Based on the theory of "disease of both blood and water" in Essentials from the Golden Cabinet （《金匮要略》）， and in combination with the dynamic syndrome evolution of heart failure with preserved ejection fraction （HFpEF）， this paper systematically clarifies the pathomechanism of HFpEF， characterized by yang deficiency as the root， blood stasis as the pivotal factor and water retention as the manifestation. Accordingly， the therapeutic principles have been proposed， which are warming yang and banking up original qi to consolidate the root， activating blood and unblocking collaterals to smooth the mechanism， and promoting urination and regulating pivot to remove the branch. On this basis， a compound formula structure of "one monarch， one minister and one assistant" is established， forming an integrated intervention strategy that synergistically combines the three methods of warming yang， activating blood， and promoting urination through combined classical formulas. Zhenwu Decoction （真武汤）， which warms yang and dissolves rheum， is used to consolidate the root and directly target the source of yang deficiency， serving as the monarch； Guizhi Fuling Pills （桂枝茯苓丸）， which activates blood， promotes urination and unblocks the pivot， assists in interrupting the binding of blood stasis and water retention， serving as the minister； Tingli Dazao Xiefei Decoction （葶苈大枣泻肺汤）， which regulates qi， disperses retained fluids， and eliminates the manifestation， alleviates acute water-retention symptoms， serving as the assistant. This compound formula is warming without being drying， diuretic without being drastic， and dispels stasis without consuming blood， thereby achieving the therapeutic effects of warming yang， activating blood， and promoting urination.

Objective: To explore the interaction between school bullying and insomnia in relation to depression-anxiety-stress emotions among primary and secondary school students,so as to provide a basis for preventing negative emotional states in adolescents. Methods: In October 2024, a stratified cluster sampling method was used to select 3 058 students in grade 5-6 of primary, junior and senior high school in Sheyang County of Jiangsu Province. The Delaware Bullying Victimization Scale, Insomnia Severity Index, Depression-Anxiety-Stress Scale-21, and Study Condition Questionnaire were employed to investigate school bullying, insomnia, depression-anxiety-stress emotions, and academic performance. The χ 2 test and Logistic regression were used to analyze the association between school bullying and insomnia interactions and depression-anxiety-stress emotions among primary and secondary school students, multiplicative interaction analysis was conducted, and additive interaction analysis was performed using R software. Results: The detection rates of depression-anxiety-stress emotions among primary and secondary school students were 21.6%, 28.4% and 10.8%, respectively. The detection rates of physical bullying, relationship bullying, verbal bullying and cyberbullying in school bullying were 10.6%, 14.0%, 22.3%, and 6.2%, respectively. The detection rate for insomnia was 23.1%. Results from Logistic regression analysis showed that, after adjusting for relevant factors, physical, relational, verbal, and cyberbullying and insomnia were positively correlated with the detection rates of depression ( OR = 5.72- 10.93), anxiety ( OR =6.35-12.17), and stress emotions ( OR =5.97-14.52) among primary and secondary school students (all P <0.01). The multiplicative interaction between physical, relational, verbal, and cyberbullying and insomnia was positively correlated with the detection rates of depression ( OR =8.00-18.01), anxiety ( OR =11.35-17.76), and stress emotions ( OR =7.64-9.12) in primary and secondary school students (all P <0.01). Additive interactions were observed between physical, relational, verbal, and cyberbullying and insomnia in relation to the detection rates of depression, anxiety, and stress emotions among primary and secondary school students (both RERI and AP >0 and the credible interval excluded 0, SI >1 and the credible interval excluded 1). Conclusion School bullying and insomnia are associated with depression, anxiety, and stress emotions among primary and secondary school students, and they exhibit both multiplicative and additive interactions.

