BMC Medicine最新文献

Background: Metabolic syndrome (MetS) confers a high risk of cardiovascular disease, type 2 diabetes, and premature mortality. Dyslipidemia, particularly abnormalities in pro-atherogenic lipid profiles, is a key pathophysiological feature. Although exercise is a cornerstone intervention for MetS, the optimal modalities and doses for improving pro-atherogenic lipid profiles remain unclear. This study compared the effects of different exercise interventions on pro-atherogenic lipid profiles in adults with MetS.

Methods: We systematically searched PubMed, Embase, Web of Science, and the Cochrane Library through September 2025 for randomized controlled trials (RCTs) in adults with MetS. Pairwise meta-analyses, Bayesian network meta-analyses (NMAs), and dose-response models were performed. Risk of bias was assessed using RoB 2, and certainty of evidence was evaluated with the GRADE approach.

Results: Forty-nine RCTs involving 4144 participants were included, comprising 88 intervention arms: 28 high-intensity interval training (HIIT), 25 conventional aerobic exercise (CAE), 15 resistance training (RT), 14 combined aerobic and resistance exercise (CAREX), and 6 mind-body exercise (MBE). NMA showed that MBE ranked highest across most lipid outcomes, although its results were sensitive to a single trial. CAREX produced consistent and clinically meaningful reductions in non-high-density lipoprotein cholesterol (non-HDL-C), triglycerides (TG), and total cholesterol (TC), particularly at 500-1000 METs-min/week, while HIIT was most effective at 600-1000 METs-min/week. CAE and RT yielded overall favorable effects, but their dose-response thresholds were uncertain due to clustering of available trials around 600-900 METs-min/week. Low-density lipoprotein cholesterol (LDL-C) improved at≈244 METs-min/week (- 0.02 to - 0.28 mmol/L) and TG at≈510 METs-min/week(- 0.05 to - 0.10 mmol/L), with benefits plateauing above≈900 METs-min/week. Most outcomes were rated as moderate certainty using GRADE, with some downgraded for risk of bias and imprecision.

Conclusions: Structured exercise may improve pro-atherogenic lipid profiles in MetS. CAREX and HIIT appear promising at moderate doses, while MBE could serve as a feasible low-impact alternative for individuals with reduced exercise tolerance. These findings suggest preliminary dose-based targets that may help guide personalized exercise prescriptions in clinical practice.

Trial registration: PROSPERO CRD420251082352.

Background: Early discontinuation of dual antiplatelet therapy (DAPT) within 3 months after implantation of drug-eluting stents may reduce bleeding risk without increasing ischaemic events. This study aimed to assess whether 3-month DAPT is as safe as the conventional 12-month regimen in patients treated with Firehawk stents, which have demonstrated 99.9% reendothelialisation at 3 months by optical coherence tomography.

Methods: From January 1, 2019, to April 30, 2022, 2445 patients were randomly assigned to a 3-month (n = 1222) or 12-month DAPT regimen (n = 1223) in this randomised, open-label, non-inferiority trial, patients from 36 centres in China who underwent percutaneous coronary intervention with Firehawk stents. The primary endpoint was a composite of all-cause death, myocardial infarction, cerebrovascular accident, and major bleeding (Bleeding Academic Research Consortium type 2, 3, or 5) at 18 months. The co-equal secondary endpoints were major adverse cardiovascular events, defined as a composite of all-cause death, myocardial infarction and ischaemia-driven target lesion revascularisation, and major bleeding.

Results: From January 1, 2019, to April 30, 2022, 2445 patients were randomly assigned to 3-month (N = 1222) or 12-month DAPT regimen (N = 1223). Adherence to the protocol-defined DAPT duration was 71.0% and 95.5%, respectively. Rates of the primary endpoint were comparable between both groups (10.1% vs 10.9%). Non-inferiority of 3-month DAPT was established (absolute rate difference, - 0.76%; upper limit of 1-sided 97.5% CI, 1.70%; p non-inferiority = 0.0003, with a predefined non-inferiority margin of 3.5%). Rates of co-secondary endpoints showed no significant difference (both p > 0.05). Landmark analysis (3-18 months) showed significant lower rate of major bleeding (2.7% vs 4.4%; p = 0.03) with 3-month DAPT.

