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Table of Content
18 June 2024, Volume 56 Issue 3
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  • A ssociations of short-term ambient particulate matter exposure and MTNR1B gene with triglyceride-glucose index: A family-based study
    Huangda GUO,Hexiang PENG,Siyue WANG,Tianjiao HOU,Yixin LI,Hanyu ZHANG,Mengying WANG,Yiqun WU,Xueying QIN,Xun TANG,Jing LI,Dafang CHEN,Yonghua HU,Tao WU
    2024, (3):  375-383.  doi: 10.19723/j.issn.1671-167X.2024.03.001    
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    Objective: To explore the effects of short-term particulate matter (PM) exposure and the melatonin receptor 1B (MTNR1B) gene on triglyceride-glucose (TyG) index utilizing data from Fang-shan Family-based Ischemic Stroke Study in China (FISSIC). Methods: Probands and their relatives from 9 rural areas in Fangshan District, Beijing, were included in the study. PM data were obtained from fixed monitoring stations of the National Air Pollution Monitoring System. TyG index was calculated by fasting triglyceride and glucose concentrations. The associations of short-term PM exposure and rs10830963 polymorphism of the MTNR1B gene with the TyG index were assessed using mixed linear models, in which covariates such as age, sex, and lifestyles were adjusted for. Gene-environment inter-action analysis was furtherly performed using the maximum likelihood methods to explore the potential effect modifier role of rs10830963 polymorphism in the association of PM with TyG index. Results: A total of 4 395 participants from 2 084 families were included in the study, and the mean age of the study participants was (58.98±8.68) years, with 53. 90% females. The results of association analyses showed that for every 10 μg/m3 increase in PM2.5 concentration, TyG index increased by 0.017 (95%CI: 0.007-0.027), while for per 10 μg/m3 increment in PM10, TyG index increased by 0.010 (95%CI: 0.003-0.017). And the associations all had lagged effects. In addition, there was a positive association between the rs10830963 polymorphism and the TyG index. For per increase in risk allele G, TyG index was elevated by 0.040 (95%CI: 0.004-0.076). The TyG index was 0.079 (95%CI: 0.005-0.152) higher in carriers of the GG genotype compared with carriers of the CC genotype. The interaction of rs10830963 polymorphism with PM exposure had not been found to be statistically significant in the present study. Conclusion: Short-term exposure to PM2.5 and PM10 were associated with higher TyG index. The G allele of rs10830963 polymorphism in the MTNR1B gene was associated with the elevated TyG index.

    Gene-gene/gene-environment interaction of transforming growth factor-β signaling pathway and the risk of non-syndromic oral clefts
    Tianjiao HOU,Zhibo ZHOU,Zhuqing WANG,Mengying WANG,Siyue WANG,Hexiang PENG,Huangda GUO,Yixin LI,Hanyu ZHANG,Xueying QIN,Yiqun WU,Hongchen ZHENG,Jing LI,Tao WU,Hongping ZHU
    2024, (3):  384-389.  doi: 10.19723/j.issn.1671-167X.2024.03.002    
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    Objective: To explore the association between polymorphisms of transforming growth factor-β (TGF-β) signaling pathway and non-syndromic cleft lip with or without cleft palate (NSCL/P) among Asian populations, while considering gene-gene interaction and gene-environment interaction. Methods: A total of 1 038 Asian NSCL/P case-parent trios were ascertained from an international consortium, which conducted a genome-wide association study using a case-parent trio design to investigate the genes affec-ting risk to NSCL/P. After stringent quality control measures, 343 single nucleotide polymorphism (SNP) spanning across 10 pivotal genes in the TGF-β signaling pathway were selected from the original genome-wide association study(GWAS) dataset for further analysis. The transmission disequilibrium test (TDT) was used to test for SNP effects. The conditional Logistic regression models were used to test for gene-gene interaction and gene-environment interaction. Environmental factors collected for the study included smoking during pregnancy, passive smoking during pregnancy, alcohol intake during pregnancy, and vitamin use during pregnancy. Due to the low rates of exposure to smoking during pregnancy and alcohol consumption during pregnancy (<3%), only the interaction between maternal smoking during pregnancy and multivitamin supplementation during pregnancy was analyzed. The threshold for statistical significance was rigorously set at P =1.46×10-4, applying Bonferroni correction to account for multiple testing. Results: A total of 23 SNPs in 4 genes yielded nominal association with NSCL/P (P<0.05), but none of these associations was statistically significant after Bonferroni' s multiple test correction. However, there were 6 pairs of SNPs rs4939874 (SMAD2) and rs1864615 (TGFBR2), rs2796813 (TGFB2) and rs2132298 (TGFBR2), rs4147358 (SMAD3) and rs1346907 (TGFBR2), rs4939874 (SMAD2) and rs1019855 (TGFBR2), rs4939874 (SMAD2) and rs12490466 (TGFBR2), rs2009112 (TGFB2) and rs4075748 (TGFBR2) showed statistically significant SNP-SNP interaction (P<1.46×10-4). In contrast, the analysis of gene-environment interactions did not yield any significant results after being corrected by multiple testing. Conclusion: The comprehensive evaluation of SNP associations and interactions within the TGF-β signaling pathway did not yield any direct associations with NSCL/P risk in Asian populations. However, the significant gene-gene interactions identified suggest that the genetic architecture influencing NSCL/P risk may involve interactions between genes within the TGF-β signaling pathway. These findings underscore the necessity for further investigations to unravel these results and further explore the underlying biological mechanisms.

    A prospective cohort study of association between early childhood body mass index trajectories and the risk of overweight
    Zhihan YUE,Na HAN,Zheng BAO,Jinlang LYU,Tianyi ZHOU,Yuelong JI,Hui WANG,Jue LIU,Haijun WANG
    2024, (3):  390-396.  doi: 10.19723/j.issn.1671-167X.2024.03.003    
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    Objective: To compare the association between body mass index (BMI) trajectories determined by different methods and the risk of overweight in early childhood in a prospective cohort study, and to identify children with higher risk of obesity during critical growth windows of early childhood. Methods: A total of 1 330 children from Peking University Birth Cohort in Tongzhou (PKUBC-T) were included in this study. The children were followed up at birth, 1, 3, 6, 9, 12, 18, and 24 months and 3 years of age to obtain their height/length and weight data, and calculate BMI Z-score. Latent class growth mixture modeling (GMM) and longitudinal data-based k-means clustering algorithm (KML) were used to determine the grouping of early childhood BMI trajectories from birth to 24 mouths. Linear regression was used to compare the association between early childhood BMI trajectories determined by different methods and BMI Z-score at 3 years of age. The predictive performance of early childhood BMI trajectories determined by different methods in predicting the risk of overweight (BMI Z-score > 1) at 3 years was compared using the average area under the curve (AUC) of 5-fold cross-validation in Logistic regression models. Results: In the study population included in this research, the three-category trajectories determined using GMM were classified as low, medium, and high, accounting for 39.7%, 54.1%, and 6.2% of the participants, respectively. The two-category trajectories determined using the KML method were classified as low and high, representing 50. 3% and 49. 7% of the participants, respectively. The three-category trajectories determined using the KML method were classified as low, medium, and high, accounting for 31.1%, 47.4%, and 21.5% of the participants, respectively. There were certain differences in the growth patterns reflected by the early childhood BMI trajectories determined using different methods. Linear regression analysis found that after adjusting for maternal ethnicity, educational level, delivery mode, parity, maternal age at delivery, gestational week at delivery, children' s gender, and breastfeeding at 1 month of age, the association between the high trajectory group in the three-category trajectories determined by the KML method (manifested by a slightly higher BMI at birth, followed by rapid growth during infancy and a stable-high BMI until 24 months) and BMI Z-scores at 3 years was the strongest. Logistic regression analysis revealed that the three-category trajectory grouping determined by the KML method had the best predictive performance for the risk of overweight at 3 years. The results were basically consistent after additional adjustment for the high bound score of the child' s diet balanced index, average daily physical activity time, and screen time. Conclusion: This study used different methods to identify early childhood BMI trajectories with varying characteristics, and found that the high trajectory group determined by the KML method was better able to identify children with a higher risk of overweight in early childhood. This provides scientific evidence for selecting appropriate methods to define early childhood BMI trajectories.

