Abstract In order to explore the influence of different environmental endocrine disruptors (EEDs) on the onset of youth in children and adolescents, the study introduces the advance trend of the onset of youth in children and adolescents at home and abroad, and the influence of EEDs, such as bisphenol A, organophosphate esters, phthalic acid esters, per and polyfluoroalkyl substances, which children and adolescents often contact on the onset of youth. The related mechanisms are expounded from the aspects of direct interference of EEDs on neuroendocrine axis, hormone simulation and antagonism mediated by receptors, epigenetic programming changes, indirect pathways mediated by obesity and inflammation, etc., in order to provide scientific basis for formulating preventive measures for abnormal puberty onset of children and adolescents in EEDs exposure and promote their health.

Objective: To investigate the longitudinal associations between dietary patterns in early childhood and myopia among children, so as to provide evidence for improving early childhood dietary patterns and promoting healthy ocular development among children. Methods: Participants were derived from the Ma-anshan Birth Cohort (MABC). A total of 1 432 children were included. Dietary patterns at 2.5 years of age were collected in 2017 using a food frequency questionnaire completed by parents. In 2022, cycloplegic refraction and ocular biometric parameters were measured in children aged 7-8 years. Food components were grouped into tertiles ( T1-T 3), and latent class analysis (LCA) was used to identify dietary pattern at the age of 2.5. Log-binomial regression and multiple linear regression model were applied to examine the associations of dietary patterns and their latent classes with myopia, spherical equivalent (SE), and axial length (AL). Results: The prevalence of myopia among children was 23.9%. After adjusting for covariates, the T 2 group of cereals and tubers was negatively associated with myopia rate ( RR=0.72, 95%CI =0.57-0.90) and AL ( β=-0.15, 95%CI =-0.24 to -0.05), and positively associated with SE ( β=0.21, 95%CI =0.06-0.35)(all P ＜0.05). Linear regression models showed that the T 2 group of fruits and vegetables was positively associated with AL ( β=0.09, 95%CI =0.00- 0.19 ); the T 3 group of high sugar foods ( β=0.11, 95%CI =0.00-0.21) and the T 3 group of processed foods ( β= 0.10 , 95%CI =0.00-0.19) were positively associated with AL; total scores for high sugar foods ( β=0.07, 95%CI =0.00-0.14) and processed foods ( β=0.09, 95%CI =0.01-0.17) were positively associated with AL (all P <0.05). After adjusting for sex, age, and parental myopia, the comprehensive high intake pattern was positively associated with AL ( β=0.12, 95%CI =0.00-0.23, P <0.05). After further adjusting for daily screen time and daily outdoor activity time, the association was no longer statistically significant ( β= 0.11 , 95%CI =-0.00-0.23, P >0.05). Conclusions Moderate consumption of cereals and tubers in early childhood may reduce the risk of myopia and delay AL growth. In contrast, high sugar and highly processed diets may promote AL and increase myopia risk. Establishing healthy dietary habits in early childhood and limiting intake of high sugar and processed foods is crucial for promoting ocular development in children.

Objective To investigate the influencing factors of advanced bone age in early adolescence, and to provide a scientific basis for the early identification of children and adolescents with abnormal bone age development. Methods A prospective cohort study design was adopted. From July 2022 to September 2023, height, weight, and body composition data of children were collected, with the baseline age of the study participants being 8.42±0.50 years. Subsequently, from March 2024 to November 2025, these children in the cohort were followed up and their bone age development was monitored. In the end, a total of 1142 participants with complete data were included in the study. Results In early adolescence, there were 239 individuals (20.93%) with early bone age development and 103 (9.02%) with delayed development. The proportion of early bone age development was higher among individuals whose mothers had gestational hypertension during pregnancy, and the difference was statistically significant (χ²=8.90, P<0.05). The proportion of early bone age development was higher among boys, and the difference was statistically significant (χ²=41.69, P＜0.001). Disordered multiclass logistic regression analysis showed that after adjusting for demographic factors, overweight (OR=2.65, 95%CI:1.81-3.88), obesity (OR=6.51, 95%CI: 4.45-9.53), and excessive body fat percentage (OR=4.60, 95% CI: 3.01-7.03) were associated with an increased risk of early bone age development in children and adolescents. Conclusion Being overweight/obese and having an excessive body fat percentage can increase the risk of early bone age development in adolescents.

