Objective To investigate the potential mechanism of atorvastatin in treating chronic subdural hematoma(CSDH)through network pharmacology and experimental validation,thereby providing theoretical foundation and experimental evidence for further basic and clinical research.Methods The target genes of atorvastatin and CSDH-related genes were identified through network databases including chEMBL,NCBI PubChem Compound,SwissTargetPrediction,GeneCards,and DisGeNET.Potential target genes of atorvastatin for CSDH treatment were screened using Venn diagrams,followed by enrichment analysis performed with R software.Protein-protein interaction(PPI)analysis was conducted using the STRING database,and molecular docking was employed to verify the binding capability between atorvastatin and the proteins encoded by the target genes.An endothelial cell inflammation model was established to assess the effects of atorvastatin on the expression and secretion of inflammation-related genes using Real-time quantitative reverse transcription polymerase chain reaction(RT-qPCR)and enzyme-linked immunosorbent assay(ELISA).The impact of atorvastatin on endothelial barrier function in the inflammation model was evaluated using the FITC-Dextran permeability assay.Results A total of 19 potential target genes of atorvastatin for CSDH treatment were identified.Enrichment analysis indicated that these genes are primarily involved in the regulation of inflammation,angiogenesis,and coagulation/fibrinolysis processes.Based on the PPI analysis,five key target genes-matrix metalloproteinase 2(MMP-2),matrix metalloproteinase 9(MMP-9),interleukin-6(IL-6),C-X-C motif chemokine ligand 8/interleukin 8(CXCL-8/IL-8),and serpin family E member 1(SERPINE-1)—were selected for molecular docking,which revealed favorable binding interactions between atorvastatin and these proteins.In the endothelial cell inflammation model,atorvastatin suppressed the expression and secretion of the aforementioned genes as well as inflammatory markers such as intercellular adhesion molecule 1(ICAM-1)and vascular cell adhesion molecule 1(VCAM-1)(IL-6:F=64.526,P＜0.001;CXCL-8/IL-8:F=37.779,P＜0.001;ICAM-1:F=86.253,P＜0.001;VCAM-1:F=39.631,P＜0.001;MMP-2:F=264.413,P＜0.001;MMP-9:F=86.675,P＜0.001;SERPINE-1:F=71.180,P＜0.001).Furthermore,atorvastatin alleviated endothelial barrier dysfunction caused by inflammation(F=343.890,P＜0.001).Conclusion Atorvastatin may exert therapeutic effects on CSDH by inhibiting inflammatory responses.

Objective To investigate the potential mechanism of atorvastatin in treating chronic subdural hematoma(CSDH)through network pharmacology and experimental validation,thereby providing theoretical foundation and experimental evidence for further basic and clinical research.Methods The target genes of atorvastatin and CSDH-related genes were identified through network databases including chEMBL,NCBI PubChem Compound,SwissTargetPrediction,GeneCards,and DisGeNET.Potential target genes of atorvastatin for CSDH treatment were screened using Venn diagrams,followed by enrichment analysis performed with R software.Protein-protein interaction(PPI)analysis was conducted using the STRING database,and molecular docking was employed to verify the binding capability between atorvastatin and the proteins encoded by the target genes.An endothelial cell inflammation model was established to assess the effects of atorvastatin on the expression and secretion of inflammation-related genes using Real-time quantitative reverse transcription polymerase chain reaction(RT-qPCR)and enzyme-linked immunosorbent assay(ELISA).The impact of atorvastatin on endothelial barrier function in the inflammation model was evaluated using the FITC-Dextran permeability assay.Results A total of 19 potential target genes of atorvastatin for CSDH treatment were identified.Enrichment analysis indicated that these genes are primarily involved in the regulation of inflammation,angiogenesis,and coagulation/fibrinolysis processes.Based on the PPI analysis,five key target genes-matrix metalloproteinase 2(MMP-2),matrix metalloproteinase 9(MMP-9),interleukin-6(IL-6),C-X-C motif chemokine ligand 8/interleukin 8(CXCL-8/IL-8),and serpin family E member 1(SERPINE-1)—were selected for molecular docking,which revealed favorable binding interactions between atorvastatin and these proteins.In the endothelial cell inflammation model,atorvastatin suppressed the expression and secretion of the aforementioned genes as well as inflammatory markers such as intercellular adhesion molecule 1(ICAM-1)and vascular cell adhesion molecule 1(VCAM-1)(IL-6:F=64.526,P＜0.001;CXCL-8/IL-8:F=37.779,P＜0.001;ICAM-1:F=86.253,P＜0.001;VCAM-1:F=39.631,P＜0.001;MMP-2:F=264.413,P＜0.001;MMP-9:F=86.675,P＜0.001;SERPINE-1:F=71.180,P＜0.001).Furthermore,atorvastatin alleviated endothelial barrier dysfunction caused by inflammation(F=343.890,P＜0.001).Conclusion Atorvastatin may exert therapeutic effects on CSDH by inhibiting inflammatory responses.