    Association between self-control and co-occurrence of depressive symptoms and overweight or obesity during adolescence and early adulthood: A ten-year prospective cohort study based on national surveys
    Jing CHEN,Rui SHAN,Wucai XIAO,Xiaorui ZHANG,Zheng LIU
    2024, (3):  397-402.  doi: 10.19723/j.issn.1671-167X.2024.03.004    
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    Objective: To explore the association between self-control and the co-occurrence of depressive symptoms and overweight or obesity from adolescence to early adulthood in the Chinese population, and to provide a scientific basis for personalized interventions targeting individuals with different risks in the future. Methods: From a prospective cohort study that lasted for 10 years: The China family panel studies (CFPS), a total of 608 children and adolescents meeting the following inclusion and exclusion criteria were included as study subjects: (1) Aged 10 to 19 years, at normal weight according to Chinese standards, and without depressive symptom in 2010; (2) Had self-control scores, and with at least two measurements of depressive symptoms and body mass index (BMI) between 2010 and 2020; (3) The only one or the youngest child and adolescent from each family. The co-occurrence of depressive symptoms and overweight or obesity was defined in three ways: Both of the average level of standardized scores of depressive symptoms and BMI Z-scores across multiple measurements over time were at a high level, or both of the trajectories of depressive symptoms and BMI over time based on the latent classification trajectory model (LCTM) belonging to the "risk-type", or individuals had depressive symptoms and overweight/obesity at the last follow-up survey. The multinomial Logistic regression model was used to examine the association between standardized scores of self-control and the co-occurrence of depressive symptoms and overweight or obesity. Results: The score of self-control was associated with the co-occurrence of depressive symptoms and overweight or obesity when using healthy individuals as the reference group after adjusting for age (years), gender (male/female), area (urban/rural), weekly physical activity duration (high/low), parental education level (college or above/high school or below), parental weight status (overweight or obese or not), and parental depressive symptoms (with depressive symptoms or not), regardless of the definition of the risk population. Specifically, the risk of co-occurrence of depressive symptoms and overweight or obesity was reduced by 33% (95%CI: 14% to 48%, based on the average level across multiple measurements over time) to 78% (95%CI: 6% to 95%, based on the joint trajectories of depressive symptoms and BMI over time) per 1-standard deviation (1-SD) increase in self-control score. In addition, the risk of depressive-symptom-dominant and overweight-or-obesity-dominant was reduced by 25% (95%CI: 4% to 42%, only based on the average level across multiple measurements over time) and 21% (95%CI: 1% to 37%, only based on the joint trajectories of depressive symptoms and BMI over time) per 1-SD increase in self-control score, respectively. The results from sensitivity analysis that defined individuals' weight status according to World Health Organization (WHO) standards were consistent with our main findings. Conclusion: Individuals with higher self-control scores from adolescence to early adulthood have a lower risk of co-occurrence of depressive symptoms and overweight or obesity, suggesting that personalized interventions for co-occurrence of depressive symptoms and overweight or obesity can be carried out based on self-control scores in the future.

    Status and pathways of factors influencing physical activity time among elementary and junior high school students in Beijing
    Shan CAI,Yihang ZHANG,Ziyue CHEN,Yunfe LIU,Jiajia DANG,Di SHI,Jiaxin LI,Tianyu HUANG,Jun MA,Yi SONG
    2024, (3):  403-410.  doi: 10.19723/j.issn.1671-167X.2024.03.005    
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    Objective: To describe the current distribution of daily physical activity time among elementary and junior high school students in Beijing, and to analyze the influencing factors and pathways at the individual, family, school and community levels. Methods: Data were drawn upon from a cross-sectional investigation in Beijing in 2023, and a total of 3 157 elementary and junior high school students were included in the final analysis. Questionnaire was used to collect data on basic characteristics, overall and in-school physical activity time per day, the number of sports mastered, perceived physical activity benefits and barriers scales, perceived family, school, and community physical activity supportive environment scales. Log-binomial regression model was used to analyze the associations between physical activity time and influencing factors, and structural equation modeling was used for the path analysis of the influencing factors. Results: The reported rates of ≥2 hours of overall physical activity per day and ≥1 hour of physical activity in school per day among elementary and junior high school students in Beijing in 2023 were 33.1% and 64.8%, respectively. The associations between the number of sports mastered by students and the reported rate of ≥2 hours of overall physical activity per day showed a typical dose-response relationship (P-trend<0.001). The perceived physical activity benefits-to-barriers ratio (PR=1.24, 95%CI: 1.20-1.28), scores of perceived family, school, and community physical acti-vity supportive environment scales were all positively associated with the reported rate of ≥2 hours of overall physical activity per day (PR=1.51, 95%CI: 1.38-1.66; PR=1.50, 95%CI: 1.37-1.64; PR=1.21, 95%CI: 1.16-1.27). The structural equation modeling showed that the number of sports mastered by the students (β=0.11, P<0.001), perceived physical activity benefits-to-barriers ratios (β=0.15, P<0.001), and scores of supportive environment scales consisting of family, school, and community (β=0.13, P<0.001) were associated with the reported rates of ≥2 hours of overall physical activity per day directly. In addition, the scores of supportive environment scales could indirectly influence the reported rates of ≥2 hours of overall physical activity per day by influencing the number of sports mastered by the students (β=0.21, P<0.001) and the perceived physical activity benefits-to-barriers ratio (β=0.56, P<0.001), while the number of sports mastered by the students could indirectly influence the reported rates of ≥2 hours of overall physical activity per day by influencing the perceived physical activity benefits-to-barriers ratios (β=0.05, P=0.003). The influencing factors and pathways of the reported rates of ≥1 hour of physical activity in school per day were similar with those of the reported rates of ≥2 hours of overall physical activity per day described above. Conclusion: The daily physical activity time among elementary and junior high school students in Beijing in 2023 fell short of meeting the national requirement. There was a need to build a supportive environment consisting of family, school, and community for physical activity, to promote the students ' sports skills, to establish the idea of independent physical activity, and to ensure that primary and secondary school students were given one hour of physical activity time every day, both inside and outside the school.

    Comparative research on the relationship between body mass index and physical fitness index among the Uygur, Kazakh and Han ethnic college students
    Weimin LI,Zufeiya TUERDI
    2024, (3):  411-417.  doi: 10.19723/j.issn.1671-167X.2024.03.006    
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    Objective: To understand the nutritional status and physical fitness of the Uygur, Kazak and Han ethnic college students, and to investigate the nonlinear relationship between BMI and physical fitness indexes in different ethnic groups. Methods: A total of 3 600 Uygur, Kazakh and Han students majoring in non-sports in a university in Xinjiang Uygur Autonomous Region in 2021 were selected by stratified random cluster sampling method. Height, weight, vital capacity, 50 m running, standing long jump, sit-and-reach, sit-up/pull-up and endurance running were measured. Body mass index (BMI), standardized Z score of each test score and physical fitness index (PFI) were calculated. The data were analyzed by Chi-square test, single factor analysis of variance, and nonlinear quadratic regression. Results: Prevalences of overweight (16.00%) and obesity (8.08%) of the Han college students were significantly higher than those of the Uygur (11.83% and 4.08%) and Kazakh (13.58% and 4.58%). Prevalence of low weight in the Uygur (11.92%) was the highest, and the lowest was the Kazakh (9.75%). There were significant differences in the prevalence of BMI classification among the three ethnic groups boys and girls (all P < 0.05). There were significant differences in PFI among college students of different BMI levels in the Uygur, Kazakh and Han ethnic college students (all P < 0.05), and the PFI of normal weight group was higher than the other weight groups in general, and the overweight group was higher than the obese group, but some ethnics showed the highest PFI in the low weight group. The non-linear quadratic regression results showed that the curves of the Uygur boys and girls and the Kazakh boys were inverted "J" shaped, and the PFI increased and then decreased with the increase of BMI, while the rest of the curves were arc-shaped, and the PFI decreased with the increase of BMI. Conclusion: Overweight obesity in the Uygur, Kazakh and Han ethnic college students brings about a decrease in physical fitness, but Kazakh low weight male and female and Han low weight grils have better physical fitness than the normal weight groups. Focusing on improving the physical fitness of Uygur low-weight and high-weight boys and Han high-weight girls could effectively reduce the differences in physical fitness of college students in different weight levels and ethnic groups.

    Associations between puberty timing and cardiovascular metabolic risk factors among primary and secondary students
    Zuhong ZHANG,Tianjiao CHEN,Jun MA
    2024, (3):  418-423.  doi: 10.19723/j.issn.1671-167X.2024.03.007    
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    Objective: To explore the relationship between puberty timing and cardiovascular metabolic risk factors among primary and secondary students with different genders in Beijing. Methods: Using the method of stratified cluster sampling by urban and rural areas and school sections, 3 067 students from 16 primary and secondary schools in Fangshan District of Beijing were selected in October 2012, with questionnaire survey, physical examination and serum laboratory testing. In this study, we controlled for confounding factors such as school segments, current residence of the family, birth weight, feeding method, only child, highest educational level of parents, and monthly family income, and then the associations between cardiovascular metabolic risk factors and puberty timing among the primary and secondary students was analyzed by multivariate Logistic analysis. To ensure the reliability of the data, this study adopted strict quality control. Results: A total of 3 067 primary and middle school students aged 7 to 16 years were included in this study, including 1 575 boys and 1 492 girls. The prevalence of premature puberty was 14.73% among the boys and 12.89% among the girls, respectively. The prevalence of delayed puberty was 9.49% among the boys and 10.99% among the girls, respectively. The detection rates of central obesity, hypertension, hyperglycemia, and dyslipidemia among the primary and secondary students were 35.87%, 19.95%, 2.54% and 26.31%, respectively. The detection rates of 1 risk factor clustering, 2 risk factors clustering and more than 3 risk factors clustering were 29.21%, 16.17% and 9.36%, respectively. The difference in the detection rate of cardiovascular and metabolic risk factors in different youth stages was insignificant (P>0.05), the detection rate of risk factor aggregation of 0 was lower than that of the timely group and delayed group, and the detection rate of risk factors aggregation of 2 was higher than that of the timely group (P < 0.05).After adjusting the effects of learning stage, region, birth weight, feeding patterns, one-child, family income and the parents' educational levels, multivariate Logistic regression analysis showed that, compared with the on-time puberty group, the risk of 1 risk factor clustering, 2 risk factors clustering and more than 3 risk factors clustering increased by 1.94 times (95% CI=1.29-2.91), 2.97 times (95% CI=1.89-4.67) and 2.02 times (95% CI= 1.13-3.63) among the girls; It had not been found that the relationship between puberty timing and cardiovascular risk factor clustering among the boys (P>0.05). Conclusion: Premature puberty is an independent risk factor for the clustering of cardiometabolic risk factors in girls, and primary prevention strategies should be implemented to reduce the burden of cardiovascular metabolic diseases in the population.

