AIM: To investigate and analyze serum nitric oxide synthase 4(NOX4)and matrix metalloproteinase(MMP)-2 expressions in patients with diabetes mellitus(DM)complicated with neovascular glaucoma(NVG)and their clinical significance.METHODS: A prospective study was conducted on 161 patients with DM complicated with NVG admitted to Handan City Eye Hospital(The Third Hospital of Handan)from June 2020 to June 2023. Based on whether complications occurred 1 a after trabeculectomy in the study group patients, they were divided into a group with good prognosis(n=90)and a group with poor prognosis(n=71). During the same period, 161 patients with chronic angle-closure glaucoma without iris neovascularization were selected as the control group. ELISA method was applied to detect the expression levels of serum NOX4 and MMP-2. ROC curve was plotted to evaluate the diagnostic value and postoperative complication prediction value of NOX4 and MMP-2 in patients with DM complicated with NVG. Pearson method was applied to analyze the correlation of NOX4 and MMP-2 with vascular endothelial growth factor(VEGF)and interleukin-6(IL-6). Multivariate Logistic regression was applied to analyze the influencing factors of postoperative complications in the study group.RESULTS:The general information of the study group and control group of patients is comparable. Compared with the control group, the expression levels of serum NOX4, MMP-2, VEGF, and IL-6 in the study group were significantly increased(P<0.001). According to Pearson analysis, serum NOX4 and MMP-2 levels significantly positively correlated with VEGF and IL-6 levels, respectively(P<0.001). According to ROC curve, the AUC of NOX4 combined with MMP-2 in the diagnosis of DM complicated with NVG was better than that of individual diagnosis of NOX4(Z=3.341, P<0.05)and MMP-2(Z=2.788, P<0.05). The duration of DM, the proportion of people with intraocular pressure >21 mmHg, and the expression levels of NOX4, MMP-2, VEGF, and IL-6 in the poor prognosis group were all higher than those in the good prognosis group(P<0.001). The duration of DM, intraocular pressure >21 mmHg, the levels of NOX4, MMP-2, VEGF, and IL-6 were all risk factors for poor prognosis in DM patients with NVG(P<0.001). According to ROC curve, the combined prediction of NOX4 and MMP-2 for postoperative complications in patients with DM complicated by NVG was superior to the AUC predicted by NOX4(Z=3.727, P<0.05)and MMP-2(Z=2.219, P<0.05), respectively.CONCLUSION:NOX4 and MMP-2 are upregulated in the serum of patients with DM complicated by NVG. Combined detection of these two markers holds significant clinical value for the early diagnosis and prognosis of patients with DM complicated by NVG.

ObjectiveTo explore the mechanism by which Sini San （SNS） inhibits ferroptosis， alleviates inflammation and myocardial injury， and improves myocardial infarction （MI）. MethodsThe active ingredients of SNS were obtained by searching the Traditional Chinese Medicine System Pharmacology Platform （TCMSP） database， its target sites were predicted using the SwissTargetPrediction Database， and the core components were screened out using the CytoNCA plug-in. The targets of MI and ferroptosis were obtained by using GeneCards， Online Mendelian Inheritance in Man （OMIM） database， DrugBank， Therapeutic Target Database （TTD）， FerrDb database and literature review， respectively. The intersection of these targets of SNS-MI-ferroptosis was plotted as a Venn diagram. The protein-protein interaction （PPI） network was constructed using the STRING database， and the visualization graph was prepared using Cytoscape. The core targets were screened out using the CytoNCA plug-in， and the biological functions were clustered by the MCODE plug-in. Gene Ontology （GO） functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analysis were performed using the David database. Molecular docking was performed using AutoDock and visualized with PyMOL2.5.2. The Kunming mice were randomly divided into the control group， the model group， the SNS group， and the trimetazidine （TMZ） group. The mice were subcutaneously injected with isoprenaline （ISO， 5 mg·kg^-1·d^-1） to establish an MI model. The drug was continuously intervened for 7 days. The ST-segment changes were recorded by electrocardiogram （ECG）， and the tissue morphology changes were observed by hematoxylin-eosin （HE） staining. Cardiomyocyte ferroptosis was investigated by transmission electron microscopy. Serum creatine kinase （CK）， creatine kinase isoenzyme （CK-MB）， lactate dehydrogenase （LDH）， reduced glutathione （GSH）， and malondialdehyde （MDA） levels were detected by biochemical assay. Enzyme-linked immunosorbent assay （ELISA） was used to detect serum levels of interleukin （IL）-6 and 4-hydroxynonenal （4-HNE）. Immunohistochemical staining was employed to detect IL-6 and phosphorylated signal transducer and transcription activator 3 （p-STAT3） in cardiac tissues. Western blot was used to detect STAT3 and p-STAT3 in cardiac tissues. Real-time PCR was used to detect the levels of IL-6， IL-18， solute carrier family 7 member 11 （SLC7A11）， arachidonic acid 15-lipoxygenase （ALOX15）， and glutathione peroxidase 4 （GPx4） in cardiac tissues. ResultsA total of 121 active ingredients of SNS were obtained， and 58 potential targets of SNS in the treatment of MI by regulating ferroptosis were screened. The three protein modules with a score5 were mainly related to the inflammatory response. The GO function was mainly related to inflammation， and KEGG enrichment analysis showed that SNS mainly regulated ferroptosis- and inflammation- related signaling pathways. Molecular docking indicated that the core component had a higher binding force to the target site. Animal experiments confirmed that SNS reduced the level of p-STAT3 （P0.01）， down-regulated the expression of ALOX15 mRNA （P0.01）， up-regulated the level of serum GSH， and the expressions of SLC7A11 and GPx4 mRNA， reduced MDA and 4-HNE levels （P0.05， P0.01）. Additionally， SNS improved the mitochondrial injury induced by cardiomyocyte ferroptosis， reduced the area of MI， alleviated inflammation and myocardial injury， lowered the levels of serum CK， CK-MB， LDH， IL-6， and the mRNA expression levels of IL-16 and IL-18 （P0.05）， and improved ST segment elevation. ConclusionSNS can reduce ISO-induced STAT3 phosphorylation levels， inhibit ferroptosis in cardiomyocytes， alleviate inflammation and myocardial injury， thereby improving MI.

ObjectiveTo explore the mechanism by which Sini San （SNS） inhibits ferroptosis， alleviates inflammation and myocardial injury， and improves myocardial infarction （MI）. MethodsThe active ingredients of SNS were obtained by searching the Traditional Chinese Medicine System Pharmacology Platform （TCMSP） database， its target sites were predicted using the SwissTargetPrediction Database， and the core components were screened out using the CytoNCA plug-in. The targets of MI and ferroptosis were obtained by using GeneCards， Online Mendelian Inheritance in Man （OMIM） database， DrugBank， Therapeutic Target Database （TTD）， FerrDb database and literature review， respectively. The intersection of these targets of SNS-MI-ferroptosis was plotted as a Venn diagram. The protein-protein interaction （PPI） network was constructed using the STRING database， and the visualization graph was prepared using Cytoscape. The core targets were screened out using the CytoNCA plug-in， and the biological functions were clustered by the MCODE plug-in. Gene Ontology （GO） functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analysis were performed using the David database. Molecular docking was performed using AutoDock and visualized with PyMOL2.5.2. The Kunming mice were randomly divided into the control group， the model group， the SNS group， and the trimetazidine （TMZ） group. The mice were subcutaneously injected with isoprenaline （ISO， 5 mg·kg^-1·d^-1） to establish an MI model. The drug was continuously intervened for 7 days. The ST-segment changes were recorded by electrocardiogram （ECG）， and the tissue morphology changes were observed by hematoxylin-eosin （HE） staining. Cardiomyocyte ferroptosis was investigated by transmission electron microscopy. Serum creatine kinase （CK）， creatine kinase isoenzyme （CK-MB）， lactate dehydrogenase （LDH）， reduced glutathione （GSH）， and malondialdehyde （MDA） levels were detected by biochemical assay. Enzyme-linked immunosorbent assay （ELISA） was used to detect serum levels of interleukin （IL）-6 and 4-hydroxynonenal （4-HNE）. Immunohistochemical staining was employed to detect IL-6 and phosphorylated signal transducer and transcription activator 3 （p-STAT3） in cardiac tissues. Western blot was used to detect STAT3 and p-STAT3 in cardiac tissues. Real-time PCR was used to detect the levels of IL-6， IL-18， solute carrier family 7 member 11 （SLC7A11）， arachidonic acid 15-lipoxygenase （ALOX15）， and glutathione peroxidase 4 （GPx4） in cardiac tissues. ResultsA total of 121 active ingredients of SNS were obtained， and 58 potential targets of SNS in the treatment of MI by regulating ferroptosis were screened. The three protein modules with a score5 were mainly related to the inflammatory response. The GO function was mainly related to inflammation， and KEGG enrichment analysis showed that SNS mainly regulated ferroptosis- and inflammation- related signaling pathways. Molecular docking indicated that the core component had a higher binding force to the target site. Animal experiments confirmed that SNS reduced the level of p-STAT3 （P0.01）， down-regulated the expression of ALOX15 mRNA （P0.01）， up-regulated the level of serum GSH， and the expressions of SLC7A11 and GPx4 mRNA， reduced MDA and 4-HNE levels （P0.05， P0.01）. Additionally， SNS improved the mitochondrial injury induced by cardiomyocyte ferroptosis， reduced the area of MI， alleviated inflammation and myocardial injury， lowered the levels of serum CK， CK-MB， LDH， IL-6， and the mRNA expression levels of IL-16 and IL-18 （P0.05）， and improved ST segment elevation. ConclusionSNS can reduce ISO-induced STAT3 phosphorylation levels， inhibit ferroptosis in cardiomyocytes， alleviate inflammation and myocardial injury， thereby improving MI.

