ABSTRACT
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.
ABSTRACT
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.
ABSTRACT
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.
ABSTRACT
Objective:To investigate the relationship between anti-Helicobacter pylori antibody(Hp-IgG)and anti-aquaporin 4 antibody which are in neuromyelitis optica(NMO)and multiple sclerosis(MS).Methods: Serum specimens were collected from the 33 patients with MS,7 patients with NMO,and 35 health examination cases.Hp-IgG were detected by enzyme-linked immunosorbent assasy and anti-aquaporin 4 antibody were detected by cell based assay respectively.The positive rate of Hp-IgG and anti-aquaporin 4 antibody were analyzed,and the difference of Hp-IgG positive rate was compared between patients with Hp-IgG positive and negative.Results: Serum Hp-IgG positive rate of MS,NMO and normal control groups were 69.70％,85.71％ and 42.86％ respectively with a significant statistically difference of Hp-IgG(P0.05).Serum anti AQP4 antibody positive rate of MS,NMO and normal control groups were 4.2％,85.71％ and 0％ respectively with a significant statistically difference of anti AQP4 antibody(P0.05).Conclusion: HP infection is a risk factor for the occurrence of MS and NMO,but not associated with MS and NMO patients with anti AQP4 antibodies.
ABSTRACT
Objective To evaluate the detection of culture filtrate protein 10 (CFP10) and 6000 early secretory antigenic target (ESAT-6) in cerebrospinal fluid to be used in diagnosing tuberculous meningitis. Methods Dot enzyme linked immunosorbent assay ( Dot ELISA) method that was improved by applying concentrated cerebrospinal fluid was used to detect CFP10 and ESAT-6 in cerebrospinal fluid to analyze small protein antigen secreted by M. tuberculosis. Cerebrospinal fluid of 111 subjects were collected,in which 58 specimens were clinically diagnosed as tuberculous meningitis and 53 as non-tuberculous.CFP10 and ESAT-6 were detected in cerebrospinal fluid using Dot ELISA method and the results were analyzed. Results The sensitivities of detecting CFP10 and ESAT-6 antigen were 93.1% and 91.4% respectively, and the specificities were 92. 5% and 94. 3% respectively. The sensitivities and specificities are generally higher compared with the other methods of detecting M. tuberculosis or materials of M. tuberculosis by acid-fast staining or mycobacterium tuberculosis culture and polymerase chain reaction.Conclusions Using Dot ELISA method to detect CFP10 and ESAT-6 in cerebrospinal fluid to diagnose tuberculous meningitis has a high sensitivity and specificity. Our study provided the evidence of detecting the specific antigen of M. tuberculosis to be used in diagnosing tuberculosis.
ABSTRACT
Objective To investigate the therapeutic effect and the detailed mechanisms of intraarterially delivery of bone marrow mesenchymal stem cells ( BMSCs) for treatment of middle cerebral artery occlusion (MCAO) in rats.Methods BMSCs were isolated,purified and amplified with the adherence culture method.BMSCs were labeled with 5-bromo-2-deoxyuridine ( BrdU ) (10 μmol/L) for 48 h before transplation.Surface antigens of CD90,CD29,CD106,CD34,CD45,CD11b were identified by flow cytometry.The MCAO model was established with suture emboli method.In this study,3×106 BMSCs were injected into rats with MCAO through intraarterial route at day 7 after stroke.The effects on functional and physical recovery were assessed with the behavioral tests (mNSS test and adhesive test) and body weight.Bielshowsky-Luxol Fast Blue double staining was used to demonstrate the reconstruction of axon and myelin.The Brdu-labeled BMSCs in vitro and in vivo were detected with direct immunofluorescent staining.The expression of neuron specific enolase ( NSE),neurite outgrowth inhibitor-A ( Nogo-A),synaptophysin (SYN),ki-67 nuclear antigen (Ki-67),glial fibrillary acid protein( GFAP),vascular endothelial growth factor ( VEGF) in brain were analyzed with immunohistochemical staining.Results Flow cytometry indicated that the positive rates of high expression of CD90,CD29,CD106 in BMSCs were respectively 91.70%,88.40% and 52.20%.Meanwhile,the positive rates of low expression of CD34,CD45,CD11b in BMSCs were 2.70%,5.65% and 7.82%,respectively.There was a significant difference in behavioral tests ( mNSS test and adhesive test) between BMSCs group and PBS group at day 21,28,35 after MCAO (mNSS:4.89 ±1.36,7.00 ±1.67,3.78 ±1.30 and 6.33 ±1.21,2.44 ±1.13,5.67 ± 1.51;t =2.69,3.83,4.75;adhesive test:54.00 ± 10.48,68.17 ± 11.09,36.89 ±9.80 and 59.33 ± 12.40,23.44 ± 9.04,46.50 ±9.38;t =2.51,3.92,4.77;P ＜0.05).Meanwhile,a significant difference in body weight was discovered between them at day 28,35 after MCAO.In BMSCs group,the area of corpus callosum in the ipsilateral hemisphere was significantly enlarged,the positive number of Brdu,SYN,Ki-67,GFAP,VEGF in brain was significantly increased,the expression of Nogo-A in brain was significantly decreased,nevertheless,the number of NSE-positive cells in brain and the infarct volume were not significant different from PBS group at day 35 after MCAO.Conclusions These results suggest that intra-arterial transplantation of BMSCs is an efficient treatment protocol for stroke.Treatment with BMSCs increases endogenous cells proliferation,angiogenesis,synaptogenesis,enhances axonal regeneration and the protective function of astrocytes,all of which may contribute to neurological functional recovery.