Objective:Selective fetal growth restriction (sFGR) in dichorionic-diamniotic (DCDA) twins is associated with the risk of adverse neurodevelopment; however, the underlying metabolic dysregulation remains poorly characterized. We aimed to characterize the neonatal hair metabolome associated with sFGR in DCDA twins and assess its predictive value for long-term neurodevelopment. Methods:Forty-two pairs of DCDA twins were stratified into the sFGR-DCDA (twins with birth weight [BW] discordance) and DCDA-C (twins with BW concordance) groups. Neonatal hair metabolites were profiled using gas chromatography-mass spectrometry (GC-MS). Pathway analysis and machine learning were used to identify metabolic signatures predictive of neurodevelopment, which were assessed using the Ages and Stages Questionnaire (Third Edition) at 2-3 and 5-6 years of age. Results:The smaller neonates in the sFGR-DCDA group (DCDA-S) showed significant downregulation of cysteine, methionine, glutathione, aminoacyl-tRNA, and nicotinate and nicotinamide metabolism in comparison with the neonates in the DCDA-C group. Reduced glutathione and aminoacyl-tRNA pathway activity correlated with lower problem-solving scores. An exploratory machine learning model incorporating pantothenate and coenzyme A biosynthesis, cysteine and methionine metabolism, and nicotinate and nicotinamide metabolism showed a preliminary discriminatory capacity for low personal-social scores in DCDA-S children at 2-3 years of age. Conclusion:Neonatal hair metabolomics in DCDA-S children reflect intrauterine disturbances in antioxidant and protein synthesis pathways associated with later neurodevelopmental outcomes, providing a non-invasive window into metabolic programming in sFGR.
Objective:To investigate the effects of metabolic syndrome (MetS) and its interaction with genetic factors on lung cancer incidence and mortality. Methods:The cohort analysis included 355,344 participants from the UK Biobank. MetS was defined using the modified National Cholesterol Education Program Adult Treatment Panel III criteria. Cox proportional hazards models were used to evaluate the associations between MetS-related variables, their interactions with genetic factors, and lung cancer outcomes (incidence and mortality). Results:MetS was associated with increased risks of lung cancer incidence (hazard ratio [ HR]: 1.31, 95% confidence interval [ CI]: 1.22-1.42) and mortality ( HR: 1.35, 95% CI: 1.24-1.48). Risk increased proportionally to the number of metabolic abnormalities. Increased waist circumference, reduced high-density lipoprotein cholesterol, and elevated glycated hemoglobin were independently associated with both outcomes. Participants with both high genetic risk and MetS had the highest risk of lung cancer incidence ( HR: 2.07, 95% CI: 1.82-2.35) and mortality ( HR: 2.12, 95% CI: 1.83-2.45) compared with those with low genetic risk and no MetS. A significant positive additive interaction was observed between waist circumference and genetic risk. Conclusion:Metabolic abnormalities are important modifiable risk factors for lung cancer. Integrating metabolic health assessment with genetic risk profiling may improve risk stratification and targeted prevention of lung cancer.
Objective:Immunoglobulin G (IgG) N-glycosylation is associated with mild cognitive impairment through the regulation of inflammatory balance; however, the underlying mechanisms remain unclear. Methods:Our study utilized a post-genome-wide association studies (GWAS) method that integrated GWAS data for cognitive function with gene expression quantitative trait loci (eQTL), protein QTL (pQTL), and IgG N-glycan-QTL data. Results:Mendelian randomization (MR) analyses suggested bidirectional causalities between glycan peaks (GPs) and cognitive function, with GP7, GP12, and GP19 showing a causal effect on cognitive function, while cognitive function conversely showed a causal effect on GP1 and GP8. Two proteins and 10 genes were implicated in the regulation of IgG N-glycosylation. Furthermore, multivariable MR results suggested complex causalities between genes/proteins and IgG N-glycans, which jointly promote or independently affect cognitive function. Conclusion:Our study reveals a novel mechanism by which genes, proteins, and modified IgG N-glycans converge to pathologically affect cognitive function.
