Restoration of cerebral blood flow is particularly important for the treatment of ischemic cerebrovascular disease. It is notable that surgical approaches play a unique role in treating this devastating disease. Among them, mechanical thrombectomy facilitates rapid and effective recanalization of occluded intracranial large vessels causing ischemic stroke, which contributes to improvement of cerebral perfusion in the ischemic penumbra; decompressive craniectomy is an important therapeutic option for acute massive cerebral infarction, and the timing of surgery determines the final clinical outcomes; for carotid endarterectomy in carotid-artery stenosis, individualized surgical plan is important for the safety and effectiveness of the operation; in the surgical revascularization of Moyamoya disease, precise evaluation of clinical and radiological characteristics, optimal surgical strategies and accuracy of intraoperative judgment will yield maximal therapeutic effects; and hybrid surgery is feasible for the therapy of complex ischemic cerebrovascular diseases, such as extracranial/intracranial arteries tandem stenosis and symptomatic chronic total occlusion of carotid artery. This paper reviews recent technical and clinical advances in the surgical treatment of ischemic cerebrovascular disease.

Objective: To investigate the effect of emergency medical service (EMS) on the prognosis of ischemic stroke patients treated with intravenous thrombolysis. Methods: Clinical data of 2123 ischemic stroke patients treated with intravenous thrombolysis in 70 hospitals in Zhejiang province were retrospectively analyzed. There were 808 patients sent to the hospital by ambulance (EMS group) and 1315 patients by other transportations (non-EMS group). Good outcome was defined as modified Rankin Scale (mRS) ≤ 2 at 3-month. The onset to needle time (ONT), onset to door time (ODT), door to needle time (DNT) and outcome were compared between EMS group and non-EMS group. Binary logistic regression was used to explore the influencing factors for the outcome at 3-month. Results: Compared with the non-EMS group, patients in the EMS group were older, with higher baseline National Institute of Health Sroke Scale (NIHSS) score, and had a higher proportion of atrial fibrillation (all P < 0.05), but there were no significant differences in ONT, ODT and DNT between two groups (all P>0.05). Binary logistic regression showed that EMS was not independently associated with good outcome (OR=0.856, 95%CI:0.664-1.103, P>0.05). Conclusion: EMS had not improve the outcome of patients receiving intravenous thrombolysis in Zhejiang province.

Objective: To investigate the effect of treatment time on the outcome of patients with ischemic stroke undergoing reperfusion therapy. Methods: The clinical data of 3229 ischemic stroke patients who received intravenous thrombolysis with or without arterial thrombolysis from 71 hospitals in Zhejiang province from June 2017 to September 2018 were retrospectively reviewed. The good outcome was defined as modified Rankin Scale (mRS) ≤ 2. Binary logistic regression analysis was used to investigate the association of door to needle time (DNT), or door to reperfusion time (DRT) with the outcomes in patients treated by intravenous thrombolysis or bridging arterial thrombolysis, respectively. Results: Binary logistic regression showed that DNT (OR=0.994, 95%CI:0.991-0.997, P < 0.01) or DRT (OR=0.989, 95%CI:0.983-0.995, P < 0.01) were independently associated with good outcomes, respectively. Every hour decreases in DNT resulted in a 4.7%increased probability of functional independence (mRS 0-2) in patients treated by intravenous thrombolysis; Every hour decreases in DRT was associated with a 11.4%increased probability of functional independence in patients treated by intravenous thrombolysis with arterial thrombolysis. Conclusion: Good outcomes are associated with lower DNT in ischemic stroke patients treated by intravenous thrombolysis or lower DRT in patients treated by intravenous thrombolysis bridging arterial thrombolysis.

Objective: To investigate the association of atrial fibrillation (AF) with hemorrhagic transformation (HT) in patients with ischemic stroke treated by intravenous thrombolysis. Methods: Clinical data of 3272 patients treated by intravenous thrombolysis from 71 hospitals in Zhejiang Province during June 2017 and December 2018 were retrospectively reviewed. Intracranial HT was defined as intracranial hemorrhage suggested by imaging examination 24 hours after intravenous thrombolysis. Patients were dichotomized into HT group (n=533) and non-HT group (n=2739). The association of AF and HT was analyzed by univariate analysis and binary logistic regression. Results: Compared with the non-HT group, the HT group were older, had longer onset to needle time (ONT), higher baseline National Institute of Health Stroke Scale (NIHSS) score, higher baseline glucose level, and higher AF rate (P < 0.05 or P < 0.01). Binary logistic regression analysis revealed that AF was independently associated with HT (OR=2.527, 95%CI:2.030-3.146, P < 0.01). Conclusion: AF is independently associated with the occurrence of HT in ischemic stroke patients treated with intravenous thrombolysis.

