Life's Essential 8 (LE8) is a comprehensive metric of cardiovascular health (CVH). Higher LE8 scores have been associated with lower risks of chronic diseases, but evidence regarding pancreatic cancer (PC) in Chinese populations is scarce. We analyzed data from 60,556 cancer-free adults in the Shanghai Suburban Adult Cohort and Biobank. LE8 includes four health behaviors (diet, physical activity, nicotine exposure, sleep) and four health factors (BMI, blood lipids, blood glucose, blood pressure), measured by questionnaires, physical examinations, and biochemical tests. Total scores (0-100) were categorized as low (< 50), moderate (50-79), and high (≥ 80) CVH. Incident PC was identified through cancer registries, hospital systems, and death records. Associations were assessed using multivariable Cox models. Over a median 7.4-year follow-up, 200 participants (0.3%) developed PC. Compared with participants with low CVH, those with moderate CVH (hazard ratio [HR] = 0.65, 95% confidence interval [CI] = 0.46-0.92) and high CVH (HR = 0.39, 95% CI = 0.19-0.82) had lower risks of PC. Each one standard deviation increase in LE8 score was associated with an 18% lower risk of PC (HR = 0.82, 95% CI = 0.70-0.96), with a linear inverse relationship. The association was attenuated after excluding the nicotine exposure component. The estimated population attributable fraction for suboptimal CVH was 40.5%. Stronger associations appeared in men and participants aged ≥ 60; a significant interaction with sex was observed. Overall, better LE8-defined CVH was associated with reduced PC risk, and smoking-related exposure may have contributed importantly to the observed association.
Transpeptidases (TPDs), which belong to the penicillin-binding protein (PBP) families, are crucial for bacterial survival and are targeted by β-lactam antibiotics. We sought to determine the prevalence and positions of substitutions across the TPDs of the PBPs and their potential association with β-lactam resistance in pneumococcal strains. A total of 337 pneumococcal isolates were collected from pediatric patients in Suzhou, China, from 2013 to 2022. The serotype, antimicrobial susceptibility, and sequence in PBP1a, 2b, and 2x of these isolates were determined by Quellung reaction, E-test, and polymerase chain reaction sequencing, respectively. Homology modeling was utilized to compare the three-dimensional structure of the aberrant PBP strains with that of a reference R6 strain. Alterations within the PBPs conserved motifs and adjacent sequences SXXK and SXN contributed to penicillin resistance. Substitutions in TPDs were common and have a high degree of diversity. Two insertion amino acid (AA) motif variations, Tyr-Thr-Try(YTW) and Try-Thr-Tyr(WYT), located between AA 424 and 425 in PBP2b, were found to change the conformation of PBP2b in seven strains, and the YTW alteration has not been documented previously. The mutation rate of the TPDs in the PCV13 serotype strains was found to be higher than that observed in strains of non-vaccine serotypes. A high degree of diversity of TPD sequence in different PBPs was observed among the antibiotic non-susceptible pneumococcal isolates. The modeling analysis revealed conformational changes in the PBP2b following the insertion of the AA. IMPORTANCE:Since sequence variations both within and outside the penicillin-binding proteins have been reported to influence β-lactam minimum inhibitory concentrations (MICs), we examined the variability of isolates with transpeptidase (TPD) substitutions. Further quantification of the potential contributions of individual TPD positions and their interactions to β-lactam MICs could provide insights into resistance mechanisms and should be a priority of future investigation.
