Background Long-term exposure to ambient fine particulate matter (PM_2.5) is a significant risk factor for cardiometabolic disorders. However, the mechanisms of its interaction with the endogenous circadian system remain incompletely understood. Objective To investigate whether chronic PM_2.5 exposure interferes with the rhythmic expression of the cardiac circadian clock, thereby disrupting downstream antioxidant defenses and metabolic homeostasis, and ultimately driving cardiometabolic dysfunction. Methods Seventy-two male C57BL/6 mice were randomly divided into a PM_2.5 exposure group (PM group) and a filtered air control group (FA group). Whole-body exposure was conducted for 8 weeks in a meteorological environmental animal exposure system. Samples were collected at six distinct zeitgeber time (ZT) points post-exposure. The 24 h ambulatory blood pressure and serum lipid profiles were monitored. Rhythm parameters were derived via cosinor analysis to compare differences in Midline statistic of rhythm (Mesor), amplitude, and phase between the two groups. The rhythmic expression of core circadian clock genes and antioxidant genes in the myocardium was detected by quantitative polymerase chain reaction (qPCR). Myocardial reactive oxygen species (ROS) levels and downstream pathway protein expression were analyzed by immunofluorescence and Western blot (WB), respectively. The expression changes of the clock gene retinoic acid receptor-related orphan receptor α (RORα) were assessed at both the mRNA and protein levels. Finally, Spearman correlation analysis was used to explore the relationships among myocardial RORα expression, lipid profiles, and oxidative stress indicators. Results Compared to the FA group, mice in the PM group exhibited a blunted circadian rhythm in blood pressure, characterized by sustained elevation throughout the day. Chronic PM_2.5 exposure showed a significant interaction with ZT on systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial pressure (MAP) (F-interaction=9.11, 5.70, and 6.02, respectively; P<0.05), as well as on serum triglycerides (TG), total cholesterol (T-CHO), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) (F-interaction=16.32, 11.12, 15.39, and 28.09, respectively; P<0.05). Cosinor analysis further revealed that the Mesor values of T-CHO, TG, and LDL-C were significantly increased (P<0.05), while that of HDL-C was significantly decreased in the PM group (P<0.05). The oscillation amplitudes of SBP, DBP, and MAP showed a decreasing trend, whereas those of TG and LDL-C were significantly increased (P<0.05). Furthermore, SBP, T-CHO, and HDL-C all exhibited a significant phase delay (P<0.05). Mechanistically, PM_2.5 exposure significantly suppressed the expression of the positive circadian regulator RORα in the myocardium, leading to disordered rhythmic expression of core clock genes (Bmal1, Clock, Per1/2, and Cry1/2). This exposure also inhibited the rhythmic expression of antioxidant genes (GPX1, SOD2, and CAT), resulting in increased ROS generation and elevated expression of calcium/calmodulin-dependent protein kinase II (CaMKII) and reduced nicotinamide adenine dinucleotide phosphate (NADPH) proteins. Correlation analysis further revealed that myocardial RORα expression level was negatively correlated with T-CHO, TG, and LDL-C (r=−0.55, −0.63, and −0.51, respectively; P<0.001), and positively correlated with HDL-C (r=0.37, P=0.010), and antioxidant genes GPX1, SOD2, and CAT expression (r=0.34, 0.35, and 0.56, respectively; P < 0.001). Conclusion Chronic PM_2.5 exposure induces cardiometabolic dysfunction by suppressing myocardial RORα expression. This suppression disrupts the cardiac circadian clock and the diurnal balance of oxidative stress, triggering oxidative damage and elevating expression of CaMKII/NADPH pathway proteins. Collectively, these alterations precipitate the loss of cardiac metabolic rhythms and subsequent functional impairment.

