Objective:To investigate the regulatory role and mechanism of synaptic vesicle protein 2A (SV2A) in apoptosis of drug-resistant epilepsy neurons.Methods:One hundred and fifty specific pathogen-free (SPF) Sprague-Dawley (SD) rats were randomly numbered; 20 rats were selected as a normal control group (NC group), and the remaining 130 rats were subjected to chronic epilepsy models of lithium-pilocarpine. Phenobarbital and phenytoin sodium for 2 weeks were given to these rats after modeling; fanally, 94 rats with chronic epilepsy were divided into a drug-resistant group (phenobarbital and phenytoin sodium-resistant epilepsy [PRE] group, reduction in episodes<50%, n= 55) and a drug-sensitive group (phenobarbital and phenytoin sodium-sensitive epilepsy [PSE] group, reduction in episodes by≥50%, n=38). Rats in the PRE group were further randomly divided into 5 groups, namely a up-regulated-SV2A PRE group (UPRE group), a down-regulated-SV2A PRE group (DPRE group), a up-regulated-SV2A control group (UPRC group), a down-regulated-SV2A control group (DPRC group), and a non-transfected PRE group; different types of lentivirus were given to the first 4 groups via stereotactic brain injection. Ten days after lentiviral transfection, virus detection was performed; and 2 weeks after lentiviral transfection, occurrence of epileptic seizures was observed, and after that, rats were sacrificed and the hippocampal tissues were collected for subsequent experiments. Western blotting was used to detect the expressions of SV2A, cyclophilin A (CyPA), apoptosis-inducing factor (AIF), and superoxide dismutase 2 (SOD2) in the cell nucleus or mitochondria; coimmunoprecipitation experiment was performed to observe the interaction among SV2A, CyPA and AIF proteins; immunofluorescent co-staining was used to observe the CyPA/AIF localization; mitochondrial damage was detected by electron microscopy; ATP content in the hippocampal tissues was detected by luciferase method, 8-hydroxy-2-deoxyguanosine (8-OHDG) expression was detected by immunofluorescent staining, and neuronal apoptosis rate was calculated by double staining with neuron-specific nuclear protein (NeuN) and TUNEL. Results:(1) Confocal microscopy revealed that the hippocampal tissues in the 4 transfected groups showed green fluorescence inherent to the lentivirus, indicating successful viral infection. Compared with the UPRC group, the UPRE group had significantly reduced frequency of epileptic seizures and seizure duration ( P<0.05). (2) Western blotting showed that, in mitochondria, the UPRE group had significantly higher expressions of SV2A (0.475± 0.105 vs. 0.136±0.043), CyPA (0.473±0.041 vs. 0.175±0.047), AIF (0.443±0.058 vs. 0.131±0.037), and SOD2 (0.457±0.037 vs. 0.152±0.038) compared with the UPRC group ( P<0.05); the DPRE group had significantly decreased expressions of SV2A (0.038±0.013 vs. 0.184±0.047), CyPA (0.041±0.010 vs. 0.214±0.040), AIF (0.040±0.019 vs. 0.175±0.046), and SOD2 (0.043±0.017 vs. 0.187±0.039) compared with the DPRC group ( P<0.05). In the cell nucleus, the UPRE group had significantly lower expressions of AIF (0.336±0.084 vs. 0.649±0.209) and CyPA (0.331±0.086 vs. 0.620±0.162) compared with the UPRC group ( P<0.05); the DPRE group had statistically higher expressions of AIF (0.771± 0.180 vs. 0.519±0.144) and CyPA (0.738±0.223 vs. 0.488±0.091) compared with the DPRC group ( P< 0.05). (3) Co-immunoprecipitation experiment results showed that the bidirectional precipitation results of SV2A and AIF, SV2A and CyPA, and AIF and CyPA were all positive, suggesting existence of interactions. (4) Immunofluorescent co-staining showed that the fluorescence changes of CyPA and AIF were consistent. (5) Electron microscopy showed that mitochondria in the NC group had intact structure; mitochondria in the UPRE group, UPRC group, DPRC group and DPRE group showed swelling and cristae fragmentation; among them, injury in the UPRE group was relatively less severe than that in the UPRC group, while that in the DPRC group was more severe than that in the DPRE group. (6) Compared with the UPRC group, the UPRE group had statistically higher ATP content ( P<0.05); compared with the DPRC group, the DPRE group had significantly lower ATP content ( P<0.05).(7) Immunofluorescent staining results showed that the UPRE group had significantly lower 8-OHDG expression than the UPRC group ( P<0.05); compared with the DPRC group, the DPRE group had statistically higher 8-OHDG expression ( P<0.05). (8) The UPRE group had significantly lower NeuN-TUNEL double staining positive rate than the UPRC group ( P<0.05); compared with the DPRC group, the DPRE group had significantly higher NeuN-TUNEL double staining positive rate ( P<0.05). Conclusion:SV2A can play a role in the apoptosis of hippocampal neurons in rats with drug-resistant epilepsy by regulating the nuclear translocation of AIF/CyPA and mitochondrial damage.

