Objective:To confirm the efficacy and safety of cinepazide maleate injection in acute ischemic stroke patients with obvious motor function deficit.Methods:This study is a subgroup analysis of multi-center, randomized, double-blind, placebo-controlled phase Ⅳ clinical trial. A total 812 patients of acute ischemic stroke with obvious limb motor deficit [motor function of limbs score in National Institutes of Health Stroke Scale (NIHSS) ≥4] were enrolled in this subgroup analysis. Patients received either cinepazide maleate injection or placebo. The treatment period was 14 days and follow-up was 90 days. The efficacy endpoints included the proportions of patients with a modified Rankin Scale (mRS) score ≤2, mRS score ≤1 and Barthel Index <95 on day 90. Safety was evaluated by recording all adverse events, monitoring vital signs, laboratory parameters and electrocardiogram.Results:A total of 732 patients were involved in the final efficacy analysis (361 in cinepazide maleate group and 371 in control group). The baseline limb motor function score of NIHSS was 5.23±1.43 in the cinepazide maleate group whereas 5.20±1.36 in the control group. Logistic regression analysis showed that following treatment for 90 days, the proportion of patients with a mRS score ≤2 was significantly higher in the cinepazide maleate group than in the control group [56.0% (202/361) vs 44.2% (164/371), OR=0.60, 95% CI 0.44-0.82, P=0.002]. The proportion of patients with a mRS score ≤1 was higher in the cinepazide maleate group than in the control group [43.3% (139/361) vs 35.2% (118/371), OR=0.69, 95% CI 0.50-0.97, P=0.031]. The proportion of patients with a Barthel Index <95 on day 90 was significantly lower in the cinepazide maleate group than in the control group [45.2% (145/361) vs 55.2% (185/371), OR=0.64, 95% CI 0.46-0.88, P=0.007]. During the treatment and follow-up period, the incidence of the most common adverse events in the cinepazide maleate group was 50.4% (199/395). Constipation and abnormal liver function were more common, but there were no statistically significant differences between the two groups. Conclusion:Cinepazide maleate injection is superior to placebo in improving neurological function and activities of daily living, reducing disability, and promoting functional recovery and safe in patients with acute ischemic stroke with obvious limb motor deficit.

Objective:To investigate the blood pressure change in patients with acute ischemic stroke (AIS) and hypertension treated with cinepazide maleate injection.Methods:This was a subgroup analysis of post-marketing clinical confirmation study of cinepazide maleate injection for acute ischemic stroke: a randomized, double-blinded, multicenter, placebo-parallel controlled trial, which conducted in China from August 2016 to February 2019. Eligible patients fulfilled the inclusive criteria of acute anterior circulation ischemic stroke with National Institutes of Health Stroke Scale (NIHSS) scores of 7-25. The primary endpoints were mean blood pressure of AIS patients treated with cinepazide maleate or control, which were assessed during the treatment period (14 days), and the proportion of the patients with normal blood pressure was analyzed after the treatment period. Furthermore, a subgroup analysis was performed to investigate a possible effect of the history of hypertension on outcomes.Results:This analysis included 809 patients with hypertension. There was no significant difference in patients blood pressure and the proportion of patients with normal blood pressure (60.5% vs. 59.0%, P>0.05) between cinepazide maleate group and control group. Conclusion:Administration of cinepazide maleate injection does not affect the management of clinical blood pressure in patients with AIS.