Conclusions: In patients treated with Firehawk stents, 3-month DAPT was non-inferior to 12-month DAPT for the primary composite endpoint of all-cause death, myocardial infarction, cerebrovascular accident, and major bleeding at 18 months.

Trial registration: NCT03008083 (clinicaltrials.gov).

Background: Most studies on HPV vaccination have focused on the antibody response and on bivalent and quadrivalent vaccines. For these reasons, an evaluation of T-cell responses in PWH on effective ART to the Gardasil 9® vaccine according to prior HPV infection and baseline CD4 T-cell count was performed.

Methods: We prospectively enrolled PWH on effective ART. T-cell responses were assessed by flow cytometry at pre-vaccination (T0), on the same day of the third dose (T1) and 6 months after the third dose (T2) after stimulation with a pool of HPV16 and HPV18 L1 peptide libraries. An evaluation of IFN-γ in supernatants was also carried out. Baseline CD4 T-cell count was defined at the first dose.

Results: An increase in the percentage of responding and polyfunctional T-cells was found in both HPV - and HPV + groups, with no significant differences between them at any time point. When the population was stratified according to baseline CD4 T-cell count, an increase was found only in > 500 cells/μL group for both the responding and polyfunctional T-cells. Furthermore, a higher frequency of responding CD4 T-cells at T1 (p = 0.0049), a higher frequency of responding CD8 T-cells at T1 and T2 (p = 0.05 and p = 0.02, respectively), a higher frequency of polyfunctional CD4 T-cells at T1 (p = 0.0242) and a higher frequency of polyfunctional CD8 T-cells at T2 (p = 0.02) were found in > 500 cells/μL group than in their relative counterpart. The analysis of the estimated change from T0 revealed no statistically significant differences between PWH with or without prior HPV infection, whereas significant associations between higher CD4 counts and improved immune responses were found.

Conclusions: Our study revealed a coordinated T-cell response against HPV16 and 18 after Gardasil9® vaccine in PWH, including those with a history of HPV infection. PWH with a lower CD4 T-cell count remains a group who may not mount a fully protective immune response and, therefore, may require additional protection or ad hoc vaccination strategies. These data reinforce the key role of basal CD4 level in modulating the immune response over time, while prior HPV infection did not significantly affect the rate and quality of the response.

Background: Amyotrophic lateral sclerosis (ALS) shows a male predominance, yet the underlying mechanism remains unclear. Although the loss of Y chromosome (LOY) in peripheral blood - a male-specific genetic alteration - has been implicated in certain neurodegenerative disorders (NDDs), its association with ALS in men remains unexplored and has not been explored.

Methods: We focused on men in the UK Biobank to investigate whether LOY influences the risk and prognosis of ALS. Initially, the LOY level for each male participant was determined using sequencing data. Subsequently, Cox proportional hazards (Cox PH) model analysis was used to assess LOY-associated risk of ALS; thirdly, piecewise linear regression, Kaplan-Meier, and Cox PH analysis assessed LOY's associations with ALS age at onset (AAO) and survival. Fourthly, multiple analytical methods were implemented to explore the relationship between LOY and ALS indicators, including plasma GFAP (glial fibrillary acidic protein) and NfL (neurofilament light chain). Finally, sensitivity analysis was carried out.

Results: Our final cohort consisted of 158,953 male participants, with a mean follow-up of 11.7 years. Among them, 297 individuals developed ALS. After adjusted multiple confounding factors, including C9orf72 hexanucleotide repeat expansion (HRE), male participants with LOY exhibited an elevated risk of developing ALS (HR [95% CI]: 1.619 [1.059-2.475], p = 0.026). LOY carrier may be more likely to be associated with a later AAO and shorter survival; however, this association did not reach statistical significance in multivariate models. Additionally, our findings revealed that LOY was significantly associated with elevated plasma NfL levels (p = 0.004). Moreover, the median Log2 R ratios of Y chromosome (mLRRY value) exhibited a modest inverse correlation with plasma GFAP levels (Pearson's r = - 0.059). Nevertheless, LOY did not exert an influence on the longitudinal trends of NfL and GFAP and was not clearly associated with C9orf72 HRE status.