Objective: To investigate the current status of healthy school construction in public junior and senior high schools of Yinchuan, so as to provide data support and practical references for the optimized development of healthy school construction. Methods: In March 2026, a total of 60 schools (senior high school, urban junior high school and rural junior high school) in Yinchuan City, were selected combining stratified random sampling and convenience sampling methods. The survey was conducted using the "Reference Standards for Healthy School Construction in Primary and Secondary Schools and Kindergartens", comprising 16 indicators across three dimensions: indicator based, guarantee based, and measure based categories. Data were collected through on site inspections and document reviews. The compliance rates of various school types across different dimensions and indicators were calculated, and between group comparisons were performed using the Chi-square test. Results: A total of 28 public junior and senior high schools (46.7%) met the "healthy school" standard. The compliance rates for senior high schools, urban junior high schools and rural junior high schools were 61.1%, 53.8%, and 18.8%, respectively, with statistically significant differences ( χ 2=16.28, P <0.01). The overall compliance rates for indicator based, guarantee based, and measure based standards were 51.7%, 66.7%, and 63.3%, respectively, with statistically significant differences ( χ 2=18.42, P < 0.01 ). The compliance rates across all 16 indicators within the three dimensions differed significantly among different types of schools ( χ 2=6.32-26.47, all P <0.05), consistently showing a pattern of senior high schools > urban junior high schools > rural junior high schools. Conclusions The overall compliance of healthy school construction in public junior and senior high schools in Yinchuan City is suboptimal, with significant disparities across school types and unbalanced development across dimensions. Rural junior high schools exhibit notable deficiencies in healthy school construction.

In recent years, the incidence of dry eye disease(DED)is increasing, positioning it as one of the most prevalent diseases affecting the ocular surface. Inflammatory response is the pathological basis of DED, involving various inflammatory mediators and inflammatory signaling pathways. Consequently, anti-inflammatory treatment emerges as a fundamental strategy for preventing and managing DED. This review summarizes the classic inflammatory factors involved in the development and progression of DED, including interleukins, tumor necrosis factor, matrix metalloproteinases, chemokines, and cell adhesion molecules. It also discusses the relevant inflammatory signaling pathways: the MAPKs pathway, NF-κB pathway, Wnt pathway and TLR pathway. Additionally, this review addresses the mechanisms of action and alterations in relevant biomarkers associated with current first-line recommended anti-inflammatory therapies, including corticosteroids, immunosuppressants, nonsteroidal anti-inflammatory drugs, and traditional Chinese medicine approaches to inflammation management. This comprehensive overview aims to enhance understanding of the inflammatory mechanisms underlying DED while exploring future therapeutic prospects.

In recent years, the incidence of dry eye disease(DED)is increasing, positioning it as one of the most prevalent diseases affecting the ocular surface. Inflammatory response is the pathological basis of DED, involving various inflammatory mediators and inflammatory signaling pathways. Consequently, anti-inflammatory treatment emerges as a fundamental strategy for preventing and managing DED. This review summarizes the classic inflammatory factors involved in the development and progression of DED, including interleukins, tumor necrosis factor, matrix metalloproteinases, chemokines, and cell adhesion molecules. It also discusses the relevant inflammatory signaling pathways: the MAPKs pathway, NF-κB pathway, Wnt pathway and TLR pathway. Additionally, this review addresses the mechanisms of action and alterations in relevant biomarkers associated with current first-line recommended anti-inflammatory therapies, including corticosteroids, immunosuppressants, nonsteroidal anti-inflammatory drugs, and traditional Chinese medicine approaches to inflammation management. This comprehensive overview aims to enhance understanding of the inflammatory mechanisms underlying DED while exploring future therapeutic prospects.