ObjectiveZheng’s San Qi San (ZSQS) power, a classic traditional Chinese medicine (TCM) formula, is used for treating soft tissue injuries involving muscles, tendons, and ligaments. However, its underlying therapeutic mechanisms remain unclear. This study aimed to screen and identify pharmaceutically active ingredients and their candidate biomolecule targets, and further elucidate the molecular mechanism of ZSQS in the treatment of skeletal muscle injury. MethodsNetwork pharmacology was employed to construct “ZSQS-component-target”, “protein-protein interaction (PPI)” and “active ingredient-core protein-pathway” networks to predict the key active ingredients and potential core targets of ZSQS for skeletal muscle injury. The predicted results were then validated via microarray data from the GEO database. Molecular docking was then performed to assess the binding ability between the screened active ingredients of ZSQS and the candidate core targets. Moreover, liquid chromatography-mass spectrometry (LC-MS) was used for qualitative and quantitative analysis to verify the active components of the drug and ZSQS serum. Finally, an animal model of eccentric exercise-induced skeletal muscle injury and a myotube cell model of oxidative stress-induced injury were established to validate the effects of ZSQS and its interventional effects on the biological functions of critical targets, thereby demonstrating the potential therapeutic mechanism of ZSQS. ResultsAmong the 111 active components identified in ZSQS and their corresponding 204 targets related to the skeletal muscle injury repair process, 14 core targets (including AKT1) and 4 core active components (quercetin, luteolin, kaempferol, and β‑sitosterol) were screened out, while the corresponding metabolites of quercetin, luteolin and kaempferol were detected in the ZSQS serum. Among these targets, 5 candidate genes (IL-6, CASP3, HIF1A, STAT3, and JUN) overlapped with the differential expression screening results with GEO data, and IL-6 was confirmed to be enriched in the PI3K/AKT pathway. Combined with the prediction results of the AKT expression levels, these findings suggest that the phosphorylation level of AKT1 plays a core role in the therapeutic mechanism of ZSQS. Molecular docking analysis further revealed that the PH domain of AKT1 had high binding energy with all 4 core active components, as verified by LC-MS. Finally, animal model studies have shown the promoting effect of ZSQS administration on skeletal muscle injury repair and its possible antioxidant damage mechanism. Cell model studies further demonstrated that ZSQS-containing serum, core active ingredient combination therapy, and quercetin monomer could increase the phosphorylation level of AKT, promote the nuclear translocation of Nrf2, upregulate the expression of downstream antioxidant enzymes (SOD, GPx, and GR), and inhibit the expression of inflammatory factors (IL-6 and TNF-α), thereby alleviating oxidative stress and the inflammatory response. ConclusionZSQS alleviates skeletal muscle injury mainly by activating the AKT/Nrf2 signaling pathway, enhancing cellular antioxidant and anti-inflammatory capabilities. The results of this study provide a scientific basis for the clinical application and modernized development of ZSQS.

Objective: To explore the developmental trajectories of depression in children and adolescents and their association with family types, and to analyze the role of being an only child in the context, so as to provide a basis for early identification of mental health issues in children and adolescents. Methods: The study was a secondary analysis based on the existing database of the Jiangsu Provincial Student Common Diseases and Health Influencing Factors Monitoring and Intervention Project. A total of 11 502 students who had completed at least two measurements using the Chinese version of the Center for Epidemiologic Studies Depression Scale (CES-D) between 2022 and 2024, and had complete information on family type, gender, and age, were selected as the study subjects. Latent class trajectory modeling was used to identify depression developmental trajectories. Multinomial Logistic regression was applied to analyze the association between family type and depression developmental trajectories, and the interaction effect of family type and being an only child was tested. Results: Three types of depression developmental trajectories were identified among children and adolescents: low stable type (91.3%, 10 504 students), moderate rising type (4.3%, 500 students), and high declining type (4.3%, 498 students). Significant differences were observed among the different trajectory groups in terms of gender, age, parental education level, family type, baseline CES-D score, and baseline school type ( χ 2/H=17.48, 139.97, 19.72 , 30.77, 1 081.35, 220.81, all P <0.05). Multinomial Logistic regression analysis showed that, using the low stable type as the reference trajectory group and the nuclear family as the reference family type, after adjusting for confounding factors such as gender, age, and parental education level, single parent families ( OR=1.87, 95%CI= 1.16-3.03) and grandparent headed families ( OR=1.83, 95%CI =1.04-3.21) were significantly associated with the high declining type trajectory (both P <0.05). No significant association was found between family type and the moderate rising type trajectory (all P >0.05). The interaction effect between family type and being an only child was not statistically significant ( LRT=7.71, df=8, P =0.46). Conclusions Depressive symptoms in children and adolescents show heterogeneous developmental patterns during school age. Children and adolescents from single parent and intergenerational families are more likely to follow the high decreasing trajectory.

