BMC Medicine[JOURNAL]
Sun
200 papers
ACOD1 deficiency promotes DDX1 methylation-mediated mitochondrial dysfunction and dermal papilla cell senescence in androgenetic alopecia.
Zhao M, Wu Q, Ding Y … +8 more , Lu C, Du Y, Lin X, Bi L, Wang C, Ji J, Sun W, Fan W
BMC Med · 2026 May · PMID 42218500 · Full text
BACKGROUND: Androgenetic alopecia (AGA), the most prevalent form of hair loss, is driven by the dysfunction of dermal papilla cells (DPCs). Emerging evidence implicates DPC senescence in the pathogenesis of AGA; however,...
BACKGROUND: Androgenetic alopecia (AGA), the most prevalent form of hair loss, is driven by the dysfunction of dermal papilla cells (DPCs). Emerging evidence implicates DPC senescence in the pathogenesis of AGA; however, the underlying molecular mechanisms remain incompletely elucidated. METHODS: We employed a multi-faceted experimental approach, including analyses of human scalp tissues, primary DPCs, a dihydrotestosterone (DHT)-induced AGA mouse model, and immortalized DPCs stimulated with DHT. Cellular senescence was evaluated via expression of senescence markers (p16, p21, p53) and senescence-associated β-galactosidase staining. Cell proliferation, migration, and apoptosis were also assessed. Mitochondrial function was evaluated using transmission electron microscopy, MitoTracker, MitoSOX, JC-1, and Seahorse assays. RNA sequencing and bioinformatics analyses were performed to identify differentially expressed genes. The interaction between Aconitate Decarboxylase 1 (ACOD1) and DDX1 was verified via co-immunoprecipitation, mass spectrometry, and molecular docking. Metabolomic analysis was performed to profile intracellular metabolic alterations. Functional experiments included ACOD1 knockdown/overexpression and exogenous supplementation with 4-octyl itaconate (4-OI). Hair follicle morphology and hair loss in AGA mice were evaluated following 4-OI treatment. RESULTS: Senescence markers were significantly elevated in AGA DPCs, accompanied by increased senescence-associated β-galactosidase staining, reduced cell proliferation and migration, and enhanced apoptosis. DHT-induced mitochondrial dysfunction in DPCs was characterized by increased mitochondrial fragmentation, decreased mitochondrial cristae, superoxide accumulation, reduced membrane potential, and impaired oxidative phosphorylation. RNA sequencing identified ACOD1 as significantly downregulated in DHT-treated DPCs. ACOD1 knockdown induced mitochondrial dysfunction, cellular senescence, and functional impairment in DPCs, while ACOD1 overexpression ameliorated these DHT-induced phenotypes. Mechanistically, ACOD1 interacted with DDX1 to inhibit its methylation; ACOD1 knockdown enhanced DDX1 methylation, correlating with mitochondrial dysfunction and DPC senescence. Metabolomic analysis demonstrated that ACOD1 knockdown significantly reduced itaconate levels. Exogenous 4-OI supplementation reduced DDX1 methylation, ameliorated DHT-induced mitochondrial dysfunction and cellular senescence, promoted cell proliferation and migration, suppressed apoptosis, mitigated hair follicle miniaturization, and alleviated hair loss in AGA mice. CONCLUSIONS: Our findings reveal a novel mechanism underlying DPC senescence in AGA, wherein ACOD1 deficiency promotes DDX1 methylation, mitochondrial dysfunction, and subsequent DPC senescence. ACOD1 represents a promising therapeutic target for AGA, and 4-OI may have translational potential for the treatment of AGA.
Immune cell subsets linking insomnia trajectories and incident cognitive impairment: a prospective cohort study.
Chen L, Fu J, Jia X … +10 more , Zhang L, Jin X, Wu S, Zhu B, Sun K, Fu D, Wang Y, Liu Z, Li S, Zhang J
BMC Med · 2026 May · PMID 42218486 · Full text
BACKGROUND: This study aimed to examine the associations between insomnia trajectories and the risk of incident cognitive impairment, as well as to evaluate whether immune cell subsets mediate these associations. METHODS...
BACKGROUND: This study aimed to examine the associations between insomnia trajectories and the risk of incident cognitive impairment, as well as to evaluate whether immune cell subsets mediate these associations. METHODS: A total of 6,316 participants aged 50 years or older from the Health and Retirement Study (HRS) were included in this prospective cohort study. Insomnia symptoms, including severe insomnia, difficulty initiating sleep (DIS), difficulty maintaining sleep (DMS), early morning awakening (EMA), and nonrestorative sleep (NRS), were assessed using the Jenkins Sleep Questionnaire. Longitudinal insomnia trajectories were identified from three examination waves during 2010-2016 (waves 10, 12 and 13) using latent class trajectory modeling. Incident cognitive impairment was defined according to the Langa-Weir cognitive status classification during 2016-2022 (waves 13-16). Data on immune cell subsets were obtained through flow cytometry of peripheral blood samples collected in the 2016 HRS Venous Blood Substudy. Cox proportional hazards models and mediation analyses were performed to assess associations. RESULTS: Trajectories of DIS, EMA, and NRS were significantly associated with increased risk of incident cognitive impairment. Compared to participants with persistently good trajectories, those with worsening trajectories demonstrated significantly elevated risks of cognitive impairment, with hazard ratios of 1.37 (95% confidence interval [CI]: 1.16, 1.61) for DIS; 1.26 (95% CI: 1.07, 1.48) for EMA; and 1.16 (95% CI: 1.00, 1.35) for NRS. Mediation analysis revealed seven specific immune cell subsets as mediators of the associations of insomnia trajectories (DIS, EMA, and NRS) with the risk of incident cognitive impairment: CD4 + T cells (central memory, CM), CD4 + T cells (Naive), CD4 + T cells (Effector Memory, Tem), CD8 + T cells, CD8 + T cells (CM), CD8 + T cells (TemRA) and NK Cells (CD56LO), accounting for 1.16% to 8.21% of the total effect. Sex-stratified analysis revealed distinct mediation patterns: CD4 + T cells (Tem) and CD8 + T cells mediated the associations in males, whereas CD4 + T cells (CM), CD8 + T cells (CM) mediated the associations in females. CONCLUSIONS: These findings reveal the associations of dynamic insomnia trajectories with cognitive health, and potential immune mechanisms, suggesting that maintaining healthy sleep patterns may mitigate neurodegenerative progression.
Age-stratified associations of glycemia, blood pressure, and cholesterol with mortality in diabetes: A prospective cohort study.