Objective:To investigate the effect of oxycodone hydrochloride injection pretreatment on focal cerebral ischemia-reperfusion injury in rats.Methods:Seventy-two male SD rats weighing 200-250 g were randomly divided into 3 groups( n=24 each group): sham operation group (sham group), focal cerebral I/R group (I/R group), and oxycodone hydrochloride injection group (Oxy group). Focal cerebral I/R was induced by middle cerebral artery occlusion for 2 h followed by reperfusion. In the Oxy group, oxycodone hydrochloride 0.5 mg/kg was injected iv at 5 min before ischemia. While the same volume of saline (1 mL) was injected in the sham group and I/R group. The neurological deficit score (NDS) was assessed at 24 h of reperfusion, the rats were then sacrificed, and their brains were immediately removed for determination of brain water content and the infarct volume, and the histopathological changes were observed after HE staining. The levels of cytokines (TNF-α, IL-1β and IL-10) in the ischemia cortex were quantified by ELISA. MPO activity in the ischemia cortex was assessed. Western blot was used to detect the expression of NF-κB in the ischemia cortex. The data were analyzed using SPSS 20.0 software, multiple-group comparisons were performed using one-way ANOVA, and LSD- t test was used for pairwise comparison between groups. A P<0.05 was considered statistically significant different. Results:Compared with the sham group, NDS, brain water content, relative infarction volume and rate of nerve cell necrosis were significantly increased in the I/R and Oxy groups (all P<0.05). Levels of TNF-α, IL-1β, IL-10, NF-κB and the activities of MPO were increased in the ischemia cortex (all P<0.05). Compared the Oxy group with the I/R group, NDS, brain water content, relative infarction volume and rate of nerve cell necrosis were significantly decreased [(1.7±0.9) vs (2.6±1.1);(79.2±2.4)% vs (84.7±4.2)%; (23.0±5.4)% vs (34.8±6.0)%; (25.2±12.4)% vs (54.8±14.8)%, all P<0.05]. The levels of TNF-α, IL-1β, relative expression of NF-κB, and the activities of MPO were significantly decreased in the ischemia cortex [(4.4±1.2) pg/mg vs (6.5±1.2) pg/mg; (5.4±0.7) pg/mg vs (7.8±0.8) pg/mg; (0.83±0.11) vs (1.23±0.33); (0.27±0.09) U/g vs (0.36±0.14) U/g, all P<0.05] , while the concentration of IL-10 was significantly increased [(20.9±4.5) pg/mg vs (9.2±1.6) pg/mg, t=6.036, P=0.000 1]. Conclusions:Oxycodone hydrochloride can attenuate focal cerebral I/R injury through inhibiting NF-κB activity.

Objective:To assess the efficacy and safety of cinepazide maleate injection in the treatment of patients with acute ischemic stroke.Methods:A multicenter, randomized, double-blind, placebo-controlled phase Ⅳ clinical trial, led by Peking Union Medical College Hospital, was conducted in 65 Hospitals in China. The efficacy of cinepazide maleate injection in patients with acute anterior circulation cerebral infarction with onset time of ≤48 hours, 7≤National Institute of Health stroke scale (NIHSS) score ≤25 was assessed from August 2016 to February 2019, using the proportion of modified Rankin scale (mRS) score≤1 and Barthel index (BI) score≤95 on day 14 as efficacy endpoint. The patients were divided into treatment group who were treated with cinepazide maleate injection and control group who were treated with placebo.Results:A total 937 patients were involved in the final efficacy analysis (466 in treatment group and 471 in control group). The proportion of subjects with mRS score≤1 on day 14 after treatment were higher in the treatment group than that in the control group (102/466(21.89%) vs76/471(16.14%)). Logistic regression analysis showed that patients treated with cinepazide maleate were significantly more likely to have a favorable outcome (mRS score≤1) than patients treated with placebo on day 14 ( OR=0.677, 95% CI 0.484-0.948 , P=0.023), and patients treated with cinepazide maleate were more likely to reach independence in activities of daily living (Barthel Index ≥95) than those treated with placebo on day 14 (125/466(26.82%) vs 91/471(19.32%); OR=0.632, 95% CI0.459-0.869, P=0.005). The rate of adverse events was similar between the treatment and control groups. Conclusion:The 14-day treatment with cinepazide maleate injection could reduce the degree of disability whereas did not increase the risk of adverse events.

Objective: To evaluate the effect of irisin preconditioning on global cerebral ischemia-reperfusion (I/R) injury in rats. Methods: Thirty-six healthy male Sprague-Dawley rats, aged 8-10 weeks, weighing 250-300 g, were divided into 3 groups (n=12 each) using a random number table method: sham operation group (group S), global cerebral I/R group (group I/R) and irisin preconditioning group (group I). Global cerebral I/R was induced by occlusion of bilateral common carotid arteries combined with hypotension (MAP maintained at 35-45 mmHg) in anesthetized rats.At 30 min before ischemia, irisin 10 μg/kg (diluted to 10 μg/ml in normal saline) was intravenously injected in group I, and the equal volume of normal saline was intravenously injected in S and I/R groups.Morris water maze test was performed at day 3 of reperfusion to assess the cognitive function.Rats were sacrificed after the end of morris water maze test, and brains were removed for determination of histopathologic changes in hippocampal CA1 region (using HE staining), neuronal apoptosis in hippocampal CA1 region (Tunel staining), glial fibrillary acidic protein (GFAP) expression (by Western blot), myeloperoxidase (MPO) activity in the hippocampal tissues (by colorimetric assay), and contents of tumor necrosis factor-alpha (TNF-α) and interleukin-1beta (IL-1β) in hippocampal tissues (by enzyme-linked immunosorbent assay). The cell necrosis rate and apoptotic rate were calculated. Results: Compared with group S, the escape latency was significantly prolonged on 1-5 days in group I/R and on 1-3 days in group I, the time of staying at 1st quadrant was significantly shortened, the cell necrosis rate and apoptotic rate were increased, the expression of GFAP was up-regulated, and the activity of MPO and contents of TNF-α and IL-1β were increased in I/R and I groups (P<0.05 or 0.01). Compared with group I/R, the escape latency was significantly shortened on 1-5 days, the time of staying at 1st quadrant was prolonged, the cell necrosis rate and apoptotic rate were decreased, the expression of GFAP was down-regulated, and the MPO activity and contents of TNF-α and IL-1β were decreased in group I (P<0.05 or 0.01). Conclusion Irisin preconditioning can reduce the global cerebral I/R injury in rats, and the mechanism may be related to inhibiting activation of astrocytes in hippocampus and reducing inflammatory responses.

