Objective To investigate the causal relationship between metabolic syndrome and breast cancer by using a bidirectional two-sample Mendelian randomization (MR) approach. Methods Genome-wide association study (GWAS) summary statistics for metabolic syndrome and breast cancer were acquired from the Integrative Epidemiology Unit GWAS database and the GWAS Catalog, with populations encompassing the United States and East Asia. A bidirectional causal design was employed: a forward analysis with metabolic syndrome as the exposure and breast cancer as the outcome, followed by a reverse analysis wherein their roles were interchanged. The inverse-variance weighting (IVW) method was primarily used for effect estimation, supplemented by MR-Egger regression, the weighted median method, the simple mode method, and the weighted mode method. Instrument variable strength was screened using the F-statistic (F>10). Robustness of the results was assessed through heterogeneity tests, horizontal pleiotropy tests, forest plots, and leave-one-out sensitivity analyses. Results The IVW analysis indicated no significant causal relationship between metabolic syndrome and breast cancer (OR=1.00, 95%CI: 0.97-1.03), P>0.05). Sensitivity analyses yielded consistent results, suggesting the good robustness of the study findings. Conclusion This study found no evidence to support a causal relationship, either positive or negative, between metabolic syndrome and breast cancer.

Objective: To explore the association between mental health and muscle strength among Chinese adolescents aged 13- 18, providing a theoretical foundation and intervention strategies for mental health promotion. Methods: Data were obtained from the 2019 Chinese National Survey on Students Constitution and Health, including 98 631 Chinese adolescents aged 13- 18. Psychological distress was assessed by using the Kessler Psychological Distress Scale (K10), and mental well being was measured with the Warwick-Edinburgh Mental Well being Scale (WEMWBS). Based on the gender and age specific Z scores of various test items [grip strength, standing long jump, pull ups (for males), and sit ups (for females)], muscle strength index (MSI) was constructed to evaluate the comprehensive level of muscle strength in adolescents. According to the Dual factor Model (DFM) of mental health, participants were categorized into four groups:troubled, symptomatic but content, vulnerable, and complete mental health. Gender differences were analyzed by using Chi-square tests, trends were tested with Cochran-Armitage tests, and multinomial Logistic regression models were applied to assess associations between muscle strength and mental health among adolescents. Results: In 2019, 37.4% of Chinese adolescents aged 13-18 were reported of high mental distress, and 59.9% were reported of low mental well being. Boys had significantly lower rates of high mental distress (35.3%) and low mental well being (55.6%) compared to girls (39.4%, 64.3%), and the differences were of statistical significance ( χ 2=176.13, 780.42, both P <0.05). In 2019, the rate of complete mental health among adolescents showed a downward trend with increasing age ( χ 2 trend = 258.47) and a gradual upward trend with increasing muscle strength levels ( χ 2 trend =123.14)，and both boys and girls exhibited similar trends ( χ 2 trend =103.83, 168.46; 57.00 , 67.34) (all P <0.05). The results of the unordered multiclass Logistic regression model showed that after controlling for confounding factors such as age and gender, when the completely pathological group as a reference, for every 1 unit increase in MSI in adolescents, the likelihood of being in a completely mental health state increased by 29% ( OR = 1.29); for every unit increase in the Z-score for pull ups, the likelihood of being in a completely mental health state increased by 6% ( OR =1.06) among boys; for every 1 unit increase in sit up Z score, the likelihood of being in a completely mental health state increased by 19% ( OR =1.19) among girls (all P <0.05). Conclusions The mental health status of Chinese adolescents is not good enough. Muscle strength is positively associated with mental health.

Objective: To systematically review the development and changes in mental health policies within the National Outline for Children s Development in China from 1992 to 2030, providing a reference basis for future formulation of mental health policies among children and adolescent in China. Methods: Based on the four editions of the National Outline for Children s Development in China across different periods from 1992 to 2030, word frequency analysis was used to reveal shifts in policy priorities, and an internationally recognized framework for adolescent health policy analysis was applied to conduct a textual review. Results: Word frequency analysis revealed that the term "psychological" appeared 6 times in the National Outline for Children s Development in China (2001-2010) but increased to 20 times in the National Outline for Children s Development in China (2021-2030) (abbreviated as the National Outline of 2021), while the term "health" rose from 4 times in the National Outline for Children s Development Plan in China in the 1990s to 68 times in the National Outline of 2021. The scope of mental health policy interventions expanded to encompass five key areas:health, safety, education, welfare and legal protection. Textual analysis highlighted that the policies of the National Outline for Children s Development in China were demand driven, prioritized vulnerable groups and continuously broadened their coverage, emphasizing sustainability and appropriateness, and monitoring/evaluation mechanisms. By 2023, 42.3% of primary schools and 64.8% of secondary schools employed full time mental health education teachers. However, the National Outline for Children s Development in China lacked direct evidence of children and adolescents participation in policy formulation, and publicly available mental health data disaggregated by age and gender remained limited. Conclusion Mental health policies of children and adolescents in China have evolved from nonexistence to gradual refinement, yet institutionalized channels for youth involvement in policy development and evaluation remain insufficient, and transparency in age and gender specific mental health data needs improvement.

