1.Exploration in Mechanism of Sini San for Inhibiting Ferroptosis and Ameliorating Isoprenaline-induced Myocardial Infarction in Mice Based on Bioinformatics and Experimental Validation
Shupeng LIU ; Zhiguang HAN ; Jiaying LI ; Jiayao XU ; Weihao GAO ; Yanping WU ; Guangguo BAN ; Yongmin LI ; Hongxia YANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(3):67-77
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.
2.Exploration in Mechanism of Sini San for Inhibiting Ferroptosis and Ameliorating Isoprenaline-induced Myocardial Infarction in Mice Based on Bioinformatics and Experimental Validation
Shupeng LIU ; Zhiguang HAN ; Jiaying LI ; Jiayao XU ; Weihao GAO ; Yanping WU ; Guangguo BAN ; Yongmin LI ; Hongxia YANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(3):67-77
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.
3.Serum nitric oxide synthase 4 and matrix metalloproteinase-2 expression in patients with diabetic neovascular glaucoma and their clinical significance
Xiaomin LIU ; Jingfei BAN ; Jing LYU ; Wenwen LI ; Jingke LI ; Shunling YANG
International Eye Science 2026;26(1):103-108
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.
4.Impact of bundle intervention measures on incidence of catheter-related infections in ICU patients of neurosurgery department
Ya YANG ; Mei HAUNG ; Jiayan DING ; Xiaofang FU ; Yu ZHENG ; Haiqun BAN
Chinese Journal of Nosocomiology 2025;35(6):945-949
OBJECTIVE To evaluate the impact of bundle intervention measures on incidence of catheter-related in-fections in patients of neurosurgery intensive care unit(NICU).METHODS The related data regarding to incidence rates of hospital-associated infections and utilization rates of catheters were collected from the NICU patients of Renji Hospital,Shanghai Jiaotong University from 2007 to 2022.The effect of the bundle intervention measures on reducing the incidence of catheter-related infections was analyzed by means of interrupted tune series(ITS)method.RESULTS There was significant difference in the decline trend of incidence of the infections during the study(the trend x2=91.978,P<0.001).ITS analysis showed that the utilization rate of catheters only presented the decline trend after the intervention(β2=-0.667,P=0.042),the utilization rate of ventilator tubes only de-clined after the intervention(β3=-26.375,P<0.001).Th utilization rate of central venous catheters showed a downward trend before the intervention(β1=-2.525,P<0.001)but did not change significantly after the inter-vention.The incidence of central line-associated bloodstream infection(CLABSI)was decreased(RR=0.268,95%CI:0.124 to 0.581),however,there was significant difference in the change of slope(RR=0.912,95%CI:0.730 to 1.140).The incidence of catheter-associated urinary tract infection(CAUTI)showed a downward trend(RR=0.796,95%CI:0.647 to 0.975),however,there was no significant difference in the change of the level(RR=1.543,95%CI:0.816 to 3.005).The incidence of ventilator-associated pneumonia(VAP)showed a downward trend(RR=0.829,95%CI:0.767 to 0.895),however,there was no significant difference in the change of the level(RR=0.817,95%CI:0.595 to 1.114).CONCLUSIONS The bundle intervention measures may effectively reduce the incidence of catheter-related infections.The incidence rates of the catheter-related infections vary in the chan-ging trends after the interventions are taken,indicating that it is necessary to comprehensively take the character-istics of catheter-related infections into account when carrying out the bundle intervention measures and continu-ously optimize the control strategies.
5.Progress of research on epidemiological characteristics and prevention measures for postoperative infections in liver transplantation children
Jiayan DING ; Ya YANG ; Yuxiao DENG ; Haiqun BAN
Chinese Journal of Nosocomiology 2025;35(5):795-800
OBJECTIVE Liver transplantation is an important mean for treatment of the children with end-stage liv-er disease,but the postoperative infections remain a major and potentially fatal complication.Due to the unique physiological and immunological characteristics of the children,the types and risk factors for the postoperative in-fections differ from those in adults.This review summarizes the current status of research on the postoperative in-fections among the liver transplantation children in recent years and focuses on the major risk factors such as pre-operative state,intraoperative procedures,immunosuppression and postoperative management.The prevention and control strategies were put forward to reduce the risk of infection and raise the rate of successful transplanta-tion by optimizing the assessment and strengthening perioperative management,individualized immunization strat-egies and multidisciplinary collaboration.
