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Articles in press have been peer-reviewed and accepted, which are not yet assigned to volumes/issues, but are citable by Digital Object Identifier (DOI).
Letter
Association between PM2.5 Chemical Constituents and Preterm Birth: The Undeniable Role of Preconception H19 Gene Variation
Yalong Wang, Panpan Sun, Xinying Wang, Junxi Zhang, Xiangyu Yu, Jian Chai, Ruo Du, Wenyi Liu, Fangfang Yu, Yue Ba, Guo Yu Zhou
, Available online  , doi: 10.3967/bes2025.076
MYCN-Mediated Transcriptional Activation of IDH2 Enhances Proliferation, Migration, and Invasion in Cervical Squamous Cell Carcinoma through the HIF1-α Pathway
Xiaojuan Liu, Hui Ma, Xiaoyan Li, Chunxing Ma, Lisha Shu, Huiying Zhang
, Available online  , doi: 10.3967/bes2025.075
Validation and Reproducibility of an Iodine-Specific Food Frequency Questionnaire for Evaluating Dietary Iodine Intake in the Elderly Population of Gansu Province, China
Qi Jin, Tao Wang, Meina Ji, Jizun Wang, Xing Ma, Xinyi Wang, Jiaqi Wang, Hexi Zhang, Yanling Wang, Wenxing Guo, Wanqi Zhang
, Available online  , doi: 10.3967/bes2025.074
Seasonal Effects of Air Pollutants on Stroke Deaths in Qingdao from 2014 to 2019
Jingkai Zhang, Bingling Wang, Lu Pan, Nan Ge, Jingya Yin, Yuan Fang, Hua Zhang, Jianjun Zhang, Xiutao Cao, Yan Ma, Li Cheng, Haiping Duan
, Available online  , doi: 10.3967/bes2025.073
Single-Cell and Multi-Dimensional Data Analysis of the Key Role of IDH2 in Cervical Squamous Cell Carcinoma Progression
Xiaojuan Liu, Zhenpeng Zhu, Chenyang Hou, Hui Ma, Xiaoyan Li, Chunxing Ma, Lisha Shu, Huiying Zhang
, Available online  , doi: 10.3967/bes2025.067
Trends Analysis on Vaccination Coverage of Influenza in Shandong Province, China
Guijie Luan, Liang Sun, Weiyan Zhang, Yao Liu, Shaonan Liu
, Available online  , doi: 10.3967/bes2025.063
Is There an Association Between Per- and Poly-Fluoroalkyl Substances and Serum Pepsinogens? Evidence from Linear Regression and Bayesian Kernel Machine Regression Analyses
Jing Wu, Shenglan Yang, Yiyan Wang, Yuzhong Yan, Ming Li
, Available online  , doi: 10.3967/bes2025.060
Waist Circumference Status and Distribution in Chinese Adults: China Nutrition and Health Surveillance (2015–2017)
Jing Nan, Mulei Chen, Hongtao Yuan, Qiuye Cao, Dongmei Yu, Wei Piao, Fusheng Li, Yuxiang Yang, Liyun Zhao, Shuya Cai
, Available online  , doi: 10.3967/bes2025.059
Role of Folic Acid Supplementation on Association between Short Inter-Pregnancy Intervals and Adverse Birth Outcomes: A Retrospective Cohort Study in Changsha, China
Zhiqing Zhao, Ling Chen, Wenbin Ouyang, Jing Deng, Xiaohui Chen, Xin Huang
, Available online  , doi: 10.3967/bes2025.057
Future Projections of Temperature-related Excess Morbidity Due to Influenza Under Climate Change Scenarios: A Case Study in a Temperate Japanese City
Keita Wagatsuma
, Available online  , doi: 10.3967/bes2025.034
Review
Climate-sensitive infectious diseases under global climate change
Qiao Liu, Min Liu, Jue Liu
, Available online  , doi: 10.3967/bes2025.077
Climate and weather significantly influence the duration, timing, and intensity of disease outbreaks, reshaping the global landscape of infectious diseases. Rising temperatures and shifts in precipitation patterns driven by climate change can directly impact the survival and reproduction of pathogens and vector organisms. Moreover, climate change is expected to exacerbate extreme weather events, including floods and droughts, which can disrupt infrastructure and increase the risk of water- and foodborne diseases. There are potential shifts in the temporal and spatial patterns of infectious disease transmission owing to climate change. Furthermore, climate change may alter the epidemiology of vaccine-preventable diseases. These climatic variations not only affect the ecological characteristics of pathogens and vectors but also indirectly influence human behaviors and socioeconomic conditions, further amplifying disease transmission risks. Addressing this challenge requires an interdisciplinary collaboration and comprehensive public health strategies. This review aims to synthesize the current evidence on the impact of climate change on climate-sensitive infectious diseases and elucidate the underlying mechanisms and transmission pathways. Additionally, we explored adaptive policy strategies to mitigate the public health burden of infectious diseases in the context of climate change, offering insights for global health governance and disease control efforts.