Zhu Y, Lin L, Zhang J … +45 more , Jia X, Chen Y, Qiao H, Li M, Xu Y, Xu M, Wang T, Zhao Z, Qin G, Qin Y, Tang X, Ye Z, Shi L, Su Q, Yu X, Yan L, Wan Q, Chen G, Gao Z, Wang G, Shen F, Gu X, Luo Z, Chen L, Hou X, Huo Y, Li Q, Zhang Y, Zeng T, Liu C, Wang Y, Wu S, Yang T, Deng H, Chen L, Zhao J, Mu Y, Ning G, Liu J, Hu R, Bi Y, Wang W, Lu J, Hu W, 4C Study Group
BMC Med · 2026 May · PMID 42218468 · Full text
BACKGROUND: Optimization of HbA1c, blood pressure and cholesterol, referred to as the "ABCs", is central to the management of diabetes. However, the age-specific associations of these factors with mortality in patients w...
BACKGROUND: Optimization of HbA1c, blood pressure and cholesterol, referred to as the "ABCs", is central to the management of diabetes. However, the age-specific associations of these factors with mortality in patients with diabetes remains unclear. METHODS: In this prospective cohort study, 43,732 Chinese adults aged ≥ 40 years with diabetes were included from the China Cardiometabolic Disease and Cancer Cohort (4C) Study. Participants were stratified by age (< 55, 55-<65, 65-<75, ≥ 75 years). Cox proportional hazards regression and Fine-Gray competing risk models were employed to estimate the associations of HbA1c, systolic blood pressure (SBP), and low-density lipoprotein cholesterol (LDL-C) with all-cause, cardiovascular, and non-cardiovascular mortality across age groups. Relative importance and population attributable fractions (PAFs) were computed for each metabolic factor. RESULTS: During a median follow-up of 10.1 years, 3,975 deaths were documented. Age significantly modified the associations of HbA1c, SBP, and LDL-C with all mortality outcomes (all P for interaction < 0.05). Among participants aged < 75 years, HbA1c showed graded positive associations with all-cause, cardiovascular, and non-cardiovascular mortality. The SBP thresholds associated with increased mortality risk were 140 mmHg in those aged < 65 years and 160 mmHg in those aged 65-<75 years. Among those aged ≥ 75 years, however, the patterns of these associations differed markedly. Elevated mortality risk was observed only at HbA1c ≥ 9%, with a hazard ratio (HR) of 1.51 (95% confidence interval [CI]: 1.19-1.91) for all-cause mortality and a subdistribution hazard ratio (SHR) of 1.70 (95% CI: 1.23-2.36) for cardiovascular mortality, while SBP showed no significant association with any mortality outcome in this age group. Moreover, LDL-C emerged as a significant risk factor for cardiovascular mortality. Compared with participants with LDL-C < 1.8 mmol/L, those with LDL-C of 1.8-<2.6 mmol/L exhibited a significantly higher risk (SHR: 1.86; 95% CI: 1.11-3.11). Additionally, LDL-C had the largest PAF for cardiovascular mortality (9.6%) within this age group. CONCLUSIONS: The impacts of ABC factors on mortality risk vary substantially by age among adults with diabetes. In patients aged ≥ 75 years, less stringent glycemic and blood pressure targets may be appropriate, whereas lipid management remains critically important for reducing cardiovascular mortality.
Cytoreductive radical prostatectomy in patients with high-volume metastatic prostate cancer achieving deep biochemical response to contemporary systemic therapy: a multicentre, prospective cohort study.
Huang C, Guo H, Gao W … +10 more , Huang M, Ji G, Rui R, He S, Yu Y, Zhang N, Tian Y, Niu Y, Li X, Zhou L
BMC Med · 2026 May · PMID 42218463 · Full text
BACKGROUND: Cytoreductive radical prostatectomy (CRP) may improved outcomes in men with low-volume metastatic hormone-sensitive prostate cancer (mHSPC), but its roles in high-volume disease remains controversial. Contemp...
BACKGROUND: Cytoreductive radical prostatectomy (CRP) may improved outcomes in men with low-volume metastatic hormone-sensitive prostate cancer (mHSPC), but its roles in high-volume disease remains controversial. Contemporary systemic therapy has enabled an increasing proportion of patients with high metastatic burden to achieve deep disease remission, creating a potential window to assess additional benefit from primary tumor resection. We aimed to investigate the feasibility and oncological outcomes of CRP in patients with mHSPC, including those with high-volume disease. METHODS: This multicentre, prospective study recruited patients with histologically diagnosed mHSPC from September, 2018 to October, 2023. All eligible patients received lifelong androgen deprivation therapy combined with novel androgen receptor pathway inhibitors and achieved a deep biochemical response (prostate-specific antigen [PSA] < 0.2 ng/ml). Patients either underwent CRP plus standard of care (SOC) or received SOC only. The primary endpoint was radiographic progression-free survival (rPFS). Secondary endpoints were overall survival (OS) and PSA progression-free survival (PSA-PFS). Multivariable Cox proportional hazards models, incorporating CRP as a time-dependent covariate, were used to evaluate associations with outcomes. Propensity score matching (PSM) was applied to balance baseline characteristics between groups. RESULTS: Of 126 patients enrolled, 62 underwent CRP + SOC and 64 received SOC. At a median follow-up of 46.7 months, patients in the CRP + SOC group demonstrated prolonged survival compared with those receiving SOC alone. Among 74 patients with high-volume diseases, CRP remained associated with significant longer rPFS (hazard ratio [HR] 0.36, p = 0.035), OS (HR 0.10, p = 0.006), and PSA-PFS (HR 0.32, p = 0.017). Multivariate Cox regression analysis identified CRP as an independent prognostic factor (all p < 0.05). After PSM, 30 well-balanced pairs were identified. In the matched cohort, CRP + SOC was consistently showed improved rPFS (HR 0.31, p = 0.036), OS (HR 0.22, p = 0.031), and PSA-PFS (HR 0.25, p = 0.009) compared with SOC alone. CONCLUSIONS: CRP is feasible and associated with improved oncological outcomes in well-selected patients with mHSPC who achieved deep biochemical response to contemporary systemic therapy, including those with high-volume metastatic disease. However, these findings require validation in larger, prospective, randomized controlled trials.
Imaging endpoints in inflammatory bowel disease: current evidence and future directions for ultrasound and MRI.
Faggiani I, Danese S, Biroulet LP … +3 more , Jairath V, Rubin DT, Allocca M
BMC Med · 2026 May · PMID 42216172 · Full text
BACKGROUND: Imaging has become a central and rapidly evolving domain in inflammatory bowel disease (IBD) because it captures disease manifestations that extend beyond the mucosa and, therefore, beyond what can be visuali...
