1.Analysis of the influencing factors of early neurological deterioration and short-term prognosis in minor acute ischemic stroke patients
Longsheng CHU ; Xianjun HUANG ; Chenglei WANG ; Bohao WEI ; Yuepei GAO ; Ameng LI ; Ke YANG ; Junfeng XU ; Xianjin SHANG ; Zhiming ZHOU
Chinese Journal of Cerebrovascular Diseases 2025;22(8):524-536
Objective To investigate the influencing factors associated with early neurological deterioration(END)in patients with minor acute ischemic stroke(mAIS),develop a clinical prediction model for END,and identify independent risk factors for 90-day neurological functional outcomes after stroke.Methods mAIS patients admitted consecutively to the Department of Neurology,Yijishan Hospital of Wannan Medical College(the First Affiliated Hospital of Wannan Medical College),from July 2023 to July 2024 were retrospectively collected.A minor ischemic stroke was defined as acute ischemic stroke with a National Institutes of Health stroke scale(NIHSS)score≤5 on admission.Baseline,clinical,and imaging data of all mAIS patients were collected and recorded,including demographic information(age,sex),past medical history(hypertension,diabetes mellitus,hyperlipidemia,coronary heart disease,atrial fibrillation),smoking history,alcohol consumption,baseline blood pressure,pre-onset modified Rankin scale(mRS),NIHSS scores at admission and during hospitalization(24 hours,48 hours,72 hours after admission),motor component subscore of the NIHSS scores,NIHSS scores at discharge,trial of Org 10172 in acute stroke treatment(TOAST)classification,laboratory indicators(fasting blood glucose,hemoglobin A1c[HbA1c],total cholesterol,triglycerides,high-density lipoprotein,low-density lipoprotein),clinical treatment information(intravenous thrombolysis,mono antiplatelet therapy,dual antiplatelet therapy,anticoagulation therapy)and length of stay.The status of stenosis and occlusion in the culprit vessel were assessed based on imaging results.Mild-to-moderate stenosis was defined as a stenosis rate of 0%to 69%,severe stenosis as a stenosis rate of 70%to 99%,and occlusion as complete interruption of the supplying artery.END was defined as an increase in NIHSS score of ≥2 points from baseline within 72 hours after admission,combined with an increase of at least 1 point in the motor score compared to the score at admission.Prognosis was assessed via telephone follow-ups at 90-day after onset using mRS score,with an mRS score ≤ 2 indicating a favorable outcome and an mRS score>2 indicating a poor outcome.Variables with P<0.05 in the univariate analysis were incorporated into multivariate Logistic regression analysis to identify the independent risk factors for END in mAIS patients.A nomogram model was constructed,and calibration curves along with decision curve analysis were plotted to evaluate the model's goodness-of-fit and clinical utility.Univariate and multivariate Logistic regression analyses were performed to identify factors associated with poor 90-day functional outcome after mAIS.Results(1)A total of 826 patients were included,aged 33-94 years,with a median age of 67(57,76)years.There were 571 males and 255 females.The NIHSS score at admission ranged from 0 to 5,with a median NIHSS score at admission of 3(2,4).The NIHSS motor subscore at admission ranged from 0 to 5,with a median baseline NIHSS motor score of 2(0,2).Among them,119 patients(14.4%)were in the END group and 707 patients(85.6%)were included in the non-END group.At 90days after stroke,744 patients(90.1%)had a favorable outcome,while 82 patients(9.9%)had a poor outcome.(2)Univariate analysis showed that there were statistically significant differences between the END group and the non-END group in terms of HbA1c,fasting blood glucose,baseline NIHSS score,baseline NIHSS motor subscore,history of alcohol consumption,diabetes mellitus,culprit vessel stenosis and occlusion,and TOAST classification(all P<0.05).Statistically significant differences were observed between the favorable outcome group and the poor outcome group in HbA1c,fasting blood glucose,incidence of END,baseline NIHSS score,discharge NIHSS score,culprit vessel stenosis and occlusion,TOAST classification,and history of alcohol consumption(all P<0.05).(3)Multivariate Logistic regression analysis indicated that mAIS patients with severe stenosis of the culprit vessel(OR,5.88,95%CI2.32-14.91,P<0.01),occlusion of the culprit vessel(OR,5.74,95%CI 2.25-14.62,P<0.01),history of alcohol consumption(OR,5.59,95%CI3.41-9.17,P<0.01),elevated HbA1c(OR,1.67,95%CI 1.35-2.08,P<0.01),and higher baseline NIHSS motor score(OR,1.43,95%CI 1.08-1.89,P=0.012)had an increased risk of END.A higher discharge NIHSS score(OR,2.59,95%CI 1.89-3.57,P<0.01)and the occurrence of END(OR,18.42,95%CI 5.13-66.18,P<0.01)were associated with poor 90-day functional outcome after mAIS.(4)The nomogram model constructed based on independent risk factors of END in mAIS patients demonstrated an AUC of 0.78(95%CI 0.73-0.83)for predicting END,with a sensitivity of 0.8 and a specificity of 0.7.The model showed good calibration,and the Hosmer-Lemeshow test indicated good agreement between predicted and observed values(P=0.333).Decision curve analysis revealed that the model provided a high net benefit across a range of high-risk thresholds(0.1-0.7),suggesting its potential clinical utility.Conclusions Severe stenosis of the culprit vessel,occlusion of the culprit vessel,glycated hemoglobin levels,baseline NIHSS motor subscale scores,and history of alcohol consumption are independent risk factors for END in patients with mAIS.The nomogram model constructed based on these factors demonstrated good predictive performance.END and NIHSS scores at discharge are independent predictors of poor 90-day outcomes in patients with mAIS.
