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).
Ambient Fine Particulate Matter Exacerbates Ketogenesis in a Mouse Model of Type 2 Diabetes
Huihuan Luo, Yuanting Xie, Xinyi Fang, Bin Pan, Yalan Xiao, Jingyu Li, Xiaoqing Hong, Dongyang Han, Wenyue Tu, Haidong Kan, Yanyi Xu, Renjie Chen
In press  doi: 10.3967/bes2026.059
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  Objective  Prior epidemiological research demonstrated an association between short-term exposure to fine particulate matter (PM2.5) and acute diabetic events, specifically diabetic ketoacidosis (DKA). However, mechanistic investigations remain lacking to substantiate biological link.  Methods  Twenty 18-week-old male BKS db/db mice were randomly assigned to two groups (n = 10 per group). Ambient PM2.5 suspension (5 mg/kg in 50 μL) or an equal volume of phosphate-buffered saline was intratracheally instilled once daily for three consecutive days. Within 24 hours after the final instillation (Day 3), serum β-hydroxybutyrate was quantified, and liver tissues were collected for transcriptomic profiling (RNA-seq) to explore potential mechanisms linking PM2.5 to ketone body levels (i.e., β-hydroxybutyrate).  Results  The PM2.5 group exhibited higher 3-hydroxybutyric acid levels than controls. The liver transcriptome differed significantly between groups. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses indicated differentially expressed genes were primarily associated with lipid metabolism. Further, 43 genes exhibited moderate-to-strong correlations with 3-hydroxybutyric acid (16 positive, 27 negative; coefficients 0.56 – 0.76). These genes are involved in fatty acid oxidation, lipogenesis, lipid transport, glucose metabolism, and inflammation.  Conclusion  PM2.5 exposure may enhance ketogenesis through disruption of hepatic glucolipid metabolism, providing mechanistic insight into its potential role in acute diabetic metabolic decompensation.
Childhood Maltreatment and Internalizing and Externalizing Problems among Chinese Early Adolescents: A Prospective Parallel Mediation Study
Shuying Chen, Han Ding, Yan Ji, Faliang Xie, Xinhui Wang, Ting Tang, Gengfu Wang, Puyu Su
In press  doi: 10.3967/bes2026.119
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Revisiting Occupational Noise Exposure Limits in the Era of Complex Noise
Wei Qiu
In press  doi: 10.3967/bes2026.115
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Role of Gut Microbiota-Derived ILA Reduction in Mediating Hyperuricemia Induced by Circadian Rhythm Disruption
Yixin Zhang, Qinyao Li, Yuwan Wang, Hongrong Zhu, Xing Tan, Ruwen Zhang, Jiacen Sun, Weizhong Wang
In press  doi: 10.3967/bes2026.114
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  Objective  Hyperuricemia (HUA) is a growing global health concern linked to gout, kidney damage, and cardiovascular disease, with onset increasingly occurring at younger ages. Recent evidence suggests that circadian rhythm disruption (CRD) contributes to this rising incidence, although the underlying mechanisms remain unclear. Gut microbiota (GM) and their metabolites are known to mediate CRD-related metabolic disorders. Therefore, this study investigated whether circadian disruption induces hyperuricemia and explored the role of GM in this process.  Methods  Male Sprague-Dawley rats were randomly divided into four groups: a normal 12-h light/12-h dark cycle (LD), constant light (LL), constant dark (DD), and circadian disruption (CD, light-schedule shifting). The CRD model was selected based on plasma uric acid levels. GM composition (16S rRNA sequencing) and plasma metabolomics (LC-MS) were analyzed. Functional effects were validated using indole-3-lactic acid (ILA) gavage, fecal microbiota transplantation (FMT), quantitative polymerase chain reaction (qPCR) for ABCG2, GLUT9, and Ras, and HIEC-6 small interfering RNA (siRNA) experiments.  Results  Compared with the LD group, the LL group exhibited elevated UA and reduced intestinal ABCG2, without changes in hepatic xanthine oxidase (XOD, the key rate-limiting enzyme in purine synthesis), renal function, or food intake. LL altered GM composition, reduced [Eubacterium]_ruminantium_group, and downregulated ILA. Exogenous ILA alleviated HUA and upregulated ABCG2. FMT from LL rats to antibiotic-treated LD rats increased UA and decreased ABCG2. Ras silencing abolished ILA-mediated ABCG2 upregulation in vitro.  Conclusion  Light-induced CRD reduces [Eubacterium]_ruminantium_group and ILA, possibly impairing uric acid excretion by downregulating intestinal ABCG2 through Ras, and leading to HUA.
Associations of genetic risk, clinical blood biomarker, and the risk of gastric cancer: a nested case-control study
Tianhong Han, Ruobing Wang, Jia Liu, Nanxi Wang, Hai Chen, Qian Shen, Meng Zhu, Caiwang Yan, Qiufen Sun, Guangfu Jin, Yun Qian, Lu Wang
In press  doi: 10.3967/bes2026.117
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  Objective  Reliable prediction models for identifying populations at high risk for gastric cancer (GC) are lacking. We aimed to identify GC predictive biomarkers in blood and construct a score to evaluate their effectiveness for risk prediction and population stratification in different genetic backgrounds.  Methods  We performed a nested case-control study using the clinical data of 1,352 individuals with a first diagnosis of GC and 1,502 controls from the Taihu Biobank of Tumor Biomarkers (TBTB) cohort. After dividing the participants into training and testing sets (7:3), we identified GC-associated blood biomarkers and constructed a blood test score (BTS) in the training set, followed by evaluation of its predictive performance and joint effect with polygenic risk score (PRS).  Results  The BTS comprising 14 biomarkers showed good discrimination, with area under the curve (AUC) of 0.743 (95% confidence interval [CI], 0.722–0.764) in the training set and 0.736 (95% CI, 0.703–0.769) in the testing set. Calibration and decision curve analyses indicated good calibration and clinical applicability. We observed a significant increase (Ptrend < 0.001) in the relative risk of developing GC in the BTS quintiles, with a similar trend for PRS. Compared with individuals with low BTS, those with intermediate and high BTS had higher GC risk, whereas the interaction between BTS and PRS with GC risk was not significant (P = 0.473).  Conclusion  Our study revealed an association among BTS, genetic factors, and GC risk. The BTS is valuable for predicting the risk of GC and discriminating high-risk individuals.
