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.

ObjectiveTo investigate the inhibitory effect of Biejiajian Pills （BJJW） on the growth of liver cancer， as well as its potential mechanism in mediating the AMP-activated protein kinase （AMPK）/mammalian target of rapamycin （mTOR） pathway through mitochondrial energy metabolism. MethodsHuman hepatoma Huh7 cells were used to establish a nude mouse model of subcutaneous xenograft tumor. A total of 18 tumor-bearing nude mice were randomly divided into model group， BJJW group （2.2 g/kg）， and metformin group （250 mg/kg）， and the corresponding drug was given by gavage for 14 consecutive days. Tumor volume and weight were monitored during the experiment； HE staining was used to observe histopathological changes； the levels of reactive oxygen species （ROS） and adenosine triphosphate （ATP） in tumor tissue were measured； immunohistochemistry and Western blotting were used to measure the expression levels of proteins associated with the AMPK/mTOR pathway. A one-way analysis of variance was used for comparison of normally distributed continuous data between multiple groups， and the Tukey’s test was used for further comparison between two groups； the Kruskal-Wallis H test was used for comparison of non-normally distributed continuous data between multiple groups， and the Dunn’s test was used for further comparison between two groups. ResultsCompared with the model group， the BJJW group had a tumor inhibition rate of 45.73%， with significant reductions in both tumor volume and weight （P<0.01）. Pathological examination showed that compared with the model group， the BJJW group had a significant reduction in the number of tumor cells and the presence of extensive necrosis. Mechanistic studies showed that compared with the model group， the BJJW group had a significant increase in ROS level （P<0.001） and a significant reduction in ATP level （P<0.001）， as well as significant increases in p-AMPK/AMPK ratio （0.81±0.20 vs 0.13±0.04， P<0.01） and p-ULK1/ULK1 ratio （0.69±0.17 vs 0.18±0.13， P<0.01） and a significant reduction in p-mTOR/mTOR ratio （1.34±0.16 vs 3.20±0.62， P<0.01）. ConclusionBJJW may inhibit the growth of liver cancer by inducing mitochondrial energy metabolism dysfunction， increasing the level of ROS， reducing the level of ATP， and activating the AMPK/mTOR signaling pathway.

OBJECTIVE: To analyze the time characteristics of the Ethos online adaptive radiotherapy (OART) process in clinical practice and provide guidance for the comprehensive optimization of each stage of adaptive radiotherapy. METHODS: The study involved 61 patients with cervical, rectal, gastric, lung, esophageal, and breast cancers who underwent Ethos OART. The mean ± standard deviation of segmental time, total time, and target volume for these patients were tracked. The time characteristics for different cancer types were evaluated, and the average time for target and organ at risk (OAR) modifications was compared with the average target volume for each cancer type. RESULTS: Cervical cancer born the longest total treatment time, while breast cancer had the shortest. For all cancer types except breast cancer, the modification time for target and OAR was the most time-consuming segment. The average time for target and OAR modifications aligned with the trend of the average target volume. CONCLUSION The total treatment time for various cancers ranges from 15 to 35 minutes, indicating room for improvement.
Humans ; Radiotherapy Planning, Computer-Assisted/methods* ; Neoplasms/radiotherapy* ; Female

Alzheimer's disease (AD) is a common neurodegenerative disorder among the elderly, and BuChE has emerged as a potential therapeutic target. In this study, we reported the development of compound 8e, a selective reversible BuChE inhibitor (eqBuChE IC₅₀ = 0.049 μmol/L, huBuChE IC₅₀ = 0.066 μmol/L), identified through extensive virtual screening and lead optimization. Compound 8e demonstrated favorable blood-brain barrier permeability, good drug-likeness property and pronounced neuroprotective efficacy. Additionally, 8e exhibited significant therapeutic effects in zebrafish AD models and scopolamine-induced cognitive impairments in mice. Further, 8e significantly improved cognitive function in APP/PS1 transgenic mice. Proteomics analysis demonstrated that 8e markedly elevated the expression levels of very low-density lipoprotein receptor (VLDLR), offering valuable insights into its potential modulation of the Reelin-mediated signaling pathway. Thus, compound 8e emerges as a novel and potent BuChE inhibitor for the treatment of AD, with significant implications for further exploration into its mechanisms of action and therapeutic applications.

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.

Background::Substantial progress in air pollution control has brought considerable health benefits in China, but little is known about the spatio-temporal trends of economic burden from air pollution. This study aimed to explore their spatio-temporal features of disease burden from air pollution in China to provide policy recommendations for efficiently reducing the air pollution and related disease burden in an era of a growing economy.Methods::Using the Global Burden of Disease method and willingness to pay method, we estimated fine particulate matter (PM 2.5) and/or ozone (O 3) related premature mortality and its economic burden across China, and explored their spatio-temporal trends between 2005 and 2017. Results::In 2017, we estimated that the premature mortality and economic burden related to the two pollutants were RMB 0.94 million (68.49 per 100,000) and 1170.31 billion yuan (1.41% of the national gross domestic product [GDP]), respectively. From 2005 to 2017, the total premature mortality was decreasing with the air quality improvement, but the economic burden was increasing along with the economic growth. And the economic growth has contributed more to the growth of economic costs than the economic burden decrease brought by the air quality improvement. The premature mortality and economic burden from O 3 in the total loss from the two pollutants was substantially lower than that of PM 2.5, but it was rapidly growing. The O 3-contribution was highest in the Yangtze River Delta region, the Fen-Wei Plain region, and some western regions. The proportion of economic burden from PM 2.5 and O 3 to GDP significantly declined from 2005 to 2017 and showed a decreasing trend pattern from northeast to southwest. Conclusion::The disease burden from O 3 is lower than that of PM 2.5, the O 3-contribution has a significantly increasing trend with the growth of economy and O 3 concentration.

The 68 Center for Drug Evaluation recommend approved innovative drugs between 2019 and 2021 evaluation situation was summarized in this article,to analyzes the innovative drugs research and development trend and the influence of the drug evaluation and approval system reform.Meanwhile,after sorting out the clinical trials inspection report,to analyze the clinical trials on-site inspection of innovative drugs,and summarized the common defects,hope to provide reference and suggestions for subsequent innovative drug application and high-quality drug clinical trials.