2.Early endovascular treatment for cerebral infarction caused by intracranial atherosclerosis or cardioembolism:a comparative study
Youqing XU ; Haichen SHEN ; Xiangjun XU ; Junfeng XU ; Ke YANG ; Xianhui DING ; Xianjun HUANG
Journal of Interventional Radiology 2025;34(9):931-934
Objective To compare the clinical efficacy and safety of early endovascular treatment(EVT)for the stroke patients caused by large vessel occlusion(LVO)due to intracranial atherosclerosis(ICAS)or due to cardioembolism(CE).Methods The clinical data of 488 patients with acute anterior circulation LVO stroke,who received early endovascular treatment at the Yijishan Hospital of Wannan Medical College of China from October 2015 to December 2023,were retrospectively analyzed.According to the cause of disease,the patients were divided into ICAS group(n=108)and CE group(n=380).The clinical data,mainly including the proportion of patients having a good prognosis at 90 days after operation(modified Rankin Scale score ≤2 points),the incidence of symptomatic intracranial cerebral hemorrhage(sICH),and the mortality of patients at 90 days after operation.Multivariate logistic regression analysis was used to analyze the factors influencing patient's prognosis.Results Of the 488 patients,29(5.9%)developed postoperative sICH,242(49.6%)achieved a good prognosis at 90 days after the operation,and 91(18.6%)died.The above outcomes in the ICAS group were one,66,and 11 patients respectively,which in the CE group were 28,176,and 80 respectively,and the differences between the two groups were statistically significant(all P<0.05).Multivariate logistic regression analysis indicated that good prognosis at 90 days after the operation(OR=0.962,95%CI:0.404-2.288,P=0.930)and the postoperative 90-day mortality(OR=1.379,95%CI:0.436-4.362,P=0.584)were not the factors influencing prognosis,while the postoperative sICH(OR=19.132,95%CI:1.332-274.791,P=0.030)was the factor influencing prognosis.Conclusion In CE group,the incidence of sICH and the postoperative 90-day mortality are higher,while in ICAS group,the postoperative 90-day good prognosis rate is higher.The postoperative sICH is the factor influencing prognosis.
3.Analysis of the influencing factors of early neurological deterioration and short-term prognosis in minor acute ischemic stroke patients
Longsheng CHU ; Xianjun HUANG ; Chenglei WANG ; Bohao WEI ; Yuepei GAO ; Ameng LI ; Ke YANG ; Junfeng XU ; Xianjin SHANG ; Zhiming ZHOU
Chinese Journal of Cerebrovascular Diseases 2025;22(8):524-536
Objective To investigate the influencing factors associated with early neurological deterioration(END)in patients with minor acute ischemic stroke(mAIS),develop a clinical prediction model for END,and identify independent risk factors for 90-day neurological functional outcomes after stroke.Methods mAIS patients admitted consecutively to the Department of Neurology,Yijishan Hospital of Wannan Medical College(the First Affiliated Hospital of Wannan Medical College),from July 2023 to July 2024 were retrospectively collected.A minor ischemic stroke was defined as acute ischemic stroke with a National Institutes of Health stroke scale(NIHSS)score≤5 on admission.Baseline,clinical,and imaging data of all mAIS patients were collected and recorded,including demographic information(age,sex),past medical history(hypertension,diabetes mellitus,hyperlipidemia,coronary heart disease,atrial fibrillation),smoking history,alcohol consumption,baseline blood pressure,pre-onset modified Rankin scale(mRS),NIHSS scores at admission and during hospitalization(24 hours,48 hours,72 hours after admission),motor component subscore of the NIHSS scores,NIHSS scores at discharge,trial of Org 10172 in acute stroke treatment(TOAST)classification,laboratory indicators(fasting blood glucose,hemoglobin A1c[HbA1c],total cholesterol,triglycerides,high-density lipoprotein,low-density lipoprotein),clinical treatment information(intravenous thrombolysis,mono antiplatelet therapy,dual antiplatelet therapy,anticoagulation therapy)and length of stay.The status of stenosis and occlusion in the culprit vessel were assessed based on imaging results.Mild-to-moderate stenosis was defined as a stenosis rate of 0%to 69%,severe stenosis as a stenosis rate of 70%to 99%,and occlusion as complete interruption of the supplying artery.END was defined as an increase in NIHSS score of ≥2 points from baseline within 72 hours after admission,combined with an increase of at least 1 point in the motor