Objective To explore the impact of irregular shape of head CT hematomas on postoperative re-bleeding and prognosis of patients with spontaneous intracerebral hemorrhage(ICH)who undergo craniotomy for hematoma evacuation.Methods We retrospectively enrolled consecutive patients with ICH who underwent craniotomy for hematoma evacuation in the Department of Neurosurgery of the Second People's Hospital of Guiyang Affiliated to Guizhou Medical University from January 2019 to June 2024.Baseline and clinical data were collected form the patients,including age,gender,smoking history,drinking history,hypertension,diabetes,history of anticoagulant use,admission systolic and diastolic blood pressure,admission National Institutes of Health stroke scale(NIHSS)score,Glasgow coma scale(GCS)score,time from onset to the first head CT,neutrophil-to-lymphocyte ratio(NLR),and platelet-to-lymphocyte ratio(PLR).Admission head CT scans were used to assess hematoma shape(regular or irregular),hematoma location(basal ganglia,lobar,multifocal),hematoma volume,perihematomal edema volume,the presence of midline shift,and intraventricular extension.Volume of the hematoma was assessed 2 days after surgery.Postoperative re-bleeding is defined as an increase in the volume of the hematoma by 12.5 ml compared to the previous postoperative CT scan within 2 weeks after surgery,or the reappearance of high-density areas in the focal area of the head CT scan during follow-up after complete hematoma clearance.Conduct patients follow-ups via telephone at 6 months postoperatively to assess their modified Rankin scale(mRS)scores.The sliding dichotomy method was applied to define prognosis based on the patients' baseline characteristics and disease severity.The prognostic score was calculated using formula:10 × admission GCS score-age-0.64 × admission hematoma volume.A prognostic score＞27.672 was considered potentially favorable,while a score ≤ 27.672 was considered potentially unfavorable.For patients with a potentially favorable prognosis,an mRS score of 0-2 was defined as a good outcome,and a score of 3-6 as a poor outcome.For those with a potentially unfavorable prognosis,an mRS score of 0-3 was defined as a good outcome,and a score of 4-6 as a poor outcome.In the comparison of baseline and clinical data between patients with regular and irregular hematoma shapes,factors with P＜0.05 were included in propensity score matching(PSM)to adjust for confounding variables.A 1∶1 matching was performed using the nearest neighbor method with a caliper value set to 0.25.Variables with statistically significant differences between groups after PSM matching were included in the multivariate Logistic regression analysis to identify influencing factors for postoperative re-bleeding and poor prognosis in ICH patients undergoing craniotomy hematoma evacuation.The predictive value of irregular hematoma shape for postoperative rebleeding and poor prognosis in ICH patients was analyzed using receiver operating characteristic(ROC)curve analysis.Results(1)A total of 440 ICH patients were enrolled,including 342 males and 98 females,aged from 20 to 84 years with a mean age of(56±12)years.Statistically significant differences were observed in baseline and clinical data between patients with regular and irregular hematoma shapes before PSM,including age,admission GCS score,NIHSS score,NLR,proportion of patients with hematoma rupture into ventricles,preoperative hematoma volume,proportion of patients with midline shift,preoperative volume of hematoma surrounding edema,proportion of patients with hematoma located in multiple sites,and postoperative 2-day hematoma volume(all P＜0.05).After propensity score matching of these factors,298 ICH patients were included in the statistical analysis,comprising 228 males and 70 females,with an age range of 20 to 84 years and a mean age of(57±12)years.Following PSM,no statistically significant differences were observed in the baseline and clinical characteristics between patients with irregular and regular hematoma shapes(all P＞0.05).