Objective:LLC-MK2/TMPRSS2 cells constitutively express TMPRSS2, eliminating the requirement for additional trypsin during HPIV3 culture. The efficiency of LLC-MK2/TMPRSS2 for isolating HPIV3 from respiratory specimens was evaluated in comparison with Madin-Darby Canine Kidney (MDCK). Methods:HPIV3-positive respiratory specimens from children with acute respiratory infections (February-June 2025) were inoculated into LLC-MK2/TMPRSS2 and MDCK. The cytopathic effect (CPE) was monitored microscopically, and the proportion of positive cells was evaluated using direct immunofluorescence assay (DFA). Viral infection dynamics were assessed using the cycle threshold (Ct) values obtained by qPCR. Results:Among 50 specimens, 35 strains (35/50, 70%) were successfully isolated using LLC-MK2/TMPRSS2, while 14 strains were isolated using MDCK (14/50, 28%). More pronounced CPE and a higher number of virus-infected positive cells were shown in LLC-MK2/TMPRSS2 compared to that in MDCK ( P < 0.001 and P = 0.001, respectively). Among specimens with an initial Ct < 27, the isolation rate of LLC-MK2/TMPRSS2 was higher and the Ct values were lower (< 27) (82.6%, 19/23). Among specimens with an initial Ct of 23 ≤ Ct < 27, the number of specimens with a supernatant Ct ≥ 27 (63.6%, 7/11) was significantly less than that in MDCK ( P = 0.003). Conclusion:LLC-MK2/TMPRSS2 exhibits superior adaptability and replication efficiency in the isolation of HPIV3 from respiratory specimens.
Objective:We aimed to investigate the independent and combined associations of grip strength and chair-rising time with cardiovascular disease (CVD) risk among middle-aged and older adults across different glycemic status groups. Methods:This study included 7,258 CVD-free middle-aged and older adults from the China Health and Retirement Longitudinal Study (CHARLS). Muscle strength was assessed based on grip strength and chair-rising time. Incident CVD was defined as a physician-diagnosed heart disease and/or stroke. Cox proportional hazard models and restricted cubic spline analyses were used to quantify the association between muscle strength and CVD. Results:During a mean follow-up of 7.8 years, 1,785 participants (24.6%) developed incident CVD. Both lower normalized grip strength and longer chair-rising time were independently associated with increased CVD risk in a dose-dependent manner ( P for trend < 0.001), with adjusted hazard ratios ( HRs) of 1.37 (95% CI: 1.17-1.61) for the lowest vs. highest grip strength quartile and 1.53 (95% CI: 1.32-1.77) for the longest vs. shortest chair-rising time quartile. The combination of weakest grip and slowest chair-rising time conferred the highest risk ( HR = 2.12; 95% CI: 1.65-2.73). Lower grip strength and prolonged chair-rising time were associated with elevated CVD risk across all glycemic status groups. The association with grip strength reached statistical significance in the normal glucose regulation and prediabetes groups, with a similar point estimate observed in the diabetes group ( P for interaction = 0.622). Conclusion:This study revealed a dose-dependent association between muscle strength and the incidence of CVD. The associations between lower grip strength and prolonged chair-rising time with higher CVD risk were directionally consistent across the glycemic status groups, although not all strata reached statistical significance.
Objective:Fine particulate matter (PM 2.5) may impair follicular development; however, the roles of its chemical components and their time-specific effects remain unclear. This study examined how PM 2.5 and its major components are related to oocyte-related outcomes among women undergoing assisted reproductive technology (ART) and identified critical exposure windows. Methods:A total of 51,122 ART cycles were analyzed. Individual exposures to PM 2.5 and its components, sulfate (SO 4 2-), nitrate (NO 3 -), ammonium (NH 4 +), organic matter (OM), and black carbon (BC), were estimated for three periods: recent (0-3 months), distal (4-12 months), and cumulative (0-12 months). Associations between total, mature, and normally fertilized oocytes were assessed using negative binomial regression. Distributed lag non-linear models (DLNM) identified sensitive windows, and mixture models evaluated joint effects. Results:Higher PM 2.5 and component exposures were consistently associated with poorer oocyte outcomes, with stronger effects for distal exposure. Two sensitive windows, 1 month and 6-11 months before retrieval, were identified. Mixture analyses indicated SO 4 2- and NH 4 + as the dominant contributors. Conclusion:Exposure to PM 2.5 showed component-specific and time-dependent reproductive toxicity. Both short- and long-term exposure may reduce oocyte quantity and quality, highlighting the importance of improving air quality to support female reproductive health and ART success.