score compared to the score at admission.Prognosis was assessed via telephone follow-ups at 90-day after onset using mRS score,with an mRS score ≤ 2 indicating a favorable outcome and an mRS score>2 indicating a poor outcome.Variables with P<0.05 in the univariate analysis were incorporated into multivariate Logistic regression analysis to identify the independent risk factors for END in mAIS patients.A nomogram model was constructed,and calibration curves along with decision curve analysis were plotted to evaluate the model's goodness-of-fit and clinical utility.Univariate and multivariate Logistic regression analyses were performed to identify factors associated with poor 90-day functional outcome after mAIS.Results(1)A total of 826 patients were included,aged 33-94 years,with a median age of 67(57,76)years.There were 571 males and 255 females.The NIHSS score at admission ranged from 0 to 5,with a median NIHSS score at admission of 3(2,4).The NIHSS motor subscore at admission ranged from 0 to 5,with a median baseline NIHSS motor score of 2(0,2).Among them,119 patients(14.4%)were in the END group and 707 patients(85.6%)were included in the non-END group.At 90days after stroke,744 patients(90.1%)had a favorable outcome,while 82 patients(9.9%)had a poor outcome.(2)Univariate analysis showed that there were statistically significant differences between the END group and the non-END group in terms of HbA1c,fasting blood glucose,baseline NIHSS score,baseline NIHSS motor subscore,history of alcohol consumption,diabetes mellitus,culprit vessel stenosis and occlusion,and TOAST classification(all P<0.05).Statistically significant differences were observed between the favorable outcome group and the poor outcome group in HbA1c,fasting blood glucose,incidence of END,baseline NIHSS score,discharge NIHSS score,culprit vessel stenosis and occlusion,TOAST classification,and history of alcohol consumption(all P<0.05).(3)Multivariate Logistic regression analysis indicated that mAIS patients with severe stenosis of the culprit vessel(OR,5.88,95%CI2.32-14.91,P<0.01),occlusion of the culprit vessel(OR,5.74,95%CI 2.25-14.62,P<0.01),history of alcohol consumption(OR,5.59,95%CI3.41-9.17,P<0.01),elevated HbA1c(OR,1.67,95%CI 1.35-2.08,P<0.01),and higher baseline NIHSS motor score(OR,1.43,95%CI 1.08-1.89,P=0.012)had an increased risk of END.A higher discharge NIHSS score(OR,2.59,95%CI 1.89-3.57,P<0.01)and the occurrence of END(OR,18.42,95%CI 5.13-66.18,P<0.01)were associated with poor 90-day functional outcome after mAIS.(4)The nomogram model constructed based on independent risk factors of END in mAIS patients demonstrated an AUC of 0.78(95%CI 0.73-0.83)for predicting END,with a sensitivity of 0.8 and a specificity of 0.7.The model showed good calibration,and the Hosmer-Lemeshow test indicated good agreement between predicted and observed values(P=0.333).Decision curve analysis revealed that the model provided a high net benefit across a range of high-risk thresholds(0.1-0.7),suggesting its potential clinical utility.Conclusions Severe stenosis of the culprit vessel,occlusion of the culprit vessel,glycated hemoglobin levels,baseline NIHSS motor subscale scores,and history of alcohol consumption are independent risk factors for END in patients with mAIS.The nomogram model constructed based on these factors demonstrated good predictive performance.END and NIHSS scores at discharge are independent predictors of poor 90-day outcomes in patients with mAIS.
4.Association between the magnitude of systolic blood pressure reduction after successful endovascular thrombectomy with outcomes and post-procedure symptomatic intracranial hemorrhage in acute large vessel occlusion stroke patients
Xianjun HUANG ; Hao WANG ; Junfeng XU ; Xianhui DING ; Yapeng GUO ; Xiangjun XU ; Ke YANG ; Qian YANG ; Zhiming ZHOU
Chinese Journal of Cerebrovascular Diseases 2024;21(3):145-155