6.NAT10 inhibition alleviates astrocyte autophagy by impeding ac4C acetylation of Timp1 mRNA in ischemic stroke.
Li YANG ; Xiaotong LI ; Yaxuan ZHAO ; Hao CHEN ; Can WANG ; Angrong WU ; Xintong GUO ; Yue HUANG ; Qihui WANG ; Lingyun HAO ; Xiaowen LI ; Ying JI ; Jin BAN ; Guangtian WANG ; Junli CAO ; Zhiqiang PAN
Acta Pharmaceutica Sinica B 2025;15(5):2575-2592
Although a single nucleotide polymorphism for N-acetyltransferase 10 (NAT10) has been identified in patients with early-onset stroke, the role of NAT10 in ischemic injury and the related underlying mechanisms remains elusive. Here, we provide evidence that NAT10, the only known RNA N4-acetylcytidine (ac4C) modification "writer", is increased in the damaged cortex of patients with acute ischemic stroke and the peri-infarct cortex of mice subjected to photothrombotic (PT) stroke. Pharmacological inhibition of NAT10 with remodelin on Days 3-7 post-stroke or astrocytic depletion of NAT10 via targeted virus attenuates ischemia-induced infarction and improves functional recovery in PT mice. Mechanistically, NAT10 enhances ac4C acetylation of the inflammatory cytokine tissue inhibitor of metalloproteinase 1 (Timp1) mRNA transcript, which increases TIMP1 expression and results in the accumulation of microtubule-associated protein 1 light chain 3 (LC3) and progression of astrocyte autophagy. These findings demonstrate that NAT10 regulates astrocyte autophagy by targeting Timp1 ac4C after stroke. This study highlights the critical role of ac4C in the regulation of astrocyte autophagy and proposes a promising strategy to improve post-stroke outcomes via NAT10 inhibition.
7.Association Between Vitamin D Status and Insulin Resistance in Adolescents: A Cross-sectional Observational Study
Xiaoyuan GUO ; Yutong WANG ; Zhibo ZHOU ; Shi CHEN ; Mei ZHANG ; Bo BAN ; Ping LI ; Xinran ZHANG ; Qiuping ZHANG ; Kai YANG ; Hongbo YANG ; Hanze DU ; Hui PAN
Medical Journal of Peking Union Medical College Hospital 2025;16(3):577-583
To investigate the correlation between vitamin D nutritional status and insulin resistance in pubertal adolescents. This cross-sectional observational study employed convenience sampling to recruit 2021-grade(8th grade) students from Jining No.7 Middle School in Shandong Province on June 5, 2023. Data collection included questionnaires, physical examinations, and imaging assessments to obtain general information, secondary sexual characteristics development, and bone age. Venous blood samples were collected to measure fasting blood glucose(FBG), fasting insulin(FINS), homeostasis model assessment of insulin resistance(HOMA-IR), and 25-hydroxyvitamin D[25(OH)D] levels. Spearman correlation analysis and multivariate linear regression models were used to examine the associations between serum vitamin D levels and FBG, FINS, and HOMA-IR. The study included 168 pubertal adolescents[69 females(41.1%), 99 males(58.9%); mean age(13.27±0.46) years]. All participants had entered puberty based on sexual development assessment. Vitamin D deficiency was observed in 41 participants(24.4%), insufficiency in 109(64.9%), and sufficiency in 18(10.7%). The median HOMA-IR was 3.49(2.57, 5.14).Significant differences were found across vitamin D status groups for HOMA-IR [4.45(2.54, 6.62) Vitamin D deficiency/insufficiency is prevalent among pubertal adolescents, and serum vitamin D levels show a significant inverse association with insulin resistance. These findings suggest the potential importance of vitamin D status in metabolic health during puberty.