Objective To propose a novel method for verifying the isocenter in radiotherapy based on markers and conduct a preliminary test. Methods A feasibility experiment was conducted on wooden box phantom for radiotherapy resetting. Fifteen groups of displacement data were randomly generated,corresponding to the position deviations of the isocenter in the radiotherapy plan relative to the original isocenter. According to each set of displacement data,with the aid of movable lasers and a CT scanning couch,CT scanning was performed with two sets of markers (3 per set) affixed to the phantom which were corresponding to the original and treatment isocenters,respectively. In the Eclipse treatment planning system,the coordinate data of the original and treatment isocenters were manually verified,and the difference of coordinate data was calculated to obtain the actual displacement value. The treatment isocenter position was finally confirmed by comparing with the actual displacement. In addition,the study attempts to use threshold segmentation algorithm to automatically detect metal markers and obtain coordinate values of the original isocenter on patient-positioned CT images. In the wooden box experiment,the absolute value of the difference between the actual displacement value and the planned displacement value (?d) was used to represent the position accuracy of treatment isocenter,and the deviation value obtained with threshold segmentation algorithm for isocenter detection was ?s. Results The ?d in the X (left-right),Y (superior-inferior) and Z (anterior-superior) directions was (0.83±0.37) mm,0 (0,0.5) mm and (0.45±0.29) mm,respectively. The ?s in the X,Y and Z directions was (0.46±0.22) mm,0 (0,0.5) mm and (0.33±0.29) mm,respectively. The mean values of ?s in 3 directions were all lower than 2 mm,within the range of permissible clinical positioning error. Conclusion The method of automatically verifying treatment isocenter position based on markers is feasible,and the study provides a useful reference for radiotherapy resetting using CT simulator.

Objective Network pharmacology and molecular docking technology were used to analyze the potential mechanism of Sinisan(SNS)in the treatment of adolescent depression,and the relevant results were verified by experiments.Methods Through the TCMSP and ETCM databases,the effective chemical components and targets of SNS(Chaihu,Zhishi,Baishao and Gancao)were screened,and the main targets of adolescent depression were screened in the GeneCards and OMIM databases,and the common targets of drugs and disease were obtained by Venn diagram.Cytoscape 3.9.1 software was used to draw the Chinese herb-active ingredient-target action network of SNS.The STRING platform was used to construct a portein-protein interaction network(PPI)of drug-disease-common targets,and the core targets were obtained after screening.The Metascape platform was used to perform enrichment analysis of core targets.Molecular docking was carried out through the software AutoDockTools 1.5.7 to evaluate the binding ability of effective active ingredients to potential core targets.Western blotting(WB)experiments were used to verify the potential targets of SNS against adolescent depression.Results The core effective active ingredients of SNS in the treatment of adolescent depression include quercetin,kaempferol,isorhamnetin,paeoniflorin,etc.,and the potential core targets including AKT1,IL-6,PPARG,PTGS2,F7,etc.,were identified through PPI network topology analysis.The molecular docking results showed that the active substance had strong binding activity to its main target.WB experiments verified that AKT1,IL-1B and IL-6 were potential targets related to anti-adolescent depression.The main biological processes of PPI network four inverse dispersion in the treatment of adolescent depression include hormone response,and the main signaling pathways regulated such as AGE-RAGE and PI3K-AKT signaling pathway.Conclusion This study preliminarily confirmed the effective active ingredients and target information of SNS treatment in adolescent depression,and revealed the potential mechanism of SNS in the treatment of adolescent depression.

Objective Network pharmacology and molecular docking technology were used to analyze the potential mechanism of Sinisan(SNS)in the treatment of adolescent depression,and the relevant results were verified by experiments.Methods Through the TCMSP and ETCM databases,the effective chemical components and targets of SNS(Chaihu,Zhishi,Baishao and Gancao)were screened,and the main targets of adolescent depression were screened in the GeneCards and OMIM databases,and the common targets of drugs and disease were obtained by Venn diagram.Cytoscape 3.9.1 software was used to draw the Chinese herb-active ingredient-target action network of SNS.The STRING platform was used to construct a portein-protein interaction network(PPI)of drug-disease-common targets,and the core targets were obtained after screening.The Metascape platform was used to perform enrichment analysis of core targets.Molecular docking was carried out through the software AutoDockTools 1.5.7 to evaluate the binding ability of effective active ingredients to potential core targets.Western blotting(WB)experiments were used to verify the potential targets of SNS against adolescent depression.Results The core effective active ingredients of SNS in the treatment of adolescent depression include quercetin,kaempferol,isorhamnetin,paeoniflorin,etc.,and the potential core targets including AKT1,IL-6,PPARG,PTGS2,F7,etc.,were identified through PPI network topology analysis.The molecular docking results showed that the active substance had strong binding activity to its main target.WB experiments verified that AKT1,IL-1B and IL-6 were potential targets related to anti-adolescent depression.The main biological processes of PPI network four inverse dispersion in the treatment of adolescent depression include hormone response,and the main signaling pathways regulated such as AGE-RAGE and PI3K-AKT signaling pathway.Conclusion This study preliminarily confirmed the effective active ingredients and target information of SNS treatment in adolescent depression,and revealed the potential mechanism of SNS in the treatment of adolescent depression.