Objective To explore the association of the magnitude of systolic blood pressure reduction(SBPr)with post-procedure 24 h symptomatic intracranial hemorrhage(sICH)and 90-day clinical outcomes in patients with successful endovascular thrombectomy(EVT).Methods Consecutively registered patients with EVT caused by anterior circulation large vessel occlusion stroke(LVOS)in the First Affiliated Hospital of Wannan Medical College(Yijishan Hospital)between July 2015 and April 2023 and patients with successful reperfusion were analyzed.Demographic data,medical history(hypertension,diabetes),the trial of Org 10172 in acute stroke treatment(TOAST)classification,the baseline National Institutes of Health Stroke Scale(NIHSS)score and the baseline Alberta stroke early CT(ASPECT)score of patients were collected.And procedure related parameters(including time from onset to puncture,time from onset to reperfusion,occluded site[internal carotid artery,M1 segment of middle cerebral artery,M2 segment of middle cerebral artery],collateral circulation status[determined based on preoperative occluded angiography showing the range of collateral circulation in the occluded vessel area,defined as good collateral circulation with a reflux range of ≥ 50%and poor collateral circulation with a reflux range of<50%]),immediate postoperative reperfusion status(evaluated using the modified thrombolysis for cerebral infarction[mTICI]grading,successful reperfusion defined as mTICI grading of 2b-3),24 hours sICH,and 90 days clinical outcomes(evaluated using the modified Rankin scale score at 90days after EVT,with a score ≤ 2indicating a good prognosis and a score>2indicating a poor prognosis).SBPr was defined as(baseline SBP-mean SBP)/baseline SBP x 100%.According to the the magnitude of SBPr,SBPr is divided into 5 categories(<-10%,-10%-10%,>10%-20%,>20%-30%and>30%).Based on the clinical outcomes at 90 days and the occurrence of sICH at 24 hours after EVT,patients were divided into a good prognosis group and a poor prognosis group,as well as an sICH group and a non-sICH group.The relationship between SBPr and postoperative 90 days clinical prognosis or sICH was analyzed using a binary Logistic regression model.Subgroup analysis was conducted based on a history of hypertension(yes and no),continuous intravenous hypotensive therapy(yes and no),baseline ASPECT scores(3-5 and 6-10),and collateral circulation status(good and bad).Using a restricted cubic plot to depict the relationship between SBPr and sICH and clinical prognosis at 90days.Results(1)In total,731 patients were included.The median age was 71(62,77)years and 424(58.0%)were men.The median baseline NIHSS score was 14(12,18),the median baseline ASPECT was 9(7,10),405(55.4%)patients achieved 90-day modified Rankin scale score 0-2,and 35 patients(4.8%)developed sICH.(2)Multivariate analysis showed that the older age(OR,1.036,95%CI 1.017-1.056),the higher baseline NIHSS score(OR,1.095,95%CI1.049-1.144),the lower baseline ASPECT score(OR,0.704,95%CI 0.636-0.780),diabetes(OR,1.729,95%CI 1.084-2.758),bad collateral circulation(good collateral circulation vs.bad collateral circulation,OR,0.481,95%CI 0.332-0.696)and SBPr>30%(SBPr-10%-10%as a reference,OR,2.238,95%CI 1.230-4.071),the higher the risk of poor clinical outcomes at 90 days(all P<0.05).Continuous intravenous hypotensive therapy is a risk factor for postoperative 24 h sICH(OR,2.278,95%CI 1.047-4.953;P=0.038),while SBPr 20%-30%is associated with a lower risk of postoperative 24 h sICH(SBPr-10%-10%as a reference,OR,0.362,95%CI0.131-0.998;P=0.049).(3)The restrictive cube plot shows that there is a U-shaped relationship between SBPr after EVT and poor clinical outcomes at 90 days,while there is a nearly linear relationship with the occurrence of sICH.The more SBP reduction,the lower the incidence of sICH.(4)In the subgroup analyses,in the non-hypertension history and the good collateral circulation group,SBPr>30%has a higher risk of poor clinical outcomes compared to SBPr-10%-10%(OR and 95%CI were 2.921[1.000-8.528]and 2.363[1.078-5.183],respectively,with P=0.05 or P<0.05);After EVT,the group receiving continuous intravenous hypotensive therapy and the baseline ASPECT score 6-10 groups showed a significant correlation between SBPr>30%and poor clinical outcomes at 90 days(SBPr-10%-10%as a reference,OR and 95%CI were 2.646[1.168-5.993]and 2.481[1.360-4.527],respectively,with P<0.05).The correlation between SBPr and lower incidence of sICH was only found in the subgroup of poor collateral circulation(SBPr-10%-10%as a reference,SBPr>20%-30%:OR,0.133,95%CI 0.027-0.652;SBPr>30%:OR,0.104,95%CI 0.013-0.864;all P<0.05).Conclusions Among patients who achieved successful reperfusion with EVT,SBPr might be related to a worse functional outcome at 90 days and sICH 24 h after operation.However,the relationship may exhibit significant heterogeneity across different subgroups.Baseline ASPECT score,history of hypertension,collateral circulation,and the use of continuous venous hypertension after EVT have been highlighted in individualized blood pressure management after EVT.