BACKGROUND: Imaging has become a central and rapidly evolving domain in inflammatory bowel disease (IBD) because it captures disease manifestations that extend beyond the mucosa and, therefore, beyond what can be visualized by endoscopy, including transmural inflammation, extraintestinal complications and small-bowel involvement that are not adequately assessed by conventional approaches. MAIN BODY: In this narrative review, we synthesize the latest evidence on non-invasive cross-sectional imaging-intestinal ultrasound (IUS) and magnetic resonance imaging/enterography (MRI/MRE)-and outline a pragmatic framework for integrating these modalities into clinical trials. The timing of this review reflects the recent publication of two major consensus statements that specifically address how IUS and MRI can be standardized and operationalized as trial endpoints. We first summarize recommended technical standards for acquisition and reporting. We then outline trial-ready definitions of response and remission for clinical trials using validated scores and discuss the emerging but still variably defined construct of transmural healing, understood as the resolution of inflammation across the full thickness of the bowel wall and increasingly associated with improved long-term outcomes. Building on these components, we propose a practical pathway to incorporate imaging from screening, through on-treatment monitoring at predefined windows to adjudicate response/remission, and, where appropriate, to evaluate transmural healing. We emphasize central reading, harmonized timing, and standardized data repositories to minimize bias. CONCLUSION: Even though meaningful steps have been taken to integrate cross-sectional imaging, it remains essential to evaluate its use pragmatically in both trials and routine care. Furthermore, cost-effectiveness analyses are needed to determine whether widespread implementation is economically justified, and studies should examine whether incorporating IUS/MRI improves patient adherence to clinical trial protocols and follow-up compared with traditional assessment pathways.
The impact of shielding on COVID-19 hospitalisations and deaths during 2020 in England: a transmission modelling evaluation using the OpenSAFELY platform.
Filipe JAN, van Leeuwen E, Henderson A … +11 more , Davies NG, Jarvis C, Curtis HJ, Pouwels KB, Edmunds WJ, MacKenna B, Bacon S, Mehrkar A, Goldacre B, Tomlinson L, Eggo RM
BMC Med · 2026 May · PMID 42216016 · Full text
BACKGROUND: During the early phase of the COVID-19 pandemic in England, people with pre-existing conditions at severe clinical risk were advised to drastically reduce face-to-face contacts in a policy known as "shielding...
BACKGROUND: During the early phase of the COVID-19 pandemic in England, people with pre-existing conditions at severe clinical risk were advised to drastically reduce face-to-face contacts in a policy known as "shielding". The impact of shielding in preventing COVID-19 hospitalisations and deaths has not been evaluated nationally using transmission-dynamic modelling. METHODS: With the approval of NHS England, we present a retrospective cohort evaluation of the shielding policy, drawing data from electronic health records (EHRs) for 24 million patients in England accessed through the OpenSAFELY platform. The study is from 1 January-1 December 2020, prior to vaccination and SARS-CoV-2 variants. We used a dynamic model of SARS-CoV-2 transmission, infection, and hospitalisation, stratified by age and shielding status for the general population (excluding care homes). We estimated transmission rates in the shielding and non-shielding groups using data from the CoMix social contact survey and fitted the model to hospitalisations and deaths in and outside hospital. RESULTS: We found the risk of hospitalisation was higher for shielding people at all ages and increased with age. The hospitalisation fatality risk was similar between shielding and non-shielding people from January to June 2020 and greater in shielding people from July 2020 onward. By comparing the observed epidemic to a counterfactual scenario without shielding, we projected that between 7800 and 10,600 hospitalisations and 2300 to 3500 deaths due to COVID-19 were directly averted by the policy, corresponding to reductions of 25% (24, 28%) and 23% (21, 25%), respectively, in the shielding population in England up to 1 December 2020. Including also the indirect effect in the non-shielding population, we projected 14,700 - 21,800 hospitalisations and 3700-5500 deaths due to COVID-19 were averted by the policy in the total population, each corresponding to reductions of 13% (11, 16%). CONCLUSIONS: Based on our data and assumptions, we estimated the shielding policy reduced severe illness and mortality in clinically-extremely vulnerable shielding patients in England up to 1 December 2020, and, through indirectly-reduced exposure, also in the non-shielding population. Similar policies for other infections could have a comparable public health impact in reducing both mortality and pressure on health services.
Maternal factors associate with microbiota-derived extracellular vesicle profiles in pregnancy: a clinical cohort study.
Turunen J, Kyrö K, Virta J … +8 more , Suokas M, Hekkala J, Karikka S, Kaisanlahti A, Reunanen J, Paalanne N, Tejesvi MV, Ruuska-Loewald T
BMC Med · 2026 May · PMID 42210279 · Full text
BACKGROUND: While most clinical microbiome research has investigated gut microbiota, less is known about extracellular vesicles (EVs) produced by microbiota. Microbiota-derived EVs form a distinct taxonomic entity from t...
BACKGROUND: While most clinical microbiome research has investigated gut microbiota, less is known about extracellular vesicles (EVs) produced by microbiota. Microbiota-derived EVs form a distinct taxonomic entity from the gut microbiota. Recently, microbiota-derived EVs from maternal microbiota have been shown to reach the fetus, which could be an important mechanism of microbiota-host interaction during the fetal period. We hypothesized that maternal factors could change the composition of microbiota-derived EVs during pregnancy. METHODS: We compared the influence of antibiotics and maternal weight on microbiota-derived EVs secreted by maternal microbiota during pregnancy. We collected fecal samples from 60 pregnant women and 18 amniotic fluid samples from those undergoing C-section. Microbiota-derived EVs were isolated from the samples using size-exclusion chromatography and density-gradient ultracentrifugation and characterized using transmission electron microscopy (TEM) and nanoparticle tracking analysis (NTA). RNA was isolated from the microbiota-derived EVs and converted to complementary DNA (cDNA), and 16 S rRNA gene sequencing was performed. RESULTS: Altogether, 18 (30%) women had received antibiotics during pregnancy and 37 (62%) during delivery. Twenty (33%) women were lean, 27 (45%) had overweight and 13 had obesity (22%) during the first trimester. Taxonomic diversity of microbiota-secreted microbiota-derived EVs was lower in women exposed to antibiotics during pregnancy. When women exposed to antibiotics during delivery were excluded, the differences were not statistically significant. The microbiota-derived EVs differed in the amniotic fluid and maternal feces in women with overweight and obesity, gestational diabetes (GDM), and those who gained > 15 kg during pregnancy, as many bacterial origins of microbiota-derived EVs were depleted in these women. A beta diversity analysis of microbiota-derived EVs from fecal samples showed significant differences between the overweight and obesity groups. Diversity analysis showed no differences in various health factors during pregnancy, including asthma, allergies, or smoking. CONCLUSIONS: Maternal factors influence the composition of microbiota-derived extracellular vesicles in feces and amniotic fluid of pregnant women, which may change host-microbiota interaction in the fetal period.
Machine learning and natural language processing for the identification of potential mental disorders among school-age children: a prospective birth cohort study.
Chen S, Dang T, Qian M … +7 more , Liang H, Bedada DT, Louw QA, Moore A, Cardinal RN, Ford TJ, Jiang F
BMC Med · 2026 May · PMID 42210272 · Full text
BACKGROUND: Early identification of childhood mental health disorders is a critical public health objective. Existing screening approaches, largely dependent on observer reports, are resource-intensive and may overlook s...