Community-acquired pneumonia (CAP) is a significant cause of hospitalization and mortality in children. Non-pharmacological interventions (NPIs) implemented during the COVID-19 pandemic were associated with changes in the transmission dynamics of respiratory pathogens. The present study aimed to analyze changes in the pathogenic characteristics of hospitalized children with CAP in a single-center pediatric cohort in Changzhou, China, before and after the outbreak of COVID-19. We retrospectively reviewed demographic information, hospitalization records, and pathogen-detection results of children admitted for CAP at Changzhou Children’s Hospital, Jiangsu Province, China, from 2018 to 2023. The analyzed pathogens included eight target bacteria and seven respiratory viruses. A total of 29,552 children hospitalized with CAP were included, including 15,124 in the pre-pandemic period, 9024 in the pandemic period, and 5404 in the post-pandemic period. The male-to-female ratio was 1.42:1, and the median age was 16 months (IQR: 5.0–37.0). Hospitalizations generally peaked in autumn and winter from 2018 to 2022, whereas an off-season peak occurred in May 2023. The overall bacterial positivity increased from 9.94
Although previous cohort studies have examined the association between vegetable and fruit intake and cancer risk, the findings remain inconsistent. Using data from 50,987 participants in the Shanghai Suburban Adult Cohort and Biobank (2016 to 2019), we investigated the relationship between vegetable and fruit intake and the incidence of cancers through linkage with the cancer registry up to June 30, 2024. Participants in the highest quartile of total vegetable and fruit intake had a lower risk of overall cancer (HR: 0.81, 95% CI: 0.72-0.90), with similar inverse associations observed for vegetables and fruits separately. Higher intake was also associated with lower risks of lung and stomach cancers, whereas no associations were observed for colorectal cancer. In continuous analyses, each SD increase in total vegetable and fruit intake was associated with a lower risk of overall cancer (HR: 0.92, 95% CI: 0.88-0.97), and the findings were generally consistent with those from quartile-based analyses. In subgroup analyses, these inverse associations were observed among participants with favorable lifestyles and health conditions. RCS analyses identified nonlinear associations between fruit intake and the risks of overall and lung cancer, with the protective associations becoming less pronounced at excessive intake levels.
Supplementary Figure S1. Flowchart of the study population and quality control. This flowchart summarizes the selection of lung cancer cases and controls, variant- and sample-level quality control, genotype imputation, propensity score matching, and extraction of ubiquitination pathway-related SNPs in the SSACB discovery cohort. Abbreviations: IBD, Identity by descent; PI_HAT, Proportion of identity by descent; PCA, Principal component analysis; QC, Quality control.
Supplementary Figure S2. Principal Component Analysis (PCA) of the genetic components distribution between cases and controls in SSACB and FUSCC-TZL cohort. Principal component analysis was used to evaluate population structure and identify PCs that differed between cases and controls. The distribution of: (A) PC1 and PC7; (B) PC1 and PC8, and (C) PC7 and PC8 between lung cancer cases and healthy controls in SSACB cohort. (D) The distribution of PC1 and PC9 in lung cancer cases and healthy controls in FUSCC-TZL cohort.
BACKGROUND/OBJECTIVES:Although Clostridioides difficile infection (CDI) is a key cause of global morbidity and mortality, the burden of CDI in mainland China is not well-defined. The objective of this systematic literature review was to summarize the available epidemiologic evidence on the CDI disease burden (cases, hospitalizations, and deaths) in mainland China. METHODS:Six databases (three global [PubMed, Embase, Cochrane] and three Chinese [Chinese National Knowledge Infrastructure, Chinese Science Citation, Wanfang]) were searched on 5 August 2025 using CDI-related and epidemiological search terms. No date or language limits were applied. Real-world epidemiologic studies of adults and/or children with laboratory-confirmed CDI in mainland China reporting population-based CDI incidence, hospital-based CDI incidence, and/or CDI admission rates were included. All studies not meeting these criteria were excluded. Risk-of-bias (RoB) assessment was performed using the Newcastle-Ottawa Scale. Results were summarized descriptively. RESULTS:In total, 11 articles formed the evidence base for this review; each was a single-center, hospital-based study conducted in one of six cities in mainland China and published between 2014 and 2023. RoB assessment indicated that the evidence base was appropriate for this study. No study reported population-based CDI incidence. In total, 10 studies reported hospital-based CDI incidence (0 to 82.0/10,000 patient-days), and four reported CDI admission rates (0 to 23.1/1000 admissions). Eight studies reported mortality rates, which varied across studies. CONCLUSIONS:Several single-center, hospital-based studies demonstrate that CDI is present in hospitals in mainland China, but there are no published population-based CDI incidence estimates. These results should be interpreted considering this study's limitations, including potential publication and selection bias, heterogeneity, and limited generalizability. Overall, the burden of CDI is poorly understood in mainland China. Thus, prospective epidemiological studies, including those with sensitive detection methods, are needed to examine CDI burden across multiple cities in mainland China. These efforts would help illuminate the CDI burden and guide prevention efforts. (PROSPERO ID 1140152; registered 17 March 2026; funding by Pfizer Inc.).