(2)After propensity score matching,28 patients experienced postoperative re-bleeding while 270 did not.Significant differences were observed between the two groups in the following factors:proportion of patients with a history of anticoagulant use,admission PLR,NLR,irregular hematoma shape,and hematoma volume at 2 days after operation(all P＜0.05).No statistically significant differences were found in the remaining baseline and clinical characteristics(all P＞0.05).Using postoperative re-bleeding as the dependent variable and incorporating factors with P＜0.05 from the univariate analysis as independent variables,multivariate Logistic regression analysis identified irregular hematoma shape(OR,2.821,95％CI 1.142-6.968,P=0.025)and larger hematoma volume at 2 days post-operation(OR,1.062,95％CI 1.026-1.099,P＜0.01)as independent risk factors for re-bleeding following intracranial hematoma evacuation in ICH patients.ROC curve analysis demonstrated that irregular hematoma shape predicted postoperative re-bleeding with an area under the curve(AUC)of 0.62,showing a sensitivity of 71.4％and a specificity of 52.2％.(3)After propensity score matching,174 patients had poor prognosis while 124 had good prognosis.Significant intergroup differences were observed in age,admission GCS score,NIHSS score,irregular hematoma shape,proportion of patients with hematomas located in the basal ganglia and cerebral lobes,and hematoma volume at 2 days post-operation(all P＜0.05).No statistically significant differences were found in the remaining baseline and clinical characteristics(all P＞0.05).Using poor prognosis as the dependent variable and incorporating factors with P＜0.05 from univariate analysis as independent variables,multivariate Logistic regression analysis revealed that advanced age(OR,1.039,95％CI 1.015-1.064,P=0.002),high admission NIHSS score(OR,1.068,95％CI 1.025-1.113,P=0.002),irregular hematoma shape(OR,2.675,95％CI 1.582-4.524,P＜0.01),and larger hematoma volume at 2 days post-operation(OR,1.033,95％CI 1.002-1.064,P=0.038)were independent risk factors for poor prognosis.Conversely,lobar hematoma location(OR,0.192,95％CI 0.073-0.504,P＜0.01)was identified as a protective factor.ROC curve analysis showed that irregular hematoma shape predicted poor prognosis after intracranial hematoma evacuation with an AUC of 0.61,demonstrating a sensitivity of 59.2％and specificity of 62.9％.Conclusion Irregular hematoma shape on head CT is an independent risk factor for both postoperative re-bleeding and poor prognosis in ICH patients undergoing craniotomy for hematoma evacuation.

Objective To explore the impact of irregular shape of head CT hematomas on postoperative re-bleeding and prognosis of patients with spontaneous intracerebral hemorrhage(ICH)who undergo craniotomy for hematoma evacuation.Methods We retrospectively enrolled consecutive patients with ICH who underwent craniotomy for hematoma evacuation in the Department of Neurosurgery of the Second People's Hospital of Guiyang Affiliated to Guizhou Medical University from January 2019 to June 2024.Baseline and clinical data were collected form the patients,including age,gender,smoking history,drinking history,hypertension,diabetes,history of anticoagulant use,admission systolic and diastolic blood pressure,admission National Institutes of Health stroke scale(NIHSS)score,Glasgow coma scale(GCS)score,time from onset to the first head CT,neutrophil-to-lymphocyte ratio(NLR),and platelet-to-lymphocyte ratio(PLR).Admission head CT scans were used to assess hematoma shape(regular or irregular),hematoma location(basal ganglia,lobar,multifocal),hematoma volume,perihematomal edema volume,the presence of midline shift,and intraventricular extension.Volume of the hematoma was assessed 2 days after surgery.Postoperative re-bleeding is defined as an increase in the volume of the hematoma by 12.5 ml compared to the previous postoperative CT scan within 2 weeks after surgery,or the reappearance of high-density areas in the focal area of the head CT scan during follow-up after complete hematoma clearance.Conduct patients follow-ups via telephone at 6 months postoperatively to assess their modified Rankin scale(mRS)scores.The sliding dichotomy method was applied to define prognosis based on the patients' baseline characteristics and disease severity.The prognostic score was calculated using formula:10 × admission GCS score-age-0.64 × admission hematoma volume.A prognostic score＞27.672 was considered potentially favorable,while a score ≤ 27.672 was considered potentially unfavorable.For patients with a potentially favorable prognosis,an mRS score of 0-2 was defined as a good outcome,and a score of 3-6 as a poor outcome.For those with a potentially unfavorable prognosis,an mRS score of 0-3 was defined as a good outcome,and a score of 4-6 as a poor outcome.In the comparison of baseline and clinical data between patients with regular and irregular hematoma shapes,factors with P＜0.05 were included in propensity score matching(PSM)to adjust for confounding