Combined HAT score and neutrophil to lymphocyte ratio predict symptomatic intracranial hemorrhage after intravenous thrombolysis in patients with acute ischemic stroke / 国际脑血管病杂志

Objective:To investigate the value of hemorrhage after thrombolytic (HAT) score and neutrophil to lymphocyte ratio (NLR) in combination predicting symptomatic intracerebral hemorrhage (sICH) after intravenous thrombolysis in patients with acute ischemic stroke (AIS).Methods:Consective patients with AIS received intravenous thrombolysis with ateplase in Tianjin TEDA Hospital from January 2016 to December 2021 were retrospectively enrolled. sICH was defined as cerebral CT showing hemorrhage at any part of the brain after intravenous thrombolysis, and the National Institutes of Health Stroke Scale (NIHSS) score was increased by≥4 compared with the baseline, or there was a manifestation indicating clinical aggravation. Univariate analysis was used to compare the baseline data of sICH group and non-sICH group. A binary multivariate logistic regression model was used to determine the independent influencing factors of sICH. The receiver operating characteristic (ROC) curve was used to evaluate the value of HAT score and NLR in combination predicting sICH. Results:A total of 429 patients with AIS were enrolled. Univariate analysis showed that there were significant differences in atrial fibrillation, systolic blood pressure, NLR, HAT score and NIHSS score between the sICH group and the non-sICH group (all P<0.05). Multivariate analysis showed that NLR (odds ratio [ OR] 1.405, 95% confidence interval [ CI] 1.193-2.958), HAT score ( OR 1.512, 95% CI 1.207-3.169) and NIHSS score ( OR 1.221, 95% CI 1.082-2.634) had significant independent correlation with sICH after adjusting for atrial fibrillation and systolic blood pressure. The ROC curve showed that the areas under the curve of HAT score, NLR and their combination predicting sICH were 0.719 (95% CI 0.609-0.832), 0.723 (95% CI 0.618-0.835) and 0.854 (95% CI 0.765-0.931), respectively. The areas under the curve of the two methods in combination were significantly larger than those of the single method ( P=0.029 and 0.032, respectively), and their sensitivity and specificity were 74.1% and 83.5% respectively. Conclusion:Combined HAT score and NLR is of high value in predicting sICH after intravenous thrombolysis in patients with AIS, and has clinical application potential.

Predictive role of C-reactive protein in patients with intracerebral hemorrhage / 国际脑血管病杂志

Intracerebral hemorrhage is one of the important stroke types. Most survivors of intracerebral hemorrhage will leave different degrees of neurological dysfunction, resulting in their poor outcomes. Studies have shown that C-reactive protein is associated with the outcomes of patients with intracerebral hemorrhage. This article reviews the predictive role of C-reactive protein in patients with intracerebral hemorrhage.

Role of histone methylation enzyme EZH2 and VEGF165 in momymoya disease / 国际生物医学工程杂志

Objective To study on the role of histone methylation enzyme enhancer of zeste homolog 2 (EHZ2) and vascular endothelial growth factor 165 (VEGF165) in momymoya disease. Methods The animal model of moyamoya disease was established by ear vein injection of horse serum in New Zealand rabbits. VEGF165 was over-expressed in situ by packaging lentivirus. Real-time quantitative PCR and Western Blot were used to detect the expression of VEGF165, EZH2 and H3K27me3 in the brain tissues of the animal models. Results Compared with the normal control group, the expression levels of mRNA and protein of EZH2 in the moyamoya disease model group were increased (EZH2 mRNA:P<0.01), and the level of histone H3K27me3 was increased. After overexpression of VEGF165 in the moyamoya disease model group, the expression levels of mRNA and protein of EZH2 was further increased (EZH2 mRNA: P<0.01), and the level of histone H3K27me3 was also increased. Conclusions EZH2 plays a certain role in the pathogenesis of moyamoya disease, and the expression of EZH2 is regulated by VEGF 165, which provides a theoretical basis for the study of the pathogenesis of moyamoya disease.

