Objective:To investigate the influencing factors, periprocedural complications, and long-term outcomes of successful recanalization after endovascular treatment in patients with non-acute symptomatic internal carotid artery occlusion.Methods:Patients with non-acute internal carotid artery occlusion received endovascular treatment in the Nanjing Stroke Registration System between January 2010 and December 2021 were retrospectively enrolled. Clinical endpoint events were defined as successful vascular recanalization, periprocedural complications (symptomatic embolism and symptomatic intracranial hemorrhage), neurological function improvement, and recurrence of ipsilateral ischemic events. Multivariate logistic regression analysis was used to investigate the independent influencing factors of successful vascular recanalization. Cox proportional hazards regression analysis was used to investigate the correlation between endovascular treatment outcomes and neurological function improvement, as well as ipsilateral ischemic cerebrovascular events. Results:A total of 296 patients were included, of which 190 (64.2%) were successfully recanalized. Multivariate logistic regression analysis showed that symptoms manifest as ischemic stroke (odds ratio [ OR] 3.353, 95% confidence interval [ CI] 1.399-8.038; P=0.007), the time from the most recent symptom onset to endovascular therapy within 1 to 30 d ( OR 2.327, 95% CI 1.271-4.261; P=0.006), proximal conical residual cavity ( OR 2.853, 95% CI 1.242-6.552; P=0.013) and focal occlusion (C1-C2: OR 3.255, 95% CI 1.296-8.027, P=0.012; C6/C7: OR 5.079, 95% CI 1.334-19.334; P=0.017) were the independent influencing factors for successful vascular recanalization. Successful recanalization did not increase the risk of symptomatic intracranial hemorrhage within 7 d after procedure (3.2% vs. 0.9%; P=0.428). The median follow-up time after procedure was 38 months. Cox proportional hazards regression analysis showed that after adjusting for confounding factors, successful recanalization was significantly associated with postprocedural neurological improvement (hazard ratio 1.608, 95% CI 1.091-2.371; P=0.017), and significantly reduced the risk of recurrence of long-term ischemic events (hazard ratio 0.351, 95% CI 0.162-0.773; P=0.010). Conclusion:In patients with non-acute internal carotid artery occlusion, successful endovascular recanalization can effectively reduce the risk of long-term ischemic events without increasing the risk of symptomatic intracranial hemorrhage.

Objective:To investigate predictive factors for successful endovascular recanalization in patients with non-acute symptomatic internal carotid artery occlusion (SICAO), to develop a decision tree model using the Classification and Regression Tree (CART) algorithm, and to evaluate the predictive performance of the model.Methods:Patients with non-acute SICAO received endovascular therapy at 8 comprehensive stroke centers in China were included retrospectively. They were randomly assigned to a training set and a validation set. In the training set, the least absolute shrinkage and selection operator (LASSO) algorithm was used to screen important variables, and a decision tree prediction model was constructed based on CART algorithm. The model was evaluated using the receiver operating characteristic (ROC) curve, Hosmer-Lemeshow goodness-of-fit test and confusion matrix in the validation set.Results:A total of 511 patients with non-acute SICAO were included. They were randomly divided into a training set ( n=357) and a validation set ( n=154) in a 7:3 ratio. The successful recanalization rates after endovascular therapy were 58.8% and 58.4%, respectively. There was no statistically significant difference ( χ2=0.007, P=0.936). A CART decision tree model consisting of 5 variables, 5 layers and 9 classification rules was constructed using the six non-zero-coefficient variables selected by LASSO regression. The predictive factors for successful recanalization included fewer occluded segments, proximal tapered stump, ASITN/SIR collateral grading of 1-2, ischemic stroke, and a recent event to endovascular therapy time of 1-30 d. ROC analysis showed that the area under curve of the decision tree model in the training set was 0.810 (95% confidence interval 0.764-0.857), and the optimal cut-off value for predicting successful recanalization was 0.71. The area under curve in the validation set was 0.763 (95% confidence interval 0.687-0.839). The accuracy was 70.1%, precision was 81.4%, sensitivity was 63.3%, and specificity was 79.7%. The Hosmer-Lemeshow test in both groups showed P>0.05. Conclusion:Based on the type of ischemic event, the time from the latest event to endovascular therapy, proximal stump morphology, the number of occluded segments, and the ASITN/SIR collateral grading constructed the decision tree model can effectively predict successful recanalization after non-acute SICAO endovascular therapy.