Objective: To compare the time delay between in-hospital stroke and out-of-hospital stroke patients, and to explore the influence factors for the prognosis of in-hospital stroke patients treated by intravenous thrombolysis. Methods: Clinical data of 3050 patients with ischemic stroke who received intravenous thrombolysis in 71 hospitals in Zhejiang province from June 2017 to September 2018 were analyzed. Differences of time delay including door to imaging time (DIT), imaging to needle time (INT) and door to needle time (DNT) between in-hospital stroke (n=101) and out-of-hospital stroke (n=2949) were observed. The influencing factors for the outcome at 3 month after intravenous thrombolysis in patients with in-hospital stroke were analyzed using binary logistic regression analysis. Results: Patients with in-hospital stroke had longer DIT[53.5 (32.0-79.8) min vs. 20.0 (14.0-28.0) min, P < 0.01], longer IDT[47.5(27.3-64.0)min vs. 36.0(24.0-53.0)min, P < 0.01], and longer DNT[99.0 (70.5-140.5) min vs. 55.0 (41.0-74.0) min, P < 0.01], compared with patients with out-of-hospital stroke; patients in comprehensive stroke center had longer DIT[59.5(44.5-83.3) min vs. 37.5(16.5-63.5) min, P < 0.01], longer DNT[110.0(77.0-145.0) min vs. 88.0 (53.8-124.3) min, P < 0.05], but shorter INT[36.5(23.8-60.3)min vs. 53.5 (34.3-64.8) min, P < 0.05], compared with patients in primary stroke center. Age (OR=0.934, 95%CI: 0.882-0.989, P < 0.05) and baseline National Institute of Health Stroke Scale score (OR=0.912, 95%CI: 0.855-0.973, P < 0.01) were independent risk factors for prognosis of in-hospital stroke patients. Conclusion: In-hospital stroke had longer DIT and DNT than out-of-hospital stroke, which suggests that a more smooth thrombolysis process of in-hospital stroke should be established.

Objective: To investigate the effect of working time on the prognosis of patients with ischemic stroke undergoing intravenous thrombolysis. Methods: Clinical data of 3050 patients with ischemic stroke received intravenous thrombolysis from 71 hospitals in Zhejiang Province during June 2017 and September 2018 were retrospective analyzed. Whole day of Saturday and Sunday were defined as weekend; whole day of Monday to Friday were defined as weekdays; Monday to Friday 8:00-17:00 were defined as daytime of weekdays; Monday to Friday 17:01-07:59 on next day were defined as nights of weekdays; unconventional working time were defined as weekend and nights of weekdays. Good outcome was defined as mRS 0-2 at 3 months. Univariate analyses of baseline and prognostic variables in group of weekend and weekdays, nights of weekdays and daytime of weekdays, unconventional working time and daytime of weekdays were performed. Binary logistic regression was used to investigate whether weekend, nights of weekdays and unconventional working time were independent predicting factors of outcome after intravenous thrombolysis, respectively. Results: There was no difference in 7-day mortality, 3-month mortality and good outcome at 3-month between weekend group and weekdays group, nights of weekdays group and daytime of weekdays group, unconventional working time group and daytime of weekdays group (all P>0.05). Binary logistic regression results showed that weekends, nights of weekdays and unconventional working time were not independent predicting factors for outcome after intravenous thrombolysis (all P>0.05). Conclusion: The working time has not affected the outcomes of patients with ischemic stroke undergoing intravenous thrombolysis in studied hospitals of Zhejiang province.

