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).
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
In press  doi: 10.3967/bes2024.177
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  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.
Effects of Ozone Exposure on Cardiopulmonary Function and Adaptive Responses in Han and Tibetan Children During Physical Activity at High Altitudes
Mengyao Bian, Ling Qi, Qian Guo, Yuchen Zhao, Xiaoli Duan
In press  doi: 10.3967/bes2025.054
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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
In press  doi: 10.3967/bes2025.053
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  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
In press  doi: 10.3967/bes2025.052
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  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
In press  doi: 10.3967/bes2025.051
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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.
Co-Circulation of Respiratory Pathogens that Cause Severe Acute Respiratory Infections during the Autumn and Winter of 2023 in Beijing, China
Jingzhi Li, Da Huo, Daitao Zhang, Jiachen Zhao, Chunna Ma, Dan Wu, Peng Yang, Quanyi Wang, Zhaomin Feng
In press  doi: 10.3967/bes2025.050
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Synaptic Vesicle Glycoprotein 2A Slows down Amyloidogenic Processing of Amyloid Precursor Protein via Regulating Its Intracellular Trafficking
Qian Zhang, Xiaoling Wang, Yuli Hou, Jingjing Zhang, Congcong Liu, Xiaomin Zhang, Yaqi Wang, Yujian Fan, Junting Liu, Jing Liu, Qiao Song, Peichang Wang
In press  doi: 10.3967/bes2025.049
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  Objective  To reveal the effects and potential mechanisms by which synaptic vesicle glycoprotein 2A (SV2A) influences the distribution of amyloid precursor protein (APP) in the trans-Golgi network (TGN), endolysosomal system, and cell membranes and to reveal the effects of SV2A on APP amyloid degradation.  Methods  Colocalization analysis of APP with specific tagged proteins in the TGN, ensolysosomal system, and cell membrane was performed to explore the effects of SV2A on the intracellular transport of APP. APP, β-site amyloid precursor protein cleaving enzyme 1 (BACE1) expressions, and APP cleavage products levels were investigated to observe the effects of SV2A on APP amyloidogenic processing.  Results  APP localization was reduced in the TGN, early endosomes, late endosomes, and lysosomes, whereas it was increased in the recycling endosomes and cell membrane of SV2A-overexpressed neurons. Moreover, Arl5b (ADP-ribosylation factor 5b), a protein responsible for transporting APP from the TGN to early endosomes, was upregulated by SV2A. SV2A overexpression also decreased APP transport from the cell membrane to early endosomes by downregulating APP endocytosis. In addition, products of APP amyloid degradation, including sAPPβ, Aβ1-42, and Aβ1-40, were decreased in SV2A-overexpressed cells.  Conclusion  These results demonstrated that SV2A promotes APP transport from the TGN to early endosomes by upregulating Arl5b and promoting APP transport from early endosomes to recycling endosomes-cell membrane pathway, which slows APP amyloid degradation.
Identifying High-Risk Areas for Type 2 Diabetes Mellitus Mortality in Guangdong, China: Spatiotemporal Clustering and Socioenvironmental Determinants
Haiming Luo, Wenbiao Hu, Yanjun Xu, Xueyan Zheng, Qun He, Lu Lv, Ruilin Meng, Xiaojun Xu, Fei Zou
In press  doi: 10.3967/bes2025.048
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  Objective   This study aimed to identify high-risk areas for type 2 diabetes mellitus (T2DM) mortality to provide relevant evidence for interventions in emerging economies.  Methods   Empirical Bayesian Kriging and a discrete Poisson space-time scan statistic were applied to identify the spatiotemporal clusters of T2DM mortality. The relationships between economic factors, air pollutants, and the mortality risk of T2DM were assessed using regression analysis and the Poisson Log-linear Model.  Results   A coastal district in East Guangdong, China, had the highest risk (Relative Risk [RR] = 4.58, P < 0.01), followed by the 10 coastal districts/counties in West Guangdong, China (RR = 2.88, P < 0.01). The coastal county in the Pearl River Delta, China (RR = 2.24, P < 0.01), had the third-highest risk. The remaining risk areas were two coastal counties in East Guangdong, 16 districts/counties in the Pearl River Delta, and two counties in North Guangdong, China. Mortality due to T2DM was associated with gross domestic product per capita (GDP per capita). In pilot assessments, T2DM deaths were significantly associated with carbon monoxide.  Conclusion   High mortality from T2DM occurred in the coastal areas of East and West Guangdong, especially where the economy was progressing towards the upper middle-income level.