Objective: To explore the independent and interactive effects of school green space exposure and outdoor activity duration on screening myopia among primary and secondary school students, so as to provide theoretical support for the prevention and control of screening myopia in children and adolescents. Methods: From September to November 2023, 117 487 primary and secondary school students from 497 schools were selected using a cluster random sampling method, covering 98 counties (cities, districts) in Jiangsu Province. Data on the students screening myopia status and associated health influencing factors were collected and analyzed. School green space exposure was quantified using the normalized difference vegetation index (NDVI), which was extracted with ArcGIS Pro software; meanwhile, information on students outdoor activity duration was gathered through self reported questionnaires. Multivariate Logistic regression was applied to assess the independent and interactive effects of green space exposure and outdoor activity duration on screening myopia among primary and secondary school students. Results: Univariate analysis showed that there were statistically significant differences in screening myopia detection rates among primary and secondary school students of different genders, NDVI groups, every outdoor activity duration, monitoring points, school stages, parents educational level, and whether they lived on campus or had parents with screening myopia ( χ 2=88.91-1 950.08, all P <0.05); as the school age and sedentary time increased, the detection rate of screening myopia in primary and secondary school students also increased ( χ 2 trend =8 410.15, 2 028.91, both P <0.05). Independent effects showed that compared to the low NDVI group, the medium and high NDVI groups had lower risks of screening myopia ( OR =0.93, 0.95, both P <0.05). Compared to those with outdoor activity duration<2 h/d, students with outdoor activity duration≥2 h/d had a lower risk of screening myopia ( OR =0.96, P <0.05). When stratified by school level, compared to the low NDVI group, the medium NDVI group had lower risks of screening myopia in primary and junior high schools (primary school: OR =0.91; junior high school: OR =0.88, both P <0.05). Compared to those with outdoor activity duration<2 h/d, junior high school students with outdoor activity duration≥2 h/d had a lower risk of screening myopia ( OR = 0.90, P <0.05). When stratified by monitoring site, urban primary and secondary school students in the medium and high NDVI groups and those with outdoor activity duration≥2 h/d had lower risks of screening myopia ( OR =0.92, 0.92, 0.93, all P <0.05). Interactive effects showed that when medium or high NDVI was combined with outdoor activity duration≥2 h/d, the risks of screening myopia among primary and secondary school students were lower (medium NDVI×≥2 h/d: OR =0.89; high NDVI×≥ 2 h/d : OR =0.89, both P <0.05), and the combined effect was superior to that of a single factor. Conclusion Green space exposure and outdoor activity duration have negative correlations with screening myopia among primary and secondary students, and the combined effect is better than that of a single factor.

Objective: To investigate the association between outdoor light at night (LAN) exposure and sleep quality among primary and secondary school students, and to examine the pathways of negative affects including depressive, stress and anxiety symptoms, so as to provide a theoretical basis for optimizing the school environment and enhancing the physical and mental well being of students. Methods: In December 2024, a total of 36 885 students from 154 primary and secondary schools in Suzhou, Nantong, and Changzhou were included via a stratified cluster sampling method. Sleep quality and negative affect were assessed by using the Pittsburgh Sleep Quality Index (PSQI), Center for Epidemiologic Studies Depression Scale (CES-D), Generalized Anxiety Disorder-7 (GAD-7), and Depression, Anxiety and Stress Scale-21 (DASS-21), respectively. Outdoor LAN exposure data were obtained from the national polar orbiting partnership visible infrared imaging radiometer suite nighttime light(NPP-VIIRS NTL) dataset provided by the National Earth System Science Data Center. Multivariate Logistic regression model was employed to analyze the association between LAN exposure and sleep quality across different regions, with stratification by monitoring site. Spearman correlation analysis was used to examine the relationships between LAN, negative affect, and sleep quality. The mediating role of negative affect was tested by using Model 4 of the PROCESS macro. Results: The detection rates among students were 13.95%( n =5 147) for depressive symptom, 16.72%( n =6 166) for stress symptom, and 17.49%( n =6 451) for anxiety symptom. The median outdoor LAN exposure was 28.85(19.10, 41.44)nW/(cm 2 · ( sr). After adjusting for confounders, multivariate Logistic regression analysis showed that high LAN exposure ( Q 4) was positively associated with sleep problems (urban areas: OR =1.28, 95% CI = 1.17- 1.41; rural areas: OR =1.21, 95% CI =1.07-1.36; both P <0.05). Spearman correlation analysis revealed significant positive correlations between LAN exposure, depressive symptoms, stress symptoms, anxiety symptoms, and sleep quality ( r =0.03-0.75, all P < 0.01). The mediation analysis indicated that all dimensions of negative affect significantly mediated the relationship between high LAN exposure and poor sleep quality (all P <0.01). Specifically, the indirect effects were 0.03 (95% CI =0.02-0.05) for depressive symptom, 0.05(95% CI =0.03-0.08) for stress symptom, and 0.07(95% CI =0.05-0.09) for anxiety symptom. Overall, 31.9% of the total effect was mediated by negative affect, with anxiety (14.89%) being the strongest mediator, followed by stress (10.64%) and depression(6.38%). Conclusion Reducing high levels of outdoor LAN exposure and implementing interventions targeting negative affect may contribute to improved sleep quality among primary and secondary school students.