Objective:To analyze the feasibility and clinical efficacy of reperfusion-expanding-thrombectomy-stenting (RETS) technique in the endovascular treatment of acute carotid artery tandem lesion.Methods:The general clinical data of 88 patients with carotid artery tandem lesion who received emergency endovascular treatment from January 2018 to December 2020 in Department of Neurology, Linyi People′s Hospital were reviewed, the Modified Rankin Scale (mRS) was used as the evaluation standard for the prognosis of patients at 90 days after endovascular treatment, and the clinical data were analyzed, including the recanalization (modified thrombolysis in cerebral infarction ≥2b), perioperative complications and 90-day prognosis, and good prognosis was defined as a mRS score of 0-2.Results:A total of 88 patients with tandem carotid artery disease were included,48 of whom were treated with RETS technique, 40 were treated with anterograde approach. Compared with antegrade recanalization, RETS technique had significant differences in the time from puncture to recanalization [(72.06±17.29) min vs (98.88±26.09) min, t=-5.56, P<0.001] and the primary recanalization rate [35/48(73.0%) vs 21/40(52.5%),χ2=3.93 ,P=0.047], with statistically significant difference. There was no significant difference in clinical prognosis and surgical complications between the two methods (all P>0.05). Conclusions:RETS technique can shorten the operation time and increase the primary recanalization rate. RETS technique is safe and feasible for the treatment of carotid tandem lesions.

Humans ; Computed Tomography Angiography ; Deep Learning ; Coronary Angiography ; Coronary Artery Disease ; Tomography, X-Ray Computed ; Coronary Stenosis/diagnosis* ; Retrospective Studies ; Fractional Flow Reserve, Myocardial ; Predictive Value of Tests

Objective To investigate the factors that affect the progression of epileptic seizure at the acute phase of encephalitis into postencephalitic epilepsy.Methods A retrospective analysis was conducted to investigate the clinical data of 141 patients who were admitted to the First People’s Hospital of Yunnan Province and the First Affiliated Hospital of Kunming Medical University from January 2010 to June 2019，diagnosed as autoimmune encephalitis or viral encephalitis in the acute phase with epileptic seizure and treated with immunotherapy. The 141 patients were divided into 2 groups according to whether their epileptic seizure progressed to postencephalitic epilepsy. Logistic regression analysis was applied to investigate the factors that affect the progression of epileptic seizure at the acute phase of encephalitis into postencephalitic epilepsy.Results The epileptic seizure of 25 patients（17.73% of all 141 patients） progressed to postencephalitic epilepsy. The results of multi-factor Logistic regression analysis show that the risk factors involved in the progression of epileptic seizure included：a fever before treatment（OR=3.288，95％CI=1.116～9.687，P=0.031） and high seizure frequency（≥10 times/day）（OR=4.564，95％CI=1.263～16.491，P=0.021）. Compared with a course of antiepileptic drugs for less than 6 months，a course of antiepileptic drugs for 6-12 months（OR=0.672，95％CI=0.064～7.024，P=0.740） or above（OR=3.049，95％CI=0.906～10.261，P=0.072） did not affect the development of postencephalitic epilepsy. Compared with the patients with no fever before treatment，those with fever were more prone to disturbance of consciousness（P<0.001），status epilepticus（P=0.023） and a head MRI showing inflammatory lesions（P=0.007）.Conclusion Therefore，a fever before treatment and high seizure frequency（≥10 times/day） are identified as the risk factors causing postencephalitic epilepsy. The length of course of antiepileptic drugs does not affect the incidence of postencephalitic epilepsy，suggesting that it is unnecessary to prevent postencephalitic epilepsy by long-term use of antiepileptic drugs.

