1.Effect of laminin subunit α3 on epithelial-mesenchymal transition, invasion, and metastasis abilities of pancreatic cancer
Nenghong YANG ; Likun REN ; She TIAN ; Min HAN ; Zhu LI ; Yuxiang ZHAO ; Peng LIU
Journal of Clinical Hepatology 2025;41(2):322-332
ObjectiveTo investigate the effect of laminin subunit α3 (LAMA3) on the epithelial-mesenchymal transition (EMT), invasion, and metastasis abilities of pancreatic cancer (PC). MethodsA comprehensive analysis was performed for tumor- and EMT-related databases to identify the EMT genes associated with PC, especially LAMA3. The methods of qRT-PCR and Western blot were used to measure the expression level of LAMA3 in PC tissue and cell lines; immunofluorescence assay was used to determine the localization of LAMA3 in PANC-1 cells; Transwell assay was used to investigate the effect of LAMA3 on the invasion and migration abilities of PC cells. The t-test was used for comparison of continuous data between groups. ResultsThe analysis of the TCGA database identified 3 EMT-related oncogenes for PC, i.e., LAMA3, AREG, and SDC1. The LASSO-Cox regression model showed that LAMA3 had the most significant impact on the prognosis of PC (risk score=0.256 1×LAMA3+0.043 1×SDC1+0.071 4×AREG). The Cox model and nomogram showed that the high expression of LAMA3 was an independent risk factor for the poor prognosis of PC (hazard ratio=1.32, 95% confidence interval: 1.07 — 1.62, P<0.01). Experimental results showed that there was a significant increase in the expression of LAMA3 in pancreatic cancer tissue compared with the normal pancreatic tissue. Compared with the HPDE cell line, there were varying degrees of increase in the expression of LAMA3 in pancreatic cancer AsPC-1, BxPC-3, PANC-1, MIA PaCa-2, and SW1990 cell lines, with the highest expression level in PANC-1 cells. The enrichment analysis showed that LAMA3 was associated with the biological processes and signaling pathways such as EMT, collagen metabolism, extracellular matrix degradation, the TGF-β pathway, and the PI3K pathway. After the knockdown of LAMA3, there were significant reductions in the expression levels of N-Cadherin, Vimentin, and Snail, while there was a significant increase in the expression level of E-Cadherin. Transwell assay showed that there were significant reductions in the invasion and migration abilities of PANC-1 cells after the knockdown of LAMA3. ConclusionLAMA3 is highly expressed in PC and can promote the EMT, invasion, and migration of PC cells, and therefore, LAMA3 may be used as a novel diagnostic marker and a new therapeutic target for PC.
2.SV2A inhibits AIF/CyPA nuclear translocation and mitochondrial damage to alleviate apoptosis of hippocampal neurons in drug-resistant epilepsy rats
Mianmian REN ; Chen LI ; Siying REN ; Guofeng WU ; Likun WANG
Chinese Journal of Neuromedicine 2025;24(10):973-985
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.
3.Influence of irregular shape of hematoma on postoperative re-bleeding and prognosis in patients with spontaneous intracerebral hemorrhage undergoing craniotomy for hematoma evacuation
Yuanyuan FU ; Li LUO ; Jinhua YANG ; Likun WANG ; Lian HE ; Guofeng WU ; Siying REN ; Shiqi LIN
Chinese Journal of Cerebrovascular Diseases 2025;22(9):601-611
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.
4.Influence of irregular shape of hematoma on postoperative re-bleeding and prognosis in patients with spontaneous intracerebral hemorrhage undergoing craniotomy for hematoma evacuation
Yuanyuan FU ; Li LUO ; Jinhua YANG ; Likun WANG ; Lian HE ; Guofeng WU ; Siying REN ; Shiqi LIN
Chinese Journal of Cerebrovascular Diseases 2025;22(9):601-611
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.
5.SV2A inhibits AIF/CyPA nuclear translocation and mitochondrial damage to alleviate apoptosis of hippocampal neurons in drug-resistant epilepsy rats
Mianmian REN ; Chen LI ; Siying REN ; Guofeng WU ; Likun WANG
Chinese Journal of Neuromedicine 2025;24(10):973-985
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.
6.Impact of malignant cerebellar hemorrhage on prognosis of patients with small amount of spontaneous cerebellar hemorrhage
Chaozhen YANG ; Siying REN ; Guofeng WU ; Shiqi LIN ; Zhiyuan ZHANG ; Likun WANG
Chinese Journal of Geriatric Heart Brain and Vessel Diseases 2024;26(5):535-538
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.