Oringinal Article
Effectiveness of Pentavalent Rotavirus Vaccine — a Propensity Score Matched Test Negative Design Case-Control Study Using Medical Big Data in Three Provinces of China
Yuexin Xiu, Lin Tang, Fuzhen Wang, Lei Wang, Zhen Li, Jun Liu, Dan Li, Xueyan Li, Yao Yi, Fan Zhang, Lei Yu, Jingfeng Wu, Zundong Yin
, Available online  , doi: 10.3967/bes2025.056
  Objective   The objective of our study was to evaluate the vaccine effectiveness (VE) of the pentavalent rotavirus vaccine (RV5) among < 5-year-old children in three provinces of China during 2020-2024 via a propensity score-matched test-negative case-control study.  Methods   Electronic health records and immunization information systems were used to obtain data on acute gastroenteritis (AGE) cases tested for rotavirus (RV) infection. RV-positive cases were propensity score matched with RV-negative controls for age, visit month, and province.  Results   The study included 27,472 children with AGE aged 8 weeks to 4 years at the time of AGE diagnosis; 7.98% (2,192) were RV-positive. The VE (95% confidence interval, CI) of 1-2 and 3 doses of RV5 against any medically attended RV infection (inpatient or outpatient) was 57.6% (39.8%, 70.2%) and 67.2% (60.3%, 72.9%), respectively. Among children who received the 3rd dose before turning 5 months of age, 3-dose VE decreased from 70.4% (53.9%, 81.1%) (<5 months since the 3rd dose) to 63.0% (49.1%, 73.0%) (≥ 1 year since the 3rd dose). The three-dose VE rate was 69.4% (41.3%, 84.0%) for RVGE hospitalization and 57.5% (38.9%, 70.5%) for outpatient-only medically attended RVGE.  Conclusions   Three-dose RV5 VE against rotavirus gastroenteritis (RVGE) in children aged < 5 years was higher than 1-2-dose VE. Three-dose VE decreased with time since the 3rd dose in children who received the 3rd dose before turning five months of age, but remained above 60% for at least one year. VE was higher for RVGE hospitalizations than for medically attended outpatient visits.
Original Article
Chromosome 8 open reading frame 76 (C8orf76) co-expressed with cyclin-dependent kinase 4 (CDK4) as a prognostic indicator of colorectal cancer
Shang Guo, Chengcheng Liu, Zifeng Zhao, Zhongxin Li, Xia Jiang, Zengren Zhao
, Available online  , doi: 10.3967/bes2024.177
  Objective  To explore the correlation between chromosome 8 open reading frame 76 (C8orf76) and cyclin-dependent kinase 4 (CDK4) and the potential predictive effect of C8orf76 and CDK4 on the prognosis of colorectal cancer (CRC).  Methods  We constructed a protein-protein interaction network of C8orf76-related genes and analyzed the prognostic signatures of C8orf76 and CDK4. Clinicopathological features of C8orf76 and CDK4 were visualized using a nomogram.  Results  C8orf76 and CDK4 levels were positively correlated in two independent human CRC cohorts (n = 83 and n = 597). A consistent positive correlation was observed between C8orf76 and CDK4 expression in the CRC cell lines. The nomogram included prognostic genes (C8orf76 and CDK4) and pathological N and M stages. The concordance index (C-index) in our cohort was 0.776, which suggests that the ability of the indicators to predict the overall survival of patients with CRC in our cohort was strong.  Conclusions  We found that C8orf76 was positively correlated with CDK4 in both the cohorts as well as in CRC cell lines. Therefore, C8orf76 and CDK4 can be used as potential biomarkers to predict the prognosis of CRC.
Job Preferences of Centers for Disease Control and Prevention Workers: A Discrete Choice Experiment in China
Yan Guo, Hanlin Nie, Hao Chen, Stephen Nicholas, Elizabeth Maitland, Sisi Chen, Lieyu Huang, Xiumin Zhang, Xuefeng Shi
, Available online  , doi: 10.3967/bes2025.070
  Objective  This study explored the job choice preferences of Center for Disease Prevention and Control (CDC) workers to provide CDC management information and recommendations for optimizing employee retention and motivation policies.  Methods  A discrete choice experiment was conducted in nine provinces across China. Seven key attributes were identified to analyze the job preferences of CDC workers. Mixed logit models, latent class models, and policy simulation tools were used.  Results  A valid sample of 5944 cases was included in the analysis. All seven attributes significantly influenced the job choices of CDC workers. Heterogeneity analyses identified two main groups based on different levels of preference for attribute utility. Income-prioritizers were concerned with income and opportunities for career development, whereas bianzhi-prioritizers were concerned with bianzhi and welfare benefits. The policy simulation analysis revealed that income-prioritizers had a relatively higher sensitivity to multiple job preference incentives.  Conclusion  Income and bianzhi were the two key attributes influencing the job choices and retention preferences of CDC workers. Heterogeneity in job preferences was also identified. Based on the preference characteristics of different subgroups, policy content should be skewed to differentiate the importance of incentives.
Dissecting the Causal Association between Body Fat Mass and Obsessive-compulsive Disorder: A Two-sample Mendelian Randomization Study
Meiling Hu, Zhennan Lin, Hongwei Liu, Yunfeng Xi, Youxin Wang
, Available online  , doi: 10.3967/bes2025.069
Objective Previous studies link lower body mass index (BMI) with increased obsessive-compulsive disorder (OCD) risk, yet other body mass indicators may offer superior prediction. We dissected the causal association between body fat mass (FM) and OCD.Methods Summary statistics from genome-wide association studies of European ancestry were utilized to conduct two-sample Mendelian randomization analysis. Heterogeneity, horizontal pleiotropy, and sensitivity analyses were performed to assess the robustness.Results The inverse variance weighting method demonstrated that a genetically predicted decrease in FM was causally associated with an increased OCD risk [odds ratio (OR) = 0.680, 95% confidence interval (CI): 0.528–0.875, P = 0.003]. Similar estimates were obtained using the weighted median approach (OR = 0.633, 95% CI: 0.438–0.915, P = 0.015). Each standard deviation increases in genetically predicted body fat percentage corresponded to a reduced OCD risk (OR = 0.638, 95% CI: 0.455–0.896, P = 0.009). The sensitivity analysis confirmed the robustness of these findings with no outlier instrument variables identified.Conclusion The negative causal association between FM and the risk of OCD suggests that the prevention or treatment of mental disorders should include not only the control of BMI but also fat distribution and body composition.
