Objective:To investigate whether escin(ESC)and dextromethorphan(DEX)have the protective effects on the progression and symptoms of Alzheimer disease(AD).Methods:The AD model of Caenorhabditis elegans(C.elegans)was established by transgenic amyloid β-protein(Aβ protein).Different concentrations of ESC or DEX or 50 μmol/L memantine(MEM)were used to treat the AD model worms,and their lifespan was detected.The movement ability of AD model C.elegans was evalua-ted by body bending frequency and head swinging frequency.The changes in cognitive functions of AD model C.elegans before and after treatment were detected by chemotaxis experiments.The changes in A βprotein and reactive oxygen species(ROS)content in C.elegans were detected.The changes in gene pathways related to oxidative stress were detected by Real-time quantitative polymerase chain reaction(RT-qPCR).Results:At high dose 1 000 μmol/L,ESC or DEX treatment showed no significant effects on the activity of C.elegans.Compared with untreated worms,the survival time of AD model C.elegans in the 20 μmol/L ESC and 60 μmol/L DEX intervention groups was significantly extended.In the middle stage of AD progression,the body bending frequency and head swinging frequency of AD model worms after ESC or DEX treatment was significantly increased compared with the untreated control group with DEX being more effective in the recovery of head swinging frequency.For the early cognitive function tests,the chemotaxis index of ESC or DEX treated worms was significantly higher than that of the untreated worms,which correlated with marked reductions in the Aβ protein levels.The reactive oxygen species content in the drug intervention group was also lower than that in the control group.RT-qPCR results showed that ESC could inhibit oxidative stress in the AD model C.elegans by a 2-fold upregulation of skn1 expression.Conclusion:ESC and DEX could improve the reductions of movement ability and cognitive function in the AD model worms and delay the aggravation of AD-related symptoms.ESC delays the progression of AD pos-sibly by activating the SKN-1/Nrf2 pathway to protect against oxidative injury in the AD model.

Objective To analyze the effects of intravenous tirofiban following endovascular treatment on the prognosis of patients with acute anterior circulation large vessel occlusion stroke who did not achieve successful recanalization.Methods This retrospective study included consecutive patients with acute anterior circulation ischemic stroke who underwent endovascular treatment but did not achieve successful recanalization.These patients were retrospectively enrolled from the Department of Neurology at Nanjing Jinling Hospital,Affiliated Hospital of Medical School,Nanjing University,the Second Affiliated Hospital of Soochow University,Wuhan No.1 Hospital,and Yijishan Hospital of Wannan Medical College(the First Affiliated Hospital of Wannan Medical College)between January 2015 and April 2023.Baseline and clinical data were collected including age,sex,medical history(hypertension,diabetes,atrial fibrillation,hyperlipidemia),personal history(smoking and drinking),National Institutes of Health stroke scale(NIHSS)score at admission,trial of Org 10172 in acute stroke treatment(TOAST)classification(large artery atherosclerosis,cardioembolism,or other types),Alberta stroke program early CT score(ASPECTS)on admission,intravenous thrombolysis,onset-to-puncture time(OTP),collateral circulation status(poor collaterals:American Society of Interventional and Therapeutic Neuroradiology/Society of Interventional Radiology[ASTIN/SIR]score 0-2;good collateral:ASTIN/SIR score 3-4),procedure duration(from femoral or radial artery puncture to device removal),occlusion site,number of passes for thrombus retrieval,and post-procedural modified thrombolysis in cerebral infarction(mTICI)grade.Patients were divided into a tirofiban group and a non-tirofiban group based on whether they received post-procedural intravenous tirofiban.The primary outcome is a favorable functional outcome at 90-day since onset(modified Rankin scale[mRS]score ≤ 3).Safety outcomes included mortality at 90-day since onset(mRS score 6),any intracranial hemorrhage within 24 h post-procedure,and symptomatic intracranial hemorrhage within 24 h post-procedure.1∶1 propensity score matchings using the nearest neighbor method was performed based on variables with P＜0.05 in the comparison between the tirofiban and non-tirofiban groups.Differences in primary and safety outcomes between the matched groups were compared.Univariate and multivariate Logistic regression analyses were conducted with favorable outcomes at 90 days as the dependent variable to evaluate the effect of intravenous tirofiban administration after endovascular therapy on 90-day prognosis in patients without successful recanalization.Results A total of 356 patients without successful recanalization after endovascular treatment were included,comprising 195 males and 161 females,with a median age of 70(61,78)years(32-92 years).Among them,76 and 280patients were assigned to the tirofiban and non-tirofiban groups,respectively.At 90 days,114 patients had favorable outcomes,while 242 had unfavorable outcomes.(1)Before the 1∶1 propensity score matching,significant differences were observed between the tirofiban and non-tirofiban groups in terms of admission NIHSS score,ASPECTS,good collateral circulation,intravenous thrombolysis,and mTICI grade(all P＜0.05).After 1∶1 propensity score matching,66 matched pairs(132 patients)were obtained.No significant differences in the baseline and clinical characteristics were found between the two groups after matching(all P＞0.05).(2)After 1∶1 matching,a significant difference was observed in the rate of favorable outcomes at 90 days between the two groups(48.5％[32/66]vs.30.3％[20/66],P=0.033)after propensity score matching,while no significant differences were found in 90-day mortality,intracranial hemorrhage within 24h,or symptomatic intracranial hemorrhage within 24h(all P＞0.05).(3)Univariate analysis after 1∶1 matching indicated that age,atrial fibrillation,smoking history,admission NIHSS score,M2 segment middle cerebral artery occlusion,good collateral circulation,number of passes for thrombus retrieval,and tirofiban treatment were factors influencing favorable outcomes at 90 days.Multivariate Logistic regression analysis showed that younger age(aOR,0.942,95％CI 0.906-0.978,P=0.002),lower admission NIHSS score(aOR,0.855,95％CI 0.777-0.941,P=0.001),good collateral circulation(aOR,5.534,95％CI 2.141-14.301,P＜0.01),tirofiban treatment(aOR,2.774,95％CI 1.092-7.046,P=0.032),and M2 segment MCA occlusion(reference:internal carotid artery occlusion;aOR,4.874,95％CI 1.428-16.632,P=0.011)were independent predictors of favorable outcomes at 90 days.Conclusions Intravenous tirofiban administration after endovascular therapy may improve 90-day neurological outcomes in patients with acute anterior circulation large vessel occlusion stroke who did not achieve successful recanalization without increasing the risk of hemorrhage.Further large-scale randomized controlled trials are warranted to validate these findings.