Conclusions: Our results indicate that LOY makes a potential contribution to the risk of ALS and the elevation of plasma NfL levels. While LOY's impact on ALS AAO and survival requires further validation, these findings identify it as a promising sex‑specific therapeutic target and support its potential for stratifying male ALS patients toward personalized treatments.

Background: Verbal autopsies (VAs) collect information on deaths in low and middle-income countries occurring outside healthcare facilities to estimate causes of death (CODs) for use in epidemiological or planning studies. Physician coding of VAs focused on the narrative of deaths and past symptoms is current best practice. Large language models (LLM) such as GPT-5 enable possible use of the narrative portion of VAs to assign CODs. However, there are few if any robust comparisons of LLMs to physician coding.

Methods: We analyzed 6,939 VA records from a random sample of deaths in Sierra Leone (2019-2022) to compare five models: three LLMs (GPT-3.5, GPT-4, GPT-5) and two based on symptom algorithms (InterVA-5, InSilicoVA), against physician-assigned CODs. GPT models used narratives, whereas InterVA-5 and InSilicoVA relied on questionnaires. CODs were grouped into 19, 10, and 7 categories for adult, child, and neonatal deaths. We used cause specific mortality fraction (CSMF) accuracy and partial chance corrected concordance (PCCC) to assess population and individual-level agreement respectively, compared to the standard of physician coding. We stratified analyses by age group as CODs vary among neonates, children and adults.

Results: Overall, GPT-5 outperformed all models (PCCC = 0.71), followed by GPT-4 (0.61), GPT-3.5 (0.56), InSilicoVA (0.44), and InterVA-5 (0.44). GPT-5 achieved the highest performance for adult (0.68), child (0.71), and neonatal (0.65) deaths. Across ages, performance increased from 1 month to 14 years and declined from 15 to 69 years. GPT-5, GPT-4, GPT-3.5, and InSilicoVA achieved the highest PCCC in 14, 7, 7, and 2 of the 30 CODs, respectively. At the population level, GPT-5 achieved the highest CSMF accuracy (0.9), while all other models had comparable performance (0.74-0.79).

Conclusions: GPT models and InSilicoVA showed greater performance for specific CODs at the individual-level. GPT models demonstrated improvements over InterVA-5 and InSilicoVA models. This study provides foundational evidence for integrating LLM and algorithmic models with physician coding to improve the quality of VA data.

Objectives: We aimed to evaluate the safety and efficacy of cotrimoxazole for preventing infections in patients with glomerulonephritis (GN) receiving rituximab (RTX) therapy.

Study design and methods: This single-center, open-label randomized controlled trial enrolled 150 patients with GN who received RTX at Xijing Hospital between October 2022 and December 2023. Participants were randomized 1:1 to either the cotrimoxazole prophylaxis group (n = 75) or the non-cotrimoxazole group (n = 75). The primary endpoint was the cumulative incidence of infection over a 180-day follow-up period. Secondary endpoints included the incidence of severe infections and the rate of adverse events (AEs) attributed to cotrimoxazole.

Intervention: All patients received RTX at a dose of 1000 mg intravenously on days 1 and 14. CD19 + B-cell counts were monitored monthly for 6-month post-initial infusion; if CD19 + B cells remained detectable at the 6-month mark, an additional 1000-mg RTX dose was administered.

Cotrimoxazole prophylaxis protocol: Patients in the intervention group initiated oral cotrimoxazole on the same day as their first RTX infusion, with one tablet daily for seven consecutive days. Prophylaxis was repeated for 7 days following each subsequent RTX infusion, resulting in a total of 14 days of prophylaxis over the study period.

The non-cotrimoxazole group: They received no cotrimoxazole prophylaxis.

Results: Over 180 days of follow-up, 8 infectious episodes occurred in 7 patients in the cotrimoxazole group, compared with 19 episodes in 16 patients in the control group. The annualized incidence density of infections (per 100 person-years) was 20.80 (95% CI 11.36-30.24) in the cotrimoxazole group versus 54.83 (95% CI 43.09-66.57) in the control group. The hazard ratio (HR) for the cumulative incidence of infection was 0.39 (95% CI 0.17-0.88; log-rank test, P = 0.029), indicating a significant reduction in infection risk with cotrimoxazole prophylaxis.