Evaluation of fractional flow in patients with intracranial atherosclerotic stenosis / 国际脑血管病杂志

Traditionally, the determination of cerebral vascular stenosis depends on the measurement of the degree of morphological stenosis, but it lacks the understanding and evaluation of hemodynamics. At present, the degree of morphological stenosis is still a clinical indication for interventional therapy. Non-invasive brain functional assessment cannot accurately locate the specific ischemic area corresponding to the stenotic lesion. Its spatial resolution to vascular lesions is poor, and it is not possible to assist decisions in real time during interventional therapy. The theory of fractional flow reserve (FFR) of coronary stenosis and pressure guidewire technology has been applied to the evaluation of coronary function and to guide the practice of interventional therapy for many years. With the need for screening for high-risk patients with intracranial vascular stenosis and hemodynamic dysfunction, the evaluation of fractional flow in the interventional treatment of cerebral vascular stenosis is increasingly significant. The safety and feasibility of the use of pressure guidewires in intracranial arteries have been confirmed by some studies. Evaluation of fractional flow has broad application prospects in both acute and chronic ischemic cerebrovascular diseases. This article reviews the application of fractional flow evaluation in patients with intracranial atherosclerotic stenosis.

Evaluation of fractional flow in patients with intracranial atherosclerotic stenosis / 国际脑血管病杂志

Traditionally,the determination of cerebral vascular stenosis depends on the measurement of the degree of morphological stenosis,but it lacks the understanding and evaluation of hemodynamics.At present,the degree of morphological stenosis is still a clinical indication for interventional therapy.Non-invasive brain functional assessment cannot accurately locate the specific ischemic area corresponding to the stenotic lesion.Its spatial resolution to vascular lesions is poor,and it is not possible to assist decisions in real time during interventional therapy.The theory of fractional flow reserve (FFR) of coronary stenosis and pressure guidewire technology has been applied to the evaluation of coronary function and to guide the practice of interventional therapy for many years.With the need for screening for high-risk patients with intracranial vascular stenosis and hemodynamic dysfunction,the evaluation of fractional flow in the interventional treatment of cerebral vascular stenosis is increasingly significant.The safety and feasibility of the use of pressure guidewires in intracranial arteries have been confirmed by some studies.Evaluation of fractional flow has broad application prospects in both acute and chronic ischemic cerebrovascular diseases.This article review s the application of fractional flow evaluation in patients with intracranial atherosclerotic stenosis.

Association between MMP-9 gene rs20544 polymorphism and hemorrhagic transformation in patients with acute ischemic stroke / 国际脑血管病杂志

Objective To investigate the association between matrix metalloproteinase (MMP)-9 gene rs20544 polymorphism and hemorrhagic transformation (HT) in patients with acute ischemic stroke (AIS). Methods Patients with AIS admitted to the Department of Neurology, TEDA Hospital from March 2016 to September 2018 were enrolled. They were divided into HT group and non-HT group depending on whether HT occurred. HT was defined as no bleeding found in the first imaging examination, and the head CT rescaning indicated a high-density lesion in the low-density area. MMP-9 gene rs20544 single nucleotide polymorphism was determined by TaqMan ? SNP genotype analysis kit. Multivariate logistic regression analysis was used to determine the independent association between rs20544 polymorphism and HT. Results A total of 204 patients with AIS were enrolled, aged 66.91 ± 9.07 years, 89 males (43.63% ), and 45 (22.06% ) developed HT. There were significant differences in atrial fibrillation, diabetes, fasting blood glucose, and triglyceride between the HT group and the non-HT group (all P<0.05). There was also a significant difference in rs2054 genotype distribution between the HT group and the non-HT group (χ2 =7.067; P=0.029 ). Multivariate logistic regression analysis showed that after adjusting atrial fibrillation, diabetes, fasting blood glucose, triglyceride, and hyperlipidemia, rs20544 CC genotype (odds ratio 2.074, 95% confidence interval 1.368-4.041) and CT genotype (odds ratio 1.571, 95% confidence interval 1.109-2.544) were the independent risk factors for HT. Conclusion MRP-9 gene rs20544 single nucleotide polymorphism is associated with increased susceptibility to HT in patients with AIS.