Effects of Oral Vitamin D Supplementation on Vitamin D Levels and Glycemic Parameters in Patients with Type 2 Diabetes Mellitus: A Systematic Review and Network Meta-analysis
Xiujuan Zhang, Hongfei Wang, Xia Gao, Yang Zhao
, Available online  , doi: 10.3967/bes2025.066
  Background  Epidemiological studies have shown that vitamin D status affects glycemic control in individuals with type 2 diabetes mellitus (T2DM). However, findings from intervention studies remain inconsistent. Therefore, a network meta-analysis was conducted to evaluate the comparative efficacy of various vitamin D supplementation strategies on glucose indicators in adults with T2DM.  Methods  Eligible studies published before September 12, 2024, were retrieved from PubMed, EMBASE, Cochrane Library, and Web of Science. A network meta-analysis of multiple dosage strategies—low (< 1,000 IU/day, LDS), medium (1,000–2,000 IU/day, MDS), high (2,000–4,000 IU/day, HDS), and extremely high (≥ 4,000 IU/day, EHDS)—was performed.  Results  The network meta-analysis of 40 RCTs indicated that, compared with placebo, vitamin D3 supplementation increased 25-hydroxyvitamin D [25-(OH)-D] levels, with pooled mean difference (MD) showing a stepwise increase from LDS to EHDS. Ranking probabilities showed a corresponding rise in 25-(OH)-D levels from LDS (46.7%) to EHDS (91.2%). EHDS reduced fasting blood glucose (FBG) relative to no treatment. LDS significantly decreased hemoglobin A1c (HbA1c), and vitamin D2 significantly affected FBG levels. MDS led to a significant change in fasting insulin (FIN) compared to both placebo (MD: −4.76; 95% CI −8.91 to −0.61) and no treatment (MD: −7.30; 95% CI −14.44 to −0.17).  Conclusion  The findings suggest that vitamin D supplementation may be a viable approach for improving glycemic control in adults with T2DM, with lower doses potentially offering benefit. The analysis also showed a dose-dependent increase in 25-(OH)-D levels.
Does Prenatal SARS-CoV-2 Infection Exacerbate Postpartum Lower Urinary Tract Symptoms? A Multicenter Retrospective Cohort Study
Yuhan Lyu, Min Li, Huiqing Yao, Tianzi Gai, Lin Liang, Su Pan, Pingping Li, Yaxin Liang, Yue Yu, Xiaomei Wu
, Available online  , doi: 10.3967/bes2025.065
  Objective  Coronavirus disease 2019 (COVID-19) can result in fatigue and post-exertional malaise; however, whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection exacerbates lower urinary tract symptoms (LUTS) is unclear. This study investigated the association between prenatal SARS-CoV-2 infection and postpartum LUTS.  Methods  A multicenter, retrospective cohort study was conducted at two tertiary hospitals in China from November 1, 2022, to November 1, 2023. Participants were classified into infected and uninfected groups based on SARS-CoV-2 antigen results. LUTS prevalence and severity were assessed using self-reported symptoms and the Incontinence Impact Questionnaire-Short Form (IIQ-7). Pelvic floor muscle activity was measured using electromyography following the Glazer protocol. Group comparisons were performed to evaluate the association of SARS-CoV-2 infection with LUTS and electromyography parameters, with stratified analyses conducted using SPSS version 26.0.  Results  Among 3,652 participants (681 infected, 2,971 uninfected), no significant differences in LUTS prevalence or IIQ-7 scores were observed. However, SARS-CoV-2 infection was an independent factor influencing the electromyographic activity of the pelvic floor muscles (mean tonic contraction amplitudes), regardless of delivery mode (P = 0.001).  Conclusion  Prenatal SARS-CoV-2 infection was not significantly associated with an increased risk of postpartum LUTS but independently altered pelvic floor muscle electromyographic activity, suggesting potential neuromuscular effects.
National Trends in Influenza Vaccination Rates in South Korea Before and During the COVID-19 Pandemic, 2011–2022
Kyeongeun Kim, Kyeongmin Lee, Yejun Son, Seoyoung Park, Raphael Udeh, Jiseung Kang, Hayeon Lee, Soeun Kim, Jaeyu Park, Hyeon Jin Kim, Damiano Pizzol, Lee Smith, Jiyoung Hwang, Dong Keon Yon
, Available online  , doi: 10.3967/bes2025.061
  Objective  Despite the global decrease in influenza infections during the coronavirus disease 2019 (COVID-19) pandemic, seasonal influenza remains a significant health issue. South Korea, known for its robust pandemic response and high influenza vaccination rates, offers a unique context for examining changes in vaccination trends during the pandemic. Using nationally representative data, we aimed to understand the impact of the pandemic on influenza vaccination behavior over a 12-year period and to identify vulnerable groups.  Methods  We analyzed influenza vaccination rates in South Korea between 2011–2022, focusing on pandemic-related impacts. The data of 2,426,139 adults (≥ 19 years) from the Korea Community Health Survey were used to assess demographic and sociological factors influencing vaccination behaviors.  Results  We observed an increase in influenza vaccination rates during the pre-COVID-19 period from 2011–2013 (weighted prevalence: 46.68% [95% confidence interval (CI): 46.55–46.82]) to 2017–2019 (weighted prevalence: 52.50% [95% CI: 52.38–52.63]). However, a significant decline was observed in 2022, the late-COVID-19 pandemic period (weighted prevalence: 55.78% [95% CI: 55.56–56.01]), compared with the mid-pandemic period in 2021 (weighted prevalence: 59.12% [95% CI: 58.91– 59.32]), particularly among populations traditionally prioritized for influenza vaccination, including older adults (≥ 65 years) and patients with chronic diseases and low educational and income levels.  Conclusion  The influenza vaccination rate in South Korea was significantly affected by the COVID-19 pandemic, showing a notable decrease among vulnerable demographic groups. This suggests the need for targeted public health strategies to address vaccine hesitancy and improve vaccination rates, particularly among high-risk populations.