Objective To explore the risk factors influencing the prognosis by analyzing clinical data of patients with acute paraquat intoxication, and to assess the prognostic values of acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ) score, sequential organ failure assessment (SOFA) score, and Acute Kidney Injury Network (AKIN) stage.Methods The clinical data of patients with acute paraquat intoxication admitted into the First People's Hospital of Xianyang City during October 2005 to May 2015 were retrospectively analyzed.The patients were divided into death group and survival group according to 28-day outcome after poisoning.The gender, age, body weight index, toxin dose, time elapsed from poisoning to gastric lavage, time elapsed from poisoning to hemoperfusion (HP), times of HP treatment, white blood cell count (WBC), alanine aminotransferase (ALT), aspartate transaminase (AST), total bilirubin (TBil), serum creatinine (SCr), blood urea nitrogen (BUN), creatine kinase (CK) were determined at admission.Arterial partial pressure of oxygen (PaO2), arterial partial pressure of carbon dioxide (PaCO2), arterial lactate (Lac), and APACHE Ⅱ score, SOFA score and AKIN stage were recorded and compared between two groups.The receiver operating characteristic (ROC) curve was plotted for APACHE Ⅱ score, SOFA score and AKIN stage to analyze the prognostic value for patients with acute paraquat intoxication.Results There were 118 cases in total,with 64 survivors and 54 deaths in 28 days, and the fatality rate was 45.76％.Compared with survival group, the toxic dose (mL: 66.29 ± 27.40 vs.29.16 ± 19.40), time elapsed from poisoning to gastric lavage (minutes: 60.37 ± 26.68 vs.41.17± 14.82), WBC count (× 109/L: 16.86±2.77 vs.10.25 ± 2.60), ALT (U/L: 53.94± 10.85 vs.36.40±9.21),SCr (μmol/L: 159.69±42.85 vs.81.73±34.40) at admission as well as Lac (mmol/L: 3.06± 1.33 vs.1.71 ±0.88),APACHE Ⅱ score (6.46±2.38 vs.3.31 ± 1.51), SOFA score (3.31 ± 1.06 vs.2.21±0.76) 48 hours after admission were significantly higher in the death group (all P ＜ 0.01).PaO2 and PaCO2 48 hours after admission were significantly lower in death group than those in the survival group [PaO2 (mmHg, 1 mmHg =0.133 kPa): 64.07± 13.04 vs.75.40 ± 13.27, PaCO2 (mmHg): 26.20 ± 8.89 vs.31.25 ± 6.29, both P ＜ 0.01].There were 18, 15, 11 and 10 patients in AKIN 0, 1, 2, 3 stage 48 hours after admission respectively in death group, and 38, 15, 7, 4 in survival group.The difference between two groups was statistically significant (P ＜ 0.01).There were no statistically significant differences in gender, age, body mass index, time elapsed from poisoning to HP, levels of HP, and AST, TBil, BUN and CK at admission between the two groups.At 48 hours after admission, the area under the ROC curve (AUC) of APACHE Ⅱ score predicting the prognosis of patients with acute paraquat poisoning was 0.875 [95％ confidence interval (95％CI) =0.814-0.935, P =0.000].When the cut-off point of APACHE Ⅱ score was 4, the sensitivity and specificity were 79.6％ and 79.7％, and the best Youden index was 0.593.The AUC of SOFA score was 0.776 (95％CI=0.692-0.859, P =0.000).When the cut-off point of FOFA score was 3, the sensitivity was 72.2％, the specificity 67.2％, and the best Youden index 0.394.The AKIN stage of ROC curve had an area of 0.656 (95％CI =0.556-0.755, P =0.004).When the cut-off point of AKIN stage was 1, the sensitivity was 66.7％, the specificity was 59.4％, and the best Youden index was 0.261.Conclusions Amount of the poison, time elapsed from poisoning to gastric lavage, and WBC, ALT, SCr at admission as well as PaO2, PaCO2 and Lac 48 hours after admission are the risk factors for prediction of the prognosis of acute paraquat intoxication.APACHE Ⅱ score, SOFA score and AKIN stage can be used to assess the prognosis of acute paraquat poisoning, and APACHE Ⅱ score is better than SOFA score and AKIN stage.