Age- and Sex-Specific Distribution of Sex Hormones in Chinese Older Adults
Xiaoshuang Fu, Sirui Chen, Jiahao Chen, Chen Chen, Yuxin Yang, Jun Wang, Xiaoyan Ma, Jingjing Yang, Xi Meng, Huibin Jiang, Yongqiang Chen, Zenghang Zhang, Ziyue Zhu, Wenhui Shi, Zhipei Li, Jiaonan Wang, Xiaoming Shi, Yuebin Lv
In press  doi: 10.3967/bes2026.116
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To delineate the age- and sex-specific distribution patterns of key sex hormones [estradiol (E2), follicle-stimulating hormone (FSH), and testosterone (T)] in Chinese older adult population, with a particular focus on the oldest-old. Based on the “Healthy Aging and Biomarkers Cohort Study” (HABCS), this study included 5,545 participants (2,339 men and 3,206 women), and plasma concentrations of E2, FSH, and T were measured using chemiluminescence. Given the low detection rate of E2 in women (10.7%), it was analyzed as a binary variable (detected vs. undetected). Percentiles for these markers were calculated, and their distributions were analyzed according to sex, age, region, and sociodemographic factors. T levels in men showed a significant decline with age (median: 451.40 ng/dL in the 65–79-year-old group vs. 279.07 ng/dL in the centenarian group), while E2 levels remained stable (approximately 30 pg/mL). The E2 detection rate was highest in female centenarians (13.5%). FSH levels increased significantly with age in both men and women. Testosterone levels were higher in southern China and the detection rate of E2 was higher in educated women. This study provides key population-specific sex hormone reference percentiles for the elderly Chinese population and emphasizes that low E2 levels are a physiological norm in older women.
Chinese Guideline on the Diagnosis and Treatment of Cryptococcosis in Adults (2026)
Xinying Xue, Xiwei Lu
In press  doi: 10.3967/bes2026.097
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  Objective  To develop an evidence-informed, immune-risk-stratified clinical practice guideline for the diagnosis, treatment, and follow-up of adult cryptococcosis in China.  Methods  A multidisciplinary panel formulated clinical questions; reviewed the available evidence; graded evidence certainty using the Grading of Recommendations Assessment, Development and Evaluation framework, and used a modified Delphi process combining anonymous online voting through Wenjuanxing with face-to-face consultation.  Results  Forty-four recommendations address immune-risk stratification, targeted screening, pathogen detection, pulmonary and central nervous system cryptococcosis, disseminated and other-site disease, antifungal therapy, intracranial hypertension, immune reconstitution inflammatory syndrome, treatment response, treatment nonresponse, and follow-up.  Conclusion  This clinical practice guideline complements existing Chinese guidance by providing a unified, disease-specific framework for adult cryptococcosis across immune states and anatomical sites, supporting simultaneous Chinese and English dissemination.
Hypoxia Promotes Pancreatic Cancer Malignancy via HIF-1α-induced Doublecortin-like Kinase 1 Upregulation
Rui Yan, Yunting Bai, Patiguli Yisilamu, Ziwei Liang, Guangyu An, Hua Fan, Yang Ge
In press  doi: 10.3967/bes2026.107
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  Objective   Pancreatic ductal adenocarcinoma (PDAC) is characterized by numerous severely hypoxic areas that drives tumor progression. Hypoxia-inducible factor-1 (HIF-1) mediates hypoxic responses mainly through HIF-1α upregulation. However, how HIF-1α influences PDAC aggressiveness remains unclear. Doublecortin-like kinase 1 (DCLK1) is overexpressed in PDAC and facilitates tumor development. This study investigated whether hypoxia regulates DCLK1 to enhance PDAC malignancy.  Methods   Bioinformatics analyses of Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) datasets were used to assess the prognostic values of HIF-1α and hypoxia score, and the correlation between HIF-1α and DCLK1 expression. mRNA and protein levels of HIF-1α, DCLK1, and epithelial-mesenchymal transition (EMT) markers were detected by reverse transcription polymerase chain reaction and Western blot. Transwell assays detected cell migration and invasion after the inhibition of either HIF-1α or DCLK1. Immunofluorescence staining was performed to analyze the association among HIF-1α, DCLK1, and EMT markers in PDAC tissues.  Results   Our study demonstrated significant overexpression of HIF-1α and DCLK1 in pancreatic cancer cells under hypoxic conditions. Hypoxia-driven HIF-1α upregulates DCLK1, fostering EMT and enhancing PDAC malignancy. DCLK1 inhibition in PDAC mitigates hypoxia-induced proliferation, invasiveness, and EMT progression.  Conclusion   HIF-1α boosts DCLK1 in hypoxia, enhancing pancreatic cancer malignancy via EMT. Overall, targeting DCLK1 in the hypoxic tumor microenvironment of PDAC could be a promising therapeutic strategy.