Objective:To investigate whether escin(ESC)and dextromethorphan(DEX)have the protective effects on the progression and symptoms of Alzheimer disease(AD).Methods:The AD model of Caenorhabditis elegans(C.elegans)was established by transgenic amyloid β-protein(Aβ protein).Different concentrations of ESC or DEX or 50 μmol/L memantine(MEM)were used to treat the AD model worms,and their lifespan was detected.The movement ability of AD model C.elegans was evalua-ted by body bending frequency and head swinging frequency.The changes in cognitive functions of AD model C.elegans before and after treatment were detected by chemotaxis experiments.The changes in A βprotein and reactive oxygen species(ROS)content in C.elegans were detected.The changes in gene pathways related to oxidative stress were detected by Real-time quantitative polymerase chain reaction(RT-qPCR).Results:At high dose 1 000 μmol/L,ESC or DEX treatment showed no significant effects on the activity of C.elegans.Compared with untreated worms,the survival time of AD model C.elegans in the 20 μmol/L ESC and 60 μmol/L DEX intervention groups was significantly extended.In the middle stage of AD progression,the body bending frequency and head swinging frequency of AD model worms after ESC or DEX treatment was significantly increased compared with the untreated control group with DEX being more effective in the recovery of head swinging frequency.For the early cognitive function tests,the chemotaxis index of ESC or DEX treated worms was significantly higher than that of the untreated worms,which correlated with marked reductions in the Aβ protein levels.The reactive oxygen species content in the drug intervention group was also lower than that in the control group.RT-qPCR results showed that ESC could inhibit oxidative stress in the AD model C.elegans by a 2-fold upregulation of skn1 expression.Conclusion:ESC and DEX could improve the reductions of movement ability and cognitive function in the AD model worms and delay the aggravation of AD-related symptoms.ESC delays the progression of AD pos-sibly by activating the SKN-1/Nrf2 pathway to protect against oxidative injury in the AD model.