BACKGROUND: Early identification of childhood mental health disorders is a critical public health objective. Existing screening approaches, largely dependent on observer reports, are resource-intensive and may overlook subtle internalized symptoms. The analysis of children's linguistic expression presents a scalable and potentially more objective alternative. This study evaluates whether combining natural language processing (NLP) of children's essays with conventional risk factors improves the detection of mental health difficulties in school-age populations, relative to models based on a single data source. METHODS: We conducted a prospective analysis using data from the UK-based National Child Development Study (NCDS), a national birth cohort initiated in 1958. Data from birth, age 7, and age 11 assessments were analyzed. The final sample included 8,981 children (4,428 [49.3%] female) who completed a creative writing essay at age 11 describing their imagined life at age 25. Predictors comprised traditional risk factors (perinatal, socioeconomic, and parental engagement variables) and linguistic features computationally extracted from the essays. The primary outcome was potential mental health disorder at age 11, defined as scoring above the 95th or 90th percentile on the teacher-completed Bristol Social Adjustment Guide (BSAG). The mother-completed Rutter A Scale was used for sensitivity analysis. Machine learning models incorporating various predictor combinations were developed, and their predictive performance was evaluated using area under the receiver operating characteristic (AUROC) values. RESULTS: Using BSAG 95th percentile threshold, models combining top five selected variables with essay features achieved significantly higher predictive capability (AUROC:0.77, 95%CI:0.71-0.83) compared to models using all variables (AUROC:0.70, 95%CI:0.63-0.76) or essay features alone (AUROC:0.67, 95%CI:0.60-0.74). At 90th percentile threshold, this integrated approach showed similar improvement (AUROC:0.81, 95%CI:0.78-0.85). Key predictors included gestational length, maternal parity, parental age, residential characteristics, parental engagement metrics, and children's body mass index. Sensitivity analyses using Rutter A Scale confirmed these findings. CONCLUSIONS: In this prospective birth cohort study, integrating NLP analysis of children's essays with a small set of key risk factors substantially improved the identification of potential mental health disorders. This integrated approach represents a potential paradigm for developing scalable, objective screening tools, but requires validation in contemporary, diverse pediatric populations before clinical consideration.
Anti-IL-4Rα antibody SHR-1819 for moderate-to-severe atopic dermatitis: a randomized phase 2 study.
Gu C, Yin H, Yang B … +26 more , Ji S, Bian K, Man X, Lu J, Sui D, Zhou Y, Cheng F, Xu A, Li X, Jiang M, Diao Q, Ji C, Shi T, Ding Y, Ren H, Li Y, Liu H, Meng Z, Feng P, Zhang S, Bai X, Li P, Dong Y, Liu S, Zhang C, Xu J
BMC Med · 2026 May · PMID 42210243 · Full text
BACKGROUND: SHR-1819 is a novel monoclonal antibody targeting IL-4Rα, developed for the treatment of type 2 inflammatory diseases such as atopic dermatitis (AD). This phase 2 study aimed to evaluate SHR-1819 for treating...
BACKGROUND: SHR-1819 is a novel monoclonal antibody targeting IL-4Rα, developed for the treatment of type 2 inflammatory diseases such as atopic dermatitis (AD). This phase 2 study aimed to evaluate SHR-1819 for treating moderate-to-severe AD. METHODS: Patients with an Eczema Area and Severity Index (EASI) score ≥ 16, an Investigator's Global Assessment (IGA) score ≥ 3, and ≥ 10% body surface area affected by AD were randomized (1:1:1:1) to receive SHR-1819 at 300 mg every 2 weeks (Q2W), 600 mg Q2W, 600 mg every 4 weeks (Q4W), or placebo for 16 weeks. Patients were required to use topical moisturizer at least 7 days before randomization, twice daily, and continuously throughout the entire study period. Primary endpoint was the proportion of patients achieving a ≥ 75% reduction from baseline in EASI score (EASI-75) at week 16. RESULTS: A total of 157 patients received treatment (n = 39, 40, and 41 in the SHR-1819 300 mg Q2W, 600 mg Q2W, and 600 mg Q4W groups; n = 37 in the placebo group). At week 16, the EASI-75 rate was numerically higher in the SHR-1819 groups, compared with the placebo group (69.2% [95% CI: 53.6%-81.4%] at 300 mg Q2W, 75.0% [95% CI: 59.8%-85.8%] at 600 mg Q2W, and 85.4% [95% CI: 71.6%-93.1%] at 600 mg Q4W vs. 37.8% [95% CI: 24.1%-53.9%]; all nominal p < 0.01). Compared with placebo, more patients treated with SHR-1819 achieved IGA score 0-1 and ≥ 2 points reduction, and had ≥ 4 points reduction in weekly average daily Peak Pruritus Numerical Rating Scale score. Treatment-related adverse events (TRAEs) were comparable between the SHR-1819 and placebo groups (45.8% vs. 40.5%). The most common TRAE with SHR-1819 was injection site reaction (10.8%), increased blood bilirubin (5.8%), and conjunctivitis (5.0%). Dose-proportional increases in SHR-1819 concentrations were observed within the studied range. SHR-1819 revealed notable reductions in thymus and activation-regulated chemokine, immunoglobulin E, and eotaxin-3 levels across all doses. CONCLUSIONS: SHR-1819 demonstrated promising efficacy in improving the signs and symptoms of AD, with a well-tolerated safety profile and favorable pharmacokinetic, and pharmacodynamic characteristics. TRIAL REGISTRATION: ClinicalTrials.gov, NCT05549947; registered on September 22, 2022.
Gut microbiota dysbiosis and host metabolite-immune crosstalk drives the pathogenesis of neonatal lupus erythematosus: a multi-omics analysis.
Sun W, Jin X, Li Y … +9 more , Zhou M, Liu X, Wang H, Geng H, Li L, Hu J, Zhou X, Liu Y, Zhu X
BMC Med · 2026 May · PMID 42210241 · Full text
BACKGROUND: Neonatal lupus erythematosus (NLE) is a rare autoimmune condition triggered by the transplacental transfer of maternal antibodies. Despite its recognized clinical manifestations, the underlying pathogenesis r...