Cynaropicrin Targets EGFR and MET Kinases and Promotes ROS Generation to Trigger Apoptosis and Ferroptosis in Non-small Cell Lung Cancer Cells
A-Young Nam, Na Yeong Lee, Goo Yoon, Jin Woo Park, Yung Hyun Choi, Joon-Seok Choi, Sang Hoon Joo, Jung-Hyun Shim
In press  doi: 10.3967/bes2026.104
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Enhancing Multi-Center Comparability through Systematic Quality Supervision: A Three-year National Assessment of 24-Hour Urinary Sodium and Potassium Laboratory Performance
Jing Liang, Xin Xin, Huan Luo, Jinping Zhao, Xiaoyan Chang, Fanghong Zhao, Xiaozhe Tang, Kuke Ding
In press  doi: 10.3967/bes2026.103
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Machine Learning- and Molecular Docking-driven Discovery of Omega-3 Fatty Acids as Key Predictors of Serum Per- and Polyfluoroalkyl Substance Levels
Ming Yang, Jingtao Wu, Lin Tao, Weitian Tang, Weitao Su, Jiaxin Zhao, Shengmei Zhang, Yanbing Li, Yaoyu Hu, Ang Li, Yichao Huang
In press  doi: 10.3967/bes2026.100
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Global Disparities in Long-Term Mortality Risks Associated with Wildfire Activity under Climate Change
Qiao Liu, Zhiyu Zhang, Min Liu, Jue Liu, ICAID-APE
In press  doi: 10.3967/bes2026.102
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  Objective   Wildfires have intensified globally; however, evidence of their long-term, multi-disease health impacts across countries at varying development levels remains scarce. Therefore, this study aims to quantify the associations between wildfires and cause-specific mortality while accounting for socioeconomic disparities.  Methods   Using an ecological panel dataset covering 62 countries from 2000 to 2023, we quantified the global associations between annual wildfire activity, measured using a satellite-derived burn index, and age-standardized mortality from 22 outcomes.  Results   After adjusting for socioeconomic indicators and temporal trends using mixed-effects models, higher wildfire activity was found to be independently associated with increased all-cause mortality and significantly more deaths from cardiovascular, digestive, and metabolic diseases. Stratified analyses revealed pronounced heterogeneity according to the Human Development Index (HDI): high-HDI countries experienced the largest mortality burden and the broadest range of affected chronic diseases, whereas low-HDI countries showed stronger links to deaths from HIV/AIDS and violence.  Conclusion   These findings indicate that the health risks of wildfires are neither uniform nor confined to respiratory outcomes but instead reflect the intersection of climate-related hazards, demographic transitions, and disease structure. As wildfires intensify under global warming, our results underscore the need for adaptive health systems and climate policies that consider the differential vulnerabilities across developmental contexts.
Maternal Residential Greenness and Preterm Birth in Nanning, China: Critical Windows and Thresholds
Meimeng Huang, Liangqin Mao, Xiaomin Wang, Yujun Xiong, Mingxiao Wei, Mingzhen Liang, Xianyan Tang, Shun Liu
In press  doi: 10.3967/bes2026.101
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  Objective   To identify critical exposure windows and thresholds of maternal residential greenness during pregnancy in relation to preterm birth (PTB).  Methods   Using the sibling-matched birth cohort data from the "China Green City" Nanning, China (2016–2022), conditional logistic regression and restricted cubic splines (RCS) were applied to assess the nonlinear dose-response associations between normalized difference vegetation index (NDVI) and PTB risk across different pregnancy periods and buffer zones.  Results   The median seasonal NDVI in Nanning was approximately 0.80, with relatively small differences between seasons. Pre-pregnancy residential NDVI (500 m buffer) was associated with higher PTB risk (adjusted odds ratio [OR] per interquartile range [IQR] = 1.16; 95% CI: 1.05–1.27), showing an upward trend with a risk threshold above 0.80. Third-trimester residential NDVI (500 m buffer) was associated with lower PTB risk (adjusted OR per IQR= 0.59; 95% CI: 0.54–0.65), showing an L-shaped dose-response curve with an inflection point at NDVI 0.30.  Conclusion   The third trimester and pre-pregnancy periods represent critical windows for the association between maternal residential greenness and PTB. Therefore, optimal levels of maternal residential greenness during pregnancy may reduce the risk of PTB.
A Connectome-based Study of Cognitive Impairment Associated with Chronic Insomnia
Jingting Kong, Zan Wang, Mengxue Wang, Na Zhao, Xuezi Zhang, Qingguo Ren
In press  doi: 10.3967/bes2026.092
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Increasing Mortality Burden Attributable to Concurrent Heatwave-Ozone Exposure in China: Evidence from a Regional Time-Series Study
Jianan Li, Yiqi Qiu, Mike Z. He, Jianlong Fang, Yu Wang, Chenfeng Li, Yueqiao Zhou, Jiaonan Wang, Chen Chen, Chen Mao, Xiaoming Shi
In press  doi: 10.3967/bes2026.091
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  Objectives   While climate warming has driven concurrent heatwave-ozone events, the magnitude of their joint health impacts remains insufficiently quantified. Particularly, the specific ozone (O3) thresholds that trigger changes in heatwave mortality risks have not yet been determined.  Methods   A time-series study was performed using mortality data (2013–2018) from 59 counties across the Beijing-Tianjin-Hebei region and surrounding areas in China. Applying quasi-Poisson generalized linear models, the study quantified exposure-response relationships, additive interactions, and attributable fractions for the concurrent events. Heatwaves and O3 pollution events were classified by intensity and duration and combined to define different types of concurrent events.  Results   The study found that when O3 levels exceeded 130 μg/m3 for at least two days during heatwaves, significant additive interactions markedly intensified mortality risks, particularly for circulatory diseases. These concurrent events increased non-accidental mortality by 13.5%, along with circulatory (16.9%), respiratory (13.9%), nervous system (24.1%), and type 2 diabetes (27.0%) mortality. However, nervous system mortality exhibited unique sensitivity to O3 concentrations during concurrent exposure, following a distinct upward trend. Women, older adults (≥ 65 years), and individuals with circulatory diseases were identified as vulnerable populations. From 2013 to 2018, 29,730 deaths were attributable to concurrent events (52.8% circulatory), with the attributable fraction rising by 0.15% annually.  Conclusions   These findings provide essential empirical evidence for developing an integrated smart early-warning framework, establishing feasible protocols for alert grading, and supporting the design of targeted interventions for vulnerable populations.