variables.A 1∶1 matching was performed using the nearest neighbor method with a caliper value set to 0.25.Variables with statistically significant differences between groups after PSM matching were included in the multivariate Logistic regression analysis to identify influencing factors for postoperative re-bleeding and poor prognosis in ICH patients undergoing craniotomy hematoma evacuation.The predictive value of irregular hematoma shape for postoperative rebleeding and poor prognosis in ICH patients was analyzed using receiver operating characteristic(ROC)curve analysis.Results(1)A total of 440 ICH patients were enrolled,including 342 males and 98 females,aged from 20 to 84 years with a mean age of(56±12)years.Statistically significant differences were observed in baseline and clinical data between patients with regular and irregular hematoma shapes before PSM,including age,admission GCS score,NIHSS score,NLR,proportion of patients with hematoma rupture into ventricles,preoperative hematoma volume,proportion of patients with midline shift,preoperative volume of hematoma surrounding edema,proportion of patients with hematoma located in multiple sites,and postoperative 2-day hematoma volume(all P＜0.05).After propensity score matching of these factors,298 ICH patients were included in the statistical analysis,comprising 228 males and 70 females,with an age range of 20 to 84 years and a mean age of(57±12)years.Following PSM,no statistically significant differences were observed in the baseline and clinical characteristics between patients with irregular and regular hematoma shapes(all P＞0.05).(2)After propensity score matching,28 patients experienced postoperative re-bleeding while 270 did not.Significant differences were observed between the two groups in the following factors:proportion of patients with a history of anticoagulant use,admission PLR,NLR,irregular hematoma shape,and hematoma volume at 2 days after operation(all P＜0.05).No statistically significant differences were found in the remaining baseline and clinical characteristics(all P＞0.05).Using postoperative re-bleeding as the dependent variable and incorporating factors with P＜0.05 from the univariate analysis as independent variables,multivariate Logistic regression analysis identified irregular hematoma shape(OR,2.821,95％CI 1.142-6.968,P=0.025)and larger hematoma volume at 2 days post-operation(OR,1.062,95％CI 1.026-1.099,P＜0.01)as independent risk factors for re-bleeding following intracranial hematoma evacuation in ICH patients.ROC curve analysis demonstrated that irregular hematoma shape predicted postoperative re-bleeding with an area under the curve(AUC)of 0.62,showing a sensitivity of 71.4％and a specificity of 52.2％.(3)After propensity score matching,174 patients had poor prognosis while 124 had good prognosis.Significant intergroup differences were observed in age,admission GCS score,NIHSS score,irregular hematoma shape,proportion of patients with hematomas located in the basal ganglia and cerebral lobes,and hematoma volume at 2 days post-operation(all P＜0.05).No statistically significant differences were found in the remaining baseline and clinical characteristics(all P＞0.05).Using poor prognosis as the dependent variable and incorporating factors with P＜0.05 from univariate analysis as independent variables,multivariate Logistic regression analysis revealed that advanced age(OR,1.039,95％CI 1.015-1.064,P=0.002),high admission NIHSS score(OR,1.068,95％CI 1.025-1.113,P=0.002),irregular hematoma shape(OR,2.675,95％CI 1.582-4.524,P＜0.01),and larger hematoma volume at 2 days post-operation(OR,1.033,95％CI 1.002-1.064,P=0.038)were independent risk factors for poor prognosis.Conversely,lobar hematoma location(OR,0.192,95％CI 0.073-0.504,P＜0.01)was identified as a protective factor.ROC curve analysis showed that irregular hematoma shape predicted poor prognosis after intracranial hematoma evacuation with an AUC of 0.61,demonstrating a sensitivity of 59.2％and specificity of 62.9％.Conclusion Irregular hematoma shape on head CT is an independent risk factor for both postoperative re-bleeding and poor prognosis in ICH patients undergoing craniotomy for hematoma evacuation.

