yan Liu, Qin Zheng","doi":"10.1186/s12916-026-05036-y","DOIUrl":"10.1186/s12916-026-05036-y","url":null,"abstract":"<p><strong>Background: </strong>Rapid screening of hematolymphoid malignancies (HMs) by complete blood cell count (CBC) is crucial for choosing the next appropriate workup and initiating timely treatment for critical cases such as acute promyelocytic leukemia. Commonly presented as leukocytosis and abnormal differential, HMs could be misdiagnosed with diverse etiologies including reactive status of bacterial or viral infection, which also require early diagnosis and treatment to prevent severity, such as sepsis. Conventional workflow based on morphology review for HM screening remains time-consuming, labor-intensive, expertise-dependent and subjective. This study aimed to develop and validate an interpretable and cost-effective artificial intelligence (AI)-assisted model, to enable rapid and accurate prediction of HMs mixed with acute bacterial and viral infection, thus informing proper further workup and timely treatment.</p><p><strong>Methods: </strong>We retrospectively collected a multicenter dataset containing 4996 CBC records from patients presented with leukocytosis and finally diagnosed of either diseases from six prevalent HMs and acute bacterial and/or acute viral infection for model development and validation. This eight-nomial classification model, on a multimodal basis, integrates the digit parameters and its matching WBC differential scattergram from a single CBC test via a convolutional fusion deep neural network, and was compared with the digit- and scattergram-based unimodal model, as well as the current CBC review rules for performance evaluation.</p><p><strong>Results: </strong>The multimodal mDNN-cHM outperformed either unimodal model, as is demonstrated by metrics including precision, recall, F1-score and accuracy (all p < 0.05). The model showed striking diagnostic accuracy in both internal and external validations (the area under the ROC curve [AUC-ROC] all above 0.95, ranging from 0.98-1.00 internally and 0.95-1.00 externally). Further, mDNN-cHM demonstrated a higher prediction rate than the flag prompt by the current CBC review rules.</p><p><strong>Conclusions: </strong>Our study presents a proof-of-concept AI classifier for HMs in a real-time manner, which potentially maximizes the diagnostic value of the low-cost and widely-accessible CBC within 0.5 h after sample receipt. The framework also underscores the potential of interpretable AI in accelerating early disease diagnosis, mitigating human error and enlightening clinical decision-making via CBC, which complements and enhances standard-of-care diagnostics, particularly for urgent and high-risk diseases including leukemia/lymphoma and acute infection.</p>","PeriodicalId":9188,"journal":{"name":"BMC Medicine","volume":" ","pages":""},"PeriodicalIF":8.7,"publicationDate":"2026-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13440036/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148410345","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Establishing an efficacy hierarchy for breakthrough cancer pain management: a network meta-analysis of rapid-onset fentanyl formulations and morphine.","authors":"Po-Hung Tsao, Cho-Hao Lee, Jia-Hong Chen, Ching-Liang Ho, Hong-Jie Jhou, Po-Huang Chen","doi":"10.1186/s12916-026-04993-8","DOIUrl":"10.1186/s12916-026-04993-8","url":null,"abstract":"<p><strong>Background: </strong>Breakthrough cancer pain (BTP) is a common and debilitating condition affecting most patients with advanced malignancy. While multiple rapid-onset opioid formulations are available, a lack of comprehensive comparative evidence has hindered evidence-based treatment selection. We conducted a network meta-analysis (NMA) to evaluate the relative efficacy of all available formulations and characterize their temporal analgesic profiles for BTP management.</p><p><strong>Methods: </strong>We performed a systematic search of PubMed, Embase, and the Cochrane Library for randomized controlled trials (RCTs) evaluating rapid-onset fentanyl formulations (intranasal fentanyl spray [INFS], fentanyl buccal tablet [FBT], fentanyl pectin nasal spray [FPNS], fentanyl sublingual tablet [FST], fentanyl buccal soluble film [FBSF], and oral transmucosal fentanyl citrate [OTFC]) and morphine preparations (oral morphine sulfate immediate release [MSIR] and subcutaneous morphine [SCM]) for BTP in adults. The primary outcome was the standardized mean difference (SMD) in pain intensity difference (PID) at 10, 15, 30, and 60 min post-administration. A frequentist random-effects NMA was conducted for each time point, and treatments were ranked using P-scores, a frequentist metric ranging from 0 to 1 that reflects the probability of a treatment being superior to competitors (higher values indicate better ranking; distinct from p-values for statistical significance).</p><p><strong>Results: </strong>Seventeen RCTs involving 1,463 patients were included. Intranasal fentanyl spray (INFS) was consistently the most effective treatment across all time points, demonstrating statistically significant pain relief within 10 min (SMD: 0.85; 95% CI: 0.59-1.10) and showing its peak effect at 15 min (SMD: 1.05; 95% CI: 0.67-1.42). Fentanyl buccal tablet (FBT) consistently ranked as the second most effective agent. In contrast, immediate-release oral morphine (MSIR) did not achieve statistical superiority over placebo until the 30-minute mark (SMD: 0.20; 95% CI: 0.01-0.39; p = 0.036), confirming a comparatively delayed onset of action.</p><p><strong>Conclusions: </strong>This analysis provides evidence for a relative efficacy hierarchy among rapid-onset opioids for BTP. INFS demonstrated the most rapid and sustained analgesia across all evaluated time points, while FBT consistently ranked second. The delayed onset of MSIR warrants consideration when selecting agents for rapid pain relief. Treatment selection should integrate these efficacy data with safety profiles, route feasibility, and patient-specific factors.</p>","PeriodicalId":9188,"journal":{"name":"BMC Medicine","volume":" ","pages":""},"PeriodicalIF":8.7,"publicationDate":"2026-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13637205/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148410420","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}