Aging Acceleration and Multi-omics Signatures of Passive Smoking on All-cause Mortality in Never-smokers
Ziqi Wan, Jiarui Mi, Jieying Tang, Nan Zhao
In press  doi: 10.3967/bes2026.082
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Long-term Association between Ozone Exposure and Chronic Obstructive Pulmonary Disease Modified by County-level Socioeconomic Status and Temperature: A Nationwide Cross-sectional Study in China
Ning Wang, Baohua Wang, Zhiwei Xu, Jian Cheng, Xuefei Feng, Shuai Wang, Rui Zhao, Bingbing Wang, Wenbiao Hu, Jing Wu
In press  doi: 10.3967/bes2026.070
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  Objective  Evidence regarding the association between long-term ozone exposure and chronic obstructive pulmonary disease (COPD) has primarily originated from high-income countries, with limited studies in China.  Methods  This nationwide cross-sectional study included 66,752 Chinese adults. Patients with COPD were identified using post-bronchodilator spirometry. Long-term ozone exposure was estimated using the average ozone concentrations in the grid cells covering the participants’ residential counties. Logistic regression was used to analyze the ozone–COPD association, adjusting for individual-level risk factors and socioeconomic factors. Additive interaction models were employed to assess the modification of the ozone–COPD association by county-level gross domestic product (GDP) per capita and temperature.  Results  Each 10-µg/m3 increase in annual ozone exposure was significantly associated with a higher risk of COPD (odds ratio [OR]: 1.172, 95% confidence interval [CI]: 1.039−1.322). In comparison with counties in the highest quartile of GDP per capita, the association between ozone exposure and COPD was stronger in counties in the lowest quartile of GDP per capita (P < 0.05). Counties with lower winter temperatures exhibited a stronger ozone–COPD association than those with warmer winters (P < 0.05). The relative excess risks due to the interaction of ozone with GDP per capita and winter temperature were 0.219 (95% CI: 0.095–0.344) and 0.254 (95% CI: 0.103–0.404), respectively.  Conclusion  Socioeconomically disadvantaged and colder regions exhibited greater susceptibility to ozone-related COPD. Targeted interventions aimed at these vulnerable countries are needed to mitigate inequalities in ozone-related COPD.
Cover
2026-10 Cover
2026, 39(10).  
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2026-10 Contents
2026, 39(10): 1-2.  
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Editorial
Broadening Vaccine Value: Translating Comprehensive Assessment into Sustained Population Protection
Huaqing Wang
2026, 39(10): 1157-1159.   doi: 10.3967/bes2026.113
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Perspective
Extinction or Dormancy: A Perspective on B/Yamagata Lineage Influenza Viruses
Jiaxin Li, Jiayu Sang, Yan Yang, Yingze Zhao, George F. Gao, Jun Liu
2026, 39(10): 1160-1166.   doi: 10.3967/bes2026.087
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Original Article
Estimating Risk of Measles Virus Transmission in Countries with Measles Elimination Status: A Comparative Measles Seroprevalence Study
Linlin Gong, Guzainuer Abudurusuli, Fan Zheng, Jiayuan Xie, Huaqing Wang
2026, 39(10): 1167-1175.   doi: 10.3967/bes2026.106
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  Objective   Measles elimination is threatened by the virus’s high infectivity (R0 = 12–18), waning immunity, and persistent immunity gaps. No global study has compared measles seroprevalence before and after elimination. We assessed whether countries that had eliminated measles achieved and maintained the herd immunity threshold and identified key vulnerabilities.  Methods   For countries with World Health Organization (WHO)-confirmed measles elimination, we systematically searched PubMed, Web of Science, and Google Scholar for seroprevalence data covering the three years before and the three years after elimination verification. Sample-size-weighted medians and interquartile ranges were calculated to describe seroprevalence, with stratified analyses by age group and country. The overall seroprevalence in the three years before and after elimination verification was also compared.  Results  Among 31 countries with measles elimination status (351 datasets comprising 562,772 participants), the overall median seroprevalence was 92.8%. Seroprevalence increased significantly with age (P < 0.001), from 56.5% among infants (aged 0–1 years) to 96.8% among older adults (aged > 40 years). Twenty-six percent of the countries had a seroprevalence of ≥ 92%, indicating a low risk of measles transmission, whereas 45% had a seroprevalence of < 85%, indicating a substantial transmission risk. The median seroprevalence decreased significantly from 94.9% during the three years before elimination verification to 83.5% during the three years after verification (P < 0.001).  Conclusion  Achieving measles elimination does not guarantee that population-level protection will be sustained. Despite high overall seroprevalence, important immunity gaps persist among infants and young children, and some countries do not maintain the required herd immunity threshold following elimination. Targeted interventions are needed to close immunity gaps and strengthen national population immunity to prevent measles resurgence.