AIM:To analyze the influencing factors of postoperative malignant glaucoma(MG)in patients with primary angle-closure glaucoma(PACG)using logistic regression and decision tree models.METHODS:A retrospective study was conducted on PACG patients who underwent surgery at Eye Hospital of Handan City from March 2020 to March 2025. Patients were divided into two groups: the MG group, who developed MG within 6 mo postoperatively, and the non-MG group. Data were collected from the electronic medical record system. Univariate analysis was performed, followed by multivariate logistic regression to identify independent risk factors. A classification and regression tree model was constructed to visualize the hierarchical relationships among predictors. The predictive performance of the two models was evaluated and compared using receiver operating characteristic(ROC)curve analysis.RESULTS:Totally 182 cases(182 eyes)with PACG were enrolled in this study, including 91 cases(91 eyes)in the MG group and 91 cases(91 eyes)in the non-MG group. In the MG group, there were 53 males and 38 females; 69 cases were aged ≥60 y and 22 cases were aged <60 y. In the non-MG group, there were 47 males and 44 females; 33 cases were aged ≥60 y and 58 cases were aged <60 y. The non-MG group comprised 91 patients, including 47 males and 44 females. Among them, 33 cases were aged ≥60 y, and 58 cases were aged<60 y. The MG group had significantly higher proportions of patients aged ≥60 y, diabetes, moderate-stage PACG, persistent high intraocular pressure(IOP), complete anterior chamber angle closure, lens thickness <4.5 mm, axial length <22 mm, and severe postoperative inflammation compared to the non-MG group(all P<0.01). Multivariate Logistic regression identified the following as independent influencing factors for postoperative MG: age [OR (95%CI)=2.136(1.401-3.255)], PACG stage [OR (95%CI)=2.996(2.044-4.391)], IOP [OR (95%CI)=3.527(1.604-7.755)],anterior chamber angle [OR (95%CI)=4.826(2.498-9.324)], axial length [OR (95%CI)=5.125(1.265-20.771)], and severe postoperative inflammation [OR (95%CI)=2.338(1.478-3.699)](all P<0.05). The decision tree model selected six explanatory variables: age, PACG stage, IOP, anterior chamber angle status, axial length, and severe postoperative inflammation. Axial length was the primary splitting factor at the root node. The areas under the ROC curve(AUC)for the logistic regression and decision tree models were 0.913(0.863-0.950)and 0.921(0.872-0.956), respectively, with no significant difference between them(Z=0.561, P=0.575).CONCLUSION:Both the logistic regression and decision tree models effectively identify key influencing factors for postoperative MG in PACG patients, including age, PACG stage, IOP, anterior chamber angle status, axial length, and severe postoperative inflammation. The decision tree model offers an intuitive, visual representation of risk stratification, facilitating clinical decision-making. Both models are applicable for clinical risk assessment.