Objective This study aimed to examine the risk factors and prognostic factors of brucellar spondylitis for early prevention and treatment of the disease,and improving the outcomes of patients.Methods A retrospective case-control study was conducted on the patients with brucellosis who were hospitalized in the Third Hospital of Hebei Medical University from June 2020 to June 2022.Patients were assigned to brucellosis without spondylitis group or brucellar spondylitis group according to the presence of spondylitis.The patients in brucellar spondylitis group were followed for 1 year.Then they were stratified into a subgroup of good or poor prognosis according to clinical outcomes.The dataset for the demographic and clinical variables of patients were analyzed using SPSS 26.0 software.Results A total of 300 patients with brucellosis were enrolled,including 113 cases of brucellosis without spondylitis and 187 cases of brucellar spondylitis.Multivariate analysis showed that age,time from onset to diagnosis,low back pain,and erythrocyte sedimentation rate were independent risk factors for brucellar spondylitis(P＜0.05).Of the 154 cases of brucellar spondylitis with known outcomes,121 cases showed good prognosis and 33 cases had poor prognosis.COX regression analysis showed that the time from onset to diagnosis,diabetes mellitus,paravertebral abscess,and neurological impairment were independent risk factors for poor prognosis in patients with brucellar spondylitis(P＜0.05).Conclusions Old age,prolonged time from onset to diagnosis,low back pain,and increased erythrocyte sedimentation rate are independent risk factors for spondylitis in patients with brucellosis.Prolonged time from onset to diagnosis,diabetes mellitus,paravertebral abscess,and neurological impairment are independent risk factors for poor prognosis of brucellar spondylitis.

Objective:To explore the relationship between parenting styles of toddlers aged 30 months and attention deficit hyperactivity disorder (ADHD) symptom trajectories in preschool children.Methods:The subjects were 2 111 children and their parents in Ma'anshan Birth Cohort. Parenting styles were assessed at 30 months of age using the Brief Toddler Parenting Style Questionnaire, which defines parenting styles on four dimensions: warmth and interaction, attention and acceptance, outdoor and social activities, and neglect and restrictions. The Chinese version of the Conners Abbreviated Symptom Questionnaire was used to examine preschooler's ADHD symptoms aged 3, 5, and 6 years. ADHD symptom trajectories were fitted using group-based trajectory modeling. The multinomial logistic regression model was used to evaluate the relationship between parenting styles at 30 months of age and ADHD symptom trajectories in children. The additive and multiplicative models were applied to analyze the interaction effect of negative parenting styles in children's ADHD symptom trajectories.Results:ADHD symptom trajectories in children included the low-score (48.3%), moderate-score (47.7%), and high-score groups (4.0%). After adjusting for the confounding factors, the results of the multinomial logistic regression analysis showed that negative parenting styles of the father/mother were associated with ADHD symptom trajectories in children ( P<0.05). The father/mother's low warmth and interaction (father: OR=2.07,95% CI:1.68-2.54; mother: OR=2.02,95% CI:1.64-2.48), low attention and acceptance (father: OR=1.94,95% CI:1.57-2.39; mother: OR=1.47,95% CI:1.20-1.81), low outdoor and social (father: OR=1.74,95% CI:1.43-2.13; mother: OR=1.60,95% CI:1.32-1.94), and high neglect and restriction (father: OR=2.09,95% CI:1.67-2.62; mother: OR=2.06,95% CI:1.65-2.56) were associated with ADHD symptom moderate-score trajectories compared to the low-score trajectory group, mother's low warmth and interaction, low outdoor and social, and high neglect and restrictions. Statistically significant association was seen in negative parenting styles of fathers with the high-score group. There was a multiplicative interaction for hostile parenting ( P<0.05). The additive interaction results showed that there was a synergistic effect of hostile parenting, which increased the risk of the high-score trajectories of ADHD symptoms in children. Conclusions:Both parents' parenting styles influenced ADHD symptom change the trajectories in preschoolers. Negative parenting styles of the father/mother increase the risk of the moderate-score and high-score trajectories of ADHD symptoms in children. Hostile parenting by both parents has a synergistic impact on the risk of ADHD symptom trajectories in children, and the simultaneous presence of both increases the risk of the high-score trajectory of ADHD symptoms.