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
In press  doi: 10.3967/bes2025.047
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  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
In press  doi: 10.3967/bes2025.046
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  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
In press  doi: 10.3967/bes2025.045
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  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.
Lumbar Spondylolysis in Chinese Adults: Prevalence and Musculoskeletal Condition
Dong Yan, Yandong Iiu, Ling Wang, Kai Li, Wenshuang Zhang, Yi Yuan, Jian Geng, Kangkang Ma, Fengyun Zhou, Zitong Cheng, Xiaoguang Cheng
In press  doi: 10.3967/bes2025.043
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  Objective   To determine the prevalence of lumbar spondylolysis (LS) and the proportion of spondylolytic spondylolisthesis (SS) in China. To evaluate the musculoskeletal status of patients with LS and SS.  Methods   Spine Computed Tomography (CT) images were collected from community populations aged 40 and above in a nationwide multi-center project. LS was diagnosed, and SS was graded by an experienced radiologist. Bone mineral density (BMD) and paraspinal muscle parameters were quantified based on CT images.  Results   117 patients of a total of 3,317 individuals were diagnosed with LS, corresponding to a prevalence rate of 3.53%. 63 of the 1,214 males (5.18%) and 54 of the 2,103 females (2.57%) were diagnosed with LS. SS occurred in 64/121 vertebrae (52.89%). BMD was not associated with LS (P = 0.341). The L5 extensor paraspinal muscle density was higher in the LS group than in the non-LS group. In the LS group, patients with SS had a lower L5 paraspinal extensor muscle cross-sectional area than those without SS (P = 0.003).  Conclusion   The prevalence of LS in Chinese adults was 3.53%, with prevalence rates of 5.18% in males and 2.57% in females. Patients with LS have higher muscle density, whereas those with SS have smaller muscle cross-sectional areas at the L5 level.
The Disease Burden of Asthma in China, 1990 to 2021 and Projections to 2050: Based on the Global Burden of Disease 2021
Ruiyi Zhang, Miaomiao Zhang, Yuchang Zhou, Jiahuan Guo, Xuankai Wang, Maigeng Zhou
In press  doi: 10.3967/bes2025.042
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  Objective  Asthma imposes a significant global health burden. This study examines changes in the asthma-related disease burden from 1990 to 2021 and projects future burdens for 2050 under different scenarios.  Methods  Using data from the Global Burden of Disease 2021 study, we analyzed asthma incidence, prevalence, mortality, and disability-adjusted life years (DALYs) from 1990 to 2021. We projected the disease burden for 2050 based on current trends and hypothetical scenarios in which all risk factors are controlled. Temporal trends in age-standardized incidence, prevalence, mortality, and DALY rates were explored using Annual Percent Change.  Results  In 2021, the age-standardized rates for asthma incidence, prevalence, mortality, and DALYs in China were 364.17 per 100,000 (95% uncertainty interval [UI]: 283.22–494.10), 1,956.49 per 100,000 (95% UI: 1,566.68–2,491.87), 1.47 per 100,000 (95% UI: 1.15–1.79), and 103.76 per 100,000 (95% UI: 72.50–145.46), respectively. A higher disease burden was observed among Chinese men and individuals aged 70 years or older. Compared to the current trend, a combined scenario involving improvements in environmental factors, behavioral and metabolic health, child nutrition, and vaccination resulted in a greater reduction in the disease burden caused by asthma.  Conclusion  Addressing modifiable risk factors is essential for further reducing the asthma-related disease burden.
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
In press  doi: 10.3967/bes2025.041
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  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.