    Cardiovascular safety of sitagliptin added to metformin in real world patients with type 2 diabetes
    Zuoxiang LIU,Xiaowei CHEN,Houyu ZHAO,Siyan ZHAN,Feng SUN
    2024, (3):  424-430.  doi: 10.19723/j.issn.1671-167X.2024.03.008    
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    Objective: To assess the safety of sitagliptin added to metformin on cardiovascular adverse events in real world patients with type 2 diabetes mellitus (T2DM). Methods: Real world data from Yinzhou Regional Health Care Database were used to select T2DM patients with diagnosis and treatment records in the platform from January 1, 2017 to December 31, 2022. According to drug prescription records, the patients were divided into metformin plus sitagliptin group (combination group) and metformin monotherapy group(monotherapy group). A series of retrospective cohorts were constructed according to the index date.Finally, full retrospective cohorts were constructed according to propensity score model, including baseline covariates that might be related to outcomes, to match the subjects in the combination group and monotherapy group for the purpose of increasing the comparability of baseline characteristics. The participants were followed up from the index date until the first occurrence of the following events: Diagnosis of outcomes, death, or the end of the study period (December 31, 2022). Cox proportional risk model was used to estimate the hazard ratio(HR)and 95% confidence interval (CI) of sitagliptin added to metformin on 3-point major adverse cardiovascular events (3P-MACE) combination outcome and secondary cardiovascular outcomes. Results: Before propensity score matching, the proportion of the patients in combination group using insulin, α glucosidase inhibitors, sodium-glucose transporter 2 inhibitors (SGLT-2I) and glienides at baseline was higher than that in monotherapy group, and the baseline fasting blood glucose (FBG) and hemoglobin A1c (HbA1c) levels in combination group were higher than those in monotherapy group. After propensity score matching, 5 416 subjects were included in the combination group and the monotherapy group, and baseline characteristics were effectively balanced between the groups. The incidence densities of 3P-MACE were 6.41/100 person years and 6.35/100 person years, respectively. Sitagliptin added to metformin did not increase or decrease the risk of 3P-MACE compared with the metformin monotherapy (HR=1.00, 95% CI: 0.91-1.10). In secondary outcomes analysis, the incidence of cardiovascular death was lower in the combination group than in the monotherapy group (HR=0.59, 95% CI: 0.41-0.85), and no association was found between sitagliptin and the risk of myocardial infarction and stroke (HR=1.12, 95% CI: 0.89-1.41; HR=0.99, 95% CI: 0.91-1.12). Conclusion: In T2DM patients in Yinzhou district of Ningbo, compared with metformin alone, sitagliptin added to metformin may reduce the risk of cardiovascular death, and do not increase the incidence of overall cardiovascular events. The results of this study can provide real-world evidence for post-marketing cardiovascular safety evaluation of sitagliptin.

    Factors associated with the care needs of the older adults based on different disability levels
    Haoyu ZHANG,Yiwen SHI,Wei PAN,Aiping LIU,Xinying SUN,Man LI,Xuxi ZHANG
    2024, (3):  431-440.  doi: 10.19723/j.issn.1671-167X.2024.03.009    
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    Objective: To identify the factors associated with the care needs of the older adults aged 65-105 by age groups, and to compare these factors across different age groups. Methods: A total of 12 244 older adults from the Chinese longitudinal healthy longevity survey (CLHLS) conducted in 2018 were included in the analyses. The participants were categorized into three age groups: young-old (aged 65-79), middle-old (aged 80-89), and oldest-old (aged 90-105). The level of disability was measured by the disability index (DI) in four dimensions, reflecting their care needs. Potential factors associated with care needs were selected based on the health ecological model (HEM), including perspectives of personal characteristics, behavioral characteristics, interpersonal network, living and working conditions, and policy environment. Multifactor analysis was performed using multinomial Logistic regression. Results: Among China ' s 12 244 older adults, 43.4% had medium or high care needs. Factors for higher care needs of older adults included higher age, higher number of chronic diseases, no exercise habit, excessive sleep duration (≥9 h/d), depressive tendency, living with children or spouse, and uneducated (all P < 0.05). In addition, the young-old group who were past smokers (OR=2.009, 95% CI: 1.019-3.959), were past drinkers (OR=2.213, 95% CI: 1.141-4.291), and reported self-perceived poverty (OR=2.051, 95% CI: 1.189-3.540), had higher level of care needs. The middle-old group who were female (OR=1.373, 95% CI: 1.038-1.817), never drank alcohol (OR=1.551, 95% CI: 1.059-2.269), and were lack of medical insurance (OR=1.598, 95% CI: 1.053-2.426), and had higher level of care needs. The oldest-old group who were female (medium care needs vs. low care needs: OR=1.412, 95% CI: 1.062-1.878; high care needs vs. low care needs: OR=1.506, 95% CI: 1.137-1.993), reported self-perceived poverty (OR=2.064, 95% CI: 1.282-3.323), and were lack of medical insurance (OR=1.621, 95% CI: 1.148-2.291), and had higher level of care needs. Conclusion: The identical factors associated with care needs across different age groups include age, chronic disease, exercise, sleep, depression, living arrangement, and education. Smoking, alcohol consumption, and economic status are specific factors among the young-old group of the older adults, while gender and medical insurance are specific factors among the middle-old and the oldest-old group of the older adults. We recommend conducting prospective cohort studies and intervention studies among specific age groups on the above factors to provide reliable evidence for policy formulation.

    Comparison of initiation of antihypertensive therapy strategies for primary prevention of cardiovascular diseases in Chinese population: A decision-analytic Markov modelling study
    Tianjing ZHOU,Qiuping LIU,Minglu ZHANG,Xiaofei LIU,Jiali KANG,Peng SHEN,Hongbo LIN,Xun TANG,Pei GAO
    2024, (3):  441-447.  doi: 10.19723/j.issn.1671-167X.2024.03.010    
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    Objective: To evaluate the health benefits and intervention efficiency of different strategies of initiating antihypertensive therapy for the primary prevention of cardiovascular diseases in a community-based Chinese population from the Chinese electronic health records research in Yinzhou (CHERRY) study. Methods: A decision-analytic Markov model was used to simulate and compare different antihypertensive initiation strategies, including: Strategy 1, initiation of antihypertensive therapy for Chinese adults with systolic blood pressure (SBP) ≥140 mmHg (2020 Chinese guideline on the primary prevention of cardiovascular diseases); Strategy 2, initiation of antihypertensive therapy for Chinese adults with SBP ≥130 mmHg; Strategy 3, initiation of antihypertensive therapy for Chinese adults with SBP≥140 mmHg, or with SBP between 130 and 140 mmHg and at high risk of cardiovascular diseases (2017 American College of Cardiology/American Heart Association guideline for the prevention, detection, evaluation, and management of high blood pressure in adults); Strategy 4, initiation of antihypertensive therapy for Chinese adults with SBP≥160 mmHg, or with SBP between 140 and 160 mmHg and at high risk of cardiovascular diseases (2019 United Kingdom National Institute for Health and Care Excellence guideline for the hypertension in adults: Diagnosis and management). The high 10-year cardiovascular risk was defined as the predicted risk over 10% based on the 2019 World Health Organization cardiovascular disease risk charts. Different strategies were simulated by the Markov model for ten years (cycles), with parameters mainly from the CHERRY study or published literature. After ten cycles of simulation, the numbers of quality-adjusted life years (QALY), cardiovascular events and all-cause deaths were calculated to evaluate the health benefits of each strategy, and the numbers needed to treat (NNT) for each cardiovascular event or all-cause death could be prevented were calculated to assess the intervention efficiency. One-way sensitivity analysis on the uncertainty of incidence rates of cardiovascular disease and probabilistic sensitivity analysis on the uncertainty of hazard ratios of interventions were conducted. Results: A total of 213 987 Chinese adults aged 35-79 years without cardiovascular diseases were included. Compared with strategy 1, the number of cardiovascular events that could be prevented in strategy 2 increased by 666 (95% UI: 334-975), while the NNT per cardiovascular event prevented increased by 10 (95% UI: 7-20). In contrast to strategy 1, the number of cardiovascular events that could be prevented in strategy 3 increased by 388 (95% UI: 194-569), and the NNT per cardiovascular event prevented decreased by 6 (95% UI: 4-12), suggesting that strategy 3 had better health benefits and intervention efficiency. Compared to strategy 1, although the number of cardiovascular events that could be prevented decreased by 193 (95% UI: 98-281) in strategy 4, the NNT per cardiovascular event prevented decreased by 18 (95% UI: 13-37) with better efficiency. The results were consistent in the sensitivity analyses. Conclusion: When initiating antihypertensive therapy in an economically developed area of China, the strategy combined with cardiovascular risk assessment is more efficient than those purely based on the SBP threshold. The cardiovascular risk assessment strategy with different SBP thresholds is suggested to balance health benefits and intervention efficiency in diverse populations.