Objective:To explore the relationship between parenting styles of toddlers aged 30 months and attention deficit hyperactivity disorder (ADHD) symptom trajectories in preschool children.Methods:The subjects were 2 111 children and their parents in Ma'anshan Birth Cohort. Parenting styles were assessed at 30 months of age using the Brief Toddler Parenting Style Questionnaire, which defines parenting styles on four dimensions: warmth and interaction, attention and acceptance, outdoor and social activities, and neglect and restrictions. The Chinese version of the Conners Abbreviated Symptom Questionnaire was used to examine preschooler's ADHD symptoms aged 3, 5, and 6 years. ADHD symptom trajectories were fitted using group-based trajectory modeling. The multinomial logistic regression model was used to evaluate the relationship between parenting styles at 30 months of age and ADHD symptom trajectories in children. The additive and multiplicative models were applied to analyze the interaction effect of negative parenting styles in children's ADHD symptom trajectories.Results:ADHD symptom trajectories in children included the low-score (48.3%), moderate-score (47.7%), and high-score groups (4.0%). After adjusting for the confounding factors, the results of the multinomial logistic regression analysis showed that negative parenting styles of the father/mother were associated with ADHD symptom trajectories in children ( P<0.05). The father/mother's low warmth and interaction (father: OR=2.07,95% CI:1.68-2.54; mother: OR=2.02,95% CI:1.64-2.48), low attention and acceptance (father: OR=1.94,95% CI:1.57-2.39; mother: OR=1.47,95% CI:1.20-1.81), low outdoor and social (father: OR=1.74,95% CI:1.43-2.13; mother: OR=1.60,95% CI:1.32-1.94), and high neglect and restriction (father: OR=2.09,95% CI:1.67-2.62; mother: OR=2.06,95% CI:1.65-2.56) were associated with ADHD symptom moderate-score trajectories compared to the low-score trajectory group, mother's low warmth and interaction, low outdoor and social, and high neglect and restrictions. Statistically significant association was seen in negative parenting styles of fathers with the high-score group. There was a multiplicative interaction for hostile parenting ( P<0.05). The additive interaction results showed that there was a synergistic effect of hostile parenting, which increased the risk of the high-score trajectories of ADHD symptoms in children. Conclusions:Both parents' parenting styles influenced ADHD symptom change the trajectories in preschoolers. Negative parenting styles of the father/mother increase the risk of the moderate-score and high-score trajectories of ADHD symptoms in children. Hostile parenting by both parents has a synergistic impact on the risk of ADHD symptom trajectories in children, and the simultaneous presence of both increases the risk of the high-score trajectory of ADHD symptoms.