Disease burden and trends of COPD in the Asia-Pacific region (1990–2019) and predictions to 2034
Jing Ma, Hong Mi
In press  doi: 10.3967/bes2025.040
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  Objective  The Asia-Pacific region has a high Chronic obstructive pulmonary disease (COPD) burden, but studies on its trends are limited. Using the Global Burden of Disease (GBD) 2019 data, we analyzed COPD trends in 36 countries from 1990 to 2019 and predicted future incidence trends through 2034.  Methods  COPD data by age and sex from the GBD 2019 database were analyzed for incidence, prevalence, mortality, and disability-adjusted life years (DALY) rates from 1990 to 2019. Joinpoint regression identified significant annual trends, and age-standardized incidence rates were predicted through 2034 using age–period–cohort models.  Results  The incidence, prevalence, mortality, and disease burden of COPD have been decreasing, and the incidence rates will continue to decrease or remain stable until 2034 in most selected countries and territories, except for a few Southeastern Asian countries. The Lao People’s Democratic Republic and Vietnam are projected to experience an increase in COPD incidence from 165.3 per 100,000 in 2019 to 177 per 100,000 in 2034 and from 179.9 per 100,000 in 2019 to 192.5 per 100,000 in 2034, respectively. Older males had a higher incidence than any other sex or age group. The sex gap in incidence rates continues to widen, though it is smaller and less significant in the younger age group than in those in the older one.  Conclusion  COPD rates are expected to decline until 2034 but remain a health risk, especially in countries with rising rates. Urgent action on tobacco control, air pollution, and public education is needed.
Global Burden of Clostridium difficile Infection-Related Diarrhea Mortality from 1990 to 2021: A Study Based on the 2021 Global Burden of Disease Database
Ying Li, Jie Li, Hesheng Chang, Yuehua Hu, Chengdong Xu
In press  doi: 10.3967/bes2025.039
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Factors in Work-related Musculoskeletal Disorders in Dentists: A Structural Equation Model
Shunhang Li, Jian Li, Xin Xu, Yushan Huang, Yilin Zhang, Xiaoshuang Xu, Weizhen Guan, Xiaoping Liu, Jing Li
In press  doi: 10.3967/bes2025.037
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Forecast of the Burden of Lower Respiratory Infections in the Elderly Aged 70 and Above in China from 1990 to 2050, GBD2021
Miaomiao Zhang, Ruiyi Zhang, Yuchang Zhou, Maigeng Zhou
In press  doi: 10.3967/bes2025.036
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  Objective  This study aims to analyze the burden of lower respiratory infections in Chinese elderly people aged 70 and above.  Methods  This study utilized Global Burden of Disease (GBD) 1990-2050 prediction data to analyze changes in mortality rates and disability-adjusted life year (DALY) rates for lower respiratory infections in the elderly population (aged 70 and above) in China from 1990 to 2050. It also discusses future trends in the burden of lower respiratory infections (LRI) in China under different scenarios.  Results  According to GBD predictions, the burden of lower respiratory infections in the elderly aged 70 years and above in China is lower than the global average. The burden has been decreasing from 1990 to 2020, but is projected to increase from 2020 to 2050. Scenario-based predictions suggest that, under scenarios involving improvements in nutrition and vaccination, the burden of lower respiratory infections in the elderly in China is expected to be the lowest in 2050.  Conclusions  This study indicates that the burden of lower respiratory infections in elderly people aged 70 years and above in China remains a significant public health issue and may worsen. The government should consider strengthening the preventive measures and management strategies for respiratory infections in the elderly population.
Perioperative Cardiac Arrest in Mechanically Ventilated Older Patients Undergoing Thoracic Surgery
Wenjun Liu, Shuyu Zhang, Sheng Wang
In press  doi: 10.3967/bes2025.035
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Future Projections of Temperature-related Excess Morbidity Due to Influenza Under Climate Change Scenarios: A Case Study in a Temperate Japanese City
Keita Wagatsuma
In press  doi: 10.3967/bes2025.034
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Cover
2025-4 Cover
2025, 38(4).  
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2025-4 Contents
2025, 38(4): 1-2.  