5.Influencing factor of acute multivessel occlusion and its impact on prognosis of acute large vessel occlusion stroke patients after successful recanalization of endovascular treatment
Yuepei GAO ; Chenglei WANG ; Yapeng GUO ; Junfeng XU ; Xianhui DING ; Xiangjun XU ; Ke YANG ; Qian YANG ; Xianjun HUANG ; Zhiming ZHOU
Chinese Journal of Cerebrovascular Diseases 2024;21(11):767-777
Objective To investigate the influencing factors for acute multiple vessels occlusion(MVO)and its impact on the prognosis of patients with anterior circulation acute large vessel occlusion stroke(ALVOS)who achieved successful recanalization after endovascular treatment(EVT).Methods Patients with anterior circulation ALVOS who received successful EVT at the Yijishan Hospital of Wannan Medical College between July 2015 and April 2023 were retrospectively analyzed.Baseline data,including age,sex,onset-to-puncture time(OTP),onset-to-recanalization time(OTR),medical history(including atrial fibrillation,diabetes,hypertension),alcohol and smoking history,admission blood pressure(systolic and diastolic),Alberta stroke program early CT score(ASPECTS),National Institutes of Health stroke scale(NIHSS)score,trial of Org 10172 in acute stroke treatment(TOAST)classification(atherosclerotic type,cardioembolic type,and other etiology types),and 90-day modified Rankin scale(mRS)score were collected.Collateral circulation was assessed based on the degree of contrast agent reflux observed in the occluded arterial supply area during delayed DSA,and patients were classified into poor and good collateral circulation groups.Malignant cerebral edema was defined as a midline shift of ≥5 mm on the follow-up CT scan performed on day 3 post-surgery.The primary endpoint(efficacy indicator)was the 90-day mRS score,with mRS score≤ 2 considered as a good prognosis and mRS score>2 considered as a poor prognosis.The secondary endpoint(safety indicator)was the 90-day mortality rate.All patients were divided into MVO and non-MVO groups based on whether they had single or multiple intracranial vessel occlusions.Acute MVO was defined as the detection of acute occlusion of other large or medium vessels,in addition to the main vessels(internal carotid artery or M1/M2 segments of the middle crebral artery[MCA]),in CT angiography,MR angiography,or DSA,resulting in ischemia in brain regions distinct from the main occlusion area.Factors that showed statistically significant differences in univariate analysis were further analyzed using multivariate Logistic regression to identify the risk factors for the occurrence of acute MVO and the factors associated with the prognosis of ALVOS patients.Results A total of 846 patients with ALVOS were included,with ages ranging from 26 to 94 years(mean age[69±11]years).The proportion of male patients was 57.2%(484/846).The median admission ASPECTS was 8(7,9)and the median admission NIHSS score was 14(12,18).The incidence of malignant cerebral edema at 3 days post-surgery was 13.4%(112/835),and the 90-day mortality rate was 19.1%(162/846).(1)Among the 846 ALVOS patients,810(95.7%)were in the non-MVO group and 36(4.3%)were in the MVO group.Univariate analysis showed significant differences between the MVO and non-MVO groups in terms of atrial fibrillation,malignant cerebral edema,admission ASPECTS,admission NIHSS scores,TOAST classification,collateral circulation,rate of complete recanalization,and 90-day poor prognosis rate(all P<0.05).However,there was no statistically significant difference in 90-day mortality between the two groups(P=0.193).Multivariate Logistic regression analysis showed that TOAST classification of cardioembolic type(OR,16.089,95%CI 1.835-141.061,P=0.012)and other etiology types(OR,9.768,95%CI 1.078-88.540,P=0.043)were associated with the occurrence of MVO.(2)Among the 846 ALVOS patients,445 had a good prognosis at 90days,and 401 had a poor prognosis.Univariate analysis showed that,compared to the good prognosis group,the poor prognosis group had a lower proportion of males and smokers,and a higher proportion of patients with older age,higher baseline systolic blood pressure,hypertension,diabetes,and atrial fibrillation(all P<0.01).Additionally,the poor prognosis group had higher admission NIHSS scores(P<0.01),lower admission ASPECTS,lower rates of good collateral circulation and complete recanalization,higher rates of malignant cerebral edema and MVO,and statistically significant differences in TOAST classification distribution(all P<0.01).Multivariate Logistic regression analysis showed that MVO was associated with poor 90-day prognosis in ALVOS patients after EVT(OR,3.368,95%CI 1.149-9.878,P=0.027).Furthermore,older age(OR,1.045,95%CI 1.025-1.066),diabetes(OR,1.719,95%CI 1.080-2.734),higher baseline systolic blood pressure(OR,1.012,95%CI 1.004-1.019),lower admission ASPECTS(OR,0.746,95%CI 0.674-0.826),higher admission NIHSS score(OR,1.115,95%CI 1.070-1.162),without immediate postoperative complete recanalization(OR,0.413,95%CI 0.290-0.592),poor collateral circulation(OR,0.594,95%CI 0.415-0.851),and malignant cerebral edema(OR,6.191,95%CI 3.026-12.670)were all associated with poor 90-day prognosis after EVT in ALVOS patients(all P<0.05).Conclusions The TOAST classification of cardioembolic type and other etiology types is associated with MVO.MVO is a risk factor for poor outcomes after successful EVT in ALVOS patients.
