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.

Objective To investigate whether miR-15b-5p can alleviate airway inflammation in asthma by negatively regulating ubiquitin specific peptidase 9X (USP9X) to down-regulate the expression of phosphatidylinositol 4, 5-diphosphate 3-kinase catalytic subunit α/AKT serine/threonine kinase 1 (PIK3CA/AKT1) pathway. Methods USP9X was predicted to be a direct target of miR-15b-5p by using an online database (miRWalk), and the luciferase reporter gene assay was performed to verify it. Co-immunoprecipitation (CO-IP) was used to verify the direct binding between USP9X and PIK3CA and the role of USP9X and its small molecule inhibitor WP1130 in the deubiquitination of PIK3CA. C57 mice were randomly divided into Control group, OVA group, OVA combined with NC group and miR-15b-5p agomir group, with 10 mice in each group. BEAS-2B cells were induced with interleukin 13 (IL-13) and treated with miR-15b-5p mimic. HE, Masson, PAS, immunohistochemistry, immunofluorescence staining, flow cytometry, Western blot and quantitative real-time PCR(qRT-PCR) were performed. Results It was found that the administration of miR-15b-5p agomir and mimic could reduce peribronchial inflammatory cells and improve airway inflammation, and miR-15b-5p could target negative regulation of USP9X. USP9X could directly bind to PIK3CA and regulate PIK3CA level in a proteasome-dependent manner, and USP9X could deubiquitinate K29-linked PIK3CA protein. Down-regulation of USP9X could increase PIK3CA ubiquitination level. WP1130, a small molecule inhibitor of USP9X, has the same effect as knockdown of USP9X, both of which could increase the ubiquitination level of PIK3CA and reduce the protein level of PIK3CA. Conclusion The miR-15b-5p/USP9X/PIK3CA/AKT1 signaling pathway may provide potential therapeutic targets for asthma.
Animals ; MicroRNAs/metabolism* ; Asthma/pathology* ; Class I Phosphatidylinositol 3-Kinases/genetics* ; Ubiquitin Thiolesterase/metabolism* ; Proto-Oncogene Proteins c-akt/genetics* ; Mice ; Signal Transduction ; Mice, Inbred C57BL ; Humans ; Inflammation/genetics* ; Cell Line ; Female ; Male

Objective To explore the potential impact of unhealthy diets on cardiovascular diseases and all-cause mortality.Methods This study included the individuals aged 35-70 years from 45 cities and 70 rural communities across 12 provinces in China,as part of the Prospective Urban Rural Epidemiology(PURE)study.Dietary habits were assessed using a food frequency questionnaire.The dietary health status was scored using the Alternative Healthy Eating Index(AHEI),with participants in the lowest tertile of AHEI being categorized into the unhealthy diet group,while others were classified as the healthy diet group.The primary endpoints included major cardiovas-cular diseases(myocardial infarction,stroke,or heart failure)and all-cause mortality.Cox proportional hazard models were used to estimate hazard ratios(HR)for each group.Results A total of 40 925 participants were in-cluded in the study,with a median follow-up time of 11.9 years(interquartile range 9.6-12.6 years).During this period,2 066 deaths and 3 099 cases of major cardiovascular diseases were reported.The results showed that un-healthy diet increased the risk of major cardiovascular diseases by 10%(HR=1.10,95%CI:1.02-1.20,P＜0.05)and all-cause mortality by 7%(HR=1.07,95%CI:1.00-1.18,P＜0.05).Among male residents,un-healthy diet did not increase the risk of major cardiovascular diseases or all-cause mortality.However,among female residents,those with an unhealthy diet had a higher risk of major cardiovascular diseases(HR=1.12,95%CI:1.00-1.25,P＜0.05)and all-cause mortality(HR=1.26,95%CI:1.08-1.46,P＜0.05)compared to those with a healthy diet.Conclusions Unhealthy diet increases the risk of major cardiovascular diseases and all-cause mortality,particularly among women.There is a need to raise awareness about healthy dietary to prevent death and the occurrence of major cardiovascular diseases.

Objective To explore the potential impact of unhealthy diets on cardiovascular diseases and all-cause mortality.Methods This study included the individuals aged 35-70 years from 45 cities and 70 rural communities across 12 provinces in China,as part of the Prospective Urban Rural Epidemiology(PURE)study.Dietary habits were assessed using a food frequency questionnaire.The dietary health status was scored using the Alternative Healthy Eating Index(AHEI),with participants in the lowest tertile of AHEI being categorized into the unhealthy diet group,while others were classified as the healthy diet group.The primary endpoints included major cardiovas-cular diseases(myocardial infarction,stroke,or heart failure)and all-cause mortality.Cox proportional hazard models were used to estimate hazard ratios(HR)for each group.Results A total of 40 925 participants were in-cluded in the study,with a median follow-up time of 11.9 years(interquartile range 9.6-12.6 years).During this period,2 066 deaths and 3 099 cases of major cardiovascular diseases were reported.The results showed that un-healthy diet increased the risk of major cardiovascular diseases by 10%(HR=1.10,95%CI:1.02-1.20,P＜0.05)and all-cause mortality by 7%(HR=1.07,95%CI:1.00-1.18,P＜0.05).Among male residents,un-healthy diet did not increase the risk of major cardiovascular diseases or all-cause mortality.However,among female residents,those with an unhealthy diet had a higher risk of major cardiovascular diseases(HR=1.12,95%CI:1.00-1.25,P＜0.05)and all-cause mortality(HR=1.26,95%CI:1.08-1.46,P＜0.05)compared to those with a healthy diet.Conclusions Unhealthy diet increases the risk of major cardiovascular diseases and all-cause mortality,particularly among women.There is a need to raise awareness about healthy dietary to prevent death and the occurrence of major cardiovascular diseases.