    Relationship between serum 25-hydroxyvitamin D and handgrip strength in middle-aged and elderly people in five cities of Western China
    Ting JING,Hua JIANG,Ting LI,Qianqian SHEN,Lan YE,Yindan ZENG,Wenxin LIANG,Gang FENG,Man-Yau Szeto Ignatius,Yumei ZHANG
    2024, (3):  448-455.  doi: 10.19723/j.issn.1671-167X.2024.03.011    
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    Objective: To explore the association between serum 25-hydroxyvitamin D [25(OH)D] and handgrip strength in middle-aged and elderly people in 5 cities of Western China. Methods: Based on the data of a cross-sectional survey conducted in the 5 cities of Western China from February to July 2023, the relevant demographic characteristics of people were collected by questionnaire, handgrip strength was collected by physical examination, and serum 25(OH)D was detected by HPLC-MS/MS. The association between the serum 25(OH)D and handgrip strength was analyzed using Logistic regression and Chi-square test for between-group comparisons models. Results: The prevalence of 25(OH)D deficiency and insufficiency among the middle-aged and elderly people in the 5 cities of Western China was 52.9% and 34.5%, respectively. The people who were older, female, and sampled in winter had lower serum 25(OH)D levels (P < 0.05). The prevalence of loss of handgrip strength among the middle-aged and elderly people was 25.3%. The prevalence of handgrip strength loss was higher in the aged 65-80 participants with 25(OH)D deficiency (45. 0%) than in those with 25(OH)D insufficiency (32.6%) and 25(OH)D sufficiency (20.6%). The highest prevalence of loss of handgrip strength was found in the aged 75-80 participants with 25(OH)D deficiency (62. 1%), followed by the 25(OH)D insufficient group (11.1%, P < 0.05). The study found that middle-aged and elderly people with 25(OH)D deficiency had a 1.4-fold increased risk of handgrip strength loss compared with those with 25(OH)D sufficiency (OR=2.403, 95%CI: 1.202-4.804, P=0.013). No significant association was found between 25(OH)D insufficiency and handgrip strength status in the middle-aged and elderly people. For every 5 μg/L increase in total serum 25(OH)D, the risk of handgrip strength loss reduced by 13.1% (OR=0.869, 95%CI: 0.768-0.982, P=0.025). For every 5 μg/L increase in serum 25(OH)D2, the risk of handgrip strength loss reduced by 24.1% (OR=0.759, 95%CI: 0.582-0.990, P=0.042). No significant association was found between serum 25(OH)D3 levels and the risk of handgrip strength loss. The risk of handgrip strength loss in middle-aged and elderly people was reduced by 25.2% for each incremental increase in the total serum 25(OH)D levels (deficient, insufficient and sufficient) (OR=0.748, 95%CI: 0.598-0.936, P=0.011). The risk of handgrip loss was reduced by 40.0% for each incremental increase in serum 25(OH)D levels in the aged 65-80 and aged 65-69 participants, and by 80.0% for each incremental increase in 25(OH)D levels in the aged 75-80 parti-cipants. Conclusion: Serum total 25(OH)D and 25(OH)D2 levels are associated with handgrip strength status in middle-aged and elderly people in the 5 cities of Western China.

    Factors influencing cognitive function among the older adults in Beijing
    Yuting LIN,Huali WANG,Yu TIAN,Litong GONG,Chun CHANG
    2024, (3):  456-461.  doi: 10.19723/j.issn.1671-167X.2024.03.012    
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    Objective: To explore the current status of cognitive function of the older adults in Beijing, and to analyze the factors affecting their cognitive function. Methods: It was a cross-sectional study. A questionnaire survy was conducted in 2023 among the older adults in Beijing. The cognitive function of the older adults was assessed with the Hong Kong brief cognitive test (HKBC) scale, a simple cognitive assessment tool. Using SPSS 27.0 to perform the descriptive analysis and multiple linear regression analysis of factors, which affect cognitive function among the older adults. Results: Totally 349 older adults were recruited, with the highest percentage of respondents aged 60-69 years (41.3%), of whom 58.7% were female, 88.0% of the respondents had a junior high school or above education level. Most of the older adults (68.8%) worked 35-48 h/week before they retired, and 14.0% of the older adults had a family history of dementia. After controlling age and gender, the linear regression analysis showed that marital status married (β=0.501, 95%CI: 0.144-0.859) and 3-4 times physical activity per week (β=0.617, 95%CI: 0.087-1.148) were protective factors of cognitive function in the older adults, and depressive symptoms were a risk factor (β= -0.723, 95%CI: -1.198 to -0.247) of cognitive function for the older adults. Conclusion: In this study, the factors influencing cognitive function among the older adults was analyzed based on a life-cycle perspective. Lack of physical activity and depressive symptoms were risk factors for cognitive function among the older adults. It was suggested that strengthening physical activity, improving mental health of the older adults, as well as conducting preventive intervention in early stages of the life-cycle will be benefit for preventing and slowing cognitive decline in the older adults.

    Main characteristics and historical evolution of China' s health financing transition
    Qingbo WANG,Hongqiao FU
    2024, (3):  462-470.  doi: 10.19723/j.issn.1671-167X.2024.03.013    
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    Objective: To comprehend the main characteristics and historical evolution of health financing transition in China. Methods: Data were collected from various sources, including the Global Health Expenditure Database (GHED), China Health Statistics Yearbook, National Health Finance Annual Report, China ' s Total Health Expenditure Research Report, et al. Descriptive statistics and literature study was conducted. Results: Since the beginning of the 21st century, most countries in the world had witnessed a transition of health financing, characterized by the expansion of health financing scale and the strengthening of public financing responsibility. Notably, China ' s health financing transition exhibited distinctive features. Firstly, there had been a more rapid expansion in health financing scale compared with global averages. Between 2000 and 2019, total health expenditure per capita experienced a remarkable increase of 816.6% at comparable prices, significantly surpassing average growth rates observed among other countries worldwide (102.1%). Secondly, greater efforts had been made to strengthen the responsibilities of public financing. From 2000 to 2019, there was a substantial decrease of 30.6 percentage points in the proportion of out-of-pocket health expenditure as a share of total health expenditure. This decline was significantly larger than the average reduction observed among other countries worldwide (5.6 percentage points). Thirdly, there had been a significant shift in government health expenditure allocation patterns, with an increased emphasis on "demand-side subsidies" surpassing "supply-side subsidies". Within the realm of "supply-side subsidies", funding directed towards hospitals had notably increased and surpassed that allocated to primary healthcare institutions and public health institutions. Based on these distinctive characteristics, this paper expanded China ' s health financing transition into three dimensions: Scale dimension, structure dimension and flow dimension. Using a comprehensive analytical framework, the history of China ' s health financing transition was roughly divided into four stages: The planned economy stage, the economic transition stage, the post-SARS stage and the new health system reform stage. The main features and evolutionary logic associated with each stage were analyzed. Conclusion: Above all, the health financing system should be enhanced in terms of vertical "embeddedness" and horizontal "complementarity". Moreover, the significance of health financing transition in preserving hidden value and mitigating public risk should be emphasized, and there is a need for an improved two-way trade-off mechanism that balances value and risk. Additionally, the ethical principles associated with health financing transition should be considered comprehensively, while optimizing budget decision-making within the government ' s actual governance model. Lastly, it is crucial to recognize the overall and profound impact of modern medicine development and explore long-term strategies and pathways for health financing transition in China.