Objective:To investigate the regulatory role and mechanism of synaptic vesicle protein 2A (SV2A) in apoptosis of drug-resistant epilepsy neurons.Methods:One hundred and fifty specific pathogen-free (SPF) Sprague-Dawley (SD) rats were randomly numbered; 20 rats were selected as a normal control group (NC group), and the remaining 130 rats were subjected to chronic epilepsy models of lithium-pilocarpine. Phenobarbital and phenytoin sodium for 2 weeks were given to these rats after modeling; fanally, 94 rats with chronic epilepsy were divided into a drug-resistant group (phenobarbital and phenytoin sodium-resistant epilepsy [PRE] group, reduction in episodes<50%, n= 55) and a drug-sensitive group (phenobarbital and phenytoin sodium-sensitive epilepsy [PSE] group, reduction in episodes by≥50%, n=38). Rats in the PRE group were further randomly divided into 5 groups, namely a up-regulated-SV2A PRE group (UPRE group), a down-regulated-SV2A PRE group (DPRE group), a up-regulated-SV2A control group (UPRC group), a down-regulated-SV2A control group (DPRC group), and a non-transfected PRE group; different types of lentivirus were given to the first 4 groups via stereotactic brain injection. Ten days after lentiviral transfection, virus detection was performed; and 2 weeks after lentiviral transfection, occurrence of epileptic seizures was observed, and after that, rats were sacrificed and the hippocampal tissues were collected for subsequent experiments. Western blotting was used to detect the expressions of SV2A, cyclophilin A (CyPA), apoptosis-inducing factor (AIF), and superoxide dismutase 2 (SOD2) in the cell nucleus or mitochondria; coimmunoprecipitation experiment was performed to observe the interaction among SV2A, CyPA and AIF proteins; immunofluorescent co-staining was used to observe the CyPA/AIF localization; mitochondrial damage was detected by electron microscopy; ATP content in the hippocampal tissues was detected by luciferase method, 8-hydroxy-2-deoxyguanosine (8-OHDG) expression was detected by immunofluorescent staining, and neuronal apoptosis rate was calculated by double staining with neuron-specific nuclear protein (NeuN) and TUNEL. Results:(1) Confocal microscopy revealed that the hippocampal tissues in the 4 transfected groups showed green fluorescence inherent to the lentivirus, indicating successful viral infection. Compared with the UPRC group, the UPRE group had significantly reduced frequency of epileptic seizures and seizure duration ( P<0.05). (2) Western blotting showed that, in mitochondria, the UPRE group had significantly higher expressions of SV2A (0.475± 0.105 vs. 0.136±0.043), CyPA (0.473±0.041 vs. 0.175±0.047), AIF (0.443±0.058 vs. 0.131±0.037), and SOD2 (0.457±0.037 vs. 0.152±0.038) compared with the UPRC group ( P<0.05); the DPRE group had significantly decreased expressions of SV2A (0.038±0.013 vs. 0.184±0.047), CyPA (0.041±0.010 vs. 0.214±0.040), AIF (0.040±0.019 vs. 0.175±0.046), and SOD2 (0.043±0.017 vs. 0.187±0.039) compared with the DPRC group ( P<0.05). In the cell nucleus, the UPRE group had significantly lower expressions of AIF (0.336±0.084 vs. 0.649±0.209) and CyPA (0.331±0.086 vs. 0.620±0.162) compared with the UPRC group ( P<0.05); the DPRE group had statistically higher expressions of AIF (0.771± 0.180 vs. 0.519±0.144) and CyPA (0.738±0.223 vs. 0.488±0.091) compared with the DPRC group ( P< 0.05). (3) Co-immunoprecipitation experiment results showed that the bidirectional precipitation results of SV2A and AIF, SV2A and CyPA, and AIF and CyPA were all positive, suggesting existence of interactions. (4) Immunofluorescent co-staining showed that the fluorescence changes of CyPA and AIF were consistent. (5) Electron microscopy showed that mitochondria in the NC group had intact structure; mitochondria in the UPRE group, UPRC group, DPRC group and DPRE group showed swelling and cristae fragmentation; among them, injury in the UPRE group was relatively less severe than that in the UPRC group, while that in the DPRC group was more severe than that in the DPRE group. (6) Compared with the UPRC group, the UPRE group had statistically higher ATP content ( P<0.05); compared with the DPRC group, the DPRE group had significantly lower ATP content ( P<0.05).(7) Immunofluorescent staining results showed that the UPRE group had significantly lower 8-OHDG expression than the UPRC group ( P<0.05); compared with the DPRC group, the DPRE group had statistically higher 8-OHDG expression ( P<0.05). (8) The UPRE group had significantly lower NeuN-TUNEL double staining positive rate than the UPRC group ( P<0.05); compared with the DPRC group, the DPRE group had significantly higher NeuN-TUNEL double staining positive rate ( P<0.05). Conclusion:SV2A can play a role in the apoptosis of hippocampal neurons in rats with drug-resistant epilepsy by regulating the nuclear translocation of AIF/CyPA and mitochondrial damage.