The "Report on Cardiovascular Health and Diseases in China 2025", guided by the National Health Commission and compiled under the auspices of the National Center for Cardiovascular Diseases, systematically integrates multi-dimensional data on cardiovascular diseases (CVD) trends, the evolution of risk factors, advances in diagnosis and treatment, rehabilitation management, medical device innovation, and health economics evaluations in China, providing a scientific basis for policy formulation, resource allocation, and intervention prioritization. According to the data, CVD remains the leading cause of death among urban and rural residents in China, accounting for 48.98% of rural deaths and 47.35% of urban deaths in 2021, approximately 2 in every 5 deaths were attributable to CVD. Although the age-standardized mortality rate has declined, the absolute number of CVD cases and deaths continues to rise due to accelerated population aging and the high prevalence of risk factors. In 2024, the crude incidence rate of CVD among Chinese residents aged 18 years and above was 639.46 per 100,000 population, with rates higher in males than in females. The mortality rate in rural areas has consistently remained higher than in urban areas. The Healthy China Action Plan (2019-2030) sets a target to reduce the mortality rate of cardiovascular and cerebrovascular diseases to below 190.7 per 100,000 population by 2030. To achieve this goal, the report calls for a refined monitoring system to continuously track key health indicators, including tobacco use, dietary patterns, physical activity, sleep quality, body mass index, blood pressure, blood lipids, blood glucose, and environmental exposures. This effort aims to facilitate the transition from a "treatment-centered" to a "health-centered" approach.
Objective:The association between necrotizing enterocolitis (NEC) and prenatal heat exposure has not been adequately studied. We estimated the association of prenatal high ambient temperature (TM) and heatwave exposure with NEC and to identified susceptible exposure windows. Methods:Generalized linear models were applied to examine the associations between high TM and heatwaves exposures with NEC. Mediation analysis was used to investigate the role of preterm birth (PTB) in the relationship between high TM and NEC during pregnancy. Results:We included 8,334 twin pairs and their mothers: 227 (2.72%) twin pairs were NEC cases. Compared to the reference temperature (19.8 °C), prenatal exposure to the 90th percentile TM (24.8 °C) was associated with NEC risk [odds ratio ( OR), 2.68; 95% confidence interval ( CI): 1.93-3.72]. Trimester-specific ORs were 2.41 (95% CI: 1.63-3.55), 3.30 (95% CI: 2.18-4.99), and 2.06 (95% CI: 1.43-2.98) for the first, second, and third trimesters, respectively. Exposure to heatwaves during the entire pregnancy, first, and second trimesters showed ORs of 1.98 (95% CI: 1.14-3.43), 1.81 (95% CI: 1.26-2.59), and 1.81 (95% CI: 1.19-2.75), respectively. PTB mediated the association between the 90th and 95th percentile TM exposure during the entire pregnancy and NEC, with the mediation proportions of 30.10% (95% CI: 8.57-45.28) and 36.20% (95% CI: 16.18-50.28), respectively. Conclusion:Prenatal exposure to high TM levels and heat waves, especially in the first and second trimesters, was positively associated with the risk of NEC. PTB may partially mediate the relationshipbetween high TM exposure and NEC.
The rise of antibiotic-resistant bacteria has become a serious challenge in healthcare,which is exacerbated by limited development of new antimicrobial agents and the increasing prevalence of multidrug-resistant (MDR) bacteria,often leading to treatment failure. Aeromonas spp.,gram-negative bacteria commonly found in aquatic and terrestrial environments,are frequently implicated in both intestinal and extraintestinal infections[1]. Increasing numbers of MDR Aeromonas spp.