    Influence of telemedicine on the operation of public hospitals in China
    Kexin RAN,Yuhan LI,Wen FENG
    2024, (3):  471-478.  doi: 10.19723/j.issn.1671-167X.2024.03.014    
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    Objective: Telemedicine, as an information-based tool, is widely recognized as an effective solution for compensating for the imbalanced allocation of medical resources in China. This study specifi-cally aimed to analyze the impact of telemedicine functions on the operational efficiency of public hospitals, with a particular focus on their heterogeneous effects on hospitals of different levels. Methods: A cross-sectional research design was used based on the 2022 Health Informatization Statistical Survey data, and 8 944 public hospitals were used as research objects to analyze the impact of telemedicine on hospital revenues and business capacity. Multivariate linear model, propensity score matching (PSM), and grouped regression methods were employed to evaluate the impact of telemedicine on hospital revenues, number of consultations, and the number of discharges. Results: The descriptive results showed that telemedicine was available in 35.51% of public hospitals. The analysis also demonstrated that various factors, such as hospital level, academic category, area of the hospital, administrational level and number of beds all had a significant influence on the operation of the hospital. Moreover, the regression results showed that opening telemedicine could increase hospital revenues by 0.140 (P < 0.01), hospital consultations by 0.136 (P < 0.01), and the number of discharges by 0.316 (P < 0.01). After correcting for endogeneity using the propensity score matching, the results showed that the effect of opening telemedicine on hospital revenues, consultations, and the number of discharges was 0.191 (P < 0.01), 0.216 (P < 0.01), and 0.353 (P < 0.01), respectively. Further heterogeneity analysis was conducted to explore the differential effects of telemedicine on hospitals of different levels. Grouped regression showed that telemedicine had a positive impact on the income of secondary hospitals, with a coefficient of 0.088 (P < 0.05), and it had a more significant positive impact on hospital consultations in secondary hospitals, with a coefficient of 0.127 (P < 0.01). An even greater impact on the number of discharges in primary hospitals, with a coefficient of 1.203 (P < 0.01). Telemedicine, on the other hand, did not have a significant positive impact on the overall revenue and operational capacity of tertiary hospitals. Conclusion: Telemedicine had a significant promoting effect on hospital revenues, hospital consultations and the number of discharges, and this effect was differentiated between hospitals of different levels. Through the construction of telemedicine, primary hospitals were able to significantly improve their business capacity and revenue, which played a positive role in improving the operation of primary public hospitals.

    Application of the cigarette purchase tasks in achieving China' s tobacco control goals
    Xiaochen YANG,Wangnan CAO,Haoxiang LIN,Lanchao ZHANG,Yuxin LIN,Ziyan CHEN,Chun CHANG
    2024, (3):  479-486.  doi: 10.19723/j.issn.1671-167X.2024.03.015    
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    Objective: To assess cigarette demand among Chinese smokers through a cigarette purchase task (CPT) and to evaluate cigarette prices under different hypothetical scenarios in order to meet the goals of smoking prevalence reduction in China. Methods: In the study, 447 participants completed a hypothetical CPT at baseline assessments of a trial, thus, cigarette demand curves were individually fitted for each participant using an exponentiated version of the exponential demand model. Typically, five demand indices were derived, intensity (consumption when free), breakpoint (first price at which consumption is suppressed to 0), maximum output (Omax), maximum price (Pmax, price at which Omax occurred), and elasticity (the ratio of the change in quantity demanded to the change in price). A one-way analysis of variance was used to explore the correlations between the cigarette purchase task indices and socio-demographic and smoking characteristics. The one-way decay model was employed to simulate the smoking cessation rates and determine optimal cigarette prices in a series of scenarios for achieving 20% smoking prevalence. Results: The price elasticity drawn from CPT was 0.54, indicating that a 10% price increase could reduce smoking by 5.4% in the participated smokers. Smokers with higher income were less sensitive to cigarette prices (elasticity=-2.31, P=0.028). Cigarette purchase task indices varied significantly among the smokers with different prices of commonly used cigarettes, tobacco dependence, and smoking volume. The smokers who consumed cigarettes of higher prices reported higher breakpoint, Omax and Pmax, but lower intensity (P=0.001). The smokers who were moderately or highly nicotine dependent reported higher intensity, breakpoint, Omax and Pmax, and they had lower intensity (P=0.001). The smokers who had a higher volume of cigarettes reported higher intensity and Omax, and lower intensity (P < 0.001). To achieve the goal of reducing smoking prevalence to 20% in mainland China, we estimated the desired increase on smoking cessation rate and prices accordingly in a series of scenarios, considering the gender variance and reduced smoking initiation. In scenario (a), to achieve a smoking prevalence goal of 20%, it would be necessary for 24.81% of the current smokers to quit smoking when there were no new smokers. Our fitting model yielded a corresponding value of 59.64 yuan (95%CI 53.13-67.24). Given the assumption in scenario (b) that only males quitted smoking, the desired cessation rates would be 25.82%, with a higher corresponding price of 62.15 yuan (95%CI 55.40-70.06) to induce desired cessation rates. In the proposed scenario (c) where 40 percent of the reduction in smoking prevalence came from reduced smoking initiation, and females and males equally quitted smoking due to increased cigarette prices, the price of a pack of cigarettes would be at least 37.36 yuan (95%CI 32.32-42.69) (equals to $ 5.20) per pack to achieve the cessation rate of 14.89 percent. In scenario (d) where only males quitted smoking due to increased cigarette prices considering the reduced smoking initiation, the respective smoking cessation rates should be 15.49% with the desired prices of 38.60 yuan (95%CI 33.53-44.02). After adjusting for education levels and income levels in scenario (c), the price of cigarettes would be at least 37.37 yuan/pack (equals to $ 5.20) (95%CI 30.73-44.94) and 37.84 yuan/pack (equals to $ 5.26) (95%CI 31.94-44.53), respectively. Conclusion: Cigarette purchase task indices are significantly associated with income levels and prices of commonly used cigarettes, levels of tobacco dependence, and smoking volume, which is inspiring in studying price factors that influence smoking behavior. It is suggested that higher cigarette prices, surpassing the current actual market level, is imperative in mainland China. Stronger policy stra-tegies should be taken to increase tobacco taxes and retail cigarette prices to achieve the Healthy China 2030 goal of reducing smoking prevalence to 20%.

    Ursolic acid improved demyelination and interstitial fluid drainage disorders in schizophrenia mice
    Ren LONG, Xin MAO, Tianzi GAO, Qian XIE, Hanbo TAN, Ziyin LI, Hongbin HAN, Lan YUAN
    2024, (3):  487-494.  doi: 10.19723/j.issn.1671-167X.2024.03.016    
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    Objective: To unveil the pathological changes associated with demyelination in schizophrenia (SZ) and its consequential impact on interstitial fluid (ISF) drainage, and to investigate the therapeutic efficacy of ursolic acid (UA) in treating demyelination and the ensuing abnormalities in ISF drainage in SZ. Methods: Female C57BL/6J mice, aged 6-8 weeks and weighing (20±2) g, were randomly divided into three groups: control, SZ model, and UA treatment. The control group received intraperitoneal injection (ip) of physiological saline and intragastric administration (ig) of 1% carboxymethylcellulose sodium (CMC-Na). The SZ model group was subjected to ip injection of 2 mg/kg dizocilpine maleate (MK-801) and ig administration of 1% CMC-Na. The UA treatment group underwent ig administration of 25 mg/kg UA and ip injection of 2 mg/kg MK-801. The treatment group received UA pretreatment via ig administration for one week, followed by a two-week drug intervention for all the three groups. Behavioral assessments, including the open field test and prepulse inhibition experiment, were conducted post-modeling. Subsequently, changes in the ISF partition drainage were investigated through fluorescent tracer injection into specific brain regions. Immunofluorescence analysis was employed to examine alterations in aquaporin 4 (AQP4) polarity distribution in the brain and changes in protein expression. Myelin reflex imaging using Laser Scanning Confocal Microscopy (LSCM) was utilized to study modifications in myelin within the mouse brain. Quantitative data underwent one-way ANOVA, followed by TukeyHSD for post hoc pairwise comparisons between the groups. Results: The open field test revealed a significantly longer total distance [(7 949.39±1 140.55) cm vs. (2 831.01±1 212.72) cm, P < 0.001] and increased central area duration [(88.43±22.06) s vs. (56.85±18.58) s, P=0.011] for the SZ model group compared with the controls. The UA treatment group exhibited signifi-cantly reduced total distance [(2 415.80±646.95) cm vs. (7 949.39±1 140.55) cm, P < 0.001] and increased central area duration [(54.78±11.66) s vs. (88.43±22.06) s, P=0.007] compared with the model group. Prepulse inhibition test results demonstrated a markedly lower inhibition rate of the startle reflex in the model group relative to the controls (P < 0.001 for both), with the treatment group displaying significant improvement (P < 0.001 for both). Myelin sheath analysis indicated significant demyelination in the model group, while UA treatment reversed this effect. Fluorescence tracing exhibited a significantly larger tracer diffusion area towards the rostral cortex and reflux area towards the caudal thalamus in the model group relative to the controls [(13.93±3.35) mm2 vs. (2.79±0.94) mm2, P < 0.001 for diffusion area; (2.48±0.38) mm2 vs. (0.05±0.12) mm2, P < 0.001 for reflux area], with significant impairment of drainage in brain regions. The treatment group demonstrated significantly reduced tracer diffusion and reflux areas [(7.93±2.48) mm2 vs. (13.93±3.35) mm2, P < 0.001 for diffusion area; (0.50±0.30) mm2 vs. (2.48±0.38) mm2, P < 0.001 for reflux area]. Immunofluorescence staining revealed disrupted AQP4 polarity distribution and reduced AQP4 protein expression in the model group compared with the controls [(3 663.88±733.77) μm2 vs. (13 354.92±4 054.05) μm2, P < 0.001]. The treatment group exhibited restored AQP4 polarity distribution and elevated AQP4 protein expression [(11 104.68±3 200.04) μm2 vs. (3 663.88±733.77) μm2, P < 0.001]. Conclusion: UA intervention ameliorates behavioral performance in SZ mice, Thus alleviating hyperactivity and anxiety symptoms and restoring sensorimotor gating function. The underlying mechanism may involve the improvement of demyelination and ISF drainage dysregulation in SZ mice.