Objective:To investigate the behavioral, electroencephalographic, and cognitive functional differences in drug-resistant epileptic rat models of cognitive impairment prepared by intraperitoneal injection of lithium chloride-pilocarpine followed by intracranial injection of pilocarpine or carbamylcholine.Methods:One hundred and sixty adult male SD rats were randomly divided into normal control group ( n=10), lithium chloride-pilocarpine group (establishing epileptic rat models by intraperitoneal injection of lithium chloride-pilocarpine, n=50), pilocarpine-pilocarpine group (intracranial injection of pilocarpine after intraperitoneal injection of lithium chloride-pilocarpine, n=50)and pilocarpine-carbamylcholine group (intracranial injection of carbamylcholine after intraperitoneal injection of lithium chloride-pilocarpine, n=50). Frequency and duration of spontaneously recurrent seizures (SRSs) were observed by video monitoring system, and 2 weeks after that, phenobarbital and phenytoin sodium were injected intraperitoneally to screen drug-resistant models. Frequency and amplitude of the epileptic waves in EEG were recorded by BL-420 Bio-signal Acquisition and Processing System. Novel object recognition experiment was used to detect the novel exploration, Y-maze free exploration experiment and new and different arm experiment were used to detect the spatial recognition and memory ability, and Morris water maze experiment was used to detect the spatial memory ability. Results:(1) Twenty-four rats (48.00%) survived in the lithium chloride-pilocarpine group, 25 (78.00%) in the pilocarpine-pilocarpine group, and 21 (65.62%) in the pilocarpine-carbamylcholine group; and ultimately 7, 9, and 8 drug-resistant epileptic rat models were identified, respectively; frequency and duration of SRSs in the pilocarpine-pilocarpine group and pilocarpine-carbamylcholine group were significantly higher/longer than those in the lithium chloride-pilocarpine group ( P<0.05). (2) The pilocarpine-pilocarpine group and pilocarpine-carbamylcholine group had significantly higher amplitude of the epileptic waves in EEG compared with the lithium chloride-pilocarpine group ( P<0.05); the frequency of the epileptic waves in EEG increased gradually in the lithium chloride-pilocarpine group, pilocarpine-pilocarpine group, and pilocarpine-carbamylcholine group ( P<0.05). (3) Discrimination index, accuracy, ratio of distance traveled in novel arm to total distance, and time of novel arm entries gradually decreased in the normal control group, lithium chloride-pilocarpine group, pilocarpine-pilocarpine group, and pilocarpine-carbamylcholine group, with significant differences ( P<0.05). (4) Compared with the normal control group, the pilocarpine-pilocarpine group and pilocarpine-carbamylcholine group had significantly decreased frequency in crossing the original platform ( P<0.05); compared with the normal control group, lithium-pilocarpine chloride group and pilocarpine-pilocarpine group, the pilocarpine-carbamylcholine group had statistically shorter distance of target quadrant activity ( P<0.05); number of entries in the target quadrant gradually decreased in the normal control group, lithium chloride-pilocarpine group, pilocarpine-pilocarpine group, and pilocarpine-carbamylcholine group, with significant differences ( P<0.05). Conclusion:Drug-resistant epileptic rat models established by intracranial injection of carbamylcholine after intraperitoneal injection of lithium chloride-pilocarpine have high survival rate, high SRSs rate, and severe cognitive impairment, which is suitable for studying drug-resistant epilepsy combined with cognitive impairment.

Objective To investigate the effect of malignant cerebellar hemorrhage on 3-month prognosis of small spontaneous cerebellar hemorrhage.Methods Clinical data of 380 consecutive patients with spontaneous cerebellar hemorrhage admitted in Emergency Department of the Affil-iated Hospital of Guizhou Medical University,Neurosurgery Department of Jinyang Hospital Af-filiated to Guizhou Medical University,and Neurosurgery Department of the Second Affiliated Hospital of Guizhou Medical University from April 2014 to March 2023 were collected and retro-spectively analyzed,and finally,70 patients who met the requirements of small amount of sponta-neous cerebellar hemorrhage were enrolled in this study.They were assigned into benign cerebel-lar hemorrhage group(43 cases)and malignant cerebellar hemorrhage group(27 cases).Accord-ing to their clinical outcomes in 3 months after onset,they were divided into a good prognosis group(51 cases)and a poor prognosis group(19 cases).General clinical data,imaging data,com-plications,inflammatory indicators and prognosis were collected.After collinear diagnosis was used to exclude factors with collinear influence,the independent correlation between good progno-sis and poor prognosis was analyzed by binary logistic regression model.Finally,ROC curve was plotted to analyze the significant data.Results The maximum diameter of hematoma was signifi-cantly larger in the malignant cerebellar hemorrhage group than the benign group(P=0.021).The patients of the poor prognosis group had larger proportion of malignant cerebellar hemor-rhage,and higher neutrophil percentage,WBC count and NLR than those of the good prognosis group(P＜0.05,P＜0.01).Multivariate logistic regression analysis showed that malignant cere-bellar hemorrhage was an independent predictor of poor prognosis in 3 months(OR=6.218,95％CI:1.140-17.623,P=0.013).The sensitivity,specificity,positive predictive value,negative pre-dictive value and Youden index of malignant cerebellar hemorrhage in predicting the 3-month prognosis of patients were 63.2％,70.6％,44.4％,83.7％and 0.338,respectively,and the AUC value was 0.669.Conclusion Malignant cerebellar hemorrhage is an independent predictor of 3-month prognosis in patients with small spontaneous cerebellar hemorrhage.The patients with malignant cerebellar hemorrhage have poor prognosis than those with benign cerebellar hemorrhage.

Intracerebral hemorrhage (ICH) is an acute cerebrovascular disease with the highest mortality in subtype of stroke, accounting for 15%-20% of all strokes. There was no specific treatment for ICH currently. The mechanism of secondary neurological impairment after ICH remains unclear. Whether it is related to the process of ferroptosis caused by iron deposition is worth to further discuss. This paper reviews the related published articles about ferroptosis, which include mechanisms, inhibition methods and biomarker of ferroptosis.