Objective:To determine the prevalence, risk factors, and longitudinal associations of loneliness during mid- to late pregnancy with anxiety and depressive symptoms in late pregnancy.Methods:In this prospective cohort study, 1 107 pregnant women at 24-28 weeks' gestation were enrolled between June 2021 and December 2022. Psychological status was assessed during mid-pregnancy (24-28 weeks) and late pregnancy (≥32 weeks) using standardized electronic questionnaires, including the Revised University of California Los Angeles Loneliness Scale (UCLA) Loneliness Scale-Short Form (Cronbach's α=0.82), Patient Health Questionnaire-9 ( α=0.86), and Generalized Anxiety Disorder-7 ( α=0.88). Multivariate logistic regression identified independent risk factors for loneliness. Cross-lagged path models analyzed the longitudinal predictions between loneliness and anxiety/depressive symptoms. Results:The prevalence of loneliness decreased significantly from 10.8% (120/1 107) in mid-pregnancy to 4.8% (37/777) in late pregnancy ( χ2=21.81, P<0.001). Multivariate analysis identified independent risk factors for loneliness: age <30 years ( OR=1.70, 95% CI: 1.15-2.50), annual household income <50 000 CNY ( OR=2.53, 95% CI: 1.28-5.02), unemployment during pregnancy ( OR=1.57, 95% CI: 1.03-2.39), history of alcohol consumption ( OR=1.63, 95% CI: 1.03-2.56), and the presence of mid-pregnancy depressive ( OR=2.76, 95% CI: 1.51-5.04) and anxiety symptoms ( OR=1.65, 95% CI: 1.01-2.71) (all P<0.05). Cross-lagged path models indicated bidirectional associations between loneliness and both anxiety ( β=0.32, P<0.01) and depressive symptoms ( β=0.28, P<0.01). However, the predictive effect of loneliness on subsequent depressive and anxiety symptoms ( β=0.28-0.32) was substantially stronger than the reverse prediction (mid-pregnancy anxiety on late-pregnancy loneliness: β=0.12; mid-pregnancy depression on late-pregnancy loneliness: β=0.11). Loneliness demonstrated high temporal stability (autoregressive effects β=0.29-0.32). Conclusion:Loneliness in mid-pregnancy exhibits a symmetric bidirectional association with anxiety and depressive symptoms in late pregnancy, suggesting it may be a core driver in the development of these emotional symptoms. Younger maternal age (<30 years), low household income (<50 000 CNY/year), unemployment during pregnancy, and a history of alcohol consumption were associated with a higher risk of loneliness and should be prioritized for psychological screening and intervention.

Objective This study aimed to examine the risk factors and prognostic factors of brucellar spondylitis for early prevention and treatment of the disease,and improving the outcomes of patients.Methods A retrospective case-control study was conducted on the patients with brucellosis who were hospitalized in the Third Hospital of Hebei Medical University from June 2020 to June 2022.Patients were assigned to brucellosis without spondylitis group or brucellar spondylitis group according to the presence of spondylitis.The patients in brucellar spondylitis group were followed for 1 year.Then they were stratified into a subgroup of good or poor prognosis according to clinical outcomes.The dataset for the demographic and clinical variables of patients were analyzed using SPSS 26.0 software.Results A total of 300 patients with brucellosis were enrolled,including 113 cases of brucellosis without spondylitis and 187 cases of brucellar spondylitis.Multivariate analysis showed that age,time from onset to diagnosis,low back pain,and erythrocyte sedimentation rate were independent risk factors for brucellar spondylitis(P＜0.05).Of the 154 cases of brucellar spondylitis with known outcomes,121 cases showed good prognosis and 33 cases had poor prognosis.COX regression analysis showed that the time from onset to diagnosis,diabetes mellitus,paravertebral abscess,and neurological impairment were independent risk factors for poor prognosis in patients with brucellar spondylitis(P＜0.05).Conclusions Old age,prolonged time from onset to diagnosis,low back pain,and increased erythrocyte sedimentation rate are independent risk factors for spondylitis in patients with brucellosis.Prolonged time from onset to diagnosis,diabetes mellitus,paravertebral abscess,and neurological impairment are independent risk factors for poor prognosis of brucellar spondylitis.