Idiopathic pulmonary fibrosis (IPF), a chronic interstitial lung disease, is characterized by aberrant wound healing, excessive scarring and the formation of myofibroblastic foci. Although the role of alternative splicing (AS) in the pathogenesis of organ fibrosis has garnered increasing attention, its specific contribution to pulmonary fibrosis remains incompletely understood. In this study, we identified an up-regulation of serine/arginine-rich splicing factor 7 (SRSF7) in lung fibroblasts derived from IPF patients and a bleomycin (BLM)-induced mouse model, and further characterized its functional role in both human fetal lung fibroblasts and mice. We demonstrated that enhanced expression of Srsf7 in mice spontaneously induced alveolar collagen accumulation. Mechanistically, we investigated alternative splicing events and revealed that SRSF7 modulates the alternative splicing of pyruvate kinase (PKM), leading to metabolic dysregulation and fibroblast activation. In vivo studies showed that fibroblast-specific knockout of Srsf7 in conditional knockout mice conferred resistance to bleomycin-induced pulmonary fibrosis. Importantly, through drug screening, we identified lomitapide as a novel modulator of SRSF7, which effectively mitigated experimental pulmonary fibrosis. Collectively, our findings elucidate a molecular pathway by which SRSF7 drives fibroblast metabolic dysregulation and propose a potential therapeutic strategy for pulmonary fibrosis.

Osteosarcoma (OS) is the most prevalent primary malignant bone tumor affecting children and adolescents. Despite ongoing research efforts, the 5-year survival rate has remained stagnant for many years, highlighting the critical need for novel drug development to enhance current treatment protocols. Ziyuglycoside II (ZYG II), a triterpenoid saponin extracted from S. officinalis, has recently demonstrated antitumor properties. This study evaluates the antitumor effect of ZYG II on osteosarcoma and elucidates its mechanism of action through the co-regulation of p53 and estrogen-related receptor gamma (ESRRG), which inhibits disease progression. The research employs in vitro experiments using multiple established osteosarcoma cell lines, as well as in vivo studies utilizing a nude mouse model of orthotopic xenograft osteosarcoma. Additionally, ESRRG shRNA was used to construct stable ESRRG-reducing OS cell lines to investigate the molecular mechanism by which ZYG II exerts its anti-osteosarcoma effects through the co-regulation of ESRRG and p53. Results indicate that ZYG II administration led to decreased OS cell viability and reduced tumor volumes. Furthermore, cell cycles were arrested at the G₀/G₁ phase, while the proportion of apoptotic cells increased. Expression of p53, ESRRG, p21, Bax, Cleaved Caspase-9, and Cleaved Caspase-3 proteins increased, while expression of CDK4, Cyclin D1, and Bcl-2 proteins decreased. Multiple ZYG II and ESRRG docking patterns were simulated through molecular docking. Comparing the pharmacodynamic response of ZYG II to OS cell lines with reduced ESRRG and normal expression demonstrated that ZYG II inhibits osteosarcoma progression, induces cell cycle arrest, and promotes cell apoptosis through the coordination of p53 and ESRRG. In conclusion, ZYG II inhibits osteosarcoma progression, leads to cell cycle arrest, and promotes cell apoptosis through synergistic regulation of p53 and ESRRG.
Osteosarcoma/physiopathology* ; Tumor Suppressor Protein p53/genetics* ; Humans ; Animals ; Saponins/chemistry* ; Bone Neoplasms/physiopathology* ; Signal Transduction/drug effects* ; Cell Line, Tumor ; Mice, Nude ; Mice ; Apoptosis/drug effects* ; Receptors, Estrogen/genetics* ; Mice, Inbred BALB C ; Female ; Male ; Xenograft Model Antitumor Assays