Objective:To explore the correlation of damage-associated molecular pattern molecules(DAMPs) serum S100, C-reactive protein (CRP), serum amyloid A (SAA) and uric acid (UA) with age and body mass index (BMI) to provide direction for further study of metabolic inflammation and inflammaging.Methods:The observational study method was used,and three hundred and sixty-six healthy people (131 males and 235 females) were selected from the physical examination center of the Second People′s Hospital of Hunan Province from May to October 2020. They were divided into three age groups according to the age interval of 20 years, including 156 (53 males and 103 females) aged 20-40 years, 110 (36 males and 74 females) aged 41-60 years, and 100 (42 males and 58 females) aged 61-80 years. Kruskal Wallis H test was used to compare the differences of serum S100, CRP, SAA and UA levels among different age groups. According to the Health Industry Standards of the People′s Republic of China-Weight Determination for Adults, the boundary is BMI =24 kg/m 2. The healthy people were divided into non overweight (BMI<24 kg/m 2) and overweight (BMI ≥ 24 kg/m 2) two groups. The 1∶1 propensity score was used to match the age and gender. There were 96 non overweight subjects [43 males, 53 females, age 52 (35, 66) years], 96 overweight subjects [44 males, 52 females, age 52 (36, 64) years]. The serum levels of S100, CRP, SAA and UA in different BMI groups were compared by Mann-Whitney U test. Results:The median serum UA concentrations in males and females were 356 and 277 μmol/L, and the levels of serum UA of male was significantly higher than that of female ( Z=-10.428, P<0.001); the median serum SAA concentrations in males and females were 3.1 mg/L and 4.4 mg/L, while the serum SAA level of female was significantly higher than that of male ( Z=3.652, P<0.001); for 20-40, 41-60, and 61-80 years old group, the median concentration of serum S100 was 0.058, 0.057, 0.070 μg/L, and the median concentration of serum CRP was 0.32, 0.58, 0.93 mg/L; the median serum SAA concentrations were 3.2, 4.0, 5.2 mg/L; serum uric acid concentrations were (301.8±61.5), (298.6±69.8), (329.0±77.8) μmol/L. The levels of serum S100, CRP, SAA, UA in 61-80 years group were significantly higher than those of 20-40 years group ( H=-2.749, H=-6.731, H=-5.033, H=-2.521, P=0.018, P<0.001, P<0.001, P=0.035) and 41-60 years old group ( H=-2.719, H=-2.539, H=-2.540, H=-2.486, P=0.020, P=0.033, P=0.033, P=0.039).The levels of serum CRP of 41-60 years group was significantly higher than that of 20-40 years group ( H=-4.108, P<0.001). There was no significant difference in levels of serum S100, SAA and UA between 20-40 years group and 41-60 years group ( H=0.189, H=-2.360, H=-0.165, P=1.000, P=0.055, P=1.000); the levels of serum CRP and SAA were positively correlated with age ( r s =0.342, r s =0.301, P<0.001, P<0.001); for overweight, non-overweight group, the median concentrations of serum S100 were 0.065 μg/L, 0.059 μg/L, the median concentrations of serum CRP were 0.92 mg/L, 0.47 mg/L, the median concentrations of serum SAA were 5.0 mg/L, 4.1 mg/L, the median concentrations of serum UA were 339.5 μmol/L, 301.5 μmol/L, the levels of CRP, SAA and UA in the overweight group were higher than those in the non-overweight group ( Z=4.278, Z=2.025, Z=3.787, P<0.001, P=0.043, P<0.001); the levels of S100 in the overweight group was higher than those in the non-overweight group, but there was no significant difference in S100 between the two groups ( Z=0.862, P=0.388); the levels of Serum CRP and UA were positively correlated with BMI ( r s =0.348, r s =0.264, P<0.001, P=0.009). Conclusions:With the increase of age, the serum S100, CRP, SAA and UA levels of healthy people may be on the rise, especially the serum CRP and SAA levels are positively correlated with age; the serum S100, CRP, SAA and UA levels of overweight people may be higher than those of non-overweight people, especially the serum CRP, UA levels are positively correlated with BMI.