OBJECTIVE: To assess relationships between cold spells and genitourinary hospitalization risk. METHODS: Hospitalization records for genitourinary system diseases (GUDs) from 16 districts in Beijing (2013-2018) were analyzed. Cold spells were defined based on varying intensity thresholds. A two-stage analytical method was employed: first, generalized linear models assessed district-specific associations between cold spells and hospitalizations; second, random-effects meta-analysis aggregated the district-level results. Subgroup analyses were performed by admission type (emergency vs. outpatient), age, and sex. RESULTS: A total of 271,579 GUD-related hospitalizations were recorded. Cold spells (p1day2，daily mean temperature below the 1 ^st percentiles of the daily mean temperature distribution from January 1, 2013, to December 31, 2018, lasting for two or more consecutive days) were linked to a significant rise in hospitalization risks: 1.43 (95% CI: 1.32-1.56) for all GUDs, 1.35 (95% CI: 1.23-1.49) for urinary system diseases, and 1.46 (95% CI: 1.28-1.67) for renal failure, when compared to non-cold spell days. Emergency admissions showed higher risk increases than outpatient admissions. CONCLUSION Extreme cold spells significantly elevate hospitalization risks for GUDs. This highlights the urgent need for targeted public health interventions to mitigate cold-related health impacts, especially for vulnerable populations.
Humans ; Hospitalization/statistics & numerical data* ; Male ; Female ; Cold Temperature/adverse effects* ; Infant ; Child, Preschool ; Middle Aged ; Adult ; Child ; Aged ; Adolescent ; Young Adult ; Beijing/epidemiology* ; Female Urogenital Diseases/etiology* ; Male Urogenital Diseases/etiology* ; Infant, Newborn ; Risk Factors

Objective: To explore the influencing factors and pathways of suicidal ideation among children and adolescents with severe autism spectrum disorder (ASD), so as to provide references for clarifying the impact intensity and pathways of various factors on suicidal ideation in the population. Methods: A cross sectional study was conducted from June 17, 2024, to January 12, 2025, involving 96 severely affected ASD children and adolescents aged 8-18 years from Tianjin. Participants were assessed using the Puberty Development Scale (PDS), Children s Alexithymia Measure (CAM), Strengths and Difficulties Questionnaire (SDQ), and Positive and Negative Suicide Ideation (PANSI). The random forest Boruta algorithm was employed to screen core variables, and a Bayesian network model was constructed to analyze the influencing factors of suicidal ideation in children and adolescents with severe ASD. Results: Through the screening using the Boruta algorithm, the SDQ scale score, conduct problems, hyperactivity, peer relationship problems and prosocial behavior were identified as the key predictors of suicidal ideation. A Bayesian network model was established with hyperactivity as the central mediating node. The impact of hyperactivity on suicidal ideation exhibited a non linear relationship: compared to the normal state (31.6%, 68.4%), the borderline state of hyperactivity was associated with a higher probability of low risk suicidal ideation (47.1%) and a lower probability of high risk suicidal ideation (52.9%). Suicidal ideation among children and adolescents with severe ASD was closely related to hyperactivity. In the state of hyperactivity, the abnormal peer relationship (95.2%) and the abnormal prosocial behavior (77.0%) were aggravated. Conclusions Suicide ideation among children and adolescents with severe ASD is strongly associated with hyperactivity traits. It is necessary to establish a prevention and control system centered on hyperactivity intervention to reduce this risk.

Objective:To investigate the efficacy and safety of fospropofol disodium(FP)in the induction and maintenance of general anesthesia in the adult patients graded Ⅰ or Ⅱ by the American Society of Anesthesiologists(ASA)undergoing elective surgery,and to provide the theoretical basis for application of EP in the induction and maintenance of general anesthesia.Methods:Adult patients of ASA grade Ⅰ or Ⅱ undergoing elective surgery were selected with a total of 100 patients recruited sequentially according to the time of visit,and they were randomly divided into FP group(50 cases)and propofol group(50 cases).All patients were prepared preoperatively,and received a slow injection of midazolam(2 to 3 mg)and sufentanil(0.3 μg·kg-1),followed by induction of anaesthesia 1 to 2 min later.The patients in FP group were given FP(10.0-12.5 mg·kg-1)intravenously,and the patients in propofol group were given propofol(1.5-2.0 mg·kg-1)intravenously.After the Modified Obserational Assessment Alertness/Sedation(MOAA/S)score dropped to 1,muscle relaxant was administrated and the induction was completed.During the maintenance of anaesthesia,the patients in FP group received a continuous intravenous infusion of FP at a rate of 12.5-15.0 mg·kg-1·h-1,and the patients in propofol group received a continuous infusion of propofol at a starting rate of 6 mg·kg-1·h-1.The patients in two groups additionally received remifentanil(0.1-0.4 μg·kg-1·min-1)for co-analgesia,and the rate of administration was adjusted according to the patient's status.Systolic blood pressure(SBP),diastolic blood