6.Roles and mechanisms of metformin in improving cognitive dysfunction induced by chronic cerebral hypoperfusion in rats
Wanrong JIANG ; Wei WU ; Xianjun KE ; Haomiao ZHAO ; Lijie YANG ; Xiangying SHEN ; Zhaohui YAO
Chinese Journal of Behavioral Medicine and Brain Science 2023;32(2):111-118
Objective:To explore the roles and mechanisms of metformin in the improvement of cognitive dysfunction induced by chronic cerebral hypoperfusion in rats.Methods:Total 82 SD male rats (SPF grade) aged 3-4 months were randomly divided into four groups: sham operation control group (Con group, n=15), sham operation with metformin treatment group (Met group, n=20), 2-vessel occlusion group (2VO group, n=22), and 2-vessel occlusion with metformin administration group (2VO+ Met group, n=25). The chronic cerebral hypoperfusion model was established by bilateral common carotid artery ligation, and the carotid arteries of rats in Con group and Met group were only separated without ligation.After 2VO operation, rats in 2VO+ Met group and Met group were given metformin solution in drinking water at a dose of 100 mg/kg per day for 4 weeks.After 4-week continuous intervention with metformin, Morris water maze was performed to test the spatial cognitive function of the rats, in vivo electrophysiological technology was used to detect the long-term potential of the rats, and enzyme-linked immunosorbent assay(ELISA) was used to detect the concentrations of inflammatory factor tumor necrosis factor-α(TNF-α), interleukin-1β(IL-1β) and interleukin-6(IL-6) in the hippocampus.The density of dendritic spines of hippocampal neurons was observed by Golgi staining, and the synaptic structure of hippocampal neurons, especially the vesicle density, was observed by transmission electron microscopy.SPSS 16.0 software was used for statistical analysis.Repetitive measurement ANOVA was used for the escape latency data of 7 days repeated learning training in water maze.One-way ANOVA was used for the comparison of other data among multiple groups, and Dunnett's t test was used for further pairwise comparison. Results:Morris water maze results showed that during 7 days of learning training, the time and group interaction for escape latency was not significant in the 4 groups of rats ( F=0.93, P>0.05), but the time main effect ( F=25.90, P<0.05) and group main effect ( F=13.20, P<0.05) were significant.Morris water maze test showed that from the 3rd to 7th day, the escape latencies in 2VO group were significantly longer than those in Con group and 2VO+ Met group(all P<0.05). The short-term memory of rats was detected after 1 day of rest.The results showed that the escape latency in 2VO group was significantly longer than that in Con group and 2VO + Met group( P<0.01). The retention time and crossing times in the platform area of 2VO rats were less than those in Con group and 2VO + Met group ( P<0.01). Electrophysiological results showed that the relative field excitatory postsynaptic potential slope of 2VO group (1.29±0.09) was significantly lower than that in Con group (2.07±0.09) and 2VO + Met group (1.69±0.08)( P<0.01). ELISA results showed that TNF-α level in hippocampal tissue of 2VO group was significantly higher than that in Con group and 2VO+ Met group; IL-1β and IL-6 levels in hippocampal tissue of 2VO group were significantly higher than those in Con group and 2VO + Met group.Density of dendritic spines in hippocampal neurons of 2VO group was significantly lower than that in Con group and 2VO+ Met group.The density and proportion of immature dendritic spines in hippocampal neurons of 2VO group were significantly higher than those in Con group and 2VO + Met group.Synaptic vesicle density of neurons in CA1 area of hippocampus in 2VO group ((230.29±19.44) vescicles/μm 2) was significantly lower than that in the Con group ((414.52±13.17) vescicles/μm 2) and 2VO+ Met group ((313.19±12.42) vescicles/μm 2). Conclusion:Metformin can reduce neuroinflammation of hippocampus with chronic cerebral hypoperfusion and improve synaptic plasticity and cognitive dysfunction.It may have potential application value in the treatment of vascular cognitive dysfunction.
7.Protective effects and mechanisms of L-carnitine on cognitive dysfunction in rats with chronic cerebral hypoperfusion
Lijie YANG ; Wei WU ; Wanrong JIANG ; Xiangying SHEN ; Xianjun KE ; Haomiao ZHAO ; Zhaohui YAO
Chinese Journal of Behavioral Medicine and Brain Science 2023;32(5):385-392
Objective:To explore the protective effects and mechanisms of L-carnitine (LCAR) on cognitive dysfunction in chronic cerebral hypoperfusion rats.Methods:Totally 90 SD male rats (SPF class) aged 3-4 months were divided into four groups according to random number talbe: sham operated control group (SHAM group, n=15), sham operated with L-carnitine treatment group (LCAR group, n=25), 2-vessel occlusion group (2VO group, n=25), and 2-vessel occlusion with L-carnitine treatment group (2VO+ LCAR group, n=25). The chronic cerebral hypoperfusion model was established by bilateral common carotid artery ligation, and the carotid arteries from SHAM group and LCAR group were only separated without ligation.L-carnitine was administered intraperitoneally (300 mg·kg -1·d -1) for 30 days after surgery in the LCAR and 2VO+ LCAR groups.After 30 days of L-carnitine intervention, Morris water maze was performed to test the spatial cognitive function of the rats, the ATP level of hippocampal tissue was detected by chemiluminescence, the mitochondrial structure and synaptic structure of hippocampal neurons were observed by transmission electron microscopy, the degree of mitochondrial damage was scored, the vesicle density was counted and measured, the level of N-methyl-D-aspartate receptor subunit 2A or 2B(NR2A/B) and postsynaptic density 95(PSD95) in hippocampal tissue were detected by Western blot.The expression and distribution levels of transcription factor cAMP response element-binding protein(CREB) in brain tissues were observed by immunofluorescence.SPSS 16.0 software was used for statistical analysis.The escape latency data of repeated learning training in Morris water maze was conducted by repetitive measurement ANOVA, while other data were adopted by one-way ANOVA, and Dunnett's t test was used for further pairwise comparison. Results:(1)Morris water maze results showed that the time and group interaction of escape latency was not significant among the 4 groups of rats ( F=1.4, P>0.05), but the time main effect and group main effect were significant( F=21.6, 15.2, both P<0.05). Morris water maze results showed that platform position learning from 3rd to 7th day, the escape latencies in 2VO group were longer than those in SHAM group and 2VO+ LCAR group (all