    Role and mechanism of cysteine and glycine-rich protein 2 in the malignant progression of neuroblastoma
    Yao ZHANG,Jinxin GUO,Shijia ZHAN,Enyu HONG,Hui YANG,Anna JIA,Yan CHANG,Yongli GUO,Xuan ZHANG
    2024, (3):  495-504.  doi: 10.19723/j.issn.1671-167X.2024.03.017    
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    Objective: To investigate the function and underlying mechanism of cysteine and glycine-rich protein 2 (CSRP2) in neuroblastoma (NB). Methods: The correlation between the expression level of CSRP2 mRNA and the prognosis of NB children in NB clinical samples was analyzed in R2 Genomics Analysis and Visualization Platform. The small interfering RNA (siRNA) targeting CSRP2 or CSRP2 plasmid were transfected to NB cell lines SK-N-BE(2) and SH-SY5Y. Cell proliferation was observed by crystal violet staining and real-time cellular analysis. The ability of colony formation of NB cells was observed by colony-forming unit assay. Immunofluorescence assay was used to detect the expression of the proliferation marker Ki-67. Flow cytometry analysis for cell cycle proportion was used with cells stained by propidium iodide (PI). Annexin V/7AAD was used to stain cells and analyze the percentage of cell apoptosis. The ability of cell migration was determined by cell wound-healing assay. The level of protein and mRNA expression of CSRP2 in NB primary tumor and NB cell lines were detected by Western blot and quantitative real-time PCR (RT-qPCR). Results: By analyzing the NB clinical sample databases, it was found that the expression levels of CSRP2 in high-risk NB with 3/4 stages in international neuroblastoma staging system (INSS) were significantly higher than that in low-risk NB with 1/2 INSS stages. The NB patients with high expression levels of CSRP2 were shown lower overall survival rate than those with low expression levels of CSRP2. We detected the protein levels of CSRP2 in the NB samples by Western blot, and found that the protein level of CSRP2 in 3/4 INSS stages was significantly higher than that in 1/2 INSS stages. Knockdown of CSRP2 inhibited cell viability and proliferation of NB cells. Overexpression of CSRP2 increased the proliferation of NB cells. Flow cytometry showed that the proportion of sub-G1, G0/G1 and S phase cells and Annexin V positive cells were increased after CSRP2 deficiency. In the cell wound-healing assay, the healing rate of NB cells was significantly attenuated after knockdown of CSRP2. Further mechanism studies showed that the proportion of the proliferation marker Ki-67 and the phosphorylation levels of extracellular signal-regulated kinases 1/2 (ERK1/2) were significantly decreased after CSRP2 knockdown. Conclusion: CSRP2 is highly expressed in high-risk NB with 3/4 INSS stages, and the expression levels of CSRP2 are negatively correlated with the overall survival of NB patients. CSRP2 significantly increased the proliferation and cell migration of NB cells and inhibited cell apoptosis via the activation of ERK1/2. All these results indicate that CSRP2 promotes the progression of NB by activating ERK1/2, and this study will provide a potential target for high-risk NB therapy.

    Tofacitinib inhibits the transformation of lung fibroblasts into myofibroblasts through JAK/STAT3 pathway
    Shan HE,Xin CHEN,Qi CHENG,Lingjiang ZHU,Peiyu ZHANG,Shuting TONG,Jing XUE,Yan DU
    2024, (3):  505-511.  doi: 10.19723/j.issn.1671-167X.2024.03.018    
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    Objective: To investigate the effect of tofacitinib, a pan-Janus kinase (JAK) inhibitor, on transforming growth factor-beta 1 (TGF-β1)-induced fibroblast to myofibroblast transition (FMT) and to explore its mechanism. To provide a theoretical basis for the clinical treatment of connective tissue disease-related interstitial lung disease (CTD-ILD). Methods: (1) Human fetal lung fibroblast 1 (HFL-1) were cultured in vitro, and 6 groups were established: DMSO blank control group, TGF-β1 induction group, and TGF-β1 with different concentrations of tofacitinib (0.5, 1.0, 2.0, 5.0 μmol/L) drug intervention experimental groups. CCK-8 was used to measure the cell viability, and wound-healing assay was performed to measure cell migration ability. After 48 h of combined treatment, quantitative real-time PCR (RT-PCR) and Western blotting were used to detect the gene and protein expression levels of α-smooth muscle actin (α-SMA), fibronectin (FN), and collagen type Ⅰ (COL1). (2) RT-PCR and enzyme-linked immunosorbnent assay (ELISA) were used to detect the interleukin-6 (IL-6) gene and protein expression changes, respectively. (3) DMSO carrier controls, 1.0 μmol/L and 5.0 μmol/L tofacitinib were added to the cell culture media of different groups for pre-incubation for 30 min, and then TGF-β1 was added to treat for 1 h, 6 h and 24 h. The phosphorylation levels of Smad2/3 and signal transducer and activator of transcription 3 (STAT3) protein were detected by Western blotting. Results: (1) Tofacitinib inhibited the viability and migration ability of HFL-1 cells after TGF-β1 induction. (2) The expression of α-SMA, COL1A1 and FN1 genes of HFL-1 in the TGF-β1-induced groups was significantly up-regulated compared with the blank control group (P < 0.05). Compared with the TGF-β1 induction group, α-SMA expression in the 5.0 μmol/L tofacitinib intervention group was significantly inhi-bited (P < 0.05). Compared with the TGF-β1-induced group, FN1 gene was significantly inhibited in each intervention group at a concentration of 0.5-5.0 μmol/L (P < 0.05). Compared with the TGF-β1-induced group, the COL1A1 gene expression in each intervention group did not change significantly. (3) Western blotting results showed that the protein levels of α-SMA and FN1 in the TGF-β1-induced group were significantly higher than those in the control group (P < 0.05), and there was no significant difference in the expression of COL1A1. Compared with the TGF-β1-induced group, the α-SMA protein level in the intervention groups with different concentrations decreased. And the differences between the TGF-β1-induced group and 2.0 μmol/L or 5.0 μmol/L intervention groups were statistically significant (P < 0.05). Compared with the TGF-β1-induced group, the FN1 protein levels in the intervention groups with different concentrations showed a downward trend, but the difference was not statistically significant. There was no difference in COL1A1 protein expression between the intervention groups compared with the TGF-β1-induced group. (4) After TGF-β1 acted on HFL-1 cells for 48 h, the gene expression of the IL-6 was up-regulated and IL-6 in culture supernatant was increased, the intervention with tofacitinib partly inhibited the TGF-β1-induced IL-6 gene expression and IL-6 in culture supernatant. TGF-β1 induced the increase of Smad2/3 protein phosphorylation in HFL-1 cells for 1 h and 6 h, STAT3 protein phosphorylation increased at 1 h, 6 h and 24 h, the pre-intervention with tofacitinib inhibited the TGF-β1-induced Smad2/3 phosphorylation at 6 h and inhibited TGF-β1-induced STAT3 phosphorylation at 1 h, 6 h and 24 h. Conclusion: Tofacitinib can inhibit the transformation of HFL-1 cells into myofibroblasts induced by TGF-β1, and the mechanism may be through inhibiting the classic Smad2/3 pathway as well as the phosphorylation of STAT3 induced by TGF-β1, thereby protecting the disease progression of pulmonary fibrosis.

    Clinicopathological characteristics of the CD8+ T lymphocytes infiltration and its mechanism in distinct molecular subtype of medulloblastoma
    Xiaodong CHAI,Ziwen SUN,Haishuang LI,Liangyi ZHU,Xiaodan LIU,Yantao LIU,Fei PEI,Qing CHANG
    2024, (3):  512-518.  doi: 10.19723/j.issn.1671-167X.2024.03.019    
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    Objective: To investigate the characteristics of the CD8+ T cells infiltration from the 4 subtypes in medulloblastoma (MB), to analyze the relationship between CD8+ T cells infiltration and prognosis, to study the function of C-X-C motif chemokine ligand 11 (CXCL11) and its receptor in CD8+ T cells infiltration into tumors and to explore the potential mechanism, and to provide the necessary clinicopathological basis for exploring the immunotherapy of MB. Methods: In the study, 48 clinical MB samples (12 cases in each of 4 subtypes) were selected from the multiple medical center from 2012 to 2019. The transcriptomics analysis for the tumor of 48 clinical samples was conducted on the NanoString PanCancer IO360TM Panel (NanoString Technologies). Immunohistochemistry (IHC) staining of formalin-fixed, paraffin-embedded sections from MB was carried out using CD8 primary antibody to analyze diffe-rential quantities of CD8+ T cells in the MB four subtypes. Through bioinformatics analysis, the relationship between CD8+T cells infiltration and prognosis of the patients and the expression differences of various chemokines in the different subtypes of MB were investigated. The expression of CXCR3 receptor on the surface of CD8+T cells in MB was verified by double immunofluorescence staining, and the underlying molecular mechanism of CD8+T cells infiltration into the tumor was explored. Results: The characteristic index of CD8+T cells in the WNT subtype of MB was relatively high, suggesting that the number of CD8+T cells in the WNT subtype was significantly higher than that in the other three subtypes, which was confirmed by CD8 immunohistochemical staining and Gene Expression Omnibus (GEO) database analysis by using R2 online data analysis platform. And the increase of CD8+T cells infiltration was positively correlated with the patient survival. The expression level of CXCL11 in the WNT subtype MB was significantly higher than that of the other three subtypes. Immunofluorescence staining showed the presence of CXCL11 receptor, CXCR3, on the surface of CD8+T cells, suggesting that the CD8+T cells might be attracted to the MB microenvironment by CXCL11 through CXCR3. Conclusion: The CD8+T cells infiltrate more in the WNT subtype MB than other subtypes. The mechanism may be related to the activation of CXCL11-CXCR3 chemokine system, and the patients with more infiltration of CD8+T cells in tumor have better prognosis. This finding may provide the necessary clinicopathological basis for the regulatory mechanism of CD8+T cells infiltration in MB, and give a new potential therapeutic target for the future immunotherapy of MB.