Objective To analyze the effects of intravenous tirofiban following endovascular treatment on the prognosis of patients with acute anterior circulation large vessel occlusion stroke who did not achieve successful recanalization.Methods This retrospective study included consecutive patients with acute anterior circulation ischemic stroke who underwent endovascular treatment but did not achieve successful recanalization.These patients were retrospectively enrolled from the Department of Neurology at Nanjing Jinling Hospital,Affiliated Hospital of Medical School,Nanjing University,the Second Affiliated Hospital of Soochow University,Wuhan No.1 Hospital,and Yijishan Hospital of Wannan Medical College(the First Affiliated Hospital of Wannan Medical College)between January 2015 and April 2023.Baseline and clinical data were collected including age,sex,medical history(hypertension,diabetes,atrial fibrillation,hyperlipidemia),personal history(smoking and drinking),National Institutes of Health stroke scale(NIHSS)score at admission,trial of Org 10172 in acute stroke treatment(TOAST)classification(large artery atherosclerosis,cardioembolism,or other types),Alberta stroke program early CT score(ASPECTS)on admission,intravenous thrombolysis,onset-to-puncture time(OTP),collateral circulation status(poor collaterals:American Society of Interventional and Therapeutic Neuroradiology/Society of Interventional Radiology[ASTIN/SIR]score 0-2;good collateral:ASTIN/SIR score 3-4),procedure duration(from femoral or radial artery puncture to device removal),occlusion site,number of passes for thrombus retrieval,and post-procedural modified thrombolysis in cerebral infarction(mTICI)grade.Patients were divided into a tirofiban group and a non-tirofiban group based on whether they received post-procedural intravenous tirofiban.The primary outcome is a favorable functional outcome at 90-day since onset(modified Rankin scale[mRS]score ≤ 3).Safety outcomes included mortality at 90-day since onset(mRS score 6),any intracranial hemorrhage within 24 h post-procedure,and symptomatic intracranial hemorrhage within 24 h post-procedure.1∶1 propensity score matchings using the nearest neighbor method was performed based on variables with P＜0.05 in the comparison between the tirofiban and non-tirofiban groups.Differences in primary and safety outcomes between the matched groups were compared.Univariate and multivariate Logistic regression analyses were conducted with favorable outcomes at 90 days as the dependent variable to evaluate the effect of intravenous tirofiban administration after endovascular therapy on 90-day prognosis in patients without successful recanalization.Results A total of 356 patients without successful recanalization after endovascular treatment were included,comprising 195 males and 161 females,with a median age of 70(61,78)years(32-92 years).Among them,76 and 280patients were assigned to the tirofiban and non-tirofiban groups,respectively.At 90 days,114 patients had favorable outcomes,while 242 had unfavorable outcomes.(1)Before the 1∶1 propensity score matching,significant differences were observed between the tirofiban and non-tirofiban groups in terms of admission NIHSS score,ASPECTS,good collateral circulation,intravenous thrombolysis,and mTICI grade(all P＜0.05).After 1∶1 propensity score matching,66 matched pairs(132 patients)were obtained.No significant differences in the baseline and clinical characteristics were found between the two groups after matching(all P＞0.05).(2)After 1∶1 matching,a significant difference was observed in the rate of favorable outcomes at 90 days between the two groups(48.5％[32/66]vs.30.3％[20/66],P=0.033)after propensity score matching,while no significant differences were found in 90-day mortality,intracranial hemorrhage within 24h,or symptomatic intracranial hemorrhage within 24h(all P＞0.05).(3)Univariate analysis after 1∶1 matching indicated that age,atrial fibrillation,smoking history,admission NIHSS score,M2 segment middle cerebral artery occlusion,good collateral circulation,number of passes for thrombus retrieval,and tirofiban treatment were factors influencing favorable outcomes at 90 days.Multivariate Logistic regression analysis showed that younger age(aOR,0.942,95％CI 0.906-0.978,P=0.002),lower admission NIHSS score(aOR,0.855,95％CI 0.777-0.941,P=0.001),good collateral circulation(aOR,5.534,95％CI 2.141-14.301,P＜0.01),tirofiban treatment(aOR,2.774,95％CI 1.092-7.046,P=0.032),and M2 segment MCA occlusion(reference:internal carotid artery occlusion;aOR,4.874,95％CI 1.428-16.632,P=0.011)were independent predictors of favorable outcomes at 90 days.Conclusions Intravenous tirofiban administration after endovascular therapy may improve 90-day neurological outcomes in patients with acute anterior circulation large vessel occlusion stroke who did not achieve successful recanalization without increasing the risk of hemorrhage.Further large-scale randomized controlled trials are warranted to validate these findings.