Objective To explore the influencing factors and prognosis of epilepsy after operation for insular low-grade gliomas.Methods The clinical data of 120 patients with insular low-grade gliomas with pre-operative seizure symptoms in the Chinese glioma Genome Atlas Project(CGGA)database from July 2008 to June 2014 were retrospectively analyzed.The seizure control and survival prediction information of the patients were followed up one year after operation.The risk factors affecting post-operative seizures were analyzed by Logistic multiple factor regression analysis,Kapla-Meier curve was used to analyze the effect of postoperative epilepsy control factors on progression free survival(PFS)and overall survival(OS).Results Before operation,36 cases(30.0％)had simple focal seizures,53 cases(44.2％)had focal seizures with different degrees of cognitive impairment,and 31 cases(25.8％)had generalized seizures.During the follow-up after one year of surgical treatment,72 patients(60％)had a complete improvement in epilepsy symptoms(Engel grade Ⅰ),33 patients(27.5％)had a significant improvement(Engel grade Ⅱ),11 patients(9.2％)had a significant improvement(Engel grade Ⅲ),and 4 patients(3.3％)had no improvement or deterioration(Engel grade Ⅳ).Larger tumor resection degree,no putamen involved,IDH1 mutation are favorable factors for postoperative control of epilepsy.Improvement of seizures was a favorable prognostic factor for PFS and OS.Conclusion Epilepsy is the most common symptom of insular gliomas.The improvement of postoperative epilepsy symptoms is related to the degree of tumor resection,involvement of putamen and IDH1 mutation status.Complete improvement of epilepsy symptoms can prolong the progression free survival time and overall survival time of patients.

Objective:To investigate the effect of open reduction and internal fixation assisted by computer virtual surgery in the treatment of complex proximal humeral fracture.Methods:A retrospective case series study was performed on clinical data of 36 patients with complex proximal humeral fracture admitted to Dongfang Hospital Affiliated to Tongji University from January 2018 to June 2020. There were 13 males and 23 females, aged 22-86 years [(56.4±4.8)years]. They were all closed fractures. According to Neer classification, there were 20 patients with three-part fractures and 16 with four-part fractures. Precise pre-surgical designs made by using the digital orthopedic surgery planning system of the E-3D were applied to assist the implementation of precise fracture reduction and internal fixation with the locking plate. The fracture healing was observed. The effect of the real surgery assisted by the virtual surgical designs was assessed by comparing the humeral neck shaft angle and humeral head height measured at the virtual surgery and at day 1 after the real surgery. The humeral neck shaft angle, humeral head height, shoulder range of motion (abduction, external rotation and forward flexion), Constant shoulder function score and visual analogue score (VAS) were recorded at 1 day, 3 months and 12 months after the real surgery. The stability of the medial column was assessed at 1 day after the real surgery. The complications were recorded.Results:All patients were followed up for 12-38 months [(18.5±1.8)months]. The fracture showed bony union in all patients with the union time of 6.6-17.2 weeks [(10.2±1.0)weeks]. The humeral neck shaft angle and humeral head height showed no significant differences measured at the virtual surgery and at 1 day after the real surgery, and were also not significant different at 1 day, 3 months and 12 months after the real surgery (all P>0.05). At 3 months and 12 months after the real surgery, the shoulder abduction [(119.4±11.8)°, (155.3±13.7)°], external rotation [(37.6±6.3)°, (46.8±7.4)°], forward flexion [ (94.8±10.2)°, (126.9±1.6)°] and Constant function score [(66.8±8.4)points, (82.4±9.6)points] were all higher than those at 1 day after the real surgery [(53.8±4.5)°, (21.6±3.3)°, (44.6±7.8)°, (34.3±6.1)points], while the VAS [(4.1±0.5)points, (1.2±0.2)points] was lower than that at 1 day after the real surgery [(8.3±1.4)points] (all P<0.05). The medial column was stable in 34 patients and unstable in 2 at 1 day after the real surgery. Complications included screw cutting out in the articular surface in 1 patient and humeral head necrosis in 1. Conclusion:Treatment of complex proximal humeral fractures with open reduction and internal fixation assisted by computer virtual surgery is conducive to maintaining reduction effect, promoting shoulder joint function, relieving pain and reducing complications.