Objective:To evaluate the value of D-dimer(D-D) levels in the diagnosis of thromboembolism in children with severe Mycoplasma pneumoniae pneumonia (SMPP).Methods:A case control study was conducted on 51 SMPP patients admitted to Qingdao Women and Children′s Hospital Affiliated to Qingdao University and Jining First People′s Hospital from January 1, 2021 to August 1, 2024.They were divided into a thrombus group (19 cases) and a non-thrombus group (32 cases) according to whether they had thromboembolism.The characteristics of the cases were analyzed.Logistic regression was used to analyze the relationship between increased D-D levels and the risk of thrombosis.The value of D-D levels in predicting thromboembolism in SMPP patients was evaluated by the receiver operating characteristic curve.Results:Of the 19 patients with thrombosis, 11 had with pulmonary thrombosis, 6 had cerebrovascular thrombosis, 3 had heart thrombosis, 1 had spleen artery thrombosis, and 3 had multiple site thrombosis.Compared with the non-thrombus group, the thrombus group had higher D-D levels[(18.5±4.9) mg/L vs.(3.1±0.8) mg/L, t=3.118, P=0.006], higher C-reactive protein levels[25.5(15.5, 92.7) mg/L vs.7.9(3.9, 21.4) mg/L, Z=3.292, P=0.001], higher lactate dehydrogenase levels[484(351, 743) U/L vs.347(285, 396) U/L, Z=2.770, P=0.006] and a higher proportion of pleural effusion[63.1%(12/19) vs.25.0%(8/32), χ2=7.282, P=0.009].Increased D-D levels were an independent risk factor for thromboembolism in SMPP patients ( P=0.005, OR=1.254, 95% CI: 1.069-1.472).When the D-D level was used for predicting thromboembolism in SMPP patients, its cut-off value was 4.46 mg/L, its Youden index was 0.707, its area under the curve was 0.893(95% CI: 0.807-0.979), its sensitivity was 89.5%, its specificity was 81.2%, and its negative predictive value was 92.9%. Conclusions:D-D levels have high value in predicting thromboembolism in SMPP patients, and it can help timely identify patients at high risk.