Objective:To establish a screening system of adult Philadelphia chromosome-like acute lymphoblastic leukemia (Ph-like ALL) by fluorescence in situ hybridization (FISH) .Method:Based on the genetic characteristics of Ph-like ALL, FISH probes were designed for ABL1, ABL2, JAK2, EPOR, CRLF2, CSF1R, PDGFRB, and P2RY8 gene breakpoints, which were used to screen Ph-like ALL in B-ALL patients without BCR-ABL1, ETV6-RUNX1, MLL, and E2A gene arrangement. Furthermore, it was analyzed in combination with flow immunophenotype, next-generation sequencing for targeted gene mutations, and RNA sequencing (RNA-seq) .Results:A total of 189 adult B-ALL patients diagnosed in Nanfang Hospital from January 2016 to April 2019 were enrolled in this study. Using FISH and/or PCR, BCR-ABL1, ETV6-RUNX1, MLL, or E2A arrangement was detected in 83 of them, and Ph-like ALL was detected by FISH in the other 106, resulting in the presence of typical gene arrangements of Ph-like ALL in 12 patients (11.3% , 12/106) . Validated by RNA-seq, the sensitivity and specificity of FISH for Ph-like ALL were 71.4% and 95.8% , respectively. After further analysis with immunophenotype, targeted gene mutations, and RNA-seq, 14 (13.2% , 14/106) were diagnosed with Ph-like ALL.Conclusion:This data shows high specificity of FISH for identification of Ph-like ALL and combining immunophenotype and sequencing technology can improve the diagnostic system.

Objective To investigate the effects of octanol,a gap junction blocker,on the levels of pro-inflammatory cytokines after cerebral ischemia-reperfusion in rats.Methods Seventy-two male SD rats were randomly divided into sham operation group,saline control group,vehicle group,and octanol intervention group (n =18 in each group).The model of transient middle cerebral artery occlusion was induced by the modified suture method.The octanol intervention group was intraperitoneally injected with octanol solution at 5 mmol/kg body weight 30 min before ischemia.The saline control group and the vehicle group were intraperitoneally injected with the same amount of physiological saline and 5％ dimethyl sulfoxide solution 30 min before procedure.The neurological deficit score,brain water content,and cerebral infarction volume in each group were detected after ischemia for 2 h and reperfusion for 24 h.Enzyme-linked immunosorbent assay was used to detect the serum interleukin (IL)-1β,IL-6,and tumor necrosis factor-α (TNF-α) levels.Results Compared with the saline control group and the vehicle group,the neurological deficit score of the octanol intervention group was significantly lower (all P ＜0.05),the brain tissue water content was significantly decreased (P ＜ 0.05),the cerebral infarction volume was significantly reduced (P ＜0.05),and the expression levels of IL-1β,IL-6,and TNF-α were significantly decreased (all P ＜0.05).There were no significant differences in neurological deficit score,brain water content,cerebral infarction volume and serum IL-1 [β,IL-6 and TNF-α levels between the saline control group and the vehicle group.Conclusion Gap junction blocker octanol can reduce cerebral ischemic-reperfusion injury.Its mechanism may be related to the alleviation of inflammatory response.

Objective To investigate the safety and efficacy of rescue stenting after failure of endovascular treatment for acute cerebral large artery occlusive infarction, and compare the differences of safety and efficacy between bridged treatment and direct endovascular treatment in acute cerebral large artery occlusive infarction. Methods The clinical data of 60 patients with acute cerebral large artery occlusive infarction who underwent rescue stenting after failure of endovascular treatment in our hospital form March 2015 to March 2018 were retrospectively analyzed; 26 patients underwent bridged treatment+rescue stenting (bridged treatment group), while 34 patients underwent direct endovascular treatment+rescue stenting (direct treatment group). The recanalization degree immediately after the treatment was evaluated by Modified Thrombolysis in Cerebral Infarction (mTICI) scale. National Institutes of Health Stroke Scale (NIHSS) was performed 24 h and 5-7 d after the treatment, and modified Rankin Scale (mRS) was applied 90 d after treatment to evaluate the neurological functions. In addition, incidences of intracranial hemorrhage and symptomatic intracranial hemorrhage (SICH) and postoperative mortality within 90 d of treatment were calculated. Results (1) Among the 60 patients, 55 patients (91.7％) had revascularization (mTICI 2b-3) immediately after the rescue stenting. NIHSS scores before rescue stenting and NIHSS scores 24 h after rescue stenting (17.50 [15.00, 24.00) vs. 12.00 [8.25, 19.00]) showed statistically significant differences (P<0.05). Twenty-nine patients (48.3％) obtained satisfactory prognosis 90 d after rescue stenting (mRS scores≤2), 9 patients (15.0％) suffered SICH after rescue stenting, and 9 patients died (15.0％). (2) The immediate revascularization rate (92.3％ vs. 91.2％), NIHSS scores 24 h and 5-7 d after surgery (12.00 [7.75, 18.00] vs. 14.50 [10.00, 22.00] and 8.00 [3.00, 12.50] vs. 10.50 [6.75, 16.75]), good prognosis rate 90 d after treatment (57.7％ vs. 41.2％), postoperative SICH incidence (19.2％ vs. 11.8％), and mortality (11.5％ vs. 17.7％) in the bridged treatment group and direct treatment group were not significantly different (P>0.05). Conclusion Rescue stenting is safe and effective for patients with acute cerebral large artery occlusive infarction, no matter it is by bridged treatment or direct intravascular treatment; and the two methods show no significant differences in safety and efficacy