Development and Validation of a Framework for Comprehensive Vaccine Value Assessment: A Modified Delphi Study
Quanwei Song, Hong Yang, Na Liu, Linlin Gong, Zhijie An, Huaqing Wang
2026, 39(10): 1176-1188.   doi: 10.3967/bes2026.058
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  Objective  Traditional Health Technology Assessments (HTAs) commonly overlook the broader societal and economic externalities of vaccines, leading to systematic undervaluation and suboptimal resource allocation. This study aimed to develop and validate a comprehensive vaccine value framework and prioritize individual elements for future HTA integration.  Methods  A two-phase mixed-methods approach was employed for framework development. Phase 1 involved a systematic literature review of major databases to construct an initial conceptual framework. Phase 2 utilized a two-round modified Delphi study involving a multidisciplinary expert panel to validate and refine the framework. Six evaluative criteria, categorized under the dimensions of 'Relevance' and 'Feasibility', were weighted and applied to score each value element. Finally, a comparative analysis of the raw and weighted scores was conducted to identify five priority value elements for future integration into HTAs.  Results  The final validated framework comprised 5 value categories, 21 value elements, and 75 actionable value items. Although traditional metrics achieved the highest consensus, the following five 'broader' elements emerged as top priorities for future inclusion: (1) Enhancement of Health System Security, (2) Macroeconomic Gains, (3) Social Equity and Ethics, (4) Prevention of Institutional Disruptions, and (5) Value to Other Interventions.  Conclusion  This study established a standardized multitiered roadmap to capture the multifaceted value of vaccines. By introducing actionable Tier-3 indicators, the framework operationalizes the assessment of broader vaccine benefits and offers a practical tool to support equitable and comprehensive evidence-based policymaking. Furthermore, the identification of the five priority value elements provides a feasible pathway for integrating extended vaccine externalities into future HTAs. Ultimately, this standardized framework will facilitate holistic decision-making and support the optimal allocation of resources within national immunization programs.
From Phylogeny to Metabolic Potential: Reclassifying and Characterizing Nocardia through Genome-wide Analysis
Bingqian Du, Ziyu Song, Yuting Duan, Yutong Kang, Min Yuan, Shuai Xu, Zhenjun Li
2026, 39(10): 1189-1199.   doi: 10.3967/bes2026.057
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  Objective   This study aimed to comprehensively characterize the genomic diversity, evolutionary dynamics, pathogenic potential, antimicrobial resistance, and secondary metabolite capacity of the Nocardia genus using whole-genome analyses.  Methods   We analyzed 751 publicly available Nocardia genomes using genome-based species delineation, phylogenomics, pangenome analysis, and comparative functional profiling to assess taxonomy, virulence, antibiotic resistance genes (ARGs), and biosynthetic gene clusters (BGCs).  Results   Phylogenomic analyses resolved five major clades: N. farcinica, N. carnea, N. asteroides, N. transvalensis, and N. otitidiscaviarum groups. The pangenome is open, comprising 467,566 gene clusters and reflecting extensive genomic diversity. Virulence factors and ARGs exhibit clade-specific patterns: the N. farcinica group harbors the most complete virulence repertoire and diverse resistance determinants, whereas the N. carnea and N. asteroides groups carry fewer genes. Analysis of 10,196 BGCs across 46 classes revealed conserved clusters of non-ribosomal peptide synthetases, terpenes, and type I polyketide synthases, with higher biosynthetic potential in the N. farcinica, N. transvalensis, and N. otitidiscaviarum groups. Several genomes encode BGCs associated with antibacterial or anticancer compounds.  Conclusion  This comprehensive genome analysis of Nocardia, representing the most complete sampling to date, clarifies phylogeny, reclassifies misassigned strains, identifies potential novel species, and reveals clade-specific patterns of virulence, resistance, and secondary metabolism.
Regulation of Oxidative Stress Associated with an SSK2 Point Mutation Promotes Amphotericin B Resistance in Cryptococcus gattii
Hengyu Deng, Xuefeng Zang, Enqi Zhao, Yemei Huang, Jing Liu, Yangyu Zhou, Chen Yang, Wencong He, Xiaozhuo Dong, Hui Chen, Ziqi Zhao, Yuhan Zhou, Xuelei Zang, Chen Wang, Liye Zhang, Xinying Xue
2026, 39(10): 1200-1214.   doi: 10.3967/bes2026.108
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  Objective   Cryptococcus gattii (C. gattii) is a pathogenic respiratory fungus that rapidly disseminates through the central nervous system. The current clinical treatments for C. gattii infections are limited by prolonged therapeutic courses, high drug dosages, and insufficient antifungal options. This study aimed to explore the molecular mechanisms underlying amphotericin B (AmB) resistance in C. gattii and provide novel insights for developing targeted antifungal strategies.  Methods   A total of 27 clinical C. gattii isolates were subjected to antifungal susceptibility testing, multilocus sequence typing (MLST) for phylogenetic analysis and resistance-related mutation screening. The CRISPR/Cas9 system was used to construct an SSK2-knockout mutant (ssk2Δ-G4). Capsule and melanin assays, murine pulmonary infection models, and transcriptomic analyses were performed to verify gene function, evaluate therapeutic efficacy, and explore the underlying regulatory mechanisms.  Results   G4 isolates exhibited prominent AmB resistance with a novel SSK2 c.793A>G missense mutation (p.Thr265Ala; hereafter SSK2T265A). SSK2 knockout significantly enhanced AmB susceptibility, whereas SSK2T265A complementation partially restored the resistant phenotype. AmB treatment markedly reduced pulmonary fungal burden and inflammatory infiltration (P < 0.05) and improved survival (P < 0.001) in ssk2Δ-G4-infected mice. Mechanistically, this mutation upregulated CAT1 expression and enhanced the reactive oxygen species–scavenging capacity and oxidative stress tolerance.  Conclusion   SSK2 c.793A>G is closely associated with AmB resistance and functionally contributes to the resistance phenotype. SSK2 could serve as a potential therapeutic target for developing AmB synergistic sensitizers and as a research direction for future synergistic treatments of clinically resistant C. gattii strains.