Conclusions: Our findings demonstrate that cotrimoxazole prophylaxis for 1-week post-RTX infusion effectively prevents post-RTX infectious complications, reduces infection-related mortality, and does not elevate the risk of serious AEs. However, it should be noted that this study was a single-center investigation without a placebo control.

Trial registration: The study was registered on the Chinese Clinical Trial Registry (trial registration identifier: ChiCTR2200063564).

Background: Bronchopulmonary dysplasia (BPD) is one common and severe complication of preterm births. Prenatal infection/inflammation is the major cause driving preterm deliveries, but its contribution to the early-life lung development remains unclear.

Methods: Pregnant C57BL/6J mice were randomized at 15.5 or 18.5 days post coitum (dpc) to receive intraperitoneal injection of sterile saline, lipopolysaccharide (LPS) 50 μg/kg, or LPS 100 μg/kg. Animal experiments were performed compliantly to the ARRIVE guidelines. Lungs of newborn pups of mixed genders were harvested at the first postnatal day (P1) for histopathology to investigate prenatal LPS-induced structural changes. Expression of key pro- and anti-inflammatory mediators was assessed at both transcriptional and translational levels. Based on bulk RNA sequencing and exploratory transcriptomic analysis, signature gene and phenotypical expression of two major mesenchymal fibroblasts subsets, myofibroblasts (MYFs) and lipofibroblasts (LIFs), were analyzed with qPCR, immunofluorescence, and western blot. Human embryo-derived WI-38 fibroblast cell line was used as an in vitro model to investigate LPS-induced fibroblast inflammatory responses and MYFs-LIFs differentiation.

Results: Newborn mice exposed to prenatal LPS exhibited enlarged air spaces and thinner septal walls, with an enhanced interleukin 6 (IL6) response in lung tissues. The degree of lung structural changes is LPS dose- and timing-dependent. Exploratory transcriptomic analysis revealed the enrichment in myofibrogenic pathways in LPS-exposed lungs. Platelet-derived growth factor receptor alpha (PDGFRA)-expressing progenitor lung fibroblasts were generally suppressed by prenatal LPS exposure. The expression of MYFs signature markers (ELN and ACTA2) in relation to LIFs (PLIN2 and FGF10) demonstrated a highly heterogeneous and dynamic pattern, depending on LPS doses and timing. Upon LPS exposure, human WI-38 fibroblasts upregulated a panel of pro-inflammatory mediators via nuclear factor kappa B signaling and displayed diverse MYFs and LIFs differentiation depending on the dose and duration of LPS stimulation.

Conclusions: Prenatal LPS exposure induces heterogeneous structural and molecular changes in the newborn mice lung, showing LPS dose- and time-dependent modulation of mesenchymal fibroblast differentiation. These findings may contribute to refine the risk stratification of preterm infants exposed to prenatal infection/inflammation. Mesenchymal fibroblast plasticity and MYFs-LIFs phenotypic shifts may inspire preventive and therapeutic strategies for BPD.

Background: Cardia gastric cancer (CGC) is a distinct and increasingly prevalent malignancy, yet the role of air pollution in its sequential carcinogenesis remains unclear. The present cross-sectional study aimed to evaluate the associations between long-term exposure to ambient air pollution and the progression of precancerous cardia gastric lesions.

Methods: A total of 99,493 participants were enrolled from the National Opportunistic Screening Program for Upper Gastrointestinal Cancer in Zhejiang Province of China from 2022 to 2023. Long-term exposure to six air pollutants including particulate matter (PM₁₀), fine particulate matter (PM_2.5), sulfur dioxide (SO₂), nitrogen dioxide (NO₂), ozone (O₃), and carbon monoxide (CO) was assessed by using ChinaHighAirPollutants (CHAP) dataset. Cardia lesion progression was classified into five histopathological stages based on endoscopic biopsy. Ordinal logistic regression was used to examine pollutant-specific associations, restricted cubic splines (RCS) were applied to assess the potential exposure-response associations, and weighted quantile sum (WQS) regression was performed to evaluate the mixture effects.