Objective:To determine the prevalence, risk factors, and longitudinal associations of loneliness during mid- to late pregnancy with anxiety and depressive symptoms in late pregnancy.Methods:In this prospective cohort study, 1 107 pregnant women at 24-28 weeks' gestation were enrolled between June 2021 and December 2022. Psychological status was assessed during mid-pregnancy (24-28 weeks) and late pregnancy (≥32 weeks) using standardized electronic questionnaires, including the Revised University of California Los Angeles Loneliness Scale (UCLA) Loneliness Scale-Short Form (Cronbach's α=0.82), Patient Health Questionnaire-9 ( α=0.86), and Generalized Anxiety Disorder-7 ( α=0.88). Multivariate logistic regression identified independent risk factors for loneliness. Cross-lagged path models analyzed the longitudinal predictions between loneliness and anxiety/depressive symptoms. Results:The prevalence of loneliness decreased significantly from 10.8% (120/1 107) in mid-pregnancy to 4.8% (37/777) in late pregnancy ( χ2=21.81, P<0.001). Multivariate analysis identified independent risk factors for loneliness: age <30 years ( OR=1.70, 95% CI: 1.15-2.50), annual household income <50 000 CNY ( OR=2.53, 95% CI: 1.28-5.02), unemployment during pregnancy ( OR=1.57, 95% CI: 1.03-2.39), history of alcohol consumption ( OR=1.63, 95% CI: 1.03-2.56), and the presence of mid-pregnancy depressive ( OR=2.76, 95% CI: 1.51-5.04) and anxiety symptoms ( OR=1.65, 95% CI: 1.01-2.71) (all P<0.05). Cross-lagged path models indicated bidirectional associations between loneliness and both anxiety ( β=0.32, P<0.01) and depressive symptoms ( β=0.28, P<0.01). However, the predictive effect of loneliness on subsequent depressive and anxiety symptoms ( β=0.28-0.32) was substantially stronger than the reverse prediction (mid-pregnancy anxiety on late-pregnancy loneliness: β=0.12; mid-pregnancy depression on late-pregnancy loneliness: β=0.11). Loneliness demonstrated high temporal stability (autoregressive effects β=0.29-0.32). Conclusion:Loneliness in mid-pregnancy exhibits a symmetric bidirectional association with anxiety and depressive symptoms in late pregnancy, suggesting it may be a core driver in the development of these emotional symptoms. Younger maternal age (<30 years), low household income (<50 000 CNY/year), unemployment during pregnancy, and a history of alcohol consumption were associated with a higher risk of loneliness and should be prioritized for psychological screening and intervention.

Objective To investigate the effects of zalcitabine(ddC),a mitochondrial DNA polymerase γ(POLG)inhibitor,on the migration,invasion,and to preliminarily explore mitochondrial biogenesis of human tri-ple-negative breast cancer MDA-MB-231 cells.Methods The effect of ddC on cell viability was detected using the MTT assay.The migration and invasion abilities of the cells were evaluated using the cell scratch and Transwell in-vasion assays.Cell apoptosis was determined using flow cytometry and a V-FITC/PI cell apoptosis detection kit.The protein expression of POLG,NADH dehydrogenase subunit Ⅰ(NADH1),NADH dehydrogenase subunit Ⅱ(NADH2),ATP synthase subunit 6(ATPase6),cytochrome c oxidase subunit Ⅰ(COX-1)and cytochrome c ox-idase subunit Ⅲ(COX-3)were determined using Western blot.The POLG mRNA level and mtDNA copy number were determined using qPCR.The mitochondrial content and ATP levels were determined using MitoTracker Green fluorescent probe staining and an ATP determination kit.MDA-MB-231 cells were transfected with pcDNA3.1-EG-FP-POLG plasmids to overexpress POLG.The inhibitory effects of ddC on cell migration and invasion were detected in POLG-overexpressed MDA-MB-231 cells.Results POLG expression was higher in MDA-MB-231 cells than in normal mammary epithelial cells(MCF-10A)(P＜0.01).ddC inhibited cell viability in a dose-dependent man-ner.ddC inhibited the migration(P＜0.01)and invasion(P＜0.01)of MDA-MB-231 cells;however,it dis-played no significant inhibitory effects on cell viability in normal mammary epithelial cells(MCF-10A)at the same concentration.ddC downregulated the protein(P＜0.01)and mRNA(P＜0.01)levels of POLG,reduced mtD-NA copy number(P＜0.01)and downregulated mtDNA-coded NADH1,NADH2,ATPase6,COX-1 and COX-3 protein expression(P＜0.01)in MDA-MB-231 cells.Furthermore ddC inhibited mitochondrial content(P＜0.01)and ATP(P＜0.01)levels in MDA-MB-231 cells.POLG overexpression increased the migration(P＜0.05)and invasion(P＜0.05)abilities of MDA-MB-231 cells,while ddC did not significantly inhibit the migra-tion and invasion abilities of MDA-MB-231 cells overexpressing POLG.Conclusion ddC downregulates POLG ex-pression in MDA-MB-231 cells and inhibits mitochondrial biogenesis and ATP levels,thereby inhibiting the migra-tion and invasion of MDA-MB-231 cells.