CRISPR-Cas9-based site-directed knock-in of VEGF165 gene in a HEK293T cell / 国际生物医学工程杂志

Objective To construct a human renal epithelial cell line HEK293T by CRISPR-Cas9-based site-directed knock-in of vascular endothelial growth factor 165 (VEGF165) gene, and avoid the off-target effect caused by lentivirus infection. Methods The VEGF165 expression vector with homologous arm (pUCm-T-VEGF165 plasmid) and the sgRNA expression vector [pSpCas9(BB)-2A-Puro-sgRNA plasmid] were designed and constructed based on the DNA sequence of the EZH2 gene, and then co-transfected into HEK293T cells. The expression of VEGF165 mRNA was detected by qPCR and the expressions of VEGF165 proteins were detected by Western Blot. Results The qPCR and Western Blot results showed that, comparing with the control, the pUCm-T-VEGF165 plasmid and pSpCas9(BB)-2A-Puro-sgRNA plasmid, the expression of the co-transfection plasmid were significantly increased, i.e. 3.42±0.30 vs. 1.02±0.21, 1.13±0.16 and 0.98±0.18 for the VEGF165 mRNA level (all P<0.01), and 1.13±0.16 vs. 1.02±0.06, 0.88±0.03 and 0.80±0.05 for the VEGF165 protein level (all P<0.01), respectively. Besides, the expression of EZH2 was significantly down-regulated, i.e. 0.14±0.06 vs. 1.08±0.11, 1.02±0.12 and 1.13±0.16 for the EZH2 mRNA level (all P<0.01), and 0.23±0.03 vs. 1.05±0.13, 0.91±0.04 and 0.81±0.06 for the EZH2 protein level (all P<0.01), respectively. This result showed that the VEGF165 was successfully inserted into the EZH2 genome, interfering the EZH2 expression. Conclusions VEGF165 gene can be successfully knocked into HEK293T cells by CRISPR/Cas9 system.

Predictors of hemorrhagic transformations after endovascular mechanical thrombectomy in patients with acute ischemic stroke / 国际脑血管病杂志

Objective To analyze the independent risk factors for hemorrhagic transformation (HT)after endovascular mechanical thrombectomy in patients with acute ischemic stroke (AIS).Methods From March 2015 to February 2018,patients with AIS treated with mechanical thrombectomy at the Department of Neurology,TEDA Hospital were selected.The patients with hemorrhagic infarction (HI) or parenchymal hematoma (PH) were used as the case group,and those without HT were used as the control group.The independent risk factors for HI or PH after mechanical thrombectomy in patients with AIS were determined by multivariate logistic regression analysis.Results A total of 132 patients with AIS were enrolled in the study,and 60 (45.4％) developed HT,of which 37 were HI (28.03％) and 23 were PH (17.42％).Multivariate logistic regression analysis showed that after adjusting for gender,alcohol consumption,fasting blood glucose and glycated hemoglobin,diabetes (odds ratio [OR] 3.485,95％ confidence interval[CI]l.121-6.928;P=0.019),atrial fibrillation (OR 3.962,95％ CI 1.143-7.514;P =0.007) and high fasting blood glucose (OR 3.254,95％ CI 1.107-6.549;P =0.036) were the independent risk factors for HI after mechanical thrombectomy in patients with AIS;after adjusting for gender,hyperlipidemia and glycosylated hemoglobin,diabetes (OR 3.348,95％ CI 1.120-6.709;P =0.025) and high fasting blood glucose (OR 3.172,95％ CI 1.129-7.023;P =0.014) were the independent risk factors for PH after mechanical thrombectomy in patients with AIS.Conclusion Diabetes,atrial fibrillation and high fasting blood glucose were the independent risk factors for HT after mechanical thrombectomy in patients with AIS.

Solumbra thrombectomy as intravascular recanalization for treatment of acute ischemic stroke due to large cerebral artery occlusion / 中华老年医学杂志