Objective To evaluate the effect of oxycodone on acute lung injury (ALI) induced by lipopolysaecharide (LPS) in rats. Methods Thirty-six pathogen-free healthy male Sprague-Dawley rats, weighing 250-300 g, were divided into 3 groups (n= 12 each) using a random number table: sham opera-tion group (group S), LPS-induced ALI group (group A) and oxycodone group (group O). ALI was in-duced by injecting LPS 8 mg∕kg intravenously in A and O groups, while the equal volume of normal saline was given instead in group S. Oxycodone 2 mg∕kg was injected intravenously at 10 min before LPS injection in group O, while the equal volume of normal saline was given instead in S and A groups. Rats were sacri-ficed at 6 h after LPS injection, and the broncho-alveolar lavage fluid (BALF) was collected for detection of tumor necrosis factor-alpha (TNF-α) and interleukin-1beta (IL-1β) concentrations by enzyme-linked im-munosorbent assay. Pulmonary specimens were obtained for microscopic examination of the pathological changes and for determination of wet∕dry weight ratio (W∕D ratio) and expression of Toll-like receptor 4 (TLR4) in lung tissues (using real-time polymerase chain reaction and Western blot). Results Compared with group S, the TNF-α and IL-1β concentrations in BALF, W∕D ratio, pathological scores and expres-sion of TLR4 were significantly increased at 6 h after LPS injection in A and O groups (P<0. 05). Com-pared with group A, the TNF-α and IL-1β concentrations in BALF, W∕D ratio, pathological scores and expression of TLR4 were significantly decreased at 6 h after LPS injection in group O (P<0. 05). Conclu-sion Oxycodone can attenuate LPS-induced ALI in lung tissues, and the mechanism is related to down-regulating the expression of TLR4 and inhibiting inflammatory responses of rats.

Objective To evaluate the effect of quercetin pretreatment on the permeability of blood-brain barrier in a rat model of global cerebral ischemia-reperfusion ( I∕R). Methods Sixty-three clean-grade healthy male Sprague-Dawley rats, weighing 300-350 g, aged 4-5 months, were divided into 3 groups (n＝21 each) using a random number table method: sham operation group ( group S), group I∕R and quercetin pretreatment group ( group Q). Global cerebral I∕R was induced by occlusion of bilateral common carotid arteries combined with hypotension ( mean arterial pressure was maintained at 35-45 mmHg) in chloral hydrate-anesthetized rats. Quercetin 25 μmol∕kg was injected intraperitoneally twice a day for 3 consecutive days starting from 3 days before establishment of the model in group Q, while the e-qual volume of normal saline was given instead at the corresponding time points in group S and group I∕R, respectively. The animals were sacrificed at 24 h of reperfusion and brains were removed to determine the brain water content, Evans blue ( EB) content and expression of occludin protein in cerebral cortex ( by Western blot) and to observe the ultrastructure of blood-brain barrier. Results Compared with group S, the brain water content and EB content were significantly increased, the expression of occludin protein was down-regulated (P＜0. 05), and the injury to ultrastructure of blood-brain barrier was accentuated in I∕R and Q groups. Compared with group I∕R, the brain water content and EB content were significantly de-creased, the expression of occludin protein was up-regulated (P＜0. 05), and the injury to ultrastructure of blood-brain barrier was significantly attenuated in group Q. Conclusion Quercetin pretreatment can de-crease the permeability of blood-brain barrier and attenuate brain edema, and the mechanism may be related to up-regulated expression of occludin protein in a rat model of global cerebral I∕R.