Objective: To investigate the clinical features and implication of restless legs syndrome (RLS) in ischemic stroke patients. Methods: A total of 199 ischemic stroke patients were enrolled and assessed by polysomnography (PSG). RLS was identified according to criteria of International Restless Legs Syndrome Study Group. Epworth Sleepiness Scale (ESS), Mini-mental State Examination (MMSE) and Patient Health Questionnaire (PHQ-9) were used to evaluate the sleep quality, cognitive function and post-stroke depression, respectively. The National Institute of Health Stroke Scale (NIHSS) was used to evaluate the neurological function 3 months after stroke onset. Gender-and age-matched non-ischemic stroke patients with RLS (primary PLS) were selected as controls. Results: Twenty-two cases of RLS were identified among 199 ischemic stroke patients (11.1%). Generalized linear model and logistic regression showed that low serum ferritin level (β=-133.3 mg/L, 95%CI:-200.4--0.1, P < 0.01), subcortical infarction (OR=4.05, 95%CI:1.15-14.18, P < 0.05) and female (OR=2.54, 95%CI:1.04-6.23, P < 0.05) were identified as the risk factors of RLS in ischemic stroke patients. Compared with ischemic stroke patients without RLS, ESS increased by 4.37 (95%CI:2.33-6.41, P < 0.01), PHQ-9 increased by 2.17 (95%CI:0.39--3.94, P < 0.05), and reduced NIHSS from the baseline deceased by 0.97 (95%CI:-1.79--0.15, P < 0.05) in ischemic stroke patients with RLS. In addition, the incidence of moderate-severe depression increased (OR=4.27, 95%CI:1.40-13.10, P < 0.05) in ischemic stroke patients with RLS. The index of periodic leg movements of sleep (PLMS) with arousal in ischemic stroke patients with RLS was significantly higher than that in patients with primary RLS (β=12.85, 95%CI:2.04-23.67, P < 0.05). Conclusion: RLS is common in ischemic stroke patients and has adverse influences on patients.

Objective: To determine the effect of trimetazidine on cardiac function and exercise tolerance in primary hypertension patients with type 2 diabetic. Methods: In this randomized, double-blind, placebo-controlled prospective study, 60 primary hypertensive patients with diabetic were equally assigned into two groups, patients received trimetazidine (20 mg, 3 times a day) or placebo for 1 year. Echocardiography, cardiopulmonary exercise testing were performed; and the plasma N terminal pro B type natriuretic peptide (NT-ProBNP), hr-CRP, TNF-α, angiotensin Ⅱ and endothelin concentration were determined before and after treatment. Results: In trimetazidine group, the left ventricular mass index, the mitral flow velocity E wave to A wave ratio (E/A), the peak early diastolic velocity (V_E) to late diastolic velocity (V_A) ratio (V_E/V_A) and the peak systolic velocity (Vs) were significantly improved, the plasma NT-ProBNP level was significantly decreased, and the exercise time, metabolic equivalent, maximal oxygen uptake and anaerobic threshold were significantly increased (all P < 0.05); plasma concentration of hr-CRP, TNF-α, angiotensin Ⅱ and endothelin were significantly reduced after trimetazidine treatment, compared with baseline (all P < 0.05) and with placebo (all P < 0.05). There were no significant differences in any of above parameters after treatment in placebo group (all P>0.05). No severe adverse reaction was observed in both groups. Conclusion: For patients with both hypertension and diabetes, trimetazidine can improve cardiac function and increase exercise tolerance.

Objective: To investigate the effect and mechanism of glucosides of chaenomeles speciosa (GCS) on ischemia/reperfusion-induced brain injury in mouse model. Methods: Fifty 8-week C57BL/C mice were randomly divided into five groups with 10 in each group:sham group, model group, GCS 30 mg/kg group, GCS 60 mg/kg group and GCS 90 mg/kg group, and the GCS was administrated by gavage (once a day) for 14 d. HE staining was performed to investigate the cell morphology; the Zea-Longa scores were measured for neurological activity; TUNEL staining was performed to investigate the cell apoptosis; ELISA was used to detected the oxidative stress and inflammation; Western Blot was performed to investigate the key pathway and neurological functional molecules. Results: Compared with the sham group, the brain tissues in model group were seriously damaged, presenting severe cell apoptosis, oxidative stress and inflammation, associated with increased NF-κB P65 and TNF-α levels as well as decreased myelin associate glycoprotein (MAG) and oligodendrocyte-myelin glycoprotein (OMgp)levels (all P<0.01). Compared with the model group, the brain tissues in GCS groups were ameliorated, and cell apoptosis, oxidative stress and inflammation were inhibited, associated with decreased NF-κB P65 and TNF-α levels as well as increased MAG and OMgp levels (all P<0.01), which were more markedly in GCS 60 mg/kg group. Conclusion: GCS can inhibit the NF-κB P65 and TNF-α, reduce the oxidative stress and inflammation, decrease the cell apoptosis in mouse ischemia/reperfusion-induced brain injury model, and 60 mg/kg GCS may be the optimal dose.