BACKGROUND: Neonatal lupus erythematosus (NLE) is a rare autoimmune condition triggered by the transplacental transfer of maternal antibodies. Despite its recognized clinical manifestations, the underlying pathogenesis remains incompletely understood. This study seeks to explore the disruption of the gut microbiota-host metabolism-immune axis in anti-Ro/La-positive neonates, and to assess its potential role in the development of NLE. METHODS: This multicenter, cross-sectional study included 90 neonates, divided into three groups: 30 with neonatal lupus erythematosus (NLE), 30 with positive antibodies but without clinical manifestations (No-NLE), and 30 healthy controls. We performed 16 S rRNA sequencing to analyze gut microbiota composition, untargeted plasma metabolomic profiling, and proteomic analysis to identify alterations associated with the pathogenesis of NLE. RESULTS: We identified significant alterations in the gut microbiota, plasma metabolome, and proteome profiles of anti-Ro/La-positive neonates. NLE infants exhibited marked enrichment of Enterobacteriaceae and depletion of Bifidobacterium and Clostridium butyricum. Metabolomic analysis revealed hyperactivation of β-alanine and purine metabolism, along with impaired α-linolenic acid metabolism and endocannabinoid signaling. Proteomic profiling indicated aberrant protein expression that modulated IFN signaling, particularly within the C-type lectin receptor pathway. Dysregulation of the spleen tyrosine kinase (SYK) and high-affinity immunoglobulin epsilon receptor subunit gamma (FCER1G) decoupling was observed, correlating with elevated IFN-α and NF-κB p65 levels. Integrated correlation analysis revealed significant associations among differential microbial taxa, plasma metabolites, and proteins. Notably, E. coli-associated metabolites and proteins displayed inverse relationships with those associated with C. butyricum. CONCLUSIONS: These findings represent comprehensive evidence of dysregulation along the "gut microbiota-host metabolism-immune" axis in neonatal lupus erythematosus (NLE), providing novel insights into the disease's underlying heterogeneity.
Impact of atrial fibrillation on clinical outcomes in 28,492 patients following open-heart cardiac valve surgery: A statewide population-linkage study.
Anna Ne JY, Chow CK, Chow V … +4 more , Hyun K, Kritharides L, Brieger D, Ng ACC
BMC Med · 2026 May · PMID 42204578 · Full text
BACKGROUND: Atrial fibrillation (AF) is common after cardiac surgery. Few studies compared clinical outcomes associated with AF between patients undergoing aortic valve surgery (AVSx) versus mitral valve surgery (MVSx)....
BACKGROUND: Atrial fibrillation (AF) is common after cardiac surgery. Few studies compared clinical outcomes associated with AF between patients undergoing aortic valve surgery (AVSx) versus mitral valve surgery (MVSx). METHODS: Patients who had open-heart cardiac valve surgery (1- July-2003 to 31-March-2021) identified from the Admitted-Patient-Data-Collection database in Australia were stratified by AF status (No-AF vs. New-AF vs. Prior-AF during index valve surgery) and followed up to 31-March-2022. Multivariable Cox regression and Fine-Gray competing risk analyses were performed to assess the association of AF status on all-cause mortality and non-fatal outcomes respectively. RESULTS: The cohort comprised 28,492 patients (whole cohort median age 71.6yrs [interquartile range 62.7-78.3yrs]; 65.6% males): AVSx, n = 18,949, median age 73.3 [IR 65.4-79.4yrs], 67.8% males; MVSx, n = 9543, MVSx: median age 67.6 [IR 58.2-75.5yrs], 61.2% males. During a median 6.58yrs (3.4-10.5yrs) follow-up, Prior-AF and New-AF patients had significantly higher all-cause mortality (AVSx-Prior-AF: 57.9% vs. AVSx-New-AF: 41.5% vs. AVSx-No-AF: 32.8%; MVSx-Prior-AF: 41.0% vs. MVSx-New-AF: 29.8% vs. MVSx-No-AF: 22.4%) (both logrank P < 0.001). In the AVSx subgroup, both New-AF and Prior-AF were independently associated with all-cause mortality (aHR = 1.16, 95%CI = 1.10-1.22; aHR = 1.69, 95%CI = 1.59-1.79 respectively) compared to No-AF patients. In the MVSx subgroup, only Prior-AF was associated with increased all-cause mortality (aHR = 1.47, 95% CI = 1.33-1.61), all P < 0.001. Ischaemic stroke was significantly higher in the AVSx New-AF and AVSx-Prior-AF subgroups. CONCLUSIONS: Patients undergoing valve surgery have different risks of adverse clinical outcomes, with target valve and baseline AF status being associated with these outcomes.
Putative glymphatic dysfunction links extracellular fluid dysregulation to white matter degeneration and clinical impairment in amyotrophic lateral sclerosis.
Jin X, Fu Y, Qiu T … +9 more , Li J, Zhang H, Chen Y, Chen K, Zhang Y, Wang J, Yi X, Palaniyappan L, Braden BB
BMC Med · 2026 May · PMID 42204548 · Full text
BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by progressive motor neuron degeneration and prominent extra-motor involvement. Impaired clearance of neurotoxic protein...
BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by progressive motor neuron degeneration and prominent extra-motor involvement. Impaired clearance of neurotoxic proteins has led to increasing interest in the brain glymphatic system; however, its in vivo associations with brain microstructure and clinical heterogeneity remain incompletely understood. METHODS: One hundred forty-six patients with ALS and 149 demographically matched healthy controls (HCs) underwent multimodal MRI and comprehensive clinical assessments. Putative glymphatic function was quantified using diffusion tensor imaging along perivascular space (DTI-ALPS). Extracellular free water fraction (FWF) and free-water-corrected fractional anisotropy (fwcFA) were derived to characterize extracellular fluid and white matter microstructure. Group differences were assessed using vertex-wise and voxel-wise analyses with correction for multiple comparisons. Associations among imaging metrics and clinical measures were evaluated using correlation and serial mediation analyses. RESULTS: Compared with HCs, patients with ALS exhibited significantly reduced DTI-ALPS index, widespread increases in cortical FWF, bidirectional alterations in white matter FWF, and extensive reductions in fwcFA across major white matter tracts. Reduced DTI-ALPS was associated with changes in extracellular free water and white matter microstructural integrity, whereas FWF and fwcFA measures were associated with functional, cognitive, and emotional outcomes. Mediation analyses identified significant indirect associations between DTI-ALPS and both functional and cognitive measures through a pathway involving cortical FWF, white matter FWF, and fwcFA, although direct associations were not observed. CONCLUSIONS: These findings provide in vivo evidence that putative glymphatic dysfunction co-occurs with extracellular fluid alterations, white matter microstructural changes, and clinical impairment in ALS. Multi-compartment diffusion imaging may offer complementary markers for characterizing brain microstructure and its clinical relevance in ALS.
WISE-Therapy (What's Important: Schedule and Engage) and bouldering psychotherapy for depression: A randomized clinical trial.
Kornhuber J, Lewczuk P, Siegmann EM … +4 more , Schneider S, Eversmann L, Kind L, Luttenberger K
BMC Med · 2026 May · PMID 42204537 · Full text
BACKGROUND: Group therapies address the growing treatment demand-supply gap for depression. This study evaluated whether the novel WISE-Therapy (WISE-T; What's Important: Schedule and Engage) and Bouldering Psychotherapy...