Objective:To analyze the changes in the prevalence characteristics of multimorbidity among adolescents aged 13-18 in Inner Mongolia Autonomous Region from 2019 to 2022 and to explore the association between multimorbidity and moderate to high-intensity physical activity among them.Methods:A stratified random cluster sampling method was used to select students aged 13-18 in Inner Mongolia Autonomous Region every September from 2019 to 2022. Physical examinations, demographic characteristics, and depression-related surveys were conducted to analyze the multimorbidity of overweight, obesity, high blood pressure, myopia, spinal curvature abnormality, and depression. A logistic regression model was used to analyze the association between multimorbidity and moderate to high-intensity physical activity.Results:From 2019 to 2022, 70 972, 62 923, 80 254, and 78 288 study subjects were included, with the rates of multimorbidity being 56.4%, 55.4%, 57.2%, and 55.8%, respectively. The rates of multimorbidity remained relatively stable from 2019 to 2022 ( χ2=0.06, P=0.950). The incidence of multimorbidity among girls was significantly higher than that among boys ( P<0.001). The incidence of multimorbidity among urban students was significantly higher than that among suburban students ( P<0.001). The incidence of multimorbidity among high school students was higher than that among middle school students ( P<0.001). The top three multimorbidity combinations were myopia and overweight/obesity (26.4%), myopia and high blood pressure (24.4%), and myopia and depression (19.8%), while the least common combination was depression and spinal curvature abnormality (1.1%). The multimorbidity patterns showed no significant differences between years ( χ2=0.03, P=0.999). The multimorbidity status was significantly associated with the status of meeting the standard of moderate to high-intensity physical activity ( OR=0.83, 95% CI: 0.80-0.86). The association was stronger in boys ( OR=0.77, 95% CI: 0.73-0.81) compared with girls ( OR=0.90, 95% CI: 0.85-0.96), with a significant interaction term ( P<0.001). Conclusion:From 2019 to 2022, the incidence of multimorbidity among adolescents aged 13 to 18 in Inner Mongolia Autonomous Region is relatively high, mainly due to the co-occurrence of myopia and other health problems. Adequate physical activity is an important factor in reducing multimorbidity.

Objective To investigate the correlation between serum TNF super family 15(TNFSF15),growth differentiation factor 11(GDF11)and in-stent restenosis(ISR)in patients with unstable angina pectoris(UAP)undergoing percutaneous coronary intervention(PCI).Methods A total of 350 UAP patients who underwent PCI treatment in the Second Hospital of Qinhuangdao from January 1,2020 to January 1,2021 were collected as observation subjects,and they were separated into non-ISR group(n=246)and ISR group(n=104)based on whether they had experienced ISR.ELISA was applied to determine the levels of serum TNFSF15 and GDF11,ROC curve was applied to analyze the predictive value of serum TNFSF15 and GDF11 levels for postoperative ISR in UAP patients after PCI,and multivariate Logistic regression was used to analyze the factors affecting the occurrence of ISR in UAP patients after PCI.Results Compared with the non-ISR group,the ISR group showed an increase in blood glucose,smoking history and LDL-C levels(t/χ2=22.908,18.869,47.337),as well as elevated serum TNFSF15 levels(16.97±1.51 pg/ml vs 18.35±1.62pg/ml)and GDF11 levels(157.72±16.13pg/ml vs 174.11±18.65 pg/ml)decreased(t=7.429,7.811),and the differences were statistically significant(all P<0.001).The AUC(95%CI)of serum TNFSF15 and GDF11 in dependently and jointly predicting ISR after PCI in UAP patients were 0.764(0.716～0.808),0.781(0.734～0.823)and 0.849(0.807～0.885),respectively,and the joint prediction of the two was higher than the individual prediction(Z=4.365,3.257,all P<0.001).Multivariate Logistic regression analysis of serum TNFSF15,the level of GDF11 was a protective factor for ISR in UAP patients after PCI(Wald χ2=11.000,36.321,all P<0.05).Conclusion The serum levels of TNFSF15 and GDF11 decreased in UAP patients with postoperative ISR after PCI,which have good predictive value for the occurrence of ISR in UAP patients after PCI.

Objective To explore the effects of glycyrrhizic polysaccharide(GP)on the biological activity of salivary adenoid cystic carcinoma tumor cells and its mechanisms of anti-tumor action.Methods GP was prepared,and human adenoid cystic carcinoma high-metastatic cell line SACC-LM and low-metastatic cell line SACC-83 were used as target cells.Different concentrations of GP were used for intervention.The cell counting kit-8(CCK-8)assay was employed to detect cell proliferation and apoptosis.Reverse transcrip-tion polymerase chain reaction(RT-PCR)and Western blot experiments were conducted to detect the expression of genes and proteins related to tumor invasion and metastasis.The scratch assay was used to observe the effect of GP on the migration ability of SACC cells.In vivo experiments were conducted to verify the inhibitory effect of GP on tumor cells.Results Glycyrrhiza polysaccharides signifi-cantly inhibited the proliferation and migration of the highly metastatic human adenoid cystic carcinoma cell line SACC-LM by regulating the expression of epithelial-mesenchymal transition(EMT)-related markers.In vivo experiments showed that glycyrrhiza poly-saccharides had no significant hepatotoxicity,could significantly reduce the volume and weight of tumors,and inhibit the growth rate of tumors in nude mice.Conclusion GP has a certain inhibitory effect on the growth and migration ability of SACC.