(Meta)transcriptomic Insights into the Role of Ticks in Poxvirus Evolution and Transmission: A Multicontinental Analysis
Yuxi Wang, Jingjing Hu, Jingjing Hou, Xiaojie Yuan, Weijie Chen, Yanjiao Li, Qile Gao, Yue Pan, Shuiping Lu, Qi Chen, Siru Hu, Zhongjun Shao, Chenglong Xiong
, Available online  , doi: 10.3967/bes2025.062
  Objective  Poxviruses are zoonotic pathogens that infect humans, mammals, vertebrates, and arthropods. However, the specific role of ticks in transmission and evolution of these viruses remains unclear.  Methods  Transcriptomic and metatranscriptomic raw data from 329 sampling pools of seven tick species across five continents were mined to assess the diversity and abundance of poxviruses. Chordopoxviral sequences were assembled and subjected to phylogenetic analysis to trace the origins of the unblasted fragments within these sequences.  Results  Fifty-eight poxvirus species, representing two subfamilies and 20 genera, were identified, with 212 poxviral sequences assembled. A substantial proportion of AT-rich fragments were detected in the assembled poxviral genomes. These genomic sequences contained fragments originating from rodents, archaea, and arthropods.  Conclusion  Our findings indicate that ticks play a significant role in the transmission and evolution of poxviruses. These viruses demonstrate the capacity to modulate virulence and adaptability through horizontal gene transfer, gene recombination, and gene mutations, thereby promoting co-existence and co-evolution with their hosts. This study advances understanding of the ecological dynamics of poxvirus transmission and evolution and highlights the potential role of ticks as vectors and vessels in these processes.
Sex-specific Association of Telomere Length with Individualized Expected Years of Life Lost among 203,731 Males and 241,668 Females
Feifei Xu, Chenjie Li, Yifan Wang, Xiao Wang, Yumnah Babar, Shuang Liang, Fan Yang, Zhazheng He, Honggang Yi, Juncheng Dai
, Available online  , doi: 10.3967/bes2025.053
  Objective  Telomere length is a key aging biomarker, but its sex-specific impact on individualized life expectancy remains uncertain. This study explores sex differences in leukocyte telomere length (LTL) and individualized expected years of life lost (YLL).  Methods  A prospective cohort of 445,399 participants (203,731 males and 241,668 females) from the UK Biobank was analyzed. LTL values were log-transformed, and YLL was calculated using life tables. Multiple linear regression was applied to examine sex-specific associations.  Results  In males, each standard deviation (S.D.) increase in LTL was linked to a 0.965-year decrease in YLL (95% CI: –1.025, –0.900; P < 0.001). In females, longer LTL was related to a 0.102-year increase in YLL (95% CI: 0.057, 0.146; P < 0.001). Among postmenopausal females, LTL showed a protective effect similar to that in males (0.387-year decrease, 95% CI: −0.446, –0.328; P < 0.001), while premenopausal females exhibited a detrimental association (0.705-year increase, 95% CI: 0.625, 0.785; P < 0.001). Comparable trends were observed across major aging-related diseases, pointing to a consistent biological pattern.  Conclusion  The influence of LTL on life expectancy varies significantly by sex, with protective associations seen in males and postmenopausal females. This suggests hormonal involvement in telomere dynamics. The results support integrating sex-specific perspectives into aging and telomere research and clinical practice.
Association of Longitudinal Change in Fasting Blood Glucose with Risk of Cerebral Infarction in a Patients with Diabetes
Taiyang Luo, Xuan Deng, Xueyu Chen, Yuhe Liu, Shuohua Chen, Haoran Sun, Ziwei Yin, Shouling Wu, Yong Zhou, Xingdong Zheng
, Available online  , doi: 10.3967/bes2025.052
  Objective  To investigate the association between long-term glycemic control and cerebral infarction risk in patients with diabetes through a large-scale cohort study.  Methods  This prospective, community-based cohort study included 12,054 patients with diabetes. From 2006 to 2012, 38,272 fasting blood glucose (FBG) measurements were obtained from these participants. FBG trajectory patterns were generated using latent mixture modelling. Cox proportional hazards models were applied to assess the subsequent risk of cerebral infarction associated with different FBG trajectory patterns.  Results  At baseline, the mean age of the participants was 55.2 years. Four distinct FBG trajectories were identified based on FBG concentrations and their changes over the 6-year follow-up period. After a median follow-up of 6.9 years, 786 cerebral infarction events were recorded. Different trajectory patterns were associated with significantly varied outcome risks (Log-Rank P < 0.001). Compared with the low-stability group, Hazard Ratio (HR) adjusted for potential confounders were 1.37 for the moderate-increasing group, 1.23 for the elevated-decreasing group, and 2.08 for the elevated-stable group.  Conclusion  Sustained high FBG levels were found to play a critical role in the development of ischemic stroke among patients with diabetes. Controlling FBG levels may reduce the risk of cerebral infarction.