pressure(DBP),mean arterial pressure(MAP),heart rate(HR)and bispectral index(BIS)values of the patients in two groups were recorded at different time points:before induction(T1),immediately after tracheal intubation(T2),5 min after induction(T3),10 min after induction(T4),20 min after induction(T5),30 min after induction(T6),40 min after induction(T7)and at the end of the procedure(T8).The time to onset of sedation/anaesthesia(MOAA/S≤1),the time to eye opening,and the time to awakening(MOAA/S=5)of the patients in two groups were recorded.The lowest intraoperative SBP and BIS values and the time required of the patients in two groups were observed.The incidence of adverse reactions related to agitation,choking,nausea,vomiting and cardiovascular system or respiratory system were compared between two groups.Results:There were no statistically differences in the general informations and the duration of surgery of patients between two groups(P＞0.05).The induction time of the patients in FP group(2.39 min)was significantly longer than that in propofol group(0.70 min)(P＜0.05).In the recovery period of general anesthesia,the eye opening time and recovery time of the patients in FP group were significantly longer than those in propofol group(P＜0.05).There were no significant differences in MAP of the patients between two groups at different time points(P＞0.05).The HR at T4,T5,T6,and T7 time points of the patients in FP group were lower than those in propofol group(P＜0.05).The lowest value of BIS of the patients in FP group was significantly smaller than that in propofol group,and the time taken to reach the lowest value of BIS in FP group was significantly longer than that in propofol group(P＜0.05).The time taken to reach the lowest value of SBP of the patients in FP group was longer than that in propofol group(P＜0.05).However,the lowest value of SBP of the patients and the incidence of adverse reations of the patients in two groups showed no statistical differences(P＞0.05).Conclusion:Compared with propofol,FP injection is safe and effective in the induction and maintenance of general anesthesia in adult patients with ASA class Ⅰ or Ⅱ undergoing elective surgery,with a low incidence of adverse reactions,which is a new anesthesia option.

The co-occurrence of epilepsy and arrhythmia is an increasingly concerned research area, but the underlying biological mechanism is still not fully understood. In recent years, many studies have focused on how mutations in ion channel genes affect the electrophysiological properties of neurons and heart muscle cells, revealing a possible intersection between epilepsy and arrhythmia. Mutations in ion channel genes (such as SCN1A, KCNQ2, and RYR2) may simultaneously affect the electrophysiological properties of neurons and cardiomyocytes, leading to the comorbidity of epilepsy and arrhythmia. During epileptic seizures, activation of the autonomic nervous system may cause abnormal cardiac electrical activity, increasing risks of arrhythmia and sudden death resulting from epilepsy. In addition, the potential effects of antiepileptic drugs on cardiac ion channels can further increase the arrhythmia risk. This article reviews the research progress on the electrophysiological characteristics of ion channels in neurons and cardiomyocytes, the relations of ion channel gene mutations with epilepsy, arrhythmia, and their comorbidity, with the aim of providing new ideas for clinical diagnosis and treatment of epilepsy.

Objective:To investigate the association between peak growth hormone(GH) levels and body fat mass as well as body fat percentage in children with short stature.Methods:This retrospective study included 477 children diagnosed with short stature at the Affiliated Hospital of Jining Medical University between January 2021 and November 2024, based on data from the Growth and Development Disease Follow-up Cohort Study(GDDSD) in Shandong Province. Clinical data including anthropometric measurements, laboratory tests, and body composition were collected. The relationship between GH peak and body fat mass and percentage were analyzed using smooth curve fitting and multiple piecewise linear regression models.Results:In univariate linear regression analysis, both body fat mass and body fat percentage were positively correlated with age, height, weight, body mass index, triglycerides, low density lipoprotein-cholesterol, fasting blood glucose, total body water, protein, and skeletal muscle mass(all P<0.05), and negatively correlated with GH peak and high density lipoprotein-cholesterol. After adjusting for potential confounding factors, a nonlinear relationship was observed between GH peak and both body fat mass and body fat percentage, with inflection points at 6.80 ng/mL and 7.75 ng/mL, respectively. When GH peak was below the inflection point, it was significantly negatively correlated with body fat mass and percentage( P<0.001). However, when GH peak exceeded the inflection point, the associations were no longer statistically significant( P>0.05). Conclusions:This study demonstrates a nonlinear relationship between peak GH levels and body fat percentage in children with short stature. At lower GH peaks, both body fat mass and body fat percentage increase significantly, which may contribute to an elevated future risk of cardiovascular disease.