P<0.05). The results of short-term memory showed that the escape latency in 2VO group was longer than those in SHAM group and 2VO+ LCAR group (all P<0.05). Meanwhile, the retention time and crossing times in the platform area of 2VO group were less than those in SHAM group and 2VO+ LCAR group (all P<0.05). (2) The absolute and relative levels of ATP in hippocampus showed that the difference among the 4 groups were statistically significant ( F=14.6, 13.2, both P<0.05). ATP level of hippocampus in 2VO group was lower than those in SHAM group and 2VO+ LCAR group (both P<0.05). Electron microscopic observation of mitochondrial morphology showed that the Flameng score of mitochondrial damage in the hippocampus of rats in 2VO group (2.82±0.17) was higher than those in SHAM group (0.25±0.07) and 2VO+ LCAR group (1.76±0.09) (both P<0.05). (3) The density of synaptic vesicles in the hippocampus of rats in 2VO group ((289.09±22.41)/μm 2)was lower than those in SHAM group ((497.49±28.89)/μm 2)and 2VO+ LCAR group ((401.23±45.09)/μm 2) (both P<0.01). Western blot results showed that the relative levels of synaptic proteins NR2A/B, PSD95 and CREB in 2VO group were lower than those in SHAM group and 2VO+ LCAR group (all P<0.05). Immunofluorescence results showed that the relative level of CREB expression in hippocampal subregions and cortex in 2VO group was lower than those in SHAM group and 2VO+ LCAR group (both P<0.01). Conclusion:L-carnitine can improve spatial learning and memory dysfunction in rats with chronic cerebral hypoperfusion, which are related with promoting ATP production and protecting mitochondrial morphology, and promoting synaptic vesicle synthesis and synaptic protein expression.
8.Clinical efficacy of mechanical thrombectomy in advanced age patients with acute anterior circulation large vessel occlusive stroke
Yujuan ZHU ; Yachen JI ; Xin XU ; Junfeng XU ; Xiangjun XU ; Ke YANG ; Youqing XU ; Qian YANG ; Xianjun HUANG ; Zhiming ZHOU
Chinese Journal of Neuromedicine 2022;21(3):263-272
Objective:To evaluate the benefits and risks of advanced age patients with acute anterior circulation large vessel occlusive stroke (ALVOS) accepted mechanical thrombectomy (MT), and explore the related influencing factors for prognoses in these patients.Methods:Six hundred and eighty patients with acute anterior circulation ALVOS accepted MT in 3 comprehensive stroke centers from January 2014 to December 2020 were sequentially collected. (1) Patients were divided into advanced age group (≥80 years old) and non-advanced age group (<80 years old) according to age, and the differences between the two groups were compared in successful postoperative vascular recanalization rate, incidence of perioperative complications, and good prognosis rate (modified Rankin scale [mRS] scores≤2) and mortality 90 d after onset. (2) Patients were divided into good prognosis group (mRS scores≤2) and poor prognosis group (mRS scores>2) according to the prognoses 90 d after onset; univariate analysis and multivariate Logistic regression analysis were used to investigate the independent factors for prognoses of the patients after MT. (3) According to the prognoses 90 d after onset, the advanced age patients were divided into good prognosis subgroup (mRS scores≤2) and poor prognosis subgroup (mRS scores>2). Univariate analysis and multivariate Logistic regression analysis were used to investigate the independent factors for prognoses of the elderly patients after MT.Results:(1) In these 680 patients, 92 patients (13.5%) were into the advanced age group and 588 patients (86.5%) were in the non-advanced age group; patients in the advanced age group had significantly lower successful recanalization rate (67.4% vs. 77.9%), significantly lower good prognosis rate 90 d after onset (20.7% vs. 50.2%), and statically higher mortality 90 d after onset (40.2% vs. 21.1%) as compared with the non-advanced age group ( P<0.05); however, there was no significant difference between the two groups in the incidences of symptomatic intracranial hemorrhage (sICH, 15.6% vs. 10.6%) and malignant cerebral edema (MCE, 12.2% vs. 17.6%, P>0.05). The baseline data of the advanced age and non-advanced age patients were further matched with propensity score matching analysis (1:1) and statistically analyzed: the 91 elderly patients had significantly lower good prognosis rate 90 d after onset (20.9% vs. 36.3%) and MCE incidence (12.4% vs. 33.3%) than the 91 non-elderly patients ( P<0.05); there was no significant differences in successful vascular recanalization rate (67.0% vs. 71.4%), sICH incidence (15.7% vs. 17.6%) or mortality 90 d after onset (39.6% vs. 37.4%) between the two groups ( P>0.05). (2) Among the 680 patients, 314 (46.2%) had good prognosis and 366 (53.8%) had poor prognosis. As compared with the good prognosis group, the poor prognosis group had significantly higher proportion of patients at advanced age, significantly lower proportion of male patients, significantly higher proportion of patients with hypertension, diabetes or atrial fibrillation, significantly lower baseline Alberta Stroke early CT (ASPECT) scores, significantly higher baseline National Institutes of Health Stroke Scale (NIHSS) scores, statistically higher proportion of patients with cardiogenic embolism, significantly lower incidence of tandem lesions, significantly shorter time from onset to sheathing, statistically higher proportion of internal carotid artery occlusion, significantly lower proportion of patients with grading 2 collateral circulation, and significantly lower proportion of successful vascular recanalization ( P<0.05). Advanced age ( OR=3.144, 95%CI: 1.675-5.900, P<0.001) was an independent factor for prognoses 90 d after MT, in addition to baseline ASPECT scores, baseline NIHSS scores, diabetes mellitus, successful recanalization, and collateral circulation grading. (3) In the advanced age group, there were 19 patients (20.7%) with good prognosis and 73 patients (79.3%) with poor prognosis. As compared with the good prognosis subgroup, the poor prognosis subgroup had significantly lower proportion of male patients, significantly lower proportion of patients with grading 2 collateral circulation or complete recanalization, and significantly higher baseline NIHSS scores ( P<0.05). Baseline NIHSS score ( OR=1.482, 95%CI: 1.187-1.850, P=0.001) was an independent factor for prognoses 90 d after MT in advanced age patients. Conclusion:Although advanced age is an independent risk factor for prognoses of patients with acute anterior circulation ALVOS accepted MT, there are still some advanced age patients benefiting from MT without increased complications, especially for those with low baseline NIHSS scores.