Objective:To explore the correlation of damage-associated molecular pattern molecules(DAMPs) serum S100, C-reactive protein (CRP), serum amyloid A (SAA) and uric acid (UA) with age and body mass index (BMI) to provide direction for further study of metabolic inflammation and inflammaging.Methods:The observational study method was used,and three hundred and sixty-six healthy people (131 males and 235 females) were selected from the physical examination center of the Second People′s Hospital of Hunan Province from May to October 2020. They were divided into three age groups according to the age interval of 20 years, including 156 (53 males and 103 females) aged 20-40 years, 110 (36 males and 74 females) aged 41-60 years, and 100 (42 males and 58 females) aged 61-80 years. Kruskal Wallis H test was used to compare the differences of serum S100, CRP, SAA and UA levels among different age groups. According to the Health Industry Standards of the People′s Republic of China-Weight Determination for Adults, the boundary is BMI =24 kg/m 2. The healthy people were divided into non overweight (BMI<24 kg/m 2) and overweight (BMI ≥ 24 kg/m 2) two groups. The 1∶1 propensity score was used to match the age and gender. There were 96 non overweight subjects [43 males, 53 females, age 52 (35, 66) years], 96 overweight subjects [44 males, 52 females, age 52 (36, 64) years]. The serum levels of S100, CRP, SAA and UA in different BMI groups were compared by Mann-Whitney U test. Results:The median serum UA concentrations in males and females were 356 and 277 μmol/L, and the levels of serum UA of male was significantly higher than that of female ( Z=-10.428, P<0.001); the median serum SAA concentrations in males and females were 3.1 mg/L and 4.4 mg/L, while the serum SAA level of female was significantly higher than that of male ( Z=3.652, P<0.001); for 20-40, 41-60, and 61-80 years old group, the median concentration of serum S100 was 0.058, 0.057, 0.070 μg/L, and the median concentration of serum CRP was 0.32, 0.58, 0.93 mg/L; the median serum SAA concentrations were 3.2, 4.0, 5.2 mg/L; serum uric acid concentrations were (301.8±61.5), (298.6±69.8), (329.0±77.8) μmol/L. The levels of serum S100, CRP, SAA, UA in 61-80 years group were significantly higher than those of 20-40 years group ( H=-2.749, H=-6.731, H=-5.033, H=-2.521, P=0.018, P<0.001, P<0.001, P=0.035) and 41-60 years old group ( H=-2.719, H=-2.539, H=-2.540, H=-2.486, P=0.020, P=0.033, P=0.033, P=0.039).The levels of serum CRP of 41-60 years group was significantly higher than that of 20-40 years group ( H=-4.108, P<0.001). There was no significant difference in levels of serum S100, SAA and UA between 20-40 years group and 41-60 years group ( H=0.189, H=-2.360, H=-0.165, P=1.000, P=0.055, P=1.000); the levels of serum CRP and SAA were positively correlated with age ( r s =0.342, r s =0.301, P<0.001, P<0.001); for overweight, non-overweight group, the median concentrations of serum S100 were 0.065 μg/L, 0.059 μg/L, the median concentrations of serum CRP were 0.92 mg/L, 0.47 mg/L, the median concentrations of serum SAA were 5.0 mg/L, 4.1 mg/L, the median concentrations of serum UA were 339.5 μmol/L, 301.5 μmol/L, the levels of CRP, SAA and UA in the overweight group were higher than those in the non-overweight group ( Z=4.278, Z=2.025, Z=3.787, P<0.001, P=0.043, P<0.001); the levels of S100 in the overweight group was higher than those in the non-overweight group, but there was no significant difference in S100 between the two groups ( Z=0.862, P=0.388); the levels of Serum CRP and UA were positively correlated with BMI ( r s =0.348, r s =0.264, P<0.001, P=0.009). Conclusions:With the increase of age, the serum S100, CRP, SAA and UA levels of healthy people may be on the rise, especially the serum CRP and SAA levels are positively correlated with age; the serum S100, CRP, SAA and UA levels of overweight people may be higher than those of non-overweight people, especially the serum CRP, UA levels are positively correlated with BMI.

To construct an evaluation indicator system on food safety management capacity for food production enterprises by Delphi method, and to provide a scientific theoretical framework for food safety management capacity for food enterprises.
 Methods: A framework for the evaluation system on food safety management capabilities was established and experts in relevant fields were invited to conduct 2 rounds of expert consultation. Indicators were selected and determined based on expert opinions and statistical analysis results. The hierarchical model was constructed by the analytic hierarchy process to determine the weight coefficients of each indicator.
 Results: The positive coefficients of the two rounds of expert consultation were 84% and 100%, and the coefficient of experts' authority was 0.826. The coordination coefficients of the indicators in the first round of consultation were 0.439, 0.323 and 0.324, and they were 0.607, 0.351, and 0.368 in the second round, respectively, with statistically significant differences (P<0.001). The evaluation index system of food safety management capacity for food production enterprises was established after the two rounds of expert consultation, and the system consisted of 5 indicators for the first level, 18 indicators for the second level and 32 indicators for the third level, with corresponding weights. 
 Conclusion: The enthusiasm, authority and concordance of experts during this consultation are good, and the selected indicators are reasonable and comprehensive, which can provide a basis for the evaluation of food safety management capabilities for food enterprises.
Delphi Technique ; Emotions ; Safety Management