BACKGROUND: Group therapies address the growing treatment demand-supply gap for depression. This study evaluated whether the novel WISE-Therapy (WISE-T; What's Important: Schedule and Engage) and Bouldering Psychotherapy (BPT) are more effective in reducing depressive symptoms in an outpatient group therapy setting than treatment as usual (TAU). METHODS: This randomized, controlled, assessor-blinded, longitudinal, clinical trial was conducted in a naturalistic monocentric setting in Erlangen (Germany) between April 2022 and March 2023, with follow-up until July 2024. 128 adults were randomly assigned to WISE-T (44), BPT (40), or TAU (44). In 10 weekly 2-hour group sessions, WISE-T focused on identifying what is important, scheduling meaningful activities, and engaging in them for long-term mental health, and BPT combined psychotherapy with bouldering, while the control group received TAU. Depression severity was measured with the Montgomery-Asberg Depression Rating Scale at baseline, post-intervention, and one-year follow-up, and analyzed with a hybrid marginal model. RESULTS: Both intervention groups showed significantly greater reduction in depressive symptoms than controls at post-intervention (WISE-T: -5.5 points, 95%-CI [-9.5 to -1.5], P = .007, d = 0.62; BPT: -4.2 points, 95%-CI [-8.2 to -0.3], P = .037, d = 0.48). Response rates were 35.3% for WISE-T, 29.7% for BPT, and 21.1% for controls. Remission rates were significantly higher in WISE-T (17.6%) than in controls (2.6%, P = .047). Treatment adherence was good with minimal adverse events reported. The secondary outcomes showed significant results for anxiety, sense of coherence, self-efficacy, and mindfulness during physical activity. CONCLUSIONS: Both interventions demonstrated efficacy in reducing depressive symptoms compared with controls in this single-center setting. The study supports the integration of both therapies into outpatient care settings. TRIAL REGISTRATION: Study procedures received approval from the Friedrich-Alexander-Universität Erlangen-Nürnberg Ethics Committee (Ref. 21-332-B) on December 13, 2021. The Trial was preregistered in March 2022 via ISRCTN12347878 .
Thyroid-stimulating hormone receptor mediates peripheral-central neuroimmune crosstalk in autoimmune thyroid diseases.
Zhang H, Jiang S, Zhu T … +10 more , Liu Y, Li J, Fang S, Li Y, Sun J, He X, Tong C, Gao Z, Fan X, Zhou H
BMC Med · 2026 May · PMID 42204533 · Full text
BACKGROUND: Organ-specific autoimmune diseases, particularly Graves' disease (GD) and its extrathyroidal manifestation, Graves' orbitopathy (GO), are characterized by systemic autoimmunity that may extend its impact to t...
BACKGROUND: Organ-specific autoimmune diseases, particularly Graves' disease (GD) and its extrathyroidal manifestation, Graves' orbitopathy (GO), are characterized by systemic autoimmunity that may extend its impact to the central nervous system (CNS). While thyroid-stimulating hormone receptor (TSHR) is the primary driver of pathological remodeling in the thyroid and orbital tissues, emerging evidence suggests it is also expressed in the brain and may participate in neuroimmune signaling. However, the molecular mechanisms linking peripheral TSHR-driven autoimmunity to these extended systemic features remain unclear. Thus, GD and GO provide a unique window to investigate how peripheral autoantibodies influence CNS involvement as part of its broader pathological spectrum. METHODS: Genome-wide association studies (GWAS) and post-GWAS analyses were integrated with bulk RNA sequencing, single-cell and spatial transcriptomics, and brain imaging phenotypes to comprehensively characterize peripheral and central alterations in GD and GO. Mendelian randomization was applied to test causal relationships between genetic variants and brain signatures. Structural biology analyses were further conducted including protein-protein docking, small-molecule docking, and normal mode dynamics to identify prospective modulators of TSHR. Immunofluorescence staining was performed in a GO mouse model to validate the colocalization of potential interacted proteins in the specific brain region. RESULTS: Brain imaging-derived phenotypes (IDPs) alterations in GO and GO were systematically analyzed to identify neuroanatomical and functional alterations. TSHR was further identified as a shared genetic driver across peripheral and central compartments. TSHR was expressed in spiny projection neurons, microglia, and peripheral T cells, with cell-cell communication analyses highlighting TSHR-mediated interactions among neurons, endothelial cells, and microglia. Immunofluorescence staining in a GO mouse model confirmed the colocalization of TSHR with FN1 and GNAS in the basal ganglia, providing tissue-level validation of the computationally predicted ligand-receptor interactions. Immune profiling further showed immune alterations in GD and GO. Structural modeling supported plausible physical interfaces between TSHR and interacting proteins, and small-molecule screening identified three repurposable compounds - venetoclax, irinotecan, and dutasteride - with predicted favorable docking scores and stable binding poses in our simulations. CONCLUSIONS: These findings demonstrate that TSHR acts as a molecular hub mediating peripheral-central neuroimmune crosstalk in GD and GO. The results support a broader "disease-molecule axis" framework that links genetic susceptibility with multi-level immune and neural mechanisms. This work provides mechanistic insights relevant to the development of TSHR-targeted therapies, with implications for both peripheral immune modulation and central regulation. However, the limited sample size, lack of longitudinal follow-up, and absence of in vivo validation warrant cautious interpretation and further investigation.
The association between GLP-1R expression and cardiovascular-kidney-metabolic-related diseases in non-diabetic and non-obese population: evidence triangulation using Mendelian randomization, observational and polygenic score association analysis.
Chen Z, Yang Q, Liu J … +20 more , Zhao H, Ying H, Liu H, Huang L, Lin H, Wang S, Li M, Sun Y, Wang T, Zhao Z, Xu M, Chen Y, Xu Y, Lu J, Ning G, Gu Y, Wang W, Li J, Bi Y, Zheng J
BMC Med · 2026 May · PMID 42192387 · Full text
BACKGROUND: Glucagon-like peptide-1 receptor (GLP-1R) agonists are emerging as promising therapies for cardiovascular-kidney-metabolic (CKM) related diseases in individuals with type 2 diabetes mellitus (T2DM) or obesity...