HBcrAg Predicts Post-IFN-α Therapy Relapse in CHB
Linmei Yao, Chuanchun Mao, Yuan Tian, Yao Lu, Lu Zhang, Ge Shen, Shuling Wu, Min Chang, Hongxiao Hao, Leiping Hu, Yuanjiao Gao, Mengjiao Xu, Yao Xie, Minghui Li, Ruyu Liu
2026, 39(10): 1215-1224.   doi: 10.3967/bes2026.105
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  Objective  Serum markers predicting virologic relapse after pegylated interferon-alpha (Peg-IFN-α) discontinuation in patients with chronic hepatitis B (CHB) are lacking. This study aimed to evaluate serum pregenomic RNA (pgRNA), hepatitis B core-related antigen (HBcrAg), and hepatitis B surface antigen (HBsAg) as potential predictors of Peg-IFN-α treatment outcomes and post-treatment virologic relapse in treatment-naïve patients with CHB.  Methods  A total of 371 treatment-naïve patients with CHB were initially recruited for this study, and 327 patients who completed the entire follow-up period were included in the data analysis. Serum pgRNA and HBcrAg levels were measured by polymerase chain reaction (PCR)-fluorescence probing and enzyme-linked immunosorbent assay (ELISA), respectively.  Results  Among the 327 followed patients, 112 (34.25%) achieved a virologic response to Peg-IFN-α; 16 (14.29%) experienced virologic relapse over a median follow-up of 12 months. Baseline pgRNA (odds ratio [OR], 0.571), HBcrAg (OR, 0.539), and HBsAg (OR, 0.356) levels correlated with treatment efficacy, demonstrating predictive values with AUCs of 0.821, 0.879, and 0.781, respectively. HBcrAg levels at treatment discontinuation were associated with virologic relapse and showed potential as predictive biomarkers (AUC, 0.790).  Conclusion  Serum pgRNA, HBcrAg, and HBsAg correlate with Peg-IFN-α response in treatment-naïve CHB. Serum HBcrAg levels at Peg-IFN-α discontinuation show potential as a predictive biomarker for post-treatment virologic relapse and are associated with relapse risk, which may help identify high-risk patients after Peg-IFN-α cessation. Notably, this finding requires further validation in larger cohorts due to the limited number of relapse events.
Peripheral Blood WBC Count and LDH Levels in Early Severity Assessment of Bee Sting Injuries
Xuebin Pei, Yiyang Liu, Kun Zhang, Bianfang Liu, Junli Chen, Zhidong Fang, Yanqiang Jiang, Xinhua He
2026, 39(10): 1225-1237.   doi: 10.3967/bes2026.099
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  Objective  To investigate the clinical value of peripheral white blood cell (WBC) count and lactate dehydrogenase (LDH) levels in assessing early disease severity in patients with bee sting injuries after admission.  Methods  This single-center, retrospective, exploratory cohort study consecutively enrolled adult patients with bee sting injuries who presented to the Emergency Department of the Wu’an First People’s Hospital, Hebei Province, between August 2021 and September 2025. Based on their early clinical manifestations after admission and bee sting-adjusted Sequential Organ Failure Assessment (SOFA) scores, patients were classified into a mild group (adjusted SOFA score < 2) and a moderate-to-severe group (adjusted SOFA score ≥ 2). The initial peripheral venous blood test results obtained within 24 h of presentation to the emergency department were collected. A binary logistic regression model was constructed using WBC and LDH levels after natural logarithmic transformation and z-score standardization. Receiver operating characteristic (ROC) curves were generated using model-predicted probabilities, and areas under the curve (AUCs) were compared using the DeLong test. Model performance was further evaluated using calibration curves, decision curve analysis (DCA), and bootstrap internal validation with 1,000 resamples.  Results  A total of 56 patients were included in this study. After excluding three patients with missing key data, 53 were included in the final analysis: 33 in the mild group and 20 in the moderate-to-severe group, of whom three died. The WBC count, neutrophil count, blood urea nitrogen (BUN), creatinine (Cr), and LDH levels were significantly higher in the moderate-to-severe group than in the mild group, whereas albumin levels were significantly lower (all P < 0.05). In the exploratory two-variable logistic regression model, both natural log-transformed and z-score-standardized WBC count [Zln(WBC)] and LDH level [Zln(LDH)] were associated with moderate-to-severe bee sting injuries early after admission. The AUCs of the WBC count, LDH level, and the combined model for identifying moderate-to-severe bee sting injuries were 0.780 (95% confidence interval [CI]: 0.638–0.922), 0.774 (95% CI: 0.627–0.922), and 0.827 (95% CI: 0.688–0.966), respectively. Although the AUC of the combined model was numerically higher than that of each individual marker, the DeLong test showed no statistically significant differences (combined model vs. WBC count, P = 0.414; combined model vs. LDH level, P = 0.178). The optimism-corrected AUC for the combined model after bootstrap validation was approximately 0.814.  Conclusion  WBC count and LDH levels are readily available biomarkers that may serve as adjunctive indicators for early severity stratification in patients with bee sting injuries.