Objective:To analyze the changes in the prevalence characteristics of multimorbidity among adolescents aged 13-18 in Inner Mongolia Autonomous Region from 2019 to 2022 and to explore the association between multimorbidity and moderate to high-intensity physical activity among them.Methods:A stratified random cluster sampling method was used to select students aged 13-18 in Inner Mongolia Autonomous Region every September from 2019 to 2022. Physical examinations, demographic characteristics, and depression-related surveys were conducted to analyze the multimorbidity of overweight, obesity, high blood pressure, myopia, spinal curvature abnormality, and depression. A logistic regression model was used to analyze the association between multimorbidity and moderate to high-intensity physical activity.Results:From 2019 to 2022, 70 972, 62 923, 80 254, and 78 288 study subjects were included, with the rates of multimorbidity being 56.4%, 55.4%, 57.2%, and 55.8%, respectively. The rates of multimorbidity remained relatively stable from 2019 to 2022 ( χ2=0.06, P=0.950). The incidence of multimorbidity among girls was significantly higher than that among boys ( P<0.001). The incidence of multimorbidity among urban students was significantly higher than that among suburban students ( P<0.001). The incidence of multimorbidity among high school students was higher than that among middle school students ( P<0.001). The top three multimorbidity combinations were myopia and overweight/obesity (26.4%), myopia and high blood pressure (24.4%), and myopia and depression (19.8%), while the least common combination was depression and spinal curvature abnormality (1.1%). The multimorbidity patterns showed no significant differences between years ( χ2=0.03, P=0.999). The multimorbidity status was significantly associated with the status of meeting the standard of moderate to high-intensity physical activity ( OR=0.83, 95% CI: 0.80-0.86). The association was stronger in boys ( OR=0.77, 95% CI: 0.73-0.81) compared with girls ( OR=0.90, 95% CI: 0.85-0.96), with a significant interaction term ( P<0.001). Conclusion:From 2019 to 2022, the incidence of multimorbidity among adolescents aged 13 to 18 in Inner Mongolia Autonomous Region is relatively high, mainly due to the co-occurrence of myopia and other health problems. Adequate physical activity is an important factor in reducing multimorbidity.

Objective To investigate the correlation between serum TNF super family 15(TNFSF15),growth differentiation factor 11(GDF11)and in-stent restenosis(ISR)in patients with unstable angina pectoris(UAP)undergoing percutaneous coronary intervention(PCI).Methods A total of 350 UAP patients who underwent PCI treatment in the Second Hospital of Qinhuangdao from January 1,2020 to January 1,2021 were collected as observation subjects,and they were separated into non-ISR group(n=246)and ISR group(n=104)based on whether they had experienced ISR.ELISA was applied to determine the levels of serum TNFSF15 and GDF11,ROC curve was applied to analyze the predictive value of serum TNFSF15 and GDF11 levels for postoperative ISR in UAP patients after PCI,and multivariate Logistic regression was used to analyze the factors affecting the occurrence of ISR in UAP patients after PCI.Results Compared with the non-ISR group,the ISR group showed an increase in blood glucose,smoking history and LDL-C levels(t/χ2=22.908,18.869,47.337),as well as elevated serum TNFSF15 levels(16.97±1.51 pg/ml vs 18.35±1.62pg/ml)and GDF11 levels(157.72±16.13pg/ml vs 174.11±18.65 pg/ml)decreased(t=7.429,7.811),and the differences were statistically significant(all P<0.001).The AUC(95%CI)of serum TNFSF15 and GDF11 in dependently and jointly predicting ISR after PCI in UAP patients were 0.764(0.716～0.808),0.781(0.734～0.823)and 0.849(0.807～0.885),respectively,and the joint prediction of the two was higher than the individual prediction(Z=4.365,3.257,all P<0.001).Multivariate Logistic regression analysis of serum TNFSF15,the level of GDF11 was a protective factor for ISR in UAP patients after PCI(Wald χ2=11.000,36.321,all P<0.05).Conclusion The serum levels of TNFSF15 and GDF11 decreased in UAP patients with postoperative ISR after PCI,which have good predictive value for the occurrence of ISR in UAP patients after PCI.