BACKGROUND: Glucagon-like peptide-1 receptor (GLP-1R) agonists are emerging as promising therapies for cardiovascular-kidney-metabolic (CKM) related diseases in individuals with type 2 diabetes mellitus (T2DM) or obesity. But their effects in non-obese and non-diabetic individuals are unclear. This study triangulates evidence using Mendelian randomization (MR), polygenic scores (PGS) and observational analyses to estimate the associations of GLP-1R expression with chronic kidney disease (CKD), heart failure (HF) and metabolic dysfunction-associated steatotic liver disease (MASLD). METHODS: For the MR analysis, instruments mimicking GLP-1R expression were identified using pancreas-specific cis-expression quantitative trait loci from GTEx (N ≤ 305). MR-Robust method was used as the primary MR approach. PGS and observational analyses were performed both in non-diabetic and non-obese individuals separately. A genome-wide association study (GWAS) for MASLD (14,231 cases and 348,091 controls) was performed in the general population using data from UK Biobank. RESULTS: GLP-1R expression showed robust effects on CKD (odds ratio [OR] 0.96, 95%CI 0.95 to 0.97, q = 1.7 × 10 ), HF (OR = 0.96, 95%CI 0.94 to 0.97, q = 2.5 × 10) and MASLD (OR = 0.96, 95%CI 0.93 to 0.98, q = 1.3 × 10) in the general population. Consistent results were observed in validation analyses. Furthermore, PGS and observational analyses among non-T2DM and non-obese individuals found little evidence to support its association with CKD, HF or MASLD. GWAS analysis identified eight conditionally independent variants associated with MASLD, in which rs563199662 was a new signal located at TFPI region. CONCLUSIONS: This study provides multilayered evidence for GLP-1R expression in mitigating CKD, HF and MASLD risks in the general population, while de-prioritized its effect on CKM-related diseases in non-obese and non-diabetic individuals. Further clinical trials are needed to validate the effects of GLP-1R agonists in relative health population.
Handgrip weakness is associated with motor cortex atrophy in rheumatoid arthritis: a cross-sectional study with a hand exercise intervention.
Gustafsson AL, Heckemann RA, Erlandsson MC … +6 more , Lundgren VM, Dai Z, Silfverswärd ST, Pullerits R, Bokarewa MI, Wasén C
BMC Med · 2026 May · PMID 42192374 · Full text
BACKGROUND: Handgrip strength (HGS) in rheumatoid arthritis (RA) is commonly attributed to joint pathology, but may also reflect extra-articular manifestations, including atrophy of motor-related brain regions. We invest...
BACKGROUND: Handgrip strength (HGS) in rheumatoid arthritis (RA) is commonly attributed to joint pathology, but may also reflect extra-articular manifestations, including atrophy of motor-related brain regions. We investigated HGS as a marker of peripheral joint status, systemic immune regulation, and central motor integrity. METHODS: Maximal HGS was assessed using a dynamometer. Joint pathology was evaluated using radiographic and clinical measures, and upper limb disability using questionnaire. Brain volumes were quantified using MRI and MAPER software. Transcriptome sequencing was performed on circulating CD4⁺ and CD14⁺ cells. In a six-month, single-arm pilot trial, a subgroup of patients performed daily hand exercises. Associations and longitudinal changes were analysed using linear mixed-effects models accounting for repeated measurements across hands and timepoints, with variable selection performed using LASSO regression. RESULTS: A total of 59 women with established RA were included in the cross-sectional analysis (median age 64 years [range 23-76], DAS28 2.46 [1.1-5.8], disease duration 11 years [0-45]). Lower HGS was associated with greater disability. HGS was also independently associated with premotor and supplementary motor cortex (PMA/SMA) volume after adjustment for age, hand dominance, and joint pathology. Among joint pathology measures, tender joint count showed a significant negative association with HGS. Transcriptome analyses of CD4⁺ and CD14⁺ cells indicated that lower HGS was associated with reduced immune responsiveness and altered cytokine signalling pathways. In a six-month pilot hand exercise trial (n = 12; median age 54 years [28-68], DAS28 2.87 [1.2-3.6], disease duration 14 years [1-40]), HGS increased at 3 months, with a non-significant trend at 6 months. Baseline PMA/SMA volume showed a non-significant trend towards predicting HGS improvement. Longitudinal analyses revealed region-specific brain changes, with a decrease in PMA/SMA volume and an increase in insular volume over time. CONCLUSIONS: Handgrip weakness in RA may reflect both joint pathology and motor cortex atrophy in the PMA/SMA. Hand exercise improved HGS and induced certain structural changes in the brain, though effects on motor regions remain uncertain and warrant further study. TRIAL REGISTRATION: Clinical trial registration: ClinicalTrials.gov, NCT04378621. Registration date: May 5, 2020.
Executive function profiles identify stable schizophrenia subtypes with distinct symptoms, biological markers and treatment responses: a cross-time clustering and validation study.
Zhang T, Huo X, Chen J … +1 more , Zhao X
BMC Med · 2026 May · PMID 42178548 · Full text
BACKGROUND: Executive function (EF) is a heterogeneous neuropsychological construct, and impairments in EF dimensions represent a core aspect of psychopathology in schizophrenia that varies across individual patients. Cu...
BACKGROUND: Executive function (EF) is a heterogeneous neuropsychological construct, and impairments in EF dimensions represent a core aspect of psychopathology in schizophrenia that varies across individual patients. Currently, how this inter-individual variability characterizes schizophrenia subgroups, along with their distinctions in clinical characteristics and prognostic outcomes, remains unclear. METHODS: Three EF dimensions (inhibitory control, working memory, cognitive flexibility) were assessed in the main sample (N = 329), its follow-up subset, and an independently "recurring local validation" patient sample (N = 114). Fuzzy clustering was applied to baseline EF assessments to discover and validate the core subtypes after excluding cluster-ambiguous cases in the main and independent samples, respectively. Subtype-based classification trained on the main sample was then tested in the independent sample. Importantly, the stability of these subtypes and their remission statuses, along with associated longitudinal changes in clinical and biological factors, were evaluated, and baseline subtype statuses were also used to predict outcomes. RESULTS: Two longitudinally stable, independently validated core EF subtypes were identified, with Subtype I exhibiting selective deficits limited to response inhibition and cognitive flexibility ("EF-Focal") and Subtype II showing broad EF impairments across all dimensions ("EF-Global"). Compared to the "EF-Global" subtype, patients within the "EF-Focal" subtype presented significantly milder positive, affective, and cognitive symptoms, worse working memory updating, lower inflammatory markers, and better metabolic profiles at baseline. Models trained on baseline EF assessments from the main sample accurately classified patient subtypes in the independent sample (area under the curve [AUC] = 0.79); these baseline subtypes moreover classified patients' remission statuses independently of overall severity at intake (AUC = 0.78). Remitted patients were observed to have significantly greater reductions in negative and cognitive symptoms, improved working memory maintenance, lower peripheral inflammatory levels, and superior metabolic functions over time. CONCLUSIONS: EF subtyping was associated with symptomatic, biochemical, and prognostic variations in individuals with schizophrenia, which could help to stratify patients within this disorder for targeted treatments.
Community health worker-led versus facility-based type 2 diabetes care in rural Lesotho: a cluster-randomized trial within the ComBaCaL cohort study.
Gerber F, Gupta R, Sanchez-Samaniego G … +26 more , Lejone TI, Tahirsylaj T, Raeber F, Saavedra EB, Esquivel-Valdés I, Chitja M, Molulela M, Khomolishoele M, Mota M, Bane M, Masike S, Sematle MP, Mofokeng M, Makabateng R, Mphunyane M, Sao L, Tlahali M, Litaba M, Basler DB, Kindler K, Ayakaka I, Grimm P, Seelig E, Chammartin F, Labhardt ND, Amstutz A
BMC Med · 2026 May · PMID 42174613 · Full text
BACKGROUND: Type 2 diabetes poses a growing public health burden in low- and middle-income countries, where major gaps in access to chronic care persist. Task-shifting to Community Health Workers (CHWs) and the use of di...