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Editorial
Identification of High-Risk Populations: The Cornerstone of Effective and Cost-Efficient Cancer Screening
Wei Cao, Fei Wang, Ni Li
2025, 38(4): 401-402.   doi: 10.3967/bes2025.044
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Original Article
Role of Gold Nanorods Functionalized by Nucleic Acid Nanostructures Carrying Doxorubicin in Synergistic Anti-Cancer Therapy
Hao Wu, Huangshui Ma, Xinghan Wu, Qiang Sun, Lin Feng, Ruifang Jiang, Yanhong Li, Quan Shi
2025, 38(4): 403-415.   doi: 10.3967/bes2024.152
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  Objective   Cancer remains a significant global health challenge, necessitating the development of effective treatment approaches. Developing synergistic therapy can provide a highly promising strategy for anti-cancer treatment through combining the benefits of various mechanisms.  Methods   In this study, we developed a synergistic strategy for chemo-photothermal therapy by constructing nanocomposites using gold nanorods (GNRs) and tetrahedral framework nucleic acids (tFNA) loaded with the anti-tumor drug doxorubicin (DOX).  Results   Our in vitro studies have systematically clarified the anti-cancer behaviors of tFNA-DOX@GNR nanocomposites, characterized by their enhanced cellular uptake and proficient lysosomal escape capabilities. It was found that the key role of tFNA-DOX@GNR nanocomposites in tumor ablation is primarily due to their capacity to induce cytotoxicity in tumor cells via a photothermal effect, which generates instantaneous high temperatures. This mechanism introduces various responses in tumor cells, facilitated by the thermal effect and the integrated chemotherapeutic action of DOX. These reactions include the induction of endoplasmic reticulum stress, characterized by elevated reactive oxygen species levels, the promotion of apoptotic cell death, and the suppression of tumor cell proliferation.  Conclusion   This work exhibits the potential of synergistic therapy utilizing nanocomposites for cancer treatment and offers a promising avenue for future therapeutic strategies.
Construction of a Prognostic Model for Lysosome-dependent Cell Death in Gastric Cancer Based on Single-cell RNA-seq and Bulk RNA-seq Data
Peng Ni, Kaixin Guo, Tianyi Liang, Xinshuang Fan, Yanqiao Hua, Yangye Gao, Shuaiyin Chen, Guangcai Duan, Rongguang Zhang
2025, 38(4): 416-432.   doi: 10.3967/bes2024.159
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  Objective  To identify prognostic genes associated with lysosome-dependent cell death (LDCD) in patients with gastric cancer (GC).  Methods  Differentially expressed genes (DEGs) were identified using The Cancer Genome Atlas - Stomach Adenocarcinoma. Weighted gene co-expression network analysis was performed to identify the key module genes associated with LDCD score. Candidate genes were identified by DEGs and key module genes. Univariate Cox regression analysis, and least absolute shrinkage and selection operator regression and multivariate Cox regression analyses were performed for the selection of prognostic genes, and risk module was established. Subsequently, key cells were identified in the single-cell dataset (GSE183904), and prognostic gene expression was analyzed. Cell proliferation and migration were assessed using the Cell Counting Kit-8 assay and the wound healing assay.  Results  A total of 4,465 DEGs, 95 candidate genes, and 4 prognostic genes, including C19orf59, BATF2, TNFAIP2, and TNFSF18, were identified in the analysis. Receiver operating characteristic curves indicated the excellent predictive power of the risk model. Three key cell types (B cells, chief cells, and endothelial/pericyte cells) were identified in the GSE183904 dataset. C19orf59 and TNFAIP2 exhibited predominant expression in macrophage species, whereas TNFAIP2 evolved over time in endothelial/pericyte cells and chief cells. Functional experiments confirmed that interfering with C19orf59 inhibited proliferation and migration in GC cells.  Conclusion  C19orf59, BATF2, TNFAIP2, and TNFSF18 are prognostic genes associated with LDCD in GC. Furthermore, the risk model established in this study showed robust predictive power.