Objective: To understand the characteristics and causes of pesticide poisoning in Xuzhou city, and provide basis for formulating prevention and control measures. Methods: The cases of pesticide poisoning in Xuzhou City from 2005 to 2017 were collected from "Pesticide Poisoning Report Card" . The data were analyzed and assessed by EpiData. The SPSS 22.0 software was used for statistical analysis. Results: During the thirteen years, there were a total of 8092 cases of pesticide poisoning, among which, the number of occupational pesticide poisoning was 1 408, accounting for 17.4% of the total number of cases, 14 patients died, the case fatality rate was 0.1%. There were 2, 992 cases of male poisoning, accounting for 36.97% of the total number of cases, and 5, 100 cases of female poisoning, accounting for 63.03%. There were 6684 non-productive pesticide poisonings, accounting for 82.6% of the total number of cases; 387 deaths occurred, and the mortality rate was 5.8%. Among non-productive poisonings, the incidence of oral pesticide poisoning was 84.3%, and the incidence of accidental poisoning by pesticides was 15.7%. Organophosphorus pesticides poisoning cases accounted for the majority of oral pesticide poisoning cases. The overall incidence of pesticide poisoning showed a downward trend. The age of non-productive pesticide poisoning cases was mainly 15-44 years old, and the number of cases of poisoning were 4 029 cases (60.28%) . With the increase of age, the mortality rate of poisoning cases was higher, especially for those over 60 years old who died of oral pesticide poisoning (40.1%) . The peak of pesticide poisoning began to increase in the second quarter and reached its peak in the third quarter. Conclusion Although the cases of pesticide poisoning reported in Xuzhou City have been declining in recent years, the situation is still severe. The proportion of oral pesticide suicide accounts for a large proportion, and the mortality rate of elderly and female is relatively high, and the government should pay more attention. Workers should conduct safety education and psychological counseling to improve the knowledge and consciousness of safe use of pesticides.

Objective To observe the preventive effects of puerarinon development of deep vein thrombosis (DVT) in elderly women with osteoporosis after hip replacement. Methods 100 elderly women with osteoporosis who scheduled for femoral head arthrolastybetween January 2012 and January 2014 in Cangzhou Central Hospital were selected and then randomly divided into a study group (n=50) and a control group (n=50). The control group received routine anti?inflammatory and anticoagulant therapy ,while the study group received intravenous drip of puerarinof 400 mg mixed with 5%glucose liquid 500 ml daily for 15 days as a treatment course. After the treatment, DVT incidence rate ,change of early diagnostic indexes and hemorheology were compared with their baselines. Results DVT incidence rate was significantly lowerin the study group than in the control group (8.0%vs. 24.0%, P<0.05). Ascompare with the control group,thromboxane A2/prostacyclin,plasma homocysteine and hemorheology?were significantly reduced (P < 0.05). Conclusions Puerarin has a preventive effect for deep vein thrombosis in elderly women with osteoporosis after hip replacement.

Objective To evaluate the significance of serum 8-hydroxy-deoxyguanosine acid ( 8-OHdG) in the diagnosis of nonalcoholic steatohepatitis ( NASH).Methods Patients or healthy subjects were enrolled at the Second Hospital of Tianjin Medical University and the Second People ′s Hospital of Tianjin from May 2013 to December 2015.A total of 41 patients with nonalcoholic fatty liver disease were enrolled in the study , including 20 nonalcoholic simple fatty liver ( NAFL) patients and 21 NASH patients whose diagnosis were proven by liver biopsy.The other 32 healthy subjects were studied as controls.Serum 8-OHdG, ALT, AST and GGT were tested.Nonalcoholic fatty liver disease activity score ( NAS ) and expression of 8-OHdG in liver was investigated between NAFL patients and NASH patients.The correlations between serum 8-OHdG and serum ALT , AST, GGT, and 8-OHdG in liver tissue in NASH group were investigated.In addition , the receiver operating characteristic ( ROC) curve analyses for ALT and 8-OHdG levels were performed in NAFL patients and NASH patients , and the cut-off value was determined.Results Serum 8-OHdG values in healthy controls , NAFL and NASH patients were (0.19 ±0.16) μg/L, (0.22 ±0.16) μg/L, (0.42 ±0.21) μg/L respectively.The serum 8-OHdG and serum ALT, GGT and 8-OHdG in liver tissue were all positively correlated in NASH group with respective correlation coefficient r values as 0.454 7, 0.382 9, and 0.497 6.AUC of 8-OHdG was 0.901 with cut-off value 0.39 μg/L.Its sensitivity was 88.3%and specificity was 81.5%, which were higher than those of ALT.Conclusion The value of serum 8-OHdG would be used as a marker for the diagnosis of NASH.