Associations of White Blood Cell, Platelet Count, Platelet-to-White Blood Cell Ratio with Muscle Mass among Community-Dwelling Older Adults in China
Zhenwei Zhang, Yuming Zhao, Hongzhou Chen, Li Qi, Chen Chen, Jun Wang, Wenhui Shi, Yuebin Lyu, Xiaoming Shi
, Available online  , doi: 10.3967/bes2025.051
Abstract   Objective  This study aimed to evaluate the relationships of white blood cell (WBC) count, platelet (PLT) count, and PLT-to-WBC ratio (PWR) with muscle mass in Chinese older adults.  Methods  This cross-sectional analysis involved 4,033 Chinese older adults aged ≥ 65 years from the Healthy Ageing and Biomarkers Cohort Study. Muscle mass and total skeletal muscle mass index (TSMI) were measured by bioelectric impedance analysis. WBC, PLT, and PWR were measured using standard methods. Multivariate linear regression was used to examine the associations of WBC count, PLT count, and PWR with TSMI.  Results  High WBC count, PLT count, and PWR were associated with low TSMI, with coefficients of −0.0091 (95% confidence interval [CI]: −0.0142 to −0.0041), −0.0119 (95% CI: −0.0170 to −0.0068), and −0.0051 (95% CI: −0.0102 to −0.0001). The associations between the three inflammatory indices and TSMI were linear. Stratified analyses indicated that the relationship between inflammatory markers and TSMI was more evident in male participants and in individuals aged < 80 years than in their counterparts.  Conclusion  Elevated WBC count, PLT count, and PWR correlated with muscle mass loss. This study highlights the importance of regular monitoring of inflammatory markers as a potential strategy for the screening and management of sarcopenia in older adults.
Analysis of Tongue and Face Image Features of Anemic Women and Construction of Risk-Screening Model
Hongyuan Fu, Yi Chun, Yahan Zhang, Yu Wang, Yulin Shi, Tao Jiang, Xiaojuan Hu, Liping Tu, Yongzhi Li, Jiatuo Xu
, Available online  , doi: 10.3967/bes2025.047
  Objective   To identify the key features of facial and tongue images associated with anemia in female populations, establish anemia risk-screening models, and evaluate their performance.  Methods   A total of 533 female participants (anemic and healthy) were recruited from Shuguang Hospital. Facial and tongue images were collected using the TFDA-1 tongue and face diagnosis instrument. Color and texture features from various parts of facial and tongue images were extracted using Face Diagnosis Analysis System (FDAS) and Tongue Diagnosis Analysis System version 2.0 (TDAS v2.0). Least Absolute Shrinkage and Selection Operator (LASSO) regression was used for feature selection. Ten machine learning models and one deep learning model (ResNet50V2 + Conv1D) were developed and evaluated.  Results   Anemic women showed lower a-values, higher L- and b-values across all age groups. Texture features analysis showed that women aged 30–39 with anemia had higher angular second moment (ASM)and lower entropy (ENT) values in facial images, while those aged 40–49 had lower contrast (CON), ENT, and MEAN values in tongue images but higher ASM. Anemic women exhibited age-related trends similar to healthy women, with decreasing L-values and increasing a-, b-, and ASM-values. LASSO identified 19 key features from 62. Among classifiers, the Artificial Neural Network (ANN) model achieved the best performance [area under the curve (AUC): 0.849, accuracy: 0.781]. The ResNet50V2 model achieved comparable results [AUC: 0.846, accuracy: 0.818].  Conclusion   Differences in facial and tongue images suggest that color and texture features can serve as potential TCM phenotype and auxiliary diagnostic indicators for female anemia.
Association between ABO Blood Types and the Risk of Gestational Diabetes Mellitus: A Prospective Cohort Study
Shuanghua Xie, Shuangying Li, Shaofei Su, Enjie Zhang, Shen Gao, Yue Zhang, Jianhui Liu, Minhui Hu, Ruixia Liu, Wentao Yue, Chenghong Yin
, Available online  , doi: 10.3967/bes2025.046
  Objective  To investigate the association between ABO blood types and gestational diabetes mellitus (GDM) risk.  Methods  A prospective birth cohort study was conducted. ABO blood types were determined using the slide method. GDM diagnosis was based on a 75-g, 2-h oral glucose tolerance test (OGTT) according to the criteria of the International Association of Diabetes and Pregnancy Study Groups. Logistic regression was applied to calculate the Odds Ratios (ORs) and 95% Confidence Intervals (CIs) between ABO blood types and GDM risk.  Results  A total of 30,740 pregnant women with a mean age of 31.81 years were enrolled in this study. The ABO blood types distribution was: type O (30.99%), type A (26.58%), type B (32.20%), and type AB (10.23%). GDM was identified in 14.44% of participants. Using blood type O as a reference, GDM risk was not significantly higher for types A (OR = 1.05) or B (OR = 1.04). However, women with type AB had a 19% increased risk of GDM (OR = 1.19, 95% CI = 1.05–1.34; P < 0.05), even after adjusting for various factors. This increased risk for type AB was consistent across subgroup and sensitivity analyses.  Conclusion  The ABO blood types may influence GDM risk, with type AB associated with a higher risk. Incorporating it—either as a single risk factor or in combination with other known factors—could help identify individuals at risk for GDM before or during early pregnancy.
Exploration of New Susceptible Genes Associated with Non-Alcoholic Fatty Liver Disease among Children with Obesity using Whole Exome Sequencing
Xiongfeng Pan, Cailian Wei, Jiayou Luo, Junxia Yan, Xiang Xiao, Jie Wang, Yan Zhong, Miyang Luo
, Available online  , doi: 10.3967/bes2025.045
  Objective  This study aimed to evaluate the association between susceptibility genes and non-alcoholic fatty liver disease (NAFLD) in children with obesity.  Methods  We conducted a two-step case-control study. Ninety-three participants were subjected to whole-exome sequencing (exploratory set). Differential genes identified in the small sample were validated in 1,022 participants using multiplex polymerase chain reaction and high-throughput sequencing (validation set).  Results  In the exploratory set, 14 genes from the NAFLD-associated pathways were identified. In the validation set, after adjusting for sex, age, and body mass index, ECI2 rs2326408 (dominant model: OR = 1.33, 95% CI: 1.02–1.72; additive model: OR = 1.22, 95% CI: 1.01–1.47), C6orf201 rs659305 (dominant model: OR = 1.30, 95% CI: 1.01–1.69; additive model: OR = 1.21, 95% CI: 1.00–1.45), CALML5 rs10904516 (pre-ad dominant model: OR = 1.36, 95% CI: 1.01–1.83; adjusted dominant model: OR = 1.40, 95% CI: 1.03–1.91; and pre-ad additive model: OR = 1.26, 95% CI: 1.04–1.66) polymorphisms were significantly associated with NAFLD in children with obesity (P < 0.05). Interaction analysis revealed that the gene-gene interaction model of CALML5 rs10904516, COX11 rs17209882, and SCD5 rs3733228 was optional (P < 0.05), demonstrating a negative interaction between the three genes.  Conclusion  In the Chinese population, the CALML5 rs10904516, C6orf201 rs659305, and ECI2 rs2326408 variants could be genetic markers for NAFLD susceptibility.