Review
Emerging Technologies for Viability Assessment of Foodborne Pathogens: From Molecular Dyes to Artificial Intelligence
Zeyu Wang, Anum Farid, Zhiwei Chen, Jiayi Qi, Xinxin Shen, Hong Liu
2026, 39(10): 1238-1254.   doi: 10.3967/bes2026.109
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To critically examine emerging technologies for assessing foodborne-pathogen viability and to evaluate their relevance for improving food safety monitoring and public-health risk assessment. This review examines the literature on viability-detection using biological indicators such as membrane integrity, infectivity, and virulence. It addresses technologies such as viability dye-based PCR, RNA and CRISPR detection methods, biosensors, bacteriophage assays, Raman spectroscopy, and AI-supported analysis. Compared to conventional culture-based and DNA-only molecular methods, viability-focused techniques support more biologically meaningful detection, particularly for viable but non-culturable (VBNC) cells that may retain pathogenic potential. However, assay performance varies depending on food-matrix complexity, the presence of inhibitors, sensitivity limitations, and the degree of validation. Integrated systems combining multi-modal sensing, microfluidics, and machine learning have shown increasing promise for rapid on-site application, although standardization and regulatory validation remain limited. The emerging viability-focused technologies substantially refine microbial-risk assessment by accurately capturing the infectious potential of foodborne pathogens, including traditionally undetected VBNC populations. Nevertheless, integrating these technologies into routine surveillance remains constrained by matrix interference and the absence of standardized protocols. Future efforts must prioritize developing matrix-resilient methodologies and establishing regulatory validation frameworks to facilitate their practical implementation in food safety management.
Letter
Clinical and Viral Genomic Characterization of One Child Bronchopneumonia Case Caused by Recombinant Human Adenovirus D115
Ling Jing, Ying Lin, Xiaolei Guan, Yue Cui, Qiuping Li, Xiangpeng Chen, Ju Yin, Baoping Xu, Yun Zhu, Zhengde Xie
2026, 39(10): 1255-1259.   doi: 10.3967/bes2026.110
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Comparative Phenotypic Analysis and Epidemiological Implications of the Three Evolutionary Clades of Coxsackievirus A16 Subgenotype B1
Shujing Li, Ying Zhu, Shaoyong Xu, Wenxiang He, Yuwei Weng, Wei Chen
2026, 39(10): 1260-1264.   doi: 10.3967/bes2026.111
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Association of a Novel Triglyceride–glucose–creatinine Index with Depressive Symptoms: Evidence from Chinese Adults
Shaopeng Guo, Xiaohui Sun, Hongxuan Yan, Kejia Huang, Chen Chen, Chi Pan, Xianyun Wang, Xiao Liu, Ao Li, Weijing Wang, Jie Xu, Feng Ning
2026, 39(10): 1265-1270.   doi: 10.3967/bes2026.112
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Correction
Correction
2026, 39(10): 1271-1271.   doi: 10.3967/bes2026.118
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Bone Injury and Fracture Healing Biology
Ahmad Oryan, Somayeh Monazzah, Amin Bigham-Sadegh
2015, 28(1): 57-71.   doi: 10.3967/bes2015.006
[Abstract](37314) [PDF 3875KB](17594)
Report on Cardiovascular Health and Diseases in China 2021: An Updated Summary
The Writing Committee of the Report on Cardiovascular Health and Diseases in China
2022, 35(7): 573-603.   doi: 10.3967/bes2022.079
[Abstract](54249) [FullText HTML](25081) [PDF 2336KB](25081)
Report on Cardiovascular Health and Diseases in China 2022: an Updated Summary
The Writing Committee of the Report on Cardiovascular Health and Diseases in China
2023, 36(8): 669-701.   doi: 10.3967/bes2023.106
[Abstract](41363) [FullText HTML](18389) [PDF 1561KB](18389)
The Serum Exosome Derived MicroRNA-135a, -193b, and-384 Were Potential Alzheimer's Disease Biomarkers
YANG Ting Ting, LIU Chen Geng, GAO Shi Chao, ZHANG Yi, WANG Pei Chang
2018, 31(2): 87-96.   doi: 10.3967/bes2018.011
[Abstract](34842) [FullText HTML](15777) [PDF 11333KB](15777)
Burden of Cirrhosis and Other Chronic Liver Diseases Caused by Specific Etiologies in China, 1990−2016: Findings from the Global Burden of Disease Study 2016
LI Man, WANG Zhuo Qun, ZHANG Lu, ZHENG Hao, LIU Dian Wu, ZHOU Mai Geng
2020, 33(1): 1-10.   doi: 10.3967/bes2020.001
[Abstract](36140) [FullText HTML](16319) [PDF 2552KB](16319)
Effects of Short-Term Forest Bathing on Human Health in a Broad-Leaved Evergreen Forest in Zhejiang Province, China
MAO Gen Xiang, LAN Xiao Guang, CAO Yong Bao, CHEN Zhuo Mei, HE Zhi Hua, LV Yuan Dong, WANG Ya Zhen, HU Xi Lian, WANG Guo Fu, YAN Jing