Results: All six pollutants were significantly associated with cardia lesion progression. The adjusted odds ratios (95% confidence intervals, 95% CI) per standard deviation increment in 5-year mean concentration were 1.21 (1.17-1.25) for PM₁₀, 1.28 (1.23-1.32) for PM_2.5, 1.17 (1.13-1.21) for SO₂, 1.07 (1.03-1.10) for NO₂, 1.16 (1.12-1.20) for O₃, and 1.36 (1.30-1.41) for CO. RCS analyses indicated non-linear exposure-response patterns for NO₂, O₃, and CO. In mixture models, CO and PM_2.5 were identified as the predominant contributors, with a 10% increase in combined exposure associated with a 10% (95% CI: 7-13%) higher risk of cardia lesion progression. Effect modification analysis revealed that Helicobacter pylori-positive individuals were more susceptible to pollution-related progression.

Conclusions: Long-term exposure to air pollutants is associated with the progression of cardia gastric lesions, highlighting the importance of incorporating air quality improvement into cancer prevention strategies.

Background: Although socioeconomic position (SEP) is consistently associated with health outcomes, little is known about life course SEP in relation to chronic disease risk over long-term follow-up and in multiple countries. This study aimed to identify life course socioeconomic trajectories and examine their relation with chronic disease risk in later life in a cohort study of an older European population of 27 countries.

Methods: We used data from the European Longitudinal Survey of Health, Ageing, and Retirement in Europe (SHARE). SEP was measured in childhood (household overcrowding in childhood), adulthood (educational attainment) and older adulthood (income). Occurrence of eight chronic diseases was self-reported over a 16-year follow-up period. We identified life course socioeconomic trajectories with latent class growth analysis (LCGA) and assessed their association with chronic disease risk using covariate-adjusted Poisson regression.

Results: Among 30,055 participants, we identified a five-trajectory solution. The risk of chronic disease in older adulthood was lower for those in the stable high trajectory (0.87; 95% CI: 0.82-0.93) and steep upward stable (0.90; 95% CI: 0.86-0.94) trajectories compared to those in the most disadvantaged trajectory (stable low). In gender-stratified analysis, models showed similar findings as those for the main analysis.

Conclusions: Our study revealed five distinct life course SEP trajectories in a sample of European individuals aged 50 years or older. Two trajectories were associated with chronic disease risk later in life, with more advantageous trajectories associated with reduced chronic disease risk.

Background: Patients living with diabetes and chronic conditions may face a significant burden managing their health. Many of these patients use digital medicine tools such as continuous glucose monitoring systems. Although measures exist to assess treatment burden from tasks such as managing medications and attending healthcare visits, there is no patient-reported measure that captures the burden of digital care. Therefore, the purpose of this study is to validate the Treatment Burden Questionnaire Plus Digital (TBQ + D), a patient-reported measure of treatment burden that includes using digital tools for adults with diabetes.

Methods: Adult patients with type 1 or type 2 diabetes mellitus completed the 25-item TBQ + D (scored 0 [none] to 10 [maximum] per item, total score range 0-250). We evaluated ease of administration, internal consistency, and tested hypotheses about the relationship between TBQ + D scores and treatment complexity, digital tool use intensity, social risk factors, and digital comfort to assess TBQ + D's validity.

Results: Of 324 patients approached, 300 (93%) consented and completed the TBQ + D (mean age 57 [SD 17], 50% female, 50% with type 2). The mean TBQ + D score was 53.7 (SD 41.6). Internal consistency was excellent (Cronbach's α = 0.94). As hypothesized, higher TBQ + D scores were reported by patients with type 1 vs. type 2 diabetes mellitus (61.7 vs. 45.7, p = .0008), maximal/moderate vs. minimal to no digital tool use (56.5/60.7 vs. 41.3, p = .001), those on intensive insulin therapy vs. other treatments (61.4 vs. 38.0, p < .0001), and those with greater social vulnerability (p < .0106). TBQ + D scores were not significantly higher in patients with HbA1c ≥ 8% (p = .055) or less comfortable with digital technology (p = .08).

Conclusions: TBQ + D is a novel and valid measure of treatment burden in patients living with diabetes, inclusive of digital burden, which can play a role in fostering minimally disruptive care for patients with diabetes.