Objective:To explore the impact of the two-way referral model on compliance and prognosis in patients with heart failure.Methods:This bidirectional cohort study enrolled chronic heart failure (CHF) patients treated at Qilu Hospital of Shandong University or designated primary hospitals between March 2018 and March 2022. Patients were categorized into two groups based on referral status: two-way referral group (participating in the referral model with≥1 follow-up visit at primary hospitals) and the core hospital group (receiving treatment and follow-up exclusively at Qilu Hospital). Baseline clinical characteristics were collected and compared between groups. Patients underwent followed-up, with primary endpoints including follow-up rate, drug (β-blockers, angiotension converting enzyme inhibitor (ACEI)/angiotensin Ⅱ receptor blockers (ARB)/angiotensin receptor-neprilysin inhibitor (ARNI), sodium-glucose cotransporter 2 inhibitors and mineralocorticoid receptor antagonists) utilization rate and target dose achievement rate. Secondary endpoints encompassed changes from baseline in left ventricular ejection fraction (LVEF), left ventricular end-diastolic diameter (LVEDd), and N-terminal pro-brain natriuretic peptide (NT-proBNP), plus cardiovascular mortality and heart failure rehospitalization. Generalized linear mixed models analyzed longitudinal trends in LVEF, LVEDd, and NT-proBNP levels. Kaplan-Meier curves and Cox regression evaluated LVEF recovery rates, supplemented by subgroup analyses. Multivariate logistic regression was used to identify factors influencing target dose achievement rate for β-blockers and ACEI/ARB/ARNI therapies in CHF patients.Results:A total of 357 patients were enrolled, aged 53 (41, 63) years, including 256 males (71.7%). 157 patients were in the two-way referral group and 200 patients in the core hospital-treated group. Compared with the core hospital-treated group, the two-way referral group had lower baseline LVEF (28 (22, 34)% vs. 31 (23, 36)%, P=0.021) and systolic blood pressure (116 (104, 125) mmHg vs. 121 (109, 134) mmHg (1 mmHg=0.133 kPa), P=0.010). The 12-month follow-up rate of the two-way referral group was higher than the core hospital-treated group (73.8% vs. 56.0%, P=0.004). No significant between-group differences were observed in drug utilization rate of β-blockers, ACEI/ARB/ARNI, or sodium-glucose cotransporter 2 inhibitors during follow-up (all P>0.05), while mineralocorticoid receptor antagonists use showed a declining trend in both groups. Although the core hospital-treated group had higher target dose achievement rates for β-blockers (65.4% vs. 49.3%, P=0.042) and ACEI/ARB/ARNI (79.8% vs. 65.8%, P=0.046) than the two-way referral group, multivariate logistic regression indicated that the two-way referral model was not a negative predictor for these outcomes (all P>0.05). Both groups showed improved NT-proBNP, LVEDd, and LVEF from baseline (all P<0.001) with no significant difference in trends between groups (all P>0.05). There was no significant difference in the composite incidence (7.6% vs. 6.5%, P=0.674) and cumulative incidence (log-rank P=0.684) of cardiovascular death and heart failure rehospitalization at 12 months between two groups. Conclusion:The two-way referral model demonstrates advantages in improving medication adherence, drug utilization rates, and targetdoseachievement rates among CHF patients. This model not only promotes cardiac functional recovery but also reduces risks of cardiovascular mortality and heart failure rehospitalization, achieving comparable therapeutic and management outcomes to those observed in core hospital-treated patients.

Objective This study examines the factors influencing oral frailty in the elderly community,develops a risk prediction model,and validates its efficacy,so as to provide references for identifying and preventing oral weakness in the elderly.Methods 556 elderly individuals from 4 communities were selected by convenience sampling from June to August 2024 in Zigong City Sichuan Province.They were randomly divided into a training group(383 cases)and a validation group(165 cases).Data were collected by a general information questionnaire,Social Frailty Scale,Geriatric Depression Scale,and the Oral Frailty Index-8 screening tool.Logistic regression was used to determine the influencing factors,and R software was used to establish a nomogram model for predicting the risk of oral frailty.Bootstrap method and the validation group were used for internally validation of the model.Calibration curve was used to evaluate the prediction performance of the model.Results 548 valid questionnaires were collected.The final model variables included whether the age ≥80 years,wearing removable dentures,reduced frequency of going out,brushing teeth less than twice a day,frequent dry mouth,increased difficulty in eating hard foods,and choking.The area under the receiver operating characteristic curve of the training group was 0.95(95％CI:0.93～0.97),and the best cutoff value was 0.687.The model achieved an accuracy of 87％,sensitivity of 91％,specificity of 85％,positive predictive value of 0.75,and negative predictive value of 0.95.The Hosmer-Lemeshow fitting test show that x2=3.036,P=0.932,indicating a good model fit.Conclusion The oral frailty prediction model demonstrated a good discrimination,calibration,and clinical utility,which can provide a scientific basis for the prevention and early screening of oral frailty in the elderly.