2012, 25(3): 317-324.   doi: 10.3967/0895-3988.2012.03.010
[Abstract](30849) [PDF 528KB](14819)
Report on Cardiovascular Health and Diseases in China 2023: An Updated Summary
National Center for Cardiovascular Diseases The Writing Committee of the Report on Cardiovascular Health and Diseases in China
2024, 37(9): 949-992.   doi: 10.3967/bes2024.162
[Abstract](26524) [FullText HTML](12023) [PDF 2831KB](12023)
Trends in Lipids Level and Dyslipidemia among Chinese Adults, 2002-2015
SONG Peng Kun, MAN Qing Qing, LI Hong, PANG Shao Jie, JIA Shan Shan, LI Yu Qian, HE Li, ZHAO Wen Hua, ZHANG Jian
2019, 32(8): 559-570.   doi: 10.3967/bes2019.074
[Abstract](37097) [FullText HTML](17328) [PDF 3641KB](17328)
Evidence on Invasion of Blood, Adipose Tissues, Nervous System and Reproductive System of Mice After a Single Oral Exposure: Nanoplastics versus Microplastics
YANG Zuo Sen, BAI Ying Long, JIN Cui Hong, NA Jun, ZHANG Rui, GAO Yuan, PAN Guo Wei, YAN Ling Jun, SUN Wei
2022, 35(11): 1025-1037.   doi: 10.3967/bes2022.131
[Abstract](36752) [FullText HTML](17827) [PDF 10064KB](17827)
Protein Requirements in Healthy Adults:A Meta-analysis of Nitrogen Balance Studies
LI Min, SUN Feng, PIAO Jian Hua, YANG Xiao Guang
2014, 27(8): 606-613.   doi: 10.3967/bes2014.093
[Abstract](35221) [PDF 8784KB](17001)
TaqMan Real-time RT-PCR Assay for Detecting and Differentiating Japanese Encephalitis Virus
SHAO Nan, LI Fan, NIE Kai, FU Shi Hong, ZHANG Wei Jia, HE Ying, LEI Wen Wen, WANG Qian Ying, LIANG Guo Dong, CAO Yu Xi, WANG Huan Yu
2018, 31(3): 208-214.   doi: 10.3967/bes2018.026
[Abstract](30393) [FullText HTML](14373) [PDF 4691KB](14373)
Correlation between Anxiety, Depression, and Sleep Quality in College Students
ZHANG Yu Tong, HUANG Tao, ZHOU Fang, HUANG Ao Di, JI Xiao Qi, HE Lu, GENG Qiang, WANG Jia, MEI Can, XU Yu Jia, YANG Ze Long, ZHAN Jian Bo, CHENG Jing
2022, 35(7): 648-651.   doi: 10.3967/bes2022.084
[Abstract](8665) [FullText HTML](4009) [PDF 1202KB](4009)
Application of Nanopore Sequencing Technology in the Clinical Diagnosis of Infectious Diseases
ZHANG Lu Lu, ZHANG Chi, PENG Jun Ping
2022, 35(5): 381-392.   doi: 10.3967/bes2022.054
[Abstract](28737) [FullText HTML](13880) [PDF 2174KB](13880)
Health Effect of Forest Bathing Trip on Elderly Patients with Chronic Obstructive Pulmonary Disease
JIA Bing Bing, YANG Zhou Xin, MAO Gen Xiang, LYU Yuan Dong, WEN Xiao Lin, XU Wei Hong, LYU XIAO Ling
2016, 29(3): 212-218.   doi: 10.3967/bes2016.026
[Abstract](25039) [PDF 803KB](12071)
Metabolomic Profiling Differences among Asthma, COPD, and Healthy Subjects: A LC-MS-based Metabolomic Analysis
LIANG Ying, GAI Xiao Yan, CHANG Chun, ZHANG Xu, WANG Juan, LI Ting Ting
2019, 32(9): 659-672.   doi: 10.3967/bes2019.085
[Abstract](30227) [FullText HTML](13768) [PDF 2914KB](13768)
Stability of SARS Coronavirus in Human Specimens and Environment and Its Sensitivity to Heating and UV Irradiation
SHU-MING DUAN, Xin-sheng Zhao, RUI-FU WEN, JING-JING HUANG, GUO-HUA PI, SU-XIANG ZHANG, JUN HAN, SHENG-LI BI, LI RUAN, XIAO-PING DONG, SARS RESEARCH TEAM
2003, 16(3): 246-255.  
[Abstract](17093) [PDF 610KB](6696)
Validation of the Physical Activity Questionnaire for Older Children (PAQ-C) among Chinese Children
WANG Jing Jing, BARANOWSKI Tom, LAU WC Patrick, CHEN Tzu An, PITKETHLY Amanda Jane
2016, 29(3): 177-186.   doi: 10.3967/bes2016.022
[Abstract](6372) [PDF 323KB](2678)
Evaluating the Nutritional Status of Oncology Patientsand Its Association with Quality of Life
ZHANG Ya Hui, XIE Fang Yi, CHEN Ya Wen, WANG Hai Xia, TIAN Wen Xia, SUN Wen Guang, WU Jing
2018, 31(9): 637-644.   doi: 10.3967/bes2018.088
[Abstract](29922) [FullText HTML](13595) [PDF 31943KB](13595)
Hypertension Prevalence, Awareness, Treatment, and Control and Their Associated Socioeconomic Factors in China: A Spatial Analysis of A National Representative Survey
WANG Wei, ZHANG Mei, XU Cheng Dong, YE Peng Peng, LIU Yun Ning, HUANG Zheng Jing, HU Cai Hong, ZHANG Xiao, ZHAO Zhen Ping, LI Chun, CHEN Xiao Rong, WANG Li Min, ZHOU Mai Geng
2021, 34(12): 937-951.   doi: 10.3967/bes2021.130
[Abstract](34829) [FullText HTML](16696) [PDF 2205KB](16696)
Supplementation of Fermented Barley Extracts with Lactobacillus Plantarum dy-1 Inhibits Obesity via a UCP1-dependent Mechanism
XIAO Xiang, BAI Juan, LI Ming Song, ZHANG Jia Yan, SUN Xin Juan, DONG Ying
2019, 32(8): 578-591.   doi: 10.3967/bes2019.076
[Abstract](29442) [FullText HTML](13137) [PDF 9101KB](13137)

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Vol 39, No 10

(October, 2026)

ISSN 0895-3988

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