    Regulatory effect of lactate on peripheral blood CD4+ T cell subsets in patients with rheumatoid arthritis
    Huina HUANG,Jing ZHAO,Xiangge ZHAO,Ziran BAI,Xia LI,Guan WANG
    2024, (3):  519-525.  doi: 10.19723/j.issn.1671-167X.2024.03.020    
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    Objective: To investigate the serum lactate level in patients with rheumatoid arthritis (RA) and its relationship with disease activity, and to analyze the effect of sodium lactate on the activation of CD4+ T cells, the ability of secreting cytokines and CD4+T cell subsets in peripheral blood of the RA patients. Methods: The peripheral blood of healthy controls (HC) and RA patients was collected, and the content of lactate in the supernatant was detected by lactate detection kit, the correlation between the content of lactate and the disease score of the RA patients was analyzed; the activation level of CD4+ T cells, the proportion of CD4+ T cell subsets and the cytokines secreted by CD4+ T cells in peripheral blood of all the RA patients were detected by flow cytometry after being stimulated with sodium lactate. Results: The serum lactate level in the RA patients (n=66) was significantly higher than that in the HC (n=60, P < 0.001), and there was a certain correlation with disease activity score in 28 joints (DAS28)-C-reactive protein (CRP) (r=0.273, P=0.029), The levels of rheumatoid factor [RF, 197.50 (26.03, 783.00) IU/mL vs. 29.30 (0.00, 102.60) IU/mL, P < 0.01], CRP [37.40 (11.30, 72.60) mg/L vs. 5.83 (2.36, 12.45) mg/L, P < 0.001], were increased in patients with the lactate concentration greater than 5 mmol/L were significantly higher than those in patients with the lactate concentration less than or equal 5 mmol/L, however, there was no significant difference in the expression of erythrocyte sedimentation rate [ESR, 42.00 (19.00, 77.00) mm/h vs. 25.00 (12.50, 45.50) mm/h, P>0.05] and anti-cyclic citrullinated peptied (CCP) antibody [82.35 (17.70, 137.00) RU/mL vs. 68.60 (25.95, 119.70) RU/mL, P>0.05]. Compared with the control group, the expression of PD-1 (46.15%±8.54% vs. 41.67%±9.98%, P < 0.001), inducible costimulatory molecule (ICOS, 5.77%±8.60% vs. 18.65%±7.94%, P < 0.01) and CD25 (25.89%±5.80% vs. 22.25%±4.59%, P < 0.01) on the surface of CD4+ T cells in the RA patients treated with sodium lactate was significantly increased. Compared with the control group, the proportion of Th17 (4.62%±1.74% vs. 2.93%±1.92%, P < 0.05) and Tph (28.02%±6.28% vs. 20.32%±5.82%, P < 0.01) cells in CD4+T cells of the RA patients in the sodium lactate treatment group increased. Compared with the control group, the expression of IL-21 (5.73%±1.59% vs. 4.75%±1.71%, P < 0.05) in CD4+T cells was up-regulated in the RA patients treated with sodium lactate. Conclusion: The level of serum lactate in RA patients is increased, which promotes the activation of CD4+T cells and the secretion of IL-21, and up-regulates the proportion of Th17 and Tph cells in the RA patients.

    Related factors of euthyroid sick syndrome in patients with sepsis
    Yuanyuan ZENG,Yun XIE,Daonan CHEN,Ruilan WANG
    2024, (3):  526-532.  doi: 10.19723/j.issn.1671-167X.2024.03.021    
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    Objective: To evaluate the prevalence of euthyroid sick syndrome (ESS) in sepsis patients and to explore its influencing factors. Methods: In the study, 365 patients diagnosed with sepsis in the emergency critical care department of Shanghai First People's Hospital from January 2017 to January 2023 were retrospectively enrolled. The patients were divided into ESS and non-ESS groups based on whether the patients were complicated with ESS.Baseline variables and relevant clinical data of the enrolled patients were collected. The prevalence of ESS in sepsis patients and its influencing factors were evaluated by multivariate Logistic regression analysis, and the 30-day survival rates were compared between the two groups. The optimal cutoff value for free triiodothyronine (FT3) was explored to predict death in the patients with sepsis. Results: There were 103 sepsis patients with ESS, accounting for 28.2% of the total cases. The severity of sepsis in ESS group was significantly higher than that in non-ESS group (P < 0.05). The acute physiology and chronic health evaluationⅡ(APACHEⅡ)score and sequential organ failure assessment (SOFA) score of ESS group were significantly higher than those of non-ESS group (P < 0.05). C-reactive protein (CRP), procalcitonin (PCT), serum amyloid A (SAA) and interleukin-6 (IL-6) in ESS group were higher than those in non-ESS group. total cholesterol(TC)and high-density liptein cholesterol(HDL-C)in ESS group were lower than those in non-ESS group, and the differences were statistically significant (P < 0.05).Multivariate Logistic regression analysis showed that PCT, IL-6, CRP, SAA and activated partial thromboplatin time (APTT) were independent risk factors for ESS in the sepsis patients (OR values were 1.105, 1.006, 1.005, 1.009 and 1.033, respectively; 95% CI were 1.044-1.170, 1.001-1.012, 1.001-1.009, 1.005-1.014, 1.004-1.062, respectively, P < 0.05).The 30-day survival rate in ESS group was significantly lower than that in non-ESS group, the Long-rank chi-square test value was 16.611, and the difference was statistically significant (P < 0.05).The receiver operation characteristic area under the curve (AUCROC)of FT3 predicted death in the patients with sepsis was 0.924 (95% CI 0.894-0.954). The serum FT3 cutoff point was 3.705 pmol/L, the specificity was 0.868, and the sensitivity was 0.950. Conclusion: In this study, the incidence of ESS in sepsis patients was determined to be 28.2% with poor prognosis. The results showed that PCT, IL-6, CRP, SAA and APTT were independent risk factors for ESS in sepsis patients, while HDL-C was a protective factor (P < 0.05). FT3 is a novel potential biomarker for predicting death in patients with sepsis.