Independent and Interactive Effects of Air Pollutants, Meteorological Factors, and Green Space on Tuberculosis Incidence in Shanghai
Qi Ye, Jing Chen, Yating Ji, Xiaoyu Lu, Jiale Deng, Nan Li, Wei Wei, Renjie Hou, Zhiyuan Li, Jianbang Xiang, Xu Gao, Xin Shen, Chongguang Yang
, Available online  , doi: 10.3967/bes2025.041
  Objective  To assess the independent and combined effects of air pollutants, meteorological factors, and greenspace exposure on new tuberculosis (TB) cases.  Methods  TB case data from Shanghai (2013–2018) were obtained from the Shanghai Center for Disease Control and Prevention. Environmental data on air pollutants, meteorological variables, and greenspace exposure were obtained from the National Tibetan Plateau Data Center. We employed a distributed-lag nonlinear model to assess the effects of these environmental factors on TB cases.  Results  Increased TB risk was linked to PM2.5, PM10, and rainfall, whereas NO2, SO2, and air pressure were associated with a reduced risk. Specifically, the strongest cumulative effects occurred at various lags: PM2.5 (RR = 1.166, 95% CI: 1.026–1.325) at 0–19 weeks; PM10 (RR = 1.167, 95% CI: 1.028–1.324) at 0–18 weeks; NO2 (RR = 0.968, 95% CI: 0.938-0.999) at 0–1 weeks; SO2 (RR = 0.945, 95% CI: 0.894–0.999) at 0–2 weeks; air pressure (RR = 0.604, 95% CI: 0.447–0.816) at 0–8 weeks; and rainfall (RR = 1.404, 95% CI: 1.076–1.833) at 0–22 weeks. Green space exposure did not significantly impact TB cases. Additionally, low temperatures amplified the effect of PM2.5 on TB.  Conclusion  Exposure to PM2.5, PM10, and rainfall increased the risk of TB, highlighting the need to address air pollutants for the prevention of TB in Shanghai.
Deciphering the Role of VIM, STX8, and MIF in Pneumoconiosis Susceptibility: A Mendelian Randomization Analysis of the Lung-Gut Axis and Multi-Omics Insights from European and East Asian Populations
Chenwei Zhang, Binbin Wan, Yukai Zhang, Tao Xiong, Yishan Li, Xuesen Su, Gang Liu, Yangyang Wei, Yuanyuan Sun, Jingfen Zhang, Xiao Yu, Yiwei Shi
, Available online  , doi: 10.3967/bes2025.028
  Background  Pneumoconiosis, a lung disease caused by irreversible fibrosis, represents a significant public health burden. This study investigates the causal relationships between gut microbiota, gene methylation, gene expression, protein levels, and pneumoconiosis using a multi-omics approach and Mendelian randomization (MR).  Methods  We analyzed gut microbiota data from MiBioGen and Esteban et al. to assess their potential causal effects on pneumoconiosis subtypes (asbestosis, silicosis, and inorganic pneumoconiosis) using conventional and summary-data-based MR (SMR). Gene methylation and expression data from Genotype-Tissue Expression and eQTLGen, along with protein level data from deCODE and UK Biobank Pharma Proteomics Project, were examined in relation to pneumoconiosis data from FinnGen. To validate our findings, we assessed self-measured gut flora from a pneumoconiosis cohort and performed fine mapping, drug prediction, molecular docking, and Phenome-Wide Association Studies to explore relevant phenotypes of key genes.  Results  Three core gut microorganisms were identified: Romboutsia (OR = 0.249) as a protective factor against silicosis, Pasteurellaceae (OR = 3.207) and Haemophilus parainfluenzae (OR = 2.343) as risk factors for inorganic pneumoconiosis. Additionally, mapping and quantitative trait loci analyses revealed that the genes VIM, STX8, and MIF were significantly associated with pneumoconiosis risk.  Conclusions  This multi-omics study highlights the associations between gut microbiota and key genes (VIM, STX8, MIF) with pneumoconiosis, offering insights into potential therapeutic targets and personalized treatment strategies.