Objective To systematically assess the efficacy and safety of acupuncture in treating type 2 diabetes.Methods Related literature was retrieved with a computer. After the data were sifted out from the literature according to the established criteria, they were collected and crossly checked by two researchers independently. The data were input to RevMan5.2 for statistical analysis. Results A total of ten studies were included with a total of 743 patients. The results of Meta analysis showed 1) Post-treatment total efficacy rate was higher in the acupuncture or combined acupuncture and medicine group than in the control group [OR=3.60, 95%CI (2.11,6.13)] and there was a statistically significant difference (Z=4.71,P<0.00001); 2) Post-treatment range of decrease in fasting blood glucose (FBG) was significantly higher in the experiment group than in the control group [WMD=-1.20,95%CI (-1.38,-1.02)] and there was a statistically significant difference (Z=12.88,P<0.00001); 3) Post-treatment range of decrease in 2-h postprandial blood glucose (2hPBG) was significantly higher in the experiment group than in the control group [WMD=-1.27, 95%CI (-1.47,-1.06)] and there was a statistically significant difference (Z=12.02,P<0.00001).Conclusion Clinically acupuncture or combined acupuncture and medicine is more effective than Chinese herbal medicine or Western medication alone in treating T2DM and has no toxic and side effects.

Objective To evaluate the effects of dexmedetomidine on the oxidative stress responses during global cerebral ischemia-reperfusion (I/R) in rats.Methods Thirty-six male Sprague-Dawley rats,weighing 250-300 g,were randomly divided into 3 groups (n =12 each) using a random number table:sham operation group (group S),global cerebral I/R group (group I/R) and dexmedetomidine group (group D).Global cerebral ischemia was induced by occlusion of bilateral common carotid arteries combined with hypotension (MAP maintained at 35-45 mmHg).In group D,dexmedetomidine was infused at a rate of 3 μg · kg-1 · h-1until 2 h of reperfusion after a loading dose of dexmedetomidine 3 μg/kg was intravenously injected immediately after onset of reperfusion.The neurological deficit score (NDS) was assessed at 24 h of reperfusion,the rats were then sacrificed,and their brains were immediately removed for determination of cell apoptosis and levels of malondialdehyde (MDA),superoxide dismutase (SOD) and catalase (CAT).Apoptotic rate was calculated.Results Compared with group S,NDS,apoptotic rate and MDA level were significantly increased,and SOD and CAT levels were decreased in I/R and D groups.Compared with group I/R,NDS,apoptotic rate and MDA level were significantly decreased,and SOD and CAT levels were increased in group D.Conclusion Dexmedetomidine attenuates global cerebral I/R injury through inhibiting the oxidative stress responses.

PURPOSE: Synuclein-gamma (SNCG), which was initially identified as breast cancer specific gene 1, is highly expressed in advanced breast cancers, but not in normal or benign breast tissue. This study aimed to evaluate the effects of SNCG siRNA-treatment on breast cancer cells and elucidate the associated mechanisms. METHODS: Vectors containing SNCG and negative control (NC) siRNAs were transfected into MDA-MB-231 cells; mRNA levels were determined by real-time polymerase chain reaction. Cell proliferation was evaluated using the MTT assay, cell migration was assessed by the Transwell assay, apoptosis and cell cycle analyses were conducted with the flow cytometer, and Western blot analysis was performed to determine the relative levels of AKT, ERK, p-AKT, and p-ERK expression. RESULTS: SNCG mRNA levels were significantly reduced in MDA-MB-231 cells transfected with SNCG siRNA. Our results indicate that in SNCG siRNA-treated cells, cell migration and proliferation decreased significantly, apoptosis was induced, and the cell cycle was arrested. Western blot analysis indicated that the protein levels of p-AKT and p-ERK were much lower in the SNCG siRNA-treated groups, than in the control and NC groups. CONCLUSION: SNCG siRNA could decrease the migration and proliferation of breast cancer cells by downregulating the phosphorylation of AKT and ERK.
Apoptosis ; Blotting, Western ; Breast ; Breast Neoplasms ; Cell Cycle ; Cell Migration Assays ; Cell Movement* ; Cell Proliferation ; Extracellular Signal-Regulated MAP Kinases ; Phosphorylation* ; Proto-Oncogene Proteins c-akt ; Real-Time Polymerase Chain Reaction ; RNA, Messenger ; RNA, Small Interfering ; Synucleins*