Supplementary Table S2. List of ubiquitination-related genes included in pathway-based analysis.
The global rise in Type 2 Diabetes (T2D) is a particularly evident in China, where dietary patterns have shifted towards a Western diet, potentially exacerbating the issue. This necessitates effective prevention strategies, and objective dietary pattern analysis can inform such strategies. To preliminarily reveal the health benefits of the EAT-Lancet Diet in preventing T2D among adults in Shanghai, China. Information gathered from the Shanghai Suburban Adult Cohort and Biobank (SSACB) were utilized, encompassing 29 507 participants with complete dietary and health assessments. Adherence to the EAT-Lancet diet was quantified by employing a semi-quantitative Food Frequency Questionnaire (FFQ) that included 29 food categories based on participants’ responses recalling food frequency and average consumption amount over a 12-month period. The EAT-Lancet Index (ELDI) was obtained based on the intake level and reference range of 14 food components defined in the EAT-Lancet Diet (0–3 points per component; 0–42 points in total). Incident T2D cases were identified through medical records until February 28, 2023. Hazard ratios (HRs) and 95
Supplementary Figure S4. The eQTL analysis of rs11640681 genotypes and MGRN1 mRNA expression in the 1,000 Genomes dataset. MGRN1 expression was compared across rs11640681 genotype groups using data from the 1000 Genomes Project/Geuvadis dataset, comprising 445 lymphoblastoid cell line samples from European and Yoruba African ancestry populations (CEU, FIN, GBR, TSI, EUR and YRI). A trend of lower MGRN1 expression along with the rs11640681 A>G substitution was observed, although the association did not reach statistical significance.
Community-acquired pneumonia (CAP) remains an important public-health problem, and the COVID-19 pandemic and non-pharmaceutical interventions (NPIs) may have altered its burden. This study aimed to provide updated CAP burden among adults in Shanghai from 2016-2023.We analysed 61,230 participants aged 20-74 years from the Shanghai Suburban Adult Cohort and Biobank. CAP episodes were ascertained via ICD codes and clinical diagnoses. We calculated incidence rates before, during, and after NPIs, conducted subgroup analyses by age, sex, comorbidity and lifestyle. We used Poisson regression to compare stages, and Cox models to identify risk factors. The Overall CAP incidence was 42.1 per 1,000 person-years (95% CI 41.3-42.8). Incidence declined during NPIs (24.2/1,000 py) and rose after NPIs (95.9/1,000 py). The inpatient-to-outpatient ratio increased to 10.1% during NPIs and fell to 5.7% post-NPI. Among those without underlying conditions, rates were 40.1, 20.1 and 73.6/1,000 py before, during and after NPIs. Incidence was higher in participants ≥60 years and in those with multiple comorbidities, especially respiratory diseases. CAP burden temporarily fell during NPIs but resurged post-NPI, notably among high-risk groups. These findings highlight the need for targeted preventive strategies and continued CAP surveillance in the post-pandemic era.
Supplementary Figure S3.Q-Q plot of expected and observed versus expected -log10(p-values) for 70,801 SNPs in the SSACB discovery cohort. The red diagonal line represents the expected distribution under the null hypothesis, and the genomic inflation factor was λ = 1.068.