Threshold-Effect Associations of Serum 25-hydroxyvitamin D on Bone Turnover Markers and GC rs2282679 Variants in Chinese Women of Childbearing Age
Xiaoyun Shan, Yuting Li, Xiayu Zhao, Yichun Hu, Siran Li, Huidi Zhang, Yang Cao, Rui Wang, Lichen Yang
2025, 38(4): 433-446.   doi: 10.3967/bes2024.151
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  Objective  This study aimed to investigate possible serum 25-hydroxyvitamin D [25(OH)D] cutoffs for the associations between 25(OH)D and Bone turnover markers (BTMs), and how GC gene variation influences such cutoffs in Chinese women of childbearing age.  Methods  In total, 1,505 non-pregnant or non-lactating women (18–45 years) were recruited from the 2015 Chinese Adult Chronic Disease and Nutrition Surveillance. Serum 25(OH)D, osteocalcin (OC), procollagen type 1 N-terminal propeptide (P1NP), β-CrossLaps of type 1 collagen containing cross-linked C-telopeptide (β-CTX), and single nucleotide polymorphisms were determined. Locally weighted regression and smoothing scatterplot and segmented regression were performed to estimate the 25(OH)D thresholds.  Results  The median serum 25(OH)D was 16.63 (11.96–22.55) ng/mL and the prevalence of low serum 25(OH)D (< 12 ng/mL) was 25.2%. Women with the lowest 25(OH)D had the highest β-CTX. After adjustment for the confounders, 25(OH)D cutoffs for OC [14.04 (12.84–15.23) ng/mL], β-CTX [13.94 (12.49–15.39) ng/mL], and P1NP [13.87 (12.37–15.37) ng/mL] in the whole population, cutoffs for OC [12.30 (10.68–13.91) ng/mL], β-CTX [12.23 (10.22–14.23) ng/mL], and P1NP [11.85 (10.40–13.31) ng/mL] in women with the GC rs2282679 G allele, and cutoffs for OC [12.75 (11.81–13.68) ng/mL], β-CTX [13.05 (11.78–14.32) ng/mL], and P1NP [12.81 (11.57–14.06) ng/mL] in women with the GC rs2282679 T allele, were observed. Below these cutoffs, BTMs were negatively associated with 25(OH)D, while above these cutoffs, BTMs plateaued.  Conclusion  In Chinese women of childbearing age, there were thresholds effect of serum 25(OH)D concentrations on BTMs. The results indicated that serum 25(OH)D concentrations < 13.87 ng/mL in this population had adverse influences on maintaining bone remodeling. BTMs were suppressed at a relatively lower serum 25(OH)D in women with the GC rs2282679 G allele compared with those with the T allele.
Exploring the Efficacy of BMSC Transplantation via Various Pathways for Treating Cholestatic Liver Fibrosis in Mice
Junjie Ren, Zixu Li, Xinrui Shi, Tingting Lyu, Xiaonan Li, Min Ge, Qizhi Shuai, Tingjuan Huang
2025, 38(4): 447-458.   doi: 10.3967/bes2024.180
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  Objective  To compare the therapeutic efficacy of portal and tail vein transplantation of bone marrow-derived mesenchymal stem cells (BMSCs) against cholestatic liver fibrosis in mice.   Methods  BMSCs were isolated and co-cultured with starvation-activated hepatic stellate cells (HSCs). HSC activation markers were identified using immunofluorescence and qRT-PCR. BMSCs were injected into the liver tissues of bile duct ligation (BDL) mice via the tail and portal veins. Histomorphology, liver function, inflammatory cytokines, and the expression of key proteins were all determined in the liver tissues.  Results  BMSCs inhibited HSC activation by reducing α-SMA and collagen I expression. Compared to tail vein injection, DIL-labeled BMSCs injected through the portal vein maintained a high homing rate in the liver. Moreover, BMSCs transplanted through the portal vein resulted in greater improvement in liver color, hardness, and gallbladder size than did those transplanted through the tail vein. Furthermore, BMSCs injected by portal vein, but not tail vein, markedly ameliorated liver function, reduced the secretion of inflammatory cytokines, including TNF-α, IL-6, and IL-1β, and decreased α-SMA + hepatic stellate cell (HSC) activation and collagen fiber formation.  Conclusion  The therapeutic effect of BMSCs on cholestatic liver fibrosis in mice via portal vein transplantation was superior to that of tail vein transplantation. This comparative study provides reference information for further BMSC studies focused on clinical cholestatic liver diseases.
Homocysteine Levels and Determinants among Chinese Women at Mid-pregnancy, Late Pregnancy, and Postpartum
Zhenyu Guo, Hongtian Li, Yirui Ma, Ying Meng, Yubo Zhou, Jianmeng Liu
2025, 38(4): 459-468.   doi: 10.3967/bes2024.155
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  Objective   Data on homocysteine (Hcy) status and its determinants are limited among women during pregnancy and postpartum. This cross-sectional study aimed to investigate Hcy levels during pregnancy and postpartum, and to explore the determinants like geographic factor.  Methods   This study was conducted in women at mid-pregnancy, late-pregnancy and postpartum from southern, central and northern China. Approximately 132 women were included in each stratum by the three phases and regions. Plasma Hcy concentrations were assessed using high-performance liquid chromatography (HPLC), with hyperhomocysteinemia defined as > 10.0 µmol/L. Quantile regression was to estimate medians and interquartile ranges (IQRs), and logistic regression to examine the determinants of hyperhomocysteinemia.  Results   For 1,190 women included, the median (IQR) Hcy concentration was 5.66 (4.62, 7.37) μmol/L. The adjusted median in mid-pregnancy, late-pregnancy and postpartum women was 4.75 (4.13, 5.54), 5.72 (4.81, 6.85) and 7.09 (5.65, 8.75) μmol/L, respectively, showing an increasing trend (P < 0.001). This increasing trend persisted across the three regions. Higher Hcy concentrations were observed in women residing in northern region and those with younger age or lower economic status. A total of 106 (8.9%) women had hyperhomocysteinemia, with a higher prevalence in those residing in northern region (16.0%), or in postpartum women (16.5%).  Conclusion   Hcy levels, varying with geographic region, maternal age and economic status, are increased from mid-pregnancy to late-pregnancy and postpartum, indicating a need to monitor Hcy levels in pregnant and postpartum women to control potential risks related to elevated Hcy levels.