Generalized Functional Linear Models: Efficient Modeling for High-dimensional Correlated Mixture Exposures
Bingsong Zhang, Haibin Yu, Xin Peng, Haiyi Yan, Siran Li, Shutong Luo, Renhuizi Wei, Zhujiang Zhou, Yalin Kuang, Yihuan Zheng, Chulan Ou, Linhua Liu, Yuehua Hu, Jindong Ni
, Available online  , doi: 10.3967/bes2025.024
  Objective  Humans are exposed to complex mixtures of environmental chemicals and other factors that can affect their health. Analysis of these mixture exposures presents several key challenges for environmental epidemiology and risk assessment, including high dimensionality, correlated exposure, and subtle individual effects.  Methods  We proposed a novel statistical approach, the generalized functional linear model (GFLM), to analyze the health effects of exposure mixtures. GFLM treats the effect of mixture exposures as a smooth function by reordering exposures based on specific mechanisms and capturing internal correlations to provide a meaningful estimation and interpretation. The robustness and efficiency was evaluated under various scenarios through extensive simulation studies.  Results  We applied the GFLM to two datasets from the National Health and Nutrition Examination Survey (NHANES). In the first application, we examined the effects of 37 nutrients on BMI (2011–2016 cycles). The GFLM identified a significant mixture effect, with fiber and fat emerging as the nutrients with the greatest negative and positive effects on BMI, respectively. For the second application, we investigated the association between four perfluoroalkyl substances (PFAS) and gout risk (2007–2018 cycles). Unlike traditional methods, the GFLM indicated no significant association, demonstrating its robustness to multicollinearity.  Conclusion  GFLM framework is a powerful tool for mixture exposure analysis, offering improved handling of correlated exposures and interpretable results. It demonstrates robust performance across various scenarios and real-world applications, advancing our understanding of complex environmental exposures and their health impacts on environmental epidemiology and toxicology.
Association between Solid Cooking Fuel Use and Frailty Trajectories: Findings from a Nationwide Cohort in China
Yang Liu, Bingjie Wu, Bingbing Fan, Chunxia Li, Chang Su, Aidong Liu, Tao Zhang
, Available online  , doi: 10.3967/bes2025.022
  Objective   Burning solid cooking fuel contributes to household air pollution and is associated with frailty. However, how solid cooking fuel use contributes to the development of frailty has not been well illustrated.  Methods   This study recruited 8,947 participants aged ≥ 45 years from the China Health and Retirement Longitudinal Study, 2011–2018. Group-based trajectory modeling was employed to identify frailty trajectories. Multinomial logistic regression was used to assess the association between solid cooking fuel use and frailty trajectories. Population-attributable fractions were used to estimate the frailty burden from solid fuel use.  Results   We identified three frailty trajectories: low-stable (n = 5,789), moderate-increasing (n = 2,603), and fast-increasing (n = 555). Solid fuel use was associated with higher odds of being in the moderate-increasing (OR: 1.24, 95% CI: 1.08–1.42) and fast-increasing (OR: 1.48, 95% CI: 1.14–1.92) trajectories. These associations were strengthened by longer solid fuel use (P for trend < 0.001). Switching to clean fuel significantly reduced the risk of being in these trajectories compared with persistent solid fuel users. Without solid fuel, 8% of moderate- and 19% of fast-increasing trajectories demonstrated frailty development like the low-stable group.  Conclusion   Solid cooking fuel use is associated with frailty trajectories in middle-aged and older Chinese populations.
Increased Tertiary Lymphoid Structures are Associated with Exaggerated Tissue Damage in the Lung of Smoker Patients with Pulmonary Tuberculosis
Yue Zhang, Liang Li, Zikang Sheng, Yafei Rao, Xiang Zhu, Yu Pang, Mengqiu Gao, Xiaoyan Gai, Yongchang Sun
, Available online  , doi: 10.3967/bes2025.020
  Objective   Cigarette smoking exacerbates progression of pulmonary tuberculosis (TB) . The role of tertiary lymphoid structures (TLS) in chronic lung diseases has gained attention, but it remains unclear whether smoking-exacerbated lung damage in TB is associated with TLS. This study aims to analyze the characteristics of pulmonary TLS in smoking TB patients and therefore to explore the possible role of TLS in smoking-related lung injury in TB.  Methods   Lung tissues from 36 male patients (18 smokers and 18 non-smokers) who underwent surgical resection due to pulmonary TB were included in this study. Pathological and immunohistological analysis was conducted to evaluate the quantity of TLS, and chest CT was used to assess the severity of lung lesions. The correlation between TLS quantity and TB lesion severity scores was analyzed. Immune cells and chemokines for TLS formation were also evaluated and compared between smoker and nonsmoker patients.  Results   Smoking TB patients had significantly more TLS than non-smokers (P < 0.001). TLS quantity in both lung parenchyma and peribronchial regions correlated with TB lesion severity on chest CT (parenchyma: r = 0.5767; peribronchial: r = 0.7373; both P < 0.001). Immunohistochemical analysis showed increased B cells, T cells, and CXCL13 expression in smoker patients with TB (P < 0.001).  Conclusion   Smoking TB patients exhibited increased pulmonary TLS, which was associated with exacerbated lung lesions on chest CT, suggesting that cigarette smoking may exacerbate lung damage by promoting TLS formation.
Re-exploration for Dietary Iodine Intake in Chinese Adults Using the Obligatory Iodine Loss Hypothesis
Xiaobing Liu, Jun Wang, Yajie Li, Hongxing Tan, Deqian Mao, Yanyan Liu, Weidong Li, Wei Yu, Junan Yan, Jianhua Piao, Chongzheng Guo, Xiaoli Liu, Xiaoguang Yang
, Available online  , doi: 10.3967/bes2025.017
  Objective  This study aimed to explore minimum iodine excretion and to build a dietary iodine recommendation for Chinese adults using the obligatory iodine loss hypothesis.  Methods  Data from 171 Chinese adults (19–21 years old) were collected and analyzed based on three balance studies in Shenzhen, Yinchuan, and Changzhi. The single exponential equation was accordingly used to simulate the trajectory of 24 h urinary iodine excretion as the low iodine experimental diets offered (iodine intake: 11−26 μg·day−1) and to further deduce the dietary reference intakes (DRIs) for iodine, including estimated average requirement (EAR) and recommended nutrient intake (RNI).  Results  The minimum iodine excretion was estimated as 57, 58, and 51 μg·day−1 in three balance studies, respectively. Moreover, it was further suggested as 57, 58, and 51 μg·day−1 for iodine EAR, and 80, 81, and 71 μg·day−1 for iodine RNI or expressed as 1.42, 1.41, and 1.20 μg·day−1·kg−1 of body weight.  Conclusion  The iodine DRIs for Chinese adults were established based on the obligatory iodine loss hypothesis, which provides scientific support for the amendment of nutrient requirements.