Abstract Background: Dysregulation of the ubiquitin–proteasome system (UPS) promotes tumorigenesis, but population-level evidence linking UPS variants to lung cancer risk is limited. Methods: We conducted a two-stage genetic association study. In the discovery stage, using a nested case–control design, 70,801 SNPs from 750 UPS-related genes were analyzed in 612 lung cancer cases and 901 controls from the Shanghai Suburban Adult Cohort Biobank. Significant loci were validated in an independent case–control cohort consisting of 2,718 individuals. We further evaluated the predictive performance of validated SNPs and performed functional analyses, including expression quantitative trait locus, enhancer–promoter interaction, and The Cancer Genome Atlas analyses. Results: We identified 2,527 SNPs associated with lung cancer risk in the discovery cohort, six of which were validated. Incorporating these variants significantly improved risk prediction beyond traditional risk models in both cohorts (AUCdiscovery: 0.64 vs. 0.53; AUCvalidation: 0.72 vs. 0.57; all P < 0.001). The MGRN1 rs11640681 A>G variant was associated with increased risk of lung cancer [ORdiscovery(95% CI), 1.26 (1.04–1.53), P = 0.017; ORvalidation(95% CI), 1.32(1.07–1.64), P = 0.011]. Functional analyses suggest the G allele may downregulate MGRN1 expression by enhancer–promoter interaction. Higher MGRN1 expression was present in normal lung compared with non–small cell lung cancer tissues and was associated with longer survival of patients with lung cancer. Conclusions: Our findings suggest UPS genetic variants contribute to lung cancer risk, with the G allele of rs11640681 potentially increasing risk by downregulating MGRN1, a potential tumor-suppressor. Impact: These findings enhance the understanding of lung cancer etiology and highlight potential biomarkers for risk stratification in a population setting.
Infections remain a major cause of mortality and may threaten healthy aging. Previous studies have focused on isolated severe infections rather than longitudinal infection burden. We aimed to examine associations of infection trajectories with biological age acceleration (BAA) and assessed infection severity and genetic susceptibility. We included adults aged 20–74 years from the Shanghai Suburban Adult Cohort and Biobank, China, enrolled between 2016 and 2019 with valid biological age (BA) measurements at baseline and follow-up. Infection-related episodes were identified from linked local health information systems and summarized quarterly between baseline and first follow-up. Group-based trajectory modeling identified infection trajectories. BA was estimated using the Klemera-Doubal method and BAA was defined as the residual from regressing BA on chronological age. Linear mixed-effects models assessed associations with annual BAA change. Polygenic risk scores and Cox models evaluated genetic susceptibility and all-cause mortality. Among 7614 participants, four infection trajectories were identified: infrequent (71.15
Objectives To investigate the impact of early-life human rhinovirus (HRV) and respiratory syncytial virus (RSV) infections on subsequent asthma development among children with acute respiratory infections (ARI), with a focus on the timing of infection during critical developmental windows.Design Retrospective cohort study.Setting Tertiary paediatric hospital—Children’s Hospital of Soochow University in eastern China—with data linked to a regional health information system.Participants A total of 2628 children who were hospitalised with acute respiratory infections (ARI) and received respiratory virus testing between September 2017 and December 2024 were included in this study.Primary and secondary outcome measures The primary outcome was incident asthma. Associations between early-life HRV or RSV infection and asthma risk were evaluated using univariate and multivariable Cox proportional hazards models. Causal mediation analysis was applied to examine potential mediation by wheezing and bronchiolitis. Secondary outcomes were the frequency of asthma-related medical visits and number of exacerbations, analysed using multivariable negative binomial regression models.Results Overall, 616 (20.2%) children developed asthma. Cox regression showed that HRV-RSV (aHR=2.40, 95% CI 1.02 to 6.69) and s-HRV (aHR=1.56, 95% CI 1.10 to 2.22) were associated with asthma risk compared with negative controls, whereas s-RSV was not (aHR=1.31, 95% CI 0.89 to 1.89). Wheezing mediated 53.5% of the effect of HRV on asthma risk. Among asthma cases, both HRV and RSV were associated with increased asthma-related visits and exacerbations.Conclusions Early-life hospitalisation for HRV or RSV, particularly at 13–24 months of age, may be associated with increased risk of asthma and greater asthma morbidity. These findings suggest a potential role of infection timing in shaping long-term respiratory outcomes.