BACKGROUND: Type 2 diabetes poses a growing public health burden in low- and middle-income countries, where major gaps in access to chronic care persist. Task-shifting to Community Health Workers (CHWs) and the use of digital clinical decision support systems may bridge these gaps. Randomized trials evaluating CHW-led care models in which CHWs initiate, titrate, and monitor first-line diabetes treatment are lacking. METHODS: We conducted a cluster-randomised trial nested within the ComBaCaL (Community-Based Chronic Care Lesotho) cohort (NCT05596773). The cohort spans 103 rural villages in Lesotho, managed by trained, supervised CHWs. After home-based screening of cohort participants ≥40 years old or with body mass index ≥25 kg/m, all with type 2 diabetes were enrolled in the trial. In intervention villages, CHWs - guided by a tablet-based clinical decision support system - provided care, including initiation and monitoring of metformin, atorvastatin and aspirin. In control villages, participants were referred to facility-based care. The primary analysis included participants with uncomplicated and uncontrolled type 2 diabetes (fasting glucose ≥7 mmol/l) on glycated haemoglobin (HbA1c) at 12 months. RESULTS: From 13 May 2023 to 31 January 2024, 5'785 cohort participants were screened, 252 (4·4%) diagnosed with type 2 diabetes, and 103 (51 control, 52 intervention) included in the primary analysis (73·8% female, mean age 62·3 ± 12·8 years, mean HbA1c 7·2 ± 1·4%). At 12 months, HbA1c was 7·1 ± 1·9% in the control arm and 6·5 ± 1·3% in the intervention arm (adjusted mean difference -0·46%, 95%CI -1·14 to 0·22). Engagement in care was higher in the intervention arm. No relevant difference in safety outcomes was observed. CONCLUSIONS: CHW-led, clinical decision support system-assisted management of type 2 diabetes, including first-line drug prescription, may improve engagement in care and glycaemic control in rural low-resource settings. Larger studies are required to confirm these findings. TRIAL REGISTRATION: Clinicaltrials.gov: NCT05743387.
Determinants of pro- and anti-inflammatory cytokine profiles across populations.
Leonard SE, Ghanbari M, Sowa P … +12 more , van Meurs JBJ, Vallerga C, van Hagen PM, Völzke H, Ameling S, Völker U, Kondraciuk M, Dubatowka M, Kamiński K, Teumer A, Chaker L, Dalm VASH
BMC Med · 2026 May · PMID 42174607 · Full text
BACKGROUND: Cytokine dysregulation contributes to chronic inflammation and immune-mediated diseases, yet population-level determinants of pro- and anti-inflammatory cytokines remain poorly characterized. We aimed to iden...
BACKGROUND: Cytokine dysregulation contributes to chronic inflammation and immune-mediated diseases, yet population-level determinants of pro- and anti-inflammatory cytokines remain poorly characterized. We aimed to identify demographic and lifestyle determinants of plasma cytokine levels and evaluate reproducibility of inflammatory patterns across European populations. METHODS: In the population-based Rotterdam Study cohort (n = 3,456; mean age 57 years; 56% female), we examined associations between plasma levels of nine cytokines (Olink Inflammation Panel) and age, sex, smoking, body mass index (BMI), and alcohol consumption. Linear and non-linear regression models were applied, with stratified analyses where appropriate. Cytokine clustering was assessed using principal component analysis (PCA). Findings were replicated in two independent European cohorts using identical protocols. Additionally, associations between raw IL-6 levels and determinants were meta-analyzed across the two replication cohorts (total n > 4,000). RESULTS: Plasma IL-10, IL-6, IL-17 A, TNF, IFN-γ, IL-18, and IL-17 C increased with age; IL-18 and IL-17 C followed non-linear trends (P < 0.01). Females had lower IL-18 and IL-17 C levels (β: - 0.41 and - 0.32, respectively) but higher IFN-γ (β: 0.17). Smoking was associated with higher IL-10, IL-6, IL-18, and IL-17 C (β range: 0.10-0.54) and lower IFN-γ (β: -0.15) and IL-13 (β: - 0.10). BMI was positively associated with IL-6, IL-18, TNF, and IL-17 A levels (P < 0.05), and inversely with IL-10 (P < 0.001). Sex-specific associations were observed for alcohol use. PCA revealed stable pro-inflammatory cytokine clustering, consistent across cohorts. Replication in analyses confirmed a robust, shared pro-inflammatory signature, and meta-analysis supported consistent associations with older age, higher BMI, and current smoking. CONCLUSIONS: Older age, higher BMI, male sex, and current smoking are consistent and reproducible determinants of inflammatory cytokine profiles across European populations. These findings support the use of cytokine profiling in enhancing risk stratification for inflammation-related diseases.
Addressing the critical palliative care gaps in ethnic minority regions of low- and middle-income countries: a focus group study.
Wang H, Lyu X, Wang X … +3 more , Tang Y, Dong L, Xiang X
BMC Med · 2026 May · PMID 42174598 · Full text
BACKGROUND: Palliative care is an important approach to relieving suffering and improving quality of life for people living with serious illness. Yet its development remains challenging in many low- and middle-income cou...
BACKGROUND: Palliative care is an important approach to relieving suffering and improving quality of life for people living with serious illness. Yet its development remains challenging in many low- and middle-income countries, particularly among vulnerable populations such as ethnic minorities. In ethnic minority regions of China, the palliative care implementation is shaped by distinctive social-cultural and practical realities. This study aims to systematically develop the major barriers and to generate actionable recommendations to policymakers to facilitate the advancement and implementation of palliative care in these regions. METHODS: A qualitative approach was conducted using seven focus group discussions with 56 participants drawn from key stakeholder groups, including healthcare providers, policymakers, patients, and community workers. Data were analysed using reflexive thematic analysis. RESULTS: Six interrelated themes were developed: palliative care at the margins of local health systems, shortage of trained professionals, policy endorsement without local traction, palliative care as giving up rather than caring differently, linguistic distance and fragile therapeutic communication, and families carrying the burden of system absence. These themes suggested that the limited development of palliative care in ethnic minority regions of China reflected not only resource constraints, but also weak system integration and insufficient alignment with local sociocultural, linguistic, and caregiving realities. CONCLUSIONS: Advancing palliative care in ethnic minority regions requires improvements in essential resources, workforce training, culturally sensitive communication, and social support systems. The findings provide policy relevant insights for China and may also inform palliative care development in other low- and middle-income settings with underserved ethnic minority populations. TRIAL REGISTRATION: Not applicable.
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