Objective To investigate the feasibility,effectiveness,and technical superiority of Solumbra thrombectomy for treatment of acute large cerebral artery occlusion stroke.Methods 32 patients who had acute large cerebral artery occlusion stroke and received mechanical thrombectomy in TEDA Hospital of Tianjin between January 2013 and August 2016,were divided into two groups:stent group(with conventional stent-retrievers,n=21) and Solumbra group (with Solumbra thrombectomy,n =11).Clinical characteristics,variables correlated with operation,and clinical outcomes were compared and analyzed retrospectively.Results There were no differences in basic clinical and radiographic parameters between stent group versus Solumbra group (all P＞0.05).Moreover,there were no differences between Solumbra group versus Stent group in rates of embolus to new territory(18.2 ％ vs.28.6％,P=0.425),in times of thrombectomy(2.2± 1.0 vs.2.4± 1.3,P=0.657),in nonsymptomatic intracranial hemorrhage (18.2％ vs.14.3％,P =0.572),in symptomatic intracranial hemorrhage(18.2％ vs.9.5％,P =0.427),in TICI 2b/3 revascularization(81.8％ vs.81.0％,P =0.670),in puncture-to-reperfusion time[(66.4±39.0)min vs.(51.6±34.5)min,P=0.279],and in NIHSS at 7 days(11.6 ± 7.7 vs.11.3 ± 7.2,P =0.925).A modified Rankin Scale(mRS ≤2) is a variable of recovery of function and good clinical outcome at 90 days.The levels of mRS were similar(P =0.490)between Solumbra and stent groups,but there was a tendency to higher rate of good clinical outcome at 90 days in Solumbra group (63.6％,7/11)than in stent group (47.6％,10/21).Conclusions Solumbra thrombectomy as intravascular revascularization technique is an effective and safe strategy for endovascular recanalization of acute large cerebral artery occlusion stroke.Compared with conventional Stent-Retriever thrombectomy,Solumbra thrombectomy has a good clinical outcome tendency at 90 days after operation.

Endovascular recanalization with a direct aspiration first-pass thrombectomy technique for acute cerebral artery occlusion / 中华神经科杂志

Objective To investigate the feasibility, safety and technical superiority of mechanical thrombectomy using a direct aspiration first-pass thrombectomy (ADAPT) in treatment of patients with acute cerebral artery occlusion. Methods A retrospective study was conducted on all patients with acute ischemic stroke treated with mechanical thrombectomy in our institution from January 2013 to August 2016.Patients using ADAPT or stent retriever as a first-line endovascular procedure were compared for clinical characteristics, procedural variables and clinical outcomes. The technical superiority of ADAPT was analyzed in depth. Results During observation period, a total of 91 cases were performed endovascular treatment with mechanical thrombectomy. ADAPT was designed in 46 cases as a first-line endovascular procedure and was utilized in 38 cases (82.6%;ADAPT group), while primary stent retriever thrombectomy was performed in 21 patients(stent group). There was no significant difference in baseline clinical or radiographic factors between ADAPT and stent groups. Although rates of good neurological outcome (modified Rankin Scale(mRS) score≤2) at 90 days were similar between the ADAPT and stent groups (61%(23/38) vs 48%(10/21), P=0.247), National Institute of Health Stroke Scale (NIHSS) score at seven days (6.0(2.0, 9.3) vs 9.0(5.5, 18.5),Z=-2.031,P=0.021) and full recovery rate of neurological outcome (mRS score=0, 37%(14/38) vs 10%(2/21), P=0.022) were significantly better in the ADAPT group than in the stent group. There were no significant differences in rates of embolus to new territory (21%(8/38) vs 29%(6/21), P=0.365), Thrombolysis In Cerebral Infarction (TICI) 2b/3 grade revascularization (84%(32/38) vs 81%(17/21), P=0.507) and symptomatic intracerebral hemorrhage (0%(0/38) vs 10%(2/21), P=0.123) between the ADAPT and the stent groups, but the figures were better in the ADAPT group. Conclusions Mechanical thrombectomy using ADAPT is feasible and safe compared with stent retriever, with higher full recovery rate of neurological outcome and better NIHSS score.It is a method worthy of further exploration for endovascular mechanical recanalization.