Objective To investigate the effect of octanol,a gap junction blocker,on mitogen activated protein kinase (MAPK) signal pathway after ischemia reperfusion in rats.Methods Seventy-two male SD rats were randomly divided into sham-operated group,DMSO control group,saline control group and octanol group (n=1 8).The focal cerebral ischemia reperfusion models were established by suture method in the later three groups.Rats were injected 5 mmol/kg octanol solution (5％ octanol soluble in 5％ DMSO solution) into the abdominal cavity of rats in the octanol group 30 min before ischemia reperfusion;rats in the DMSO control group were injected with same amount of 5％ DMSO solution,and those in the sham-operated group and saline control group were injected with same amount of saline.At 24 h after reperfusion,Neurological Function Defect Scale was performed;water content in brain tissues was detected by dry-wet method;cerebral infarction volume percentage was detected by TTC staining;the total protein expressions of extracellular signal-regulated kinase 1/2 (ERK1/2),c-jun amino-terminal kinase (JNK),and p38,and protein expressions ofphosphorylased (p)-ERK1/2,p-JNK,and p-p38 were detected by Western blotting.Results The scores of Neurological Function Defect Scale,water content in brain tissues,and infarction volume percentage of the octanol group (1.583±0.651,78.363％±0.672％,and 24.34％±0.19％) were obviously reduced as compared with those in the DMSO control group (2.344±0.743,80.873％±0.831％,and 32.26％±0.21％) and saline control group (2.351±0.732,80.893％±0.734％,and 32.28％±0.24％),with significant differences (P＜0.05).The protein expressions ofp-ERKl/2,p-JNK,and p-p38 in the octanol group (0.201±0.009,0.211±0.011,and 0.191±0.009) were obviously reduced as compared with those in the DMSO control group (0.389±0.019,0.311±0.022,and 0.309±0.021) and saline control group (0.393±0.021,0.304±0.021,and 0.316±0.025),with significant differences (P＜0.05).Conclusion Octanol can reduce ischemic reperfusion injury,whose mechanism may be related to the regulation of MAPK signal pathway.

Neddylation is a post-translational protein modification process. MLN4924 is a newly discovered pharmaceutical neddylation inhibitor that suppresses cancer growth with several cancer types. In our study, we first investigated the effect of MLN4924 on colon cancer cells (HCT116 and HT29). MLN4924 significantly inhibited the neddylation of cullin-1 and colon cancer cell growth in a time and dose-dependent manner. MLN4924 induced G2/M cell cycle arrest and apoptosis in HCT116 and HT29 cells. Moreover, MLN4924 also triggered autophagy in HCT116 and HT29 cells via suppressing the PI3K/AKT/mTOR pathway. Inhibiting autophagy by autophagy inhibitor 3-MA or ATG5 knockdown reversed the function of MLN4924 in suppressing colon cancer cell growth and cell death. Interestingly, MLN4924 suppresses colon cell growth in a xenograft model. Together, our finding revealed that blocking neddylation is an attractive colon cancer therapy strategy, and autophagy might act as a novel anti-cancer mechanism for the treatment of colon cancer by MLN4924.
Apoptosis ; Autophagy* ; Cell Cycle Checkpoints ; Cell Death ; Colon* ; Colonic Neoplasms* ; Heterografts ; HT29 Cells ; Humans ; Protein Processing, Post-Translational