Objective:To examine the influence of metabolic dysfunction-associated steatotic liver disease (MASLD) on long-term outcomes of patients with chronic hepatitis B virus (HBV) infection. Methods:A total of 3,269 participants with chronic HBV infection from the Kailuan Cohort (median follow-up: 13.7 years) were enrolled to estimate the hazard ratios ( HRs) and 95% confidence intervals ( CIs) for outcomes associated with MASLD. In addition, 120,913 individuals without HBV infection were included to assess the independent and interactive associations between steatotic liver disease (SLD), cardiometabolic risk factors (CMRFs), and HBV infection. Results:In individuals with chronic HBV infection, MASLD was not linked to primary liver cancer but was associated with an increased risk of extrahepatic cancers ( HR= 1.50, 95% CI, 1.01-2.25) and cardiovascular diseases ( HR= 1.98, 95% CI, 1.49-2.63), especially in participants with normal alanine aminotransferase, mild SLD, and persistent MASLD. The risk of cardiovascular disease remained elevated in the participants with reversed MASLD. Joint analysis indicated a significant synergistic interaction between HBV infection, CMRFs, and primary liver cancer. Conclusions:In patients with chronic HBV infection, MASLD serves as a crucial indicator of significantly elevated systemic risk, underscoring the importance of addressing both virological control and metabolic health regardless of their current hepatic steatosis and liver enzyme status.
Objective:City-specific tools for assessing and warning about respiratory disease risks are underdeveloped, limiting effective public health response. This study aimed to develop and validate a novel city-specific prediction framework (WHA air-LSTM) for forecasting daily respiratory outpatient visits by integrating a composite air pollution health index. Methods:Based on over 223.7 million hospital visits across multiple megacities, we constructed and validated a five-level morbidity-driven composite air pollution index (WHA air) for each city using city-specific exposure-response relationships. An LSTM model was built using WHA air, temperature, humidity, and historical visit data to predict next-day visits. The proposed modeling framework was developed with city-level data, and it was externally validated using datasets from other cities. Results:Higher WHA air levels were significantly associated with increased outpatient visits. The model demonstrated excellent predictive performance (Beijing: R 2 = 0.963, RMSE = 53.5) and effectively captured visit surges. Excluding WHA air degraded model accuracy (ΔRMSE = +44.1%). The framework maintained robust performance in external validation, confirming its transferability. Conclusion:The WHA air-LSTM framework provides a scalable and practical tool for city-level respiratory disease early warning by bridging environmental monitoring with clinical practice.
Objective:Traditional disease prevention strategies that rely on fixed parameters and macro-level models struggle to capture the diversity of individual behaviors and environmental complexities. Indoor spaces with high population densities and poor ventilation, such as schools and hospitals, are particularly vulnerable to pathogen transmission. The coronavirus disease (COVID-19) pandemic highlighted the need for precise intervention strategies. Methods:We developed a spatial-individual agent-based model that integrates fine-grained spatiotemporal dynamics, where transmission risk is quantified by the exact distance and duration of contact. This model was applied to a high-resolution case study of a university dormitory floor to evaluate various testing frequencies, scopes, and isolation intensities. Results:Simulations showed that a dormitory-wide isolation policy outperformed individual restrictions by protecting uninfected rooms. Counter-intuitively, every-three-day class-based testing lowered infection risks compared to daily class-based testing by minimizing high-density interactions. In spatially constrained environments, stricter isolation reduces the overall outbreak duration but increases the contact transmission rate among individuals sharing the same enclosed space. Conclusion:Epidemic control in high-density environments requires balancing testing frequency and isolation stringency based on spatial constraints. Under strict isolation, frequent testing is vital for breaking transmission chains. In less restrictive settings, moderately reducing the testing frequency minimizes unnecessary contact. These findings provide data-driven guidance for optimizing public health policies on campuses.
Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common chronic liver disease worldwide and a growing public health concern[1].
Echinococcosis is a zoonotic disease caused by the larval stages of tapeworms belonging to the genus Echinococcus,and it presents substantial global health and economic challenges[1].