Recent studies have shown that non-alcoholic fatty liver disease (NAFLD) can influence the incidence, outcome, and recurrence risk of ischemic stroke independently of traditional risk factors. This article reviews the relationship, related mechanisms, and treatment decisions between NAFLD and ischemic stroke, in order to provide reference for clinical diagnosis and treatment decisions.

Objective:To investigate the effect of insular involvement on the outcomes of patients with acute anterior circulation ischemic stroke.Methods:Patients with acute anterior circulation ischemic stroke admitted to the Department of Neurology, Nanjing Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University from January 2015 to December 2020 were retrospectively included. Demographic data, vascular risk factors, clinical and laboratory data, as well as treatment and outcomes were collected. Firstly, the correlation between the insular involvement and the outcomes was investigated, and then the bootstrap method was used to clarify the mediating role of infarct volume between the insular involvement and the poor outcomes.Results:A total of 450 patients with acute anterior circulation ischemic stroke were enrolled, among whom 79 cases (17.6%) had insular involvement and 41 (9.1%) had left insular involvement. There were 111 (24.7%) with poor outcomes, including 5 (1.1%) died. Compared to the non-insular involvement group, the insular involvement group had a higher proportion of patients with atrial fibrillation, shorter onset to door time, higher neutrophil-to-lymphocyte ratio (NLR), higher National Institutes of Health Stroke Scale (NIHSS) score at admission, larger infarct volume, and higher proportion of patients with poor outcomes (all P<0.05). In addition, patients with left insular involvement were younger than those with right insular involvement, had a higher baseline NIHSS score, a lower proportion of patients with minor stroke (NIHSS score ≤8), and had a longer onset to door time (all P<0.05). Compared to the good outcome group, the poor outcome group was older, with a higher proportion of female patients, higher systolic blood pressure, blood glucose, NLR, and NIHSS scores at admission, larger infarct volume, and a higher proportion of patients with insular involvement (all P<0.05). Mediation analysis suggested that the mediating effect of infarct volume between the insular involvement and the poor outcomes was significant (95% confidence interval 0.033-0.230; P=0.008). Conclusions:insular involvement in patients with acute anterior circulation ischemic stroke is associated with the poor outcomes, and this association may be mediated by infarct volume. Patients with left insular involvement may have more severe symptoms than those with right insular involvement, but there is no significant difference in the outcomes.

Objective:To investigate the value of net water uptake (NWU) for predicting early neurological improvement (ENI) after endovascular treatment in patients with acute anterior circulation large vessel occlusion stroke.Methods:A case-control study. A total of 132 patients (80 men, 52 women, median age 68 years) with acute anterior circulation large vessel occlusive stroke receiving endovascular treatment were retrospectively analyzed at Jinling Hospital from October 2014 to September 2019. Patients were divided into two groups based on the occurrence of ENI, which was defined as either an improvement of NIHSS score of ≥4 points, or an NIHSS score of 0 or 1 at 24 hours after endovascular treatment. The rank sum test, Chi square test, and other methods were used to compare differences in baseline characteristics between the two groups. Logistic regression analysis was used to investigate independent predictors of postoperative ENI. Receiver operating characteristic curve analysis used to assess the capacity of NWU to predict ENI.Results:Of the 132 patients in the study, ENI occurred in 47 and did not occur in 85. In multivariate logistic regression analysis age [odds ratio ( OR)=0.940, 95% confidence interval ( CI) 0.903-0.979, P=0.003], time from stroke onset to puncture ( OR=0.995, 95% CI 0.991-0.999, P=0.025), time from puncture to recanalization/end of operation ( OR=0.985, 95% CI 0.974-0.996, P=0.007), NWU ( OR=0.762, 95% CI 0.620-0.937, P=0.010), and mTICI ( OR=1.644, 95% CI 1.043-2.590, P=0.032) were predictive factors for ENI. Receiver operating characteristic curve analysis indicated that NWU could effectively predict ENI (area under the curve=0.642, 95% CI 0.543-0.741, P=0.007), and prediction accuracy was improved when it was combined with other clinical parameters. Conclusion:NWU is an independent predictor of ENI in patients with acute anterior circulation large vessel occlusive stroke undergoing endovascular treatment.