Original Articles
Life-Course Trajectories of Body Mass Index, Insulin Resistance, and Incident Diabetes in Chinese Adults
Zhiyuan Ning, Jinglan Zhang, Bingbing Fan, Yanlin Qu, Chang Su, Tao Zhang
, Available online  , doi: 10.3967/bes2025.072
  Objective  This study aimed to explore the interplay between the life-course body mass index (BMI) trajectories and insulin resistance (IR) on incident diabetes.  Methods  This longitudinal cohort included 2,336 participants who had BMI repeatedly measured 3–8 times between 1989 and 2009, as well as glucose and insulin measured in 2009. BMI trajectories were identified using a latent class growth mixed model. The interplay between BMI trajectories and IR on diabetes was explored using the four-way effect decomposition method. Logistic regression and mediation models were used to estimate the interaction and mediation effects, respectively.  Results  Three distinct BMI trajectory groups were identified: low-stable (n = 1,625), medium-increasing (n = 613), and high-increasing (n = 98). Both interaction and mediation effects of BMI trajectories and IR on incident diabetes were significant (P < 0.05). The proportion of incident diabetes was higher in the IR-obesity than in the insulin-sensitivity (IS) obesity group (18.9% vs. 5.8%, P < 0.001). After adjusting for covariates, the odds ratios (95% confidence intervals) of the IR, IS-obesity, and IR-obesity groups vs. the normal group were 3.22 (2.05, 5.16), 2.05 (1.00, 3.97), and 7.98 (5.19, 12.62), respectively. IR mediated 10.7% of the total effect of BMI trajectories on incident diabetes (P < 0.001).  Conclusion  We found strong interactions and weak mediation effects of IR on the relationship between life-course BMI trajectories and incident diabetes. IS-obesity is associated with a lower risk of incident diabetes than IR-obesity.
Spatio-temporal Pattern and Socio-economic Influencing Factors of Tuberculosis Incidence in Guangdong Province: A Bayesian Spatiotemporal Analysis*
Huizong Wu, Xing Li, Jiawen Wang, Ronghua Jian, Jianxiong Hu, Yijun Hu, Yiting Xu, Jianpeng Xiao, Aiqiong Jin, Liang Chen
, Available online  , doi: 10.3967/bes2025.071
  Objective  To investigate the spatiotemporal patterns and socioeconomic factors influencing the incidence of tuberculosis (TB) in the Guangdong Province between 2010 and 2019.  Method  Spatial and temporal variations in TB incidence were mapped using heat maps and hierarchical clustering. Socioenvironmental influencing factors were evaluated using a Bayesian spatiotemporal conditional autoregressive (ST-CAR) model.  Results  Annual incidence of TB in Guangdong decreased from 91.85/100,000 in 2010 to 53.06/100,000 in 2019. Spatial hotspots were found in northeastern Guangdong, particularly in Heyuan, Shanwei, and Shantou, while Shenzhen, Dongguan, and Foshan had the lowest rates in the Pearl River Delta. The ST-CAR model showed that the TB risk was lower with higher per capita Gross Domestic Product (GDP) [Relative Risk (RR), 0.91; 95% Confidence Interval (CI): 0.86–0.98], more the ratio of licensed physicians and physician (RR, 0.94; 95% CI: 0.90-0.98), and higher per capita public expenditure (RR, 0.94; 95% CI: 0.90–0.97), with a marginal effect of population density (RR, 0.86; 95% CI: 0.86–1.00).  Conclusion  The incidence of TB in Guangdong varies spatially and temporally. Areas with poor economic conditions and insufficient healthcare resources are at an increased risk of TB infection. Strategies focusing on equitable health resource distribution and economic development are the key to TB control.
Occupational Hazard Factors And The Trajectory Of Fasting Blood Glucose Changes In Chinese Male Steelworkers Based On Environmental Risk Scores: A Prospective Cohort Study
Mingxia Zou, Wei Du, Qin Kang, Yuhao Xia, Nuoyun Zhang, Liu Feng, Feiyue Li, Tiancheng Ma, Yajing Bao, Hongmin Fan
, Available online  , doi: 10.3967/bes2025.058
  Objective  We aimed to investigate the patterns of fasting blood glucose (FBG) trajectories and analyze the relationship between various occupational hazard factors and FBG trajectories in male steelworkers.  Methods  The study cohort included 3,728 workers who met the selection criteria for the Tanggang Occupational Cohort between 2017 and 2022. A group-based trajectory model was used to identify the FBG trajectories. Environmental risk scores (ERS) were constructed using regression coefficients from the occupational hazard model as weights. Univariate and multivariate logistic regression analyses were performed to explore the effects of occupational hazard factors using the ERS on FBG trajectories.  Results  FBG trajectories were categorized into three groups. An association was observed between high temperature, noise exposure, and FBG trajectory (P < 0.05). Using the first quartile group of ERS1 as a reference, the fourth quartile group of ERS1 had an increased risk of medium and high FBG by 1.90 and 2.21 times, respectively (odds ratio [OR] = 1.90, 95% confidence interval [CI]: 1.17–3.10; OR = 2.21, 95% CI: 1.09–4.45).  Conclusion  An association was observed between occupational hazards based on ERS and FBG trajectories. The risk of FBG trajectory levels increase with an increase in ERS.
Editorial
Trajectory Modelling: A Novel Approach to Dig Value of Longitudinal Cohort Studies
Siyan Zhan
, Available online  , doi: 10.3967/bes2025.068