8.Impact of bundle intervention measures on incidence of catheter-related infections in ICU patients of neurosurgery department
Ya YANG ; Mei HAUNG ; Jiayan DING ; Xiaofang FU ; Yu ZHENG ; Haiqun BAN
Chinese Journal of Nosocomiology 2025;35(6):945-949
OBJECTIVE To evaluate the impact of bundle intervention measures on incidence of catheter-related in-fections in patients of neurosurgery intensive care unit(NICU).METHODS The related data regarding to incidence rates of hospital-associated infections and utilization rates of catheters were collected from the NICU patients of Renji Hospital,Shanghai Jiaotong University from 2007 to 2022.The effect of the bundle intervention measures on reducing the incidence of catheter-related infections was analyzed by means of interrupted tune series(ITS)method.RESULTS There was significant difference in the decline trend of incidence of the infections during the study(the trend x2=91.978,P<0.001).ITS analysis showed that the utilization rate of catheters only presented the decline trend after the intervention(β2=-0.667,P=0.042),the utilization rate of ventilator tubes only de-clined after the intervention(β3=-26.375,P<0.001).Th utilization rate of central venous catheters showed a downward trend before the intervention(β1=-2.525,P<0.001)but did not change significantly after the inter-vention.The incidence of central line-associated bloodstream infection(CLABSI)was decreased(RR=0.268,95%CI:0.124 to 0.581),however,there was significant difference in the change of slope(RR=0.912,95%CI:0.730 to 1.140).The incidence of catheter-associated urinary tract infection(CAUTI)showed a downward trend(RR=0.796,95%CI:0.647 to 0.975),however,there was no significant difference in the change of the level(RR=1.543,95%CI:0.816 to 3.005).The incidence of ventilator-associated pneumonia(VAP)showed a downward trend(RR=0.829,95%CI:0.767 to 0.895),however,there was no significant difference in the change of the level(RR=0.817,95%CI:0.595 to 1.114).CONCLUSIONS The bundle intervention measures may effectively reduce the incidence of catheter-related infections.The incidence rates of the catheter-related infections vary in the chan-ging trends after the interventions are taken,indicating that it is necessary to comprehensively take the character-istics of catheter-related infections into account when carrying out the bundle intervention measures and continu-ously optimize the control strategies.
9.Progress of research on epidemiological characteristics and prevention measures for postoperative infections in liver transplantation children
Jiayan DING ; Ya YANG ; Yuxiao DENG ; Haiqun BAN
Chinese Journal of Nosocomiology 2025;35(5):795-800
OBJECTIVE Liver transplantation is an important mean for treatment of the children with end-stage liv-er disease,but the postoperative infections remain a major and potentially fatal complication.Due to the unique physiological and immunological characteristics of the children,the types and risk factors for the postoperative in-fections differ from those in adults.This review summarizes the current status of research on the postoperative in-fections among the liver transplantation children in recent years and focuses on the major risk factors such as pre-operative state,intraoperative procedures,immunosuppression and postoperative management.The prevention and control strategies were put forward to reduce the risk of infection and raise the rate of successful transplanta-tion by optimizing the assessment and strengthening perioperative management,individualized immunization strat-egies and multidisciplinary collaboration.
10.Effect of hand hygiene intervention on healthcare-associated case infection incidence from 2014 to 2022
Jia-Yan DING ; Rui-Hong SHEN ; Wen-Qin ZHOU ; Ya-Yun YUAN ; Mei HUANG ; Ya YANG ; Bing-Chao CAI ; Hai-Qun BAN ; Xiao-Fang FU
Chinese Journal of Infection Control 2024;23(2):208-213
Objective To observe the effect of multi-modal hand hygiene(HH)intervention on HH compliance,as well as the relationship between HH compliance and the healthcare-associated(HA)case infection incidence.Methods From 2014 to 2022,the infection control team in a tertiary first-class hospital implemented multi-modal HH intervention for health care workers(HCWs).The changing trend of HH monitoring data,the correlation be-tween HH compliance rate and HA case infection incidence were analyzed retrospectively.Results The consump-tion of HH products in the wards showed a stable upward trend;HH compliance rate increased from 64.98%in 2014 to 85.01%in 2022(P<0.001),and HA case infection incidence decreased from 1.21%to 0.83%(P<0.05).HH compliance rate was negatively correlated with HA case infection incidence(r=-0.369,P=0.027).HH compliance rates in different regions and job posts in each quarter were increased(P<0.001).For 5 different HH moments in each quarter,HH compliance rate fluctuated slightly before sterile manipulation and after touching patient;presented rising trend after touching surroundings around patient,and decreased before touching patient and after touching patient's body fluid since 2020(P<0.001).Conclusion Multi-modal HH intervention can im-prove the HH compliance of HCWs,improving their HH awareness is conducive to reducing HA case infection incidence.

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