Objective:To evaluate the characteristics of carotid plaque and the immediate outcomes after carotid artery stenting (CAS) in diabetic and non-diabetic patients by optical coherence tomography (OCT).Methods:Patients underwent CAS and OCT before and after operation in the Department of Neurology, Jinling Hospital from January 2014 to March 2019 were enrolled retrospectively. The clinical features, the characteristics of carotid plaque on OCT and the immediate outcomes after CAS were compared between diabetic group and non-diabetic group. The risk factors of stent malapposition were analyzed.Results:A total of 46 patients were enrolled. Their age was 64.02±8.32 years and 41 were males (89.1%). There were 20 patients (43.5%) in the diabetes group and 26 (56.5%) in the non-diabetes group. The proportions of atherosclerotic plaque with thin fibrous cap (40.0% vs. 7.7%; χ2=5.166, P=0.023), plaque rupture (55.0% vs. 23.1%; χ2=4.945, P=0.026) and macrophage infiltration (60.0% vs. 30.8%; χ2=3.930, P=0.047) in the diabetic group were significantly higher than those in the non-diabetic group. Multivariate logistic regression analysis showed that older age (odds ratio [ OR] 1.208, 95% confidence interval [ CI] 1.033-1.413; P=0.018), coronary heart disease ( OR 15.953, 95% CI 1.142-222.952; P=0.040), alcohol consumption ( OR 6.192, 95% CI 1.098-34.923; P=0.039) and lower systolic blood pressure ( OR 0.944, 95% CI 0.894-0.997; P=0.037) were independently associated with stent malaposition. Conclusion:Compared with the non-diabetic patients, carotid plaque in diabetic patients may be more unstable. Older age, coronary heart disease, alcohol consumption and lower systolic blood pressure were associated with stent malaposition after carotid stenting. OCT can reveal the characteristics of carotid plaque and the immediate outcomes after CAS, which can provide strong evidence for treatment decision.

Stroke is the first cause of death in China. Intravenous thrombolysis and early endovascular treatment can significantly improve the outcome of patients with ischemic stroke. With the continuous deepening of research, the time window of endovascular interventional therapy has been extended from 6 h to 24 h. Tissue stratification plays a vital role in the expansion of time window. This article reviews the implications of tissue stratification, imaging assessment methods, and their significance in endovascular treatment.

Objective To investigate the effect of butylphthalide and sodium chloride injection on patients who received endovascular treatment for acute anterior circulation large vessel occlusive stroke.Methods A total of 173 patients were identified from February 2015 to December 2017 in the Department of Neurology of Jingling Hospital in this retrospective observational study.Propensity score-matching analysis was performed to balance differences in baseline characteristics between patients who received butylphthalide injection (butylphthalide group) and those who did not (control group).The modified Rankin Scale scores at 90 days were compared between the butylphthalide and control groups.Results A total of 144 patients who received endovascular treatment for acute anterior circulation large vessel occlusive stroke were finally analyzed,54 cases in the butylphthalide group and 90 cases in the control group.The proportion of good functional outcome at 90 days in the butylphthalide group was higher than that in the control group (63.0％ (34/54) vs 44.4％ (40/90);x2=4.633,P=0.031).Thirty-six pairs were matched successfully by the propensity score matching,36 patients in the butylphthalide group and 36 in the control group.There was no statistically significant difference in the 90-day functional outcome between the two groups (66.7％ (24/36) vs 44.4％ (16/36);x2=3.600,P=0.058).One hundred and fifteen patients were recanalized,47 cases in the butylphthalide group and 68 cases in the control group,and after the propensity score matching,30 pairs were analyzed.The proportion of good functional outcome at 90 days in the butylphthalide group was higher than that in the control group (73.3％ (22/30) vs 46.7％ (14/30);x2=4.444,P=0.035).Conclusion After propensity score-matching,butylphthalide and sodium chloride injection could improve 90-day functional outcome in patients with acute anterior circulation large vessel occlusive stroke and obtained recanalization by endovascular treatment while could not before propensity score-matching.