Antibiotic-Depleted Lung Microbiota Modulates Surfactant Proteins Expression and Reduces Experimental Silicosis
Qiang Zhou, Meiyu Chang, Ning Li, Yi Guan, Sanqiao Yao
2025, 38(4): 469-483.   doi: 10.3967/bes2025.012
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  Objective   Recent studies have overturned the traditional concept of the lung as a “sterile organ” revealing that pulmonary microbiota dysbiosis and abnormal surfactant proteins (SPs) expression are involved in the progression of silicosis. This study aimed to investigate the relationship between abnormal SPs expression and dysbiosis of lung microbiota in silica-induced lung fibrosis, providing insights into mechanisms of silicosis.  Methods   Lung pathology, SPs expression, and microbiota composition were evaluated in silica-exposed mice. A mouse model of antibiotic-induced microbiota depletion was established, and alveolar structure and SPs expression were assessed. The roles of the lung microbiota and SPs in silicosis progression were further evaluated in mice with antibiotic-induced microbiota depletion, both with and without silica exposure.  Results   Silica exposure induced lung inflammation and fibrosis, along with increased expression of SP-A expression. Antibiotics (Abx)-induced microbiota depletion elevated SP-A and SP-D expression. Furthermore, silica exposure altered lung microbiota composition, enriching potentially pathogenic taxa. However, antibiotic-induced microbiota depletion prior to silica exposure reduced silica-mediated lung fibrosis and inflammation.  Conclusion   Lung microbiota is associated with silica-induced lung injury. Overproduction of SP-A and SP-D, induced by Abx-induced microbiota depletion, may enhance the resistance of mouse lung tissue to silica-induced injury.
Hydrogen Sulfide Alleviates Lipid Peroxidation-Mediated Carbonyl Stress in Uranium-Intoxicated Kidney Cells via Nrf2/ARE Signaling
Jialin Liu, Min Wang, Rui Zhang, Jifang Zheng, Xixiu Jiang, Qiaoni Hu
2025, 38(4): 484-500.   doi: 10.3967/bes2025.021
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  Objective  To explore the protective effects and underlying mechanisms of H2S against lipid peroxidation-mediated carbonyl stress in the uranium-treated NRK-52E cells.  Methods  Cell viability was evaluated using CCK-8 assay. Apoptosis was measured using flow cytometry. Reagent kits were used to detect carbonyl stress markers malondialdehyde, 4-hydroxynonenal, thiobarbituric acid reactive substances, and protein carbonylation. Aldehyde-protein adduct formation and alcohol dehydrogenase, aldehyde dehydrogenase 2, aldo-keto reductase, nuclear factor E2-related factor 2 (Nrf2), and cystathionine β-synthase (CBS) expression were determined using western blotting or real-time PCR. Sulforaphane (SFP) was used to activate Nrf2. RNA interference was used to inhibit CBS expression.  Results  GYY4137 (an H2S donor) pretreatment significantly reversed the uranium-induced increase in carbonyl stress markers and aldehyde-protein adducts. GYY4137 effectively restored the uranium-decreased Nrf2 expression, nuclear translocation, and ratio of nuclear to cytoplasmic Nrf2, accompanied by a reversal of the uranium-decreased expression of CBS and aldehyde-metabolizing enzymes. The application of CBS siRNA efficiently abrogated the SFP-enhanced effects on the expression of CBS, Nrf2 activation, nuclear translocation, and ratio of nuclear to cytoplasmic Nrf2 and concomitantly reversed the SFP-enhanced effects of the uranium-induced mRNA expression of aldehyde-metabolizing enzymes. Simultaneously, CBS siRNA reversed the SFP-mediated alleviation of the uranium-induced increase in reactive aldehyde levels, apoptosis rates, and uranium-induced cell viability.  Conclusion  H2S induces Nrf2 activation and nuclear translocation, which modulates the expression of aldehyde-metabolizing enzymes and the CBS/H2S axis. Simultaneously, the Nrf2-controlled CBS/H2S axis may at least partially promote Nrf2 activation and nuclear translocation. These events form a cycle-regulating mode through which H2S attenuates the carbonyl stress-mediated NRK-52E cytotoxicity triggered by uranium.