9.Renin-angiotensin system inhibitor is associated with the reduced risk of all-cause mortality in COVID-19 among patients with/without hypertension.
Huai-Yu WANG ; Suyuan PENG ; Zhanghui YE ; Pengfei LI ; Qing LI ; Xuanyu SHI ; Rui ZENG ; Ying YAO ; Fan HE ; Junhua LI ; Liu LIU ; Shuwang GE ; Xianjun KE ; Zhibin ZHOU ; Gang XU ; Ming-Hui ZHAO ; Haibo WANG ; Luxia ZHANG ; Erdan DONG
Frontiers of Medicine 2022;16(1):102-110
Consecutively hospitalized patients with confirmed coronavirus disease 2019 (COVID-19) in Wuhan, China were retrospectively enrolled from January 2020 to March 2020 to investigate the association between the use of renin-angiotensin system inhibitor (RAS-I) and the outcome of this disease. Associations between the use of RAS-I (angiotensin-converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB)), ACEI, and ARB and in-hospital mortality were analyzed using multivariate Cox proportional hazards regression models in overall and subgroup of hypertension status. A total of 2771 patients with COVID-19 were included, with moderate and severe cases accounting for 45.0% and 36.5%, respectively. A total of 195 (7.0%) patients died. RAS-I (hazard ratio (HR)= 0.499, 95% confidence interval (CI) 0.325-0.767) and ARB (HR = 0.410, 95% CI 0.240-0.700) use was associated with a reduced risk of all-cause mortality among patients with COVID-19. For patients with hypertension, RAS-I and ARB applications were also associated with a reduced risk of mortality with HR of 0.352 (95% CI 0.162-0.764) and 0.279 (95% CI 0.115-0.677), respectively. RAS-I exhibited protective effects on the survival outcome of COVID-19. ARB use was associated with a reduced risk of all-cause mortality among patients with COVID-19.
Angiotensin Receptor Antagonists/therapeutic use*
;
Angiotensin-Converting Enzyme Inhibitors/therapeutic use*
;
COVID-19
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Humans
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Hypertension/drug therapy*
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Renin-Angiotensin System
;
Retrospective Studies
10.The relationship between periprocedural thrombus migration and clinical outcomes in patients with acute large vessel occlusion after mechanical thrombectomy
Chu CHEN ; Tangqin ZHANG ; Youqing XU ; Lili YUAN ; Xiangjun XU ; Ke YANG ; Qian YANG ; Xianjun HUANG ; Zhiming ZHOU
Chinese Journal of Neurology 2021;54(10):1025-1032
Objective:To investigate the early predictive factors of periprocedural thrombus migration and the relationship between periprocedural thrombus migration and prognosis after mechanical thrombectomy (MT) in stroke patients.Methods:The patients with anterior circulation acute large vessel occlusion stroke (ALVOS) who underwent MT in the Stroke Center of Yijishan Hospital of Wannan Medical College from May 2015 to December 2019 were retrospectively analyzed. The baseline characteristics, procedural and clinical outcomes were collected. Univariate and multivariate regression analysis was used to explore the risk factors of thrombus migration and the relationship between thrombus migration and prognosis of patients.Results:There were 302 ALVOS patients [(68.8±11.0) years old and 166 males (55.0%)] included, of whom thrombus migration was identified in 80 patients (26.5%), including 60 cases (75.0%) of proximal migration. Cardiogenic stroke ( OR=2.722, 95% CI 1.367-5.418, P=0.004) and clot burden score (CBS; OR=0.849, 95% CI 0.745-0.968, P=0.015) were independent risk factors of thrombus migration. Proximal migration ( OR=2.822, 95% CI 1.220-6.528, P=0.015) was an independent risk factor of 90-day clinical outcome, while the effect of distal migration on 90-day clinical outcome was not statistically significant. Conclusions:Cardiogenic stroke and lower CBS score are independent predictors of periprocedural thrombus migration in ALVOS patients who underwent MT. Proximal migration is an independent risk factor for the prognosis of patients, which has important clinical intervention significance.

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