Aim To study whether intravenous injec-tion of miR-129-3p mimetic(agomir)can resist bone loss caused by hind limb disuse,and to provide new i-deas for preventing bone loss in microgravity environ-ment.Methods Forty-eight C57BL/6J male mice were randomly divided into the control group(CON),tail suspension model group(TS),tail suspension+miR-129-3p agomir administration group(miRNA)and tail suspension+miR-129-3p negative sequence agomir control group(NC).The miRNA group was given 4 mg·kg-1 miR-129-3p agomir by intravenous injection into the medial canthus twice a week.The NC agomir group were consistent with those in the miR-129-3p agomir group,and the CON and TS groups were given only equal volumes of normal saline.After four weeks,all mice were sacrificed and samples were collected.Micro-CT scan of femur,three-point femur bending test,serum bone metabolism index detection,oxidative stress index detection and osteogenesis-related protein expression analysis in bone tissue were per-formed.Results After four weeks,the number of tra-becular bone in the TS group was significantly re-duced,and Tb.BMD,Tb.Th,Tb.N,Tb.BS/TV and Tb.BV/TV were significantly lower than those in the CON group(P＜0.01).While Tb.Sp TS group was significantly higher than the CON group(P＜0.05),the maximum load and flexural strength of the femur significantly decreased(P＜0.01),the content of ser-um bone formation index PINP was significantly lower than that of the CON group(P＜0.01),and the con-tent of bone resorption index CTX-I was significantly higher than that of the CON group(P＜0.01),the content of serum oxidative damage indexes 8-iso-PGF2α and 8-OHdG significantly increased(P＜0.01),and the expression of osteogenesis-related pro-teins in bone tissue markedly decreased(P＜0.01).However,the increase or decrease of all indexes in miRNA group was significantly lower than that in TS group.Conclusions miR-129-3p mimetic can signifi-cantly reduce bone loss caused by hind limb disuse.This experiment provides a new idea and method for preventing bone loss in microgravity environment.

Objective:To describe the prevalence of anxiety disorders and its distribution in Inner Mongolia Autonomous Region,and to explore the relevant factors of anxiety disorders.Methods:From June 2019 to Decem-ber 2019,representative multi-stage disproportionate stratified sampling procedure was used to sample in residents aged 18 and over in the Inner Mongolia Autonomous Region.All respondents were face-to-face interviewed by trained interviewers.Composite International Diagnostic Interview-3.0(CIDI-3.0)was used to diagnose anxiety disorders according to the criteria and definition of the Diagnostic and Statistical Manual of Mental Disorders,Fourth Edition(DSM-Ⅳ).Chi-square test and multivariate logistic regression analysis were used for statistical anal-ysis.Results:Totally 12 315 people were interviewed in the survey.The weighted 12-mouth prevalence rate of any anxiety disorder was 4.64％,and the lifetime prevalence rate was 6.25％.The weighted 12-month prevalence rate of anxiety disorders was higher in female than that in male(5.38％vs.3.92％).The rate was higher in rural resi-dents than that in urban residents(5.67％vs.3.95％).The rate was higher in people with chronic diseases than that in people without chronic diseases(6.81％vs.2.29％).Logistic regression analysis showed that unmarried(OR=2.32,95％CI:1.31-4.10),separated/divorced(OR=2.49,95％CI:1.33-4.67),in debt(OR=1.55,95％CI:1.04-2.32),chronic disease(OR=2.22,95％CI:1.39-3.53),family history of anxiety disorders(OR=12.05,95％CI:8.78-16.53),poor sleep(OR=2.64,95％CI:1.97-3.54)were risk factors of occurrence of anxiety disorders,while junior high school(OR=0.65,95％CI:0.44-0.96)was protective factor of anxiety disor-ders.Conclusion:Adults with chronic diseases,poor sleep,unmarried or separated/divorced,family history of anxi-ety disorders,and financial debt are at higher risk groups of anxiety disorder in Inner Mongolia Autonomous Re-gion.

This study was aimed at investigating the effects of demethylase fat mass and obesity-associated protein(FTO)and methyltransferase methyltransferase like protein 3(METTL3),key molecules in N6-methyladenosine(m6A)modification,on the replication and proliferation of Japanese encephalitis virus(JEV).Recombinant lentiviruses were generated by packaging the FTO and green fluorescent protein into lentiviral vectors.Neuro2a cells,a mouse neuroblastoma cell line,were infected with the lentivirus,and stable FTO-expressing cell lines were obtained through puromycin selection.Successful overexpression of FTO was confirmed through fluorescence microscopy,real-time quantitative PCR,and western blot analysis.When Neuro2a cells overexpressing FTO were infected with JEV,the overexpression of FTO decreased JEV replication in the cells,and increased the expression of interferon(IFN)and related molecules.Additionally,treatment of JEV-infected Neuro2a cells with the METTL3-specific inhibitor STM2457 resulted in a dose-dependent decrease in JEV replication and viral protein expression.These findings suggested that lowering m6A methylation levels inhibits JEV replication,thus shedding light on the regulatory role of methylation modification in JEV replication.