OBJECTIVES:This study investigated the impact of diabetes status, including whether individuals have diabetes and the various stages of diabetes, on the incidence of tuberculosis (TB), providing insights for more precise prevention and control of TB. METHODS:This population-based cohort study drew on a database from the Shanghai Suburban Adult Cohort and Biobank, comprising 35,842 participants. Adult participants with no prior history of TB who visited community health service centers for health screening between April 2016 and October 2017 were enrolled. Follow-up of eligible participants was conducted for incident TB cases after their health screening date until March 7, 2025. Cases were sourced from the database of new diagnoses spanning 2016-2025. Participants without TB served as controls and were selected through propensity score matching, with each case matched to four controls by age, sex, body mass index, smoking behavior, and alcohol consumption behavior. TB risk was compared across different groups using multivariate logistic regression. RESULTS:In total, 58 participants developed TB during follow-up. The TB incidence rate was higher in participants with newly diagnosed diabetes, at 44.00 cases per 100,000 person-years, compared to 18.55 cases in the non-diabetes mellitus group (P = 0.018). The nested case-control study indicated that the newly diagnosed diabetes group had a higher incidence of TB compared to the nondiabetic group (odds ratio 2.50, P = 0.039). CONCLUSION:Newly diagnosed diabetes patients have a higher risk of TB. Enhancing diabetes management through the prompt identification of undiagnosed cases could thereby indirectly contribute to TB control.
Seasonal influenza activity was disrupted due to the emergence of coronavirus disease 2019 (COVID-19) and the implementation of non-pharmaceutical interventions. In this study, we analyzed weekly influenza-like illness (ILI) cases and influenza positivity rate by subtype and age group from the Shanghai influenza surveillance system from 2015 to 2023. A wavelet analysis was conducted to explore the seasonal pattern of influenza. The average weekly ILI consultation rate was 20.28 ILI cases per 1,000 consultations, with 40,778 of 173,155 specimens (22.63 %) testing positive for influenza. During the COVID-19 pandemic, nearly no influenza viruses were detected until January 2021. Only B/Victoria was circulated for about eight months and peaked in January 2022, with a positivity rate of 47.48 %, which was lower than the peaks in each year before the COVID-19 pandemic. In 2023, the first epidemic, dominated by A(H1N1), began in week 8 (one month later than the 8-year average) and peaked at 76.89 %. The second epidemic, which was unusually not summer-based and driven by A(H3N2), started in week 38 and peaked in week 48 at 75.31 %, advancing the winter-spring epidemic by approximately one month. The age preference of influenza A changed during the era of normalized COVID-19 transmission. The seasonal patterns of influenza varied significantly across different stages of the COVID-19 pandemic, including differences in epidemic onset, peak timing, duration, periodicity, and dominant strains. Stability of seasonal changes in influenza requires longer-term surveillance, as well as further virologic and epidemiologic studies.