Objective: To investigate the effects of high dose vitamin C (VC) on proliferation of breast cancer cells and to explore its mechanisms. Methods: Human breast cancer cells Bcap37 and MDA-MB-453 were treated with VC at low dose (0.01 mmol/L), medium dose (0.10 mmol/L) and high dose (2.00 mmol/L). Cell proliferation was determined with CCK-8 assay, protein expression was evaluated by Western blot, and the secretion of lactic acid in tumor cells was detected by colorimetric method. Bcap37 cells were inoculated in nude mice, and tumor baring nude mice were intraperitoneally injected with high VC(4 g/kg, VC group, n=5)or normal saline (control group, n=5) for 24 d. Tumor weight and body weight were calculated. Results: In vitro experiments demonstrated that high dose VC significantly inhibited cell proliferation in Bcap37 and MDA-MB-453 cells (all P < 0.01); the expressions of Glut1 and mTOR signaling pathway-related proteins were decreased (all P < 0.05); and the secretion of lactic acid was also markedly reduced (all P < 0.05). In vivo experiment showed that the tumor weight was decreased in mice treated with high-dose VC as compared with control group (P < 0.05), but no difference in body weights between two groups was observed. Conclusion: High dose VC may inhibit proliferation of breast cancer cells both in vitro and in vivo through reducing glycolysis and protein synthesis.

Objective: To determine the correlation of phosphorylated ribosomal S6 protein (P-S6) content in blood and brain tissue in mice and rats with seizure. Methods: Seizure models were induced by intraperitoric injection of kainic acid (KA) in C57BL/mice and SD rats. Flow cytometry was used to detect the content of P-S6 in blood; Western blot was used to detect the expression of P-S6 in brain tissues. The correlation between P-S6 expression in blood and in brain tissue was examine by Pearson analysis, and the correlation between P-S6 expression in blood and the severity of seizure was also observed. Results: Western blotting analysis showed that the expression of P-S6 was significantly increased in peripheral blood and brain tissue in mice 1 h after KA-induced seizure, and the expression levels increased to (1.49±0.45) times (P < 0.05) and (2.55±0.66) times (P < 0.01) of the control group, respectively. Flow cytometry showed that the positive percentage and average fluorescence intensity of P-S6 in the blood of mice increased significantly 1 h after KA-induced seizures (P < 0.01), which was consistent with the expression of P-S6 in brain tissue (r=0.8474, P < 0.01). Flow cytometry showed that the average fluorescence intensity of P-S6 in blood increased from 14.89±9.75 to 52.35±21.72 (P < 0.01) in rats with seizure, which was consistent with the change of P-S6 in brain tissue (r=0.9385, P < 0.01). Rats with higher levels of seizure were of higher levels of P-S6 in peripheral blood. Conclusion: Consistent correlation of P-S6 expression is demonstrated in peripheral blood and in brain tissue after KA-induced seizure, suggesting that the expression of P-S6 in blood can accurately reflect the changes of mTOR signaling pathway in brain tissue.

The habenula is a small and bilateral nucleus above dorsal thalamus, which contains several different types of neurons. The habenula has extensive connections with the forebrain, septum and monoaminergic nuclei in the midbrain and brainstem. Habenula is known as an 'anti-reward' nucleus, which can be activated by aversive stimulus and negative reward prediction errors. Accumulating researchs have implicated that the habenula is involved in several behaviors crucial to survival. Meanwhile, the roles of the habenula in neuropsychiatric diseases have received increasing attention. This review summaries the studies regarding the roles of habenula and the related circuits in neuropathic pain, depression, drug addiction and schizophrenia, and discusses the possibility to use the habenula as a treatment target.

Proteins are the physical basis of life and perform all kinds of life activities. Proteins have different orientations and function in different tissues. The same protein, located in different subcellular regions, can perform different and even opposite functions. Both functional and structural proteins are capable of undergoing re-localization which can directly or indirectly participate in signal transduction. Due to abnormal transduction of signals during carcinogenesis, the proteins originally expressed in the cytoplasm are translocated into the nucleus and lead to functional changes in the tumor tissue. The changes of protein localization are affected by many factors, including the interaction between proteins, expression level of proteins and the cleaved intracellular domain of transmembrane protein.

Early diagnosis is the key to improve the prognosis of gastric cancer. How to screen out high-risk subjects of gastric cancer in population is a hot spot. Serum-based early detection of gastric cancer is suitable for high-risk population screening, which is more convenient and safer. This article reviews the diagnostic value of serum biomarkers for gastric cancer, including serum DNA methylation, various RNAs, pepsinogen, gastrin, osteopontin, MG7-Ag and CA724. Until now, there is still lack of ideal biomarkers for gastric cancer, and searching for specific RNAs may be promising for early diagnosis and screening of gastric cancer.