Letter
Development and Validation of Machine Learning Models for Lung Cancer Risk Prediction in High-Risk Population: A Retrospective Cohort Study
Yu Su, Haoran Zhan, Shangyao Li, Yitong Lu, Ruhuan Ma, Hai Fang, Tingting Xu, Yu Tian
2025, 38(4): 501-505.   doi: 10.3967/bes2025.038
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Risk Factors and Predictive Model for Acute Mountain Sickness among Han Chinese Travelers to Xizang Autonomous Region
Qianhui Gong, Qiong Li, Zhichao Xu, Xiaowei Chen, Xiaobing Shen
2025, 38(4): 506-510.   doi: 10.3967/bes2025.030
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Kitchen Ventilation Attenuate the Association of Solid Fuel Use with Sarcopenia: A Cross-Sectional and Prospective Study
Yinghao Yuchi, Wei Liao, Jia Qiu, Ruiying Li, Ning Kang, Xiaotian Liu, Wenqian Huo, Zhenxing Mao, Jian Hou, Lei Zhang, Chongjian Wang
2025, 38(4): 511-515.   doi: 10.3967/bes2025.031
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Experimental Study on Distribution and Deposition Characteristics of Phi-X174 and MS2 Bacteriophages in an Air Chamber
Baoying Zhang, Cuicui Ma, Yanyan Wang, Jin Shen
2025, 38(4): 516-518.   doi: 10.3967/bes2025.032
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Role of the Gut–Brain Axis in Chronotype-Driven Alzheimer’s Disease: A Mendelian Randomization Study
Jingting Kong, Mengxue Wang, Xuezi Zhang, Zan Wang, Qingguo Ren
2025, 38(4): 519-524.   doi: 10.3967/bes2025.033
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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](12163) [PDF 3875KB](5190)
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](15715) [FullText HTML](7369) [PDF 2336KB](7369)
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](8646) [FullText HTML](3022) [PDF 11333KB](3022)
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](9550) [FullText HTML](3495) [PDF 2552KB](3495)
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](8023) [FullText HTML](3752) [PDF 1561KB](3752)
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](6445) [PDF 528KB](2703)
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](7536) [FullText HTML](2750) [PDF 3641KB](2750)
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](4973) [PDF 8784KB](1969)
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](3515) [FullText HTML](1638) [PDF 10064KB](1638)
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](7341) [PDF 610KB](1860)
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](5022) [FullText HTML](1960) [PDF 4691KB](1960)
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](5454) [FullText HTML](1690) [PDF 2914KB](1690)
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](3550) [FullText HTML](1819) [PDF 2174KB](1819)
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](3079) [PDF 803KB](1214)
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](6105) [FullText HTML](1848) [PDF 31943KB](1848)
The Emergence, Epidemiology, and Etiology of Haff Disease
PEI Pei, LI Xiao Yan, LU Shuang Shuang, LIU Zhe, WANG Rui, LU Xuan Cheng, LU Kai
2019, 32(10): 769-778.   doi: 10.3967/bes2019.096
[Abstract](5293) [FullText HTML](2252) [PDF 2249KB](2252)
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](3167) [FullText HTML](1433) [PDF 1202KB](1433)
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](5299) [FullText HTML](1416) [PDF 9101KB](1416)
Mutual Impact of Diabetes Mellitus and Tuberculosis in China
CHENG Jun, ZHANG Hui, ZHAO Yan Lin, WANG Li Xia, CHEN Ming Ting
2017, 30(5): 384-389.   doi: 10.3967/bes2017.051
[Abstract](4556) [FullText HTML](1642) [PDF 671KB](1642)
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](3799) [FullText HTML](1854) [PDF 2205KB](1854)

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Vol 38, No 4

(April, 2025)

ISSN 0895-3988

CN 11-2816/Q

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