BACKGROUND:Respiratory syncytial virus (RSV) is a leading cause of acute lower respiratory tract infection (ALRI) in early life, and severe infection may increase the risk of childhood asthma. The effect of age at RSV hospitalization is not well understood. We aimed to assess the association between RSV hospitalization before age 2 and subsequent childhood asthma, and how this association was affected by age at severe infection. METHODS:We conducted a population-based retrospective cohort study of children born in 2017-2018 in Suzhou, China. Participants were classified into 3 groups based on hospitalization for ALRI and RSV testing before age 2: RSV-positive hospitalization, RSV-negative hospitalization and population controls without hospitalization. The incidence of asthma and recurrent wheeze before age 6 was compared across groups. Poisson regression with robust variance estimation was used to estimate adjusted risk ratios, and stratified analyses assessed the effect of age at severe RSV infection. RESULTS:We observed children with RSV-positive ALRI hospitalization before age 2 had approximately a 2-fold higher risk of asthma and a 2.6-fold higher risk of recurrent wheeze than matched controls, but the associations waned and were no longer significant after 4 years. The highest risk of asthma occurred in children hospitalized between 12 and <24 months, while the greatest risk of recurrent wheeze was observed between 6 and <12 months. CONCLUSIONS:Hospitalization for RSV-ALRI in the first 2 years, especially between 12 and <24 months, was associated with an increased risk of childhood asthma, providing new evidence for RSV prevention strategies.
Supplementary Figure S5. Prognostic significance and differential expression of MGRN1 in NSCLC. Kaplan-Meier Plotter analysis showed that higher MGRN1 expression was associated with (A) a trend toward longer overall survival (OS) across seven independent GEO cohorts (GSE29013, GSE31210, GSE50081, GSE68465, GSE102287, GSE37745, and GSE30219), (B) and a trend toward longer progression-free survival (PFS) across five cohorts (GSE29013, GSE31210, GSE50081, GSE68465, and GSE30219). Patients were stratified into high- and low-expression groups based on the platform-derived optimal cutoff. Survival differences were evaluated using log-rank tests, and multivariable Cox regression was performed to estimate adjusted hazard ratios (HRs) with available covariates (gender, stage, and smoking status, where available). (C) Forest plot summarizing the meta-analysis of adjusted OS results from seven cohorts using an inverse-variance weighted fixed-effect model. (D) Forest plot summarizing the meta-analysis of adjusted PFS results from five cohorts. (E) MGRN1 expression levels in tumor tissues versus adjacent normal lung tissues in lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) based on TCGA/GTEx data. Expression values were log2(TPM+1) transformed. *P < 0.05.
INTRODUCTION:Chronic obstructive pulmonary disease (COPD) is a major public health burden in China, but remains underdiagnosed, with most cases identified only after significant lung function decline. Effective, low-cost tools are therefore needed to identify high-risk individuals for targeted spirometry. This study developed risk prediction models and nomograms to guide personalized COPD prevention. METHODS:A community-based cohort of 32,327 adults aged 40-74 years without COPD was enrolled in 2016 and followed until March 2024. COPD diagnosis was obtained from Shanghai Songjiang District Healthcare Information Platform. Stepwise Cox regression analyses were conducted to select predictors, including demographics, lifestyle, disease history, and medical resources use, for overall and sex-specific prediction models. Discrimination and calibration were assessed by C-index, AUC, and Brier score, with 10-fold cross-validation and sensitivity analysis for validation. RESULTS:Over 7.0 years of follow-up, COPD incidence was 7.98 (95%CI: 7.61∼8.23) per 1,000 person-years, higher in men (10.60) than women (6.23). Sex, age, BMI, cooking habits, physical activity, smoking, occupational exposure, family history of respiratory diseases, other respiratory diseases, outpatient visits/year, and antibiotic prescriptions/year were significant predictors in the overall model. Male predictors additionally included central obesity, while female predictors additionally included fruit intake, history of tuberculosis and menopause. C-index was 0.780/0.770/0.781 (overall/male/female); Brier score was 0.035/0.044/0.028; Time-dependent AUCs at 1, 3, and 5 years ranged from 0.783 to 0.813, indicating good predictive performance over short, medium, and long term follow-up periods. Nomograms were created for overall, male and female populations. CONCLUSIONS:The study developed overall and sex-specific COPD risk prediction models with C-indices exceeding 70%. Corresponding nomograms provide practical tools for supporting routine COPD risk prediction to facilitate individualized preventive care.