    Clinical characteristics and treatment in adults and children with histiocytic necroti-zing lymphadenitis
    Xiuwen FEI,Si LIU,Bo WANG,Aimei DONG
    2024, (3):  533-540.  doi: 10.19723/j.issn.1671-167X.2024.03.022    
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    Objective: To analyze the clinical data of histiocytic necrotizing lymphadenitis(HNL), comparing the similarities and differences between children and adults, to deepen the understanding of the disease by clinical physicians, and to improve diagnostic rate and reduce misdiagnosis and mistreatment. Methods: The clinical data of hospitalized patients with histiocytic necrotizing lymphadenitis diagnosed by biopsy from January 2010 to August 2023 in Peking University First Hospital were collec-ted, and the clinical features, laboratory examinations, pathological features, treatments with antibiotics and glucocorticoids, and prognosis of histiocytic necrotic lymphadenitis were analyzed. Grouped based on age, the differences of clinical characteristics, laboratory tests, treatment, and prognosis between the children group (< 16 years old) and the adult group (≥16 years old) were compared. Results: Among the 81 enrolled patients, there were 42 males and 39 females. The median age was 21(14, 29) years, the median duration of disease was 20.0(13.0, 30.0) days, and the median length of hospital stay was 13.0 (10.0, 15.0) days. The first symptoms were fever, lymphadenopathy, and both. All the patients had enlarged lymph nodes with different parts and sizes, 96.3% (78 of 81) of the patients had cervical lymphadenopathy, 50.6% (41 of 81) had bilateral cervical lymphadenopathy, 55.6% (45 of 81) had supraclavicular, axillary or inguinal lymphadenopathy, and the median lymph node diameter was 20.0(20.0, 30.0) mm. Only one patient had no fever, the other 80 patients had fever, the median peak body temperature was 39.0(38.0, 39.8) ℃. Accompanying symptoms: rash (8.6%, 7/81), fatigue (34.6%, 28/81), night sweating (8.6%, 7/81), chills (25.3%, 25/81), muscle soreness (13.6%, 11/81), and joint pain (6.2%, 5/81). There were 17 cases (21.0%, 17/81) of hepatosplenomegaly, of which 12 cases (70.6%, 12/17) were splenomegaly. 68.8%(55/80) of patients had a decrease in white blood cell (WBC) count, with 47.5%(38/80)increased in lymphocyte(LY)proportion, 53.4%(39/73) increased in high-sensitivity C-reactive protein(CRP), 79.2%(57/72) increased in erythrocyte sedimentation rate(ESR), 22.2%(18/81) increased in alanine transaminase(ALT), 27.2%(22/81) elevated in aspartate transaminase(AST), and 81.6%(62/76) elevated in lactate dehydrogenase(LDH). All the 81 patients underwent lymph node biopsy, and 77.8%(63/81) of the patients showed that most of the structures in the lymph nodes were destroyed or disappeared, and 16.0%(13/81) of the lymph nodes were still in existence, hyperplasia and normal lymph node were 1.2%(1/81) respectively, and 3.7%(3/81) had normal lymph node structures. Immunohistochemical staining was performed in 67 cases. The percentages of CD3+ and CD68(KP1)+ were respectively 97.0%(65/67), and MPO+ were 94.0%(63/67). In the study, 51 patients (63.0%, 51/81) were treated with glucocorticoid therapy after diagnosis. The median time for temperature to return to normal was 1.0(1.0, 4.0) days after glucocorticoid therapy. when the glucocorticoid treatment worked best, the body temperature could drop to normal on the same day. There were significant differences in length of stay, predisposing factors, chills, the rate of increase in high-sensitivity CRP, antibiotic and glucocorticoid treatment between the adults and children groups (P < 0.05). Conclusion: In clinical practice, if there are cases with unexplained fever, superficial lymph node enlargement, and reduced white blood cells as clinical characteristics, and general antibiotics treatment is ineffective, histiocytic necrotic lymphadenitis should be considered. Lymph node biopsy should be performed as early as possible to clarify the diagnosis, reduce misdiagnosis and mistreatment, and symptomatic treatment should be the main treatment. Glucocorticoids therapy has a definite therapeutic effect.

    Evaluation of augmented reality technology in the recognizing of oral and maxillofacial anatomy
    Zunan TANG,Leihao HU,Zhen CHEN,Yao YU,Wenbo ZHANG,Xin PENG
    2024, (3):  541-545.  doi: 10.19723/j.issn.1671-167X.2024.03.023    
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    Objective: To evaluate the outcome of Augmented reality technology in the recognizing of oral and maxillofacial anatomy. Methods: This study was conducted on the undergraduate students in Peking University School of Stomatology who were learning oral and maxillofacial anatomy. The image data were selected according to the experiment content, and the important blood vessels and bone tissue structures, such as upper and lower jaws, neck arteries and veins were reconstructed in 3D(3-dimensional) by digital software to generate experiment models, and the reconstructed models were encrypted and stored in the cloud. The QR (quick response) code corresponding to the 3D model was scanned by a networked mobile device to obtain augmented reality images to assist experimenters in teaching and subjects in recognizing. Augmented reality technology was applied in both the theoretical explanation and cadaveric dissection respectively. Subjects' feedback was collected in the form of a post-class questionnaire to evaluate the effectiveness of augmented reality technology-assisted recognizing. Results: In the study, 83 undergraduate students were included as subjects in this study. Augmented reality technology could be successfully applied in the recognizing of oral and maxillofacial anatomy. All the subjects could scan the QR code through a connected mobile device to get the 3D anatomy model from the cloud, and zoom in/out/rotate the model on the mobile. Augmented reality technology could provide personalized 3D model, based on learners' needs and abilities. The results of likert scale showed that augmented reality technology was highly recognized by the students (9.19 points), and got high scores in terms of forming a three-dimensional sense and stimulating the enthusiasm for learning (9.01 and 8.85 points respectively). Conclusion: Augmented reality technology can realize the three-dimensional visualization of important structures of oral and maxillofacial anatomy and stimulate students' enthusiasm for learning. Besides, it can assist students in building three-dimensional space imagination of the anatomy of oral and maxillofacial area. The application of augmented reality technology achieves favorable effect in the recognizing of oral and maxillofacial anatomy.

    Acquired cystic kidney hemorrhage in peritoneal dialysis patients: A report of three cases
    Wanyin HOU,Jie DONG
    2024, (3):  546-550.  doi: 10.19723/j.issn.1671-167X.2024.03.024    
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    Spontaneous renal cyst hemorrhage is one of the clinical emergencies in peritoneal dialysis (PD) patients and is potentially life-threatening. The main complaints are sudden low back pain, paleness, and hypotensive shock with or without vomiting or fever. In contrast to inherited polycystic kidney disease, acquired cystic kidney disease (ACKD) secondary to chronic kidney disease is easily overlooked or delayed in clinical diagnosis and treatment, leading to severe clinical outcomes. We report three patients with spontaneous hemorrhage of ACKD in the peritoneal dialysis center at Peking University First Hospital. The common features are as follows, long history of dialysis, mild to severe low back pain, decrease in hemoglobulin, negative PD solutions, diagnosis established through computed tomography (CT), and continuing PD during treatment of ACKD hemorrhage. Treatments vary from conservative to unilaterally selective renal artery embolization. In this study, ACKD morbidity was investigated in PD patients. A total of 316 patients who had an abdominal ultrasound, CT, or magnetic resonance imaging (MRI) in the past 1 year were enrolled. Among them, 103 cases (32.9%) met the diagnostic criteria of ACKD. The morbidity rates were 27.5%, 37.8%, 43.8%, 59.1%, and 88.6%, when the dialysis history ranged from ≤3, >3 & ≤5, >5 & ≤7, >7 & ≤9, >9 years, respectively, showing a increasing trend. Most ACKD hemorrhages could be healed and got an acceptable prognosis after treatment, including rest, blood transfusion, selective renal artery embolization, or nephrectomy. We summarize the risk factors, including a long history of dialysis, anticoagulation or antiplatelet, and inflammation or stones of the urinary system, but with no difference in initial kidney diseases and gender. ACKD hemorrhage mainly includes intracapsular hemorrhage, cyst rupture, and spontaneous retroperitoneal hemorrhage. In addition, we also recommend an adaptive process for spontaneous kidney hemorrhage of diagnosis and treatment in peritoneal dialysis patients. The significance of these cases lies in the fact that patients with ACKD are potentially associated with complications such as cyst hemorrhage and malignancy. Thus, peritoneal dialysis physicians should place great importance on the surveillance of ACKD.

    Expert consensus on key indicators for quality control in trauma medicine center
    Wei HUANG,Tingmin XU,Tianbing WANG,Baoguo JIANG
    2024, (3):  551-555.  doi: 10.19723/j.issn.1671-167X.2024.03.025    
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    Trauma is recognized globally as a great public health challenge. It stands as the predominant cause of mortality among those under the age of 45 and is also ranked among the top five causes of death for both urban and rural populations within China. This stark reality underscores the critical urgency in establishing an efficient system for trauma care, which is pivotal for substantially enhancing the survival rates of patients. An optimally developed system for trauma care not only guarantees that patients promptly receive professional medical assistance but also facilitates significant improvements in the outcomes of trauma care through the strategic establishment of trauma centers. At present, a considerable variation exists in the quality of trauma care provided across various regions within China. The adoption of comprehensive quality management strategies for the medical processes involved in trauma care, alongside the standardized management of on-site rescue operations, pre-hospital emergency care, and in-hospital treatment protocols, stands as a fundamental approach to boost the capabilities of trauma care and, consequently, the survival rates of trauma patients. Serving as the cornerstone of comprehensive medical quality management, key quality control indicators possess the capacity to steer the development direction of trauma centers. In a concerted effort to further augment the medical quality management of trauma care, standardize clinical diagnosis and treatment methodologies, and advocate for the standardization and ho-mogenization of medical services, the Medical Quality Control Professional Committee of the National Center for Trauma Medicine has undertaken a detailed refinement and update of the 16 key quality control indicators for trauma centers. These were initially put forward in the "Notice on Further Enhancing Trauma Care Capabilities" disseminated by the National Health Commission in 2018.Consequent to this endeavor, a revised set of 19 quality control indicators has been devised. This comprehensive set, inclusive of the indicators' names, definitions, calculation methodologies, significance, and the subjects for quality control, is designed for utilization within the quality management and control operations of trauma centers across various levels. This initiative aims to furnish a concrete and executable roadmap for the quality control endeavors of trauma centers. Through the enactment of these quality control indicators, medical institutions are empowered to conduct more stringent monitoring and evaluative measures across all facets of trauma care. This not only facilitates the prompt identification and rectification of existing challenges but also substantially boosts the efficiency of internal collaboration. It enhances the synergy between different departments, thereby markedly improving the efficiency and quality of trauma care.


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Sponsor: Peking University
Editor-in-Chief: ZHAN Qi-min
Executive Editor-in-Chief: ZENG Gui-fang
Editing and Publishing: Editorial Department of Journal of Peking University (Health Sciences)
ISSN: 1671-167X
CN: 11-4691/R