Effect of atorvastatin calcium on serum hs-CRP and TNF-α levels inpatients with cerebral infarction / 中国生化药物杂志

Objective To investigate the effect of atorvastatin calcium in the treatment of cerebral infarction and its onhighsensitive C-reactive protein (hs-CRP), tumor necrosis factor α (TNF-α). Methods Selected 122 patients with cerebral infarction treated in our hospital from January 2014 to January 2016, patients were randomly divided into observation group (n=69) and control group (n=53),the control group was given conventional treatment, the observation group was given atorvastatin calcium on the basis of conventional treatment,observed the National Institutes of Health Stroke Scale (NIHSS) and the daily life ability Barthel index (BI) score in the two groups after treatment,detected hs-CRP, TNF-α and carotid artery intima media thickness.Results After treatment, the NIHSS score of the observation group was (13.41 ±1.43), significantly lower than that of the control group (15.52±1.61) (P < 0.05), while the BI score was (43.82 ± 11.21), significantly higher than that of the control group (39.04±9.82 ) (P <0.05). The observation group after treatmenths-CRP and TNF-α were (6.71 ± 1.50) mg/L and (7.41 ± 2.08) ng/mL, significantly lower than the control group(10.02±1.78)mg/L and(10.10±2.32)ng/mL (P < 0.05). The observation group after treatment carotid artery intima media thickness was (1.10±0.27) mm, significantly lower than the control group (1.36±0.21)mm (P < 0.05). The incidence of adverse reactions in the observation group was 5.80%, the adverse reaction rate of the control group was 5.66%, the difference was not statistically significant. Conclusion Atorvastatin calcium has a good effect in the treatment of cerebral infarction, can reduce serum hs-CRP and TNF-α level, promote nerve function and daily life ability recovery, improve the thickness of the carotid artery.

Expression and identification of VEGF165 in bone marrow mesenchymal stem cells of rhesus / 天津医药

Objective To detect the transferred vascular endothelial growth factor (VEGF)165 gene expression in rhesus autologous bone marrow mesenchymal stem cells (MSCs), and to explore the functional viability of transgenic MSCs. Methods MSCs from rhesus bone were isolated by Ficoll, which were used to detect the phenotype. After the culturing, the expression vector pcDNA-eGFP-VEGF165 was transfected into bone marrow MSCs. Fluorescence microscope and flow cytometry were used to detect the enhanced green fluorescent protein (eGFP) expression. At the same time, the phenotype in transfected MSCs was also indentified. The VEGF165 expression level was detected by RT-PCR. Results The highly purified MSCs were collected successfully. The transfected MSCs and daughter cells showed expressions of eGFP and VEGF165, which also remained the characteristics of MSCs. Conclusion The VEGF165 gene that is transfected into MSCs can maintain characteristics of MSCs, and stably express foreign genes.

Protective effects and mechanisms of breviscapine on endothelial cells / 中国药科大学学报

This study was to investigate the protective effects and mechanisms of breviscapine on endothelial cells.ox-LDL was used to induce oxidative damage on human umbilical vein endothelial cells(HUVEC)for 20 h with or without 4 h pretreatment of various concentrations of breviscapine(10;20;40 μmol/L);then observe the protective effect and mechanism of breviscapine on endothelial cells insulted by ox-LDL.MTT method was used to detect cell viability;flow cytometry was used to detect cell apoptosis and reactive oxygen species;and Western blot and RT-PCR was used to detect cell signaling pathways.The results showed that breviscapine recovered HUVEC cell viability in a dose-dependent manner which inhibited by ox-LDL;and it also protected cell from apoptosis induced by ox-LDL.To explore the mechanisms of breviscapine;reactive oxygen species (ROS)was determined after pretreatment of various concentrations of breviscapine or different durations(2;4;6 h)of brevis-capine.Results showed that breviscapine decreased ROS production in a dose-and time-dependent manner.Fur-thermore;cell signaling pathway analysis showed that breviscapine increased the expression of BCL-2;decreased the expression of BAX and the release of Cytochrome C and cleavage of caspase-3.Breviscapine decreased Keap1 and activated the nuclear import of Nrf2;and subsequently increased the mRNA and protein expression of down-stream antioxidant enzyme as NAD(P)H:quinone oxidoreductase 1(NQO1)and glutathione transferase-S-Mu 1(GSTM1);and increasing the activity of NQO1.Besides;breviscapine decreased IKK and IKB;and inhibited nuclear translocation of NF-κB;while increasing the expression of eNOS.This study demonstrated that breviscap-ine has a protective role on ox-LDL-induced endothelial cell injury;which may be related to its antioxidant effects and inhibition of NF-κB activation.