7.Rational analysis of the use of antiemetic drugs in tumor chemotherapy patients in our hospital
Danjun REN ; Juanli ZHANG ; Meiyou LIU ; Likun DING ; Tingting FAN ; Di ZHANG ; Jingwen WANG ; Aidong WEN
China Pharmacy 2024;35(12):1495-1499
OBJECTIVE To provide reference for the rational use of antiemetic drugs in tumor chemotherapy patients. METHODS The data of tumor patients who were given antiemetic drugs were collected from 9 departments of our hospital with hospital information system from Oct. 1st to Nov. 30th in 2022, such as oncology department, radiotherapy department, gynecology department, and gastroenterology department. The application of chemotherapy drugs and the use of antiemetic drugs were analyzed statistically, and the irrational use of antiemetic drugs was analyzed. RESULTS A total of 520 patients were included, involving 248 (47.69%) using chemotherapy drugs with a moderate emetogenic risk level and 135 (25.96%) with a high emetogenic risk level. A total of 461 cases (73.06%) of 5-hydroxytryptamine 3-receptor antagonists were used, including palonosetron in 333 cases, ondansetron in 106 cases, tropisetron in 15 cases and granisetron in 7 cases, and only 148 cases of patients were prioritized for the use of nationally procured medicines and national essential medicines (32.10%). Neurokinin-1 receptor antagonists were used in 170 cases (26.94%), including fosaprepitant in 112 cases and aprepitant in 58 cases. The use of antiemetic drugs was unreasonable in 162 patients (31.15%); among the types of irrational drugs, the antiemetic regimen was unreasonable in the largest number of cases (22.40%), followed by the irrational pharmacoeconomics (19.13%). CONCLUSIONS The emetogenic risk levels of chemotherapy drugs used for tumor patients in our hospital are primarily moderate to high, and there is irrational use of antiemetic regimen and pharmacoeconomics. Clinicians, nurses, pharmacists and hospital departments should collaborate as multiple teams to strengthen full supervision of the standardization of antiemetic drugs, reasonably select antiemetic drugs based on emetogenicity rating, and improve the compliance of doctors with the guidelines to ensure the safety, effectiveness, and cost-effective of patient medication.
8.Drug-resistant epileptic rat models of cognitive impairment established by different ways: a comparative study
Ruyue LI ; Mianmian REN ; Chen LI ; Guofeng WU ; Ping SUN ; Likun WANG
Chinese Journal of Neuromedicine 2024;23(3):217-224
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.
9.Pay attention to the prevention and supervision of important organ damage related to acetaminophen
Tingting FAN ; Juanli ZHANG ; Likun DING ; Di ZHANG ; Danjun REN ; Meiyou LIU ; Jingwen WANG ; Aidong WEN
Adverse Drug Reactions Journal 2024;26(2):65-69
Acetaminophen is currently the most widely used antipyretic analgesics in clinical practice. The conventional dose of acetaminophen is safe and reliable, and long-term use in large quantities can cause damage to important organs. In recent years, some new safety issues of acetaminophen have been found, such as its possibility to increase blood pressure in patients with hypertension, its association with increased risk of cardiovascular disease and all-cause mortality with sodium-containing acetaminophen, the discovery of multiple biomarkers for predicting and diagnosing acetaminophen-related liver injury and its prognosis, and its possibility to increase the risk of kidney injury. The safety prevention strategies for important organ injuries related to acetaminophen include strict restrictions on medication dosage and duration, and attention to medication safety for special populations. For patients who have experienced significant organ damages, their causal relationship should be evaluated, acetaminophen should be stopped, and specific treatment, and symptomatic and supportive treatments should be provided.
10.Pay attention to the prevention and supervision of important organ damage related to acetaminophen
Tingting FAN ; Juanli ZHANG ; Likun DING ; Di ZHANG ; Danjun REN ; Meiyou LIU ; Jingwen WANG ; Aidong WEN
Adverse Drug Reactions Journal 2024;26(2):65-69
Acetaminophen is currently the most widely used antipyretic analgesics in clinical practice. The conventional dose of acetaminophen is safe and reliable, and long-term use in large quantities can cause damage to important organs. In recent years, some new safety issues of acetaminophen have been found, such as its possibility to increase blood pressure in patients with hypertension, its association with increased risk of cardiovascular disease and all-cause mortality with sodium-containing acetaminophen, the discovery of multiple biomarkers for predicting and diagnosing acetaminophen-related liver injury and its prognosis, and its possibility to increase the risk of kidney injury. The safety prevention strategies for important organ injuries related to acetaminophen include strict restrictions on medication dosage and duration, and attention to medication safety for special populations. For patients who have experienced significant organ damages, their causal relationship should be evaluated, acetaminophen should be stopped, and specific treatment, and symptomatic and supportive treatments should be provided.

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