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 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 explore the clinical efficacy of removal of large and medium-sized meningiomas in the sellar region via neuroendoscope assisted supraorbital keyhole approach.Methods:The clinical data of 13 patients with large and medium-sized meningiomas in the sellar region accepted surgery via neuroendoscope assisted supraorbital keyhole approach in our hospital from March 2017 to March 2019 were analyzed retrospectively. The surgical efficacies of these patients were analyzed.Results:Total removal was achieved in all 13 patients: 2 were with Simpson I resection, and 11 with Simpson II resection. The vision was improved in all patients. After surgery, scalp hydrops appeared in 2 patients, transient diabetes insipidus in 2 patients, and recurrent hyponatremia and hypokalemia in one patient; these symptoms were relieved gradually for 2 weeks. No olfactory disturbance was noted in these 13 patients. Follow up for 3-18 months showed no recurrence, and Karnofsky performance status scores were≥80.Conclusion:Surgery via supraorbital keyhole approach is suitable for large and medium sized meningiomas in the sellar region, with advantages of beauty, minimal invasion, few postoperative complications and quick recovery.

Objective: To establish a novel stress-induced depression model by changing the lighting conditions and continuously damping cushion (L-D). Methods: The L-D stress depression animal model was established in C57BL / 6 mice with body weight of 18-22 g. Seventy-five mice with the horizontal and vertical scores higher than 30 and less than 120 in open field test were employed.In the research of model construction, mice were randomly divided into three groups: control group (n=9), chronic unpredictable mild stress(CUMS) model group (n=10) and L-D model group (n=9). In the drug intervention experiments, mice were randomly divided into five groups: control group (n=9), chronic unpredictable mild stress(CUMS) model group (n=10), L-D model group (n=9), CUMS+ fluoxetine group (n=10) and L-D model+ fluoxetine group (n=9). Open field test, forced swimming test and sucrose preference test were used to evaluate the degree of depression in animals. Results: (1) In the open field test, the horizontal score of CUMS model group (67.20±5.81) and the L-D model group (52.56±19.05) were significantly lower than that of the control group (76.44±9.22) (t=2.645, t=3.387, both P<0.05). And horizontal score of the L-D model was significantly lower than that of the CUMS model (t=2.321, both P<0.05). In forced swimming experiment, compared with the control group ((39.67±21.12)s), the immobility time of the CUMS model group ((60.90±10.34)s) and the L-D model group ((74.89±16.10)s) were significantly prolonged (t=2.831, 3.979, both P<0.05). The immobility time of the L-D model group was also significantly higher than that of the CUMS model group (t=2.278, P<0.05). In the sucrose preference experiment, the percentage of sucrose preference in CUMS model group ((72±7)%) and L-D model group ((65±5)%) was lower than that in the control group ((81±12)%) (t=2.195, 3.875, both P<0.05). The percentage of sucrose preference of L-D model group was significantly higher than that of CUMS model group (t=2.286, P<0.05). (2) After intervention with antidepressants, the horizontal scores of the CUMS model group (65.60±6.43) and the L-D model group (54.33±14.67) were significantly lower than that of the control group (75.78±8.27) in open field test (t=3.011, t=3.861, both P<0.05), and the score of L-D group was lower than that of CUMS group(t=2.235, P<0.05). The vertical score of the L-D model group (33.44±4.54) was significantly lower than that of the control group (39.22±5.56) (t=2.553, P<0.05). There was significant increase in the level score and vertical score of CUMS model and L-D model after fluoxetine intervention (t=3.090, t=2.692, both P<0.05), and significant twist in the vertical score of CUMS model and L-D model (t=2.681, t=2.354; both P<0.05). In the forced swimming experiment, the immobility time of the L-D model((64.11±13.06)s) was significantly longer than that of the control group ((42.00±13.77)s) (t=3.494, P<0.05). The immobility time of CUMS model and L-D model mice was significantly longer than that of non-intervention group (t=2.137, 2.940, both P<0.05). After the intervention of fluoxetine, there was no significant difference between the CUMS group, L-D group, the control group(all P>0.05). Conclusion Changing the lighting conditions and continuously damping cushion is a new method to establish mice model with depression behavior.Shorter modeling duration and simple operation are the main advantages of this model.

Voltage-gated sodium channels (VGSCs) in primary sensory neurons play a key role in transmitting pain signals to the central nervous system. BmK I, a site-3 sodium channel-specific toxin from scorpion Buthus martensi Karsch, induces pain behaviors in rats. However, the subtypes of VGSCs targeted by BmK I were not entirely clear. We therefore investigated the effects of BmK I on the current amplitude, gating and kinetic properties of Nav1.8, which is associated with neuronal hyperexcitability in DRG neurons. It was found that BmK I dose-dependently increased Nav1.8 current in small-sized (<25 μm) acutely dissociated DRG neurons, which correlated with its inhibition on both fast and slow inactivation. Moreover, voltage-dependent activation and steady-state inactivation curves of Nav1.8 were shifted in a hyperpolarized direction. Thus, BmK I reduced the threshold of neuronal excitability and increased action potential firing in DRG neurons. In conclusion, our data clearly demonstrated that BmK I modulated Nav1.8 remarkably, suggesting BmK I as a valuable probe for studying Nav1.8. And Nav1.8 is an important target related to BmK I-evoked pain.
Aniline Compounds ; pharmacology ; Animals ; Cell Size ; Cells, Cultured ; Electrophysiological Phenomena ; drug effects ; Furans ; pharmacology ; Ganglia, Spinal ; cytology ; Kinetics ; Male ; NAV1.8 Voltage-Gated Sodium Channel ; metabolism ; Rats ; Rats, Sprague-Dawley ; Scorpion Venoms ; antagonists & inhibitors ; pharmacology ; Scorpions ; Sensory Receptor Cells ; drug effects ; metabolism ; physiology ; Sodium Channel Blockers ; pharmacology ; Voltage-Gated Sodium Channel Agonists ; pharmacology

Objective Using the technology of siRNA to inhibit gene expression of T cells'nonreceptor tyrosine protein kinase Lck in asthmatic mice,and to study the effect of siRNA inhibited Lck to the function of T cells in asthmatic mice.Methods The 21 - 23 bp RNA fragments of mouse T cell Lck were made by chemosynthesis.INTERFERinTMsiRNA Transfection Reagent was used as transfection reagent to transfect the siRNA into the spleen T cells of asthmatic mice for 48 hours.Then T cells were mixed with bone marrow dendritic cells (DC) of asthmatic mice for another 48 hours.Cell culture suspension was collected and the level of IL-4,IL-13,IL-2,INF-γ were detected with respondent ELISA kits; Western Blot was used to identify if the expression of Lck was blocked.Results The expression of Lck in T cells almost could not be detected in siRNA interference group.The levels of IL-4 and IL-13 in siRNA interference group( 10.19 ± 1.66,12.34 ±0.79) were lower than no-siRNA interference(28.06 ±2.88,27.87 ± 1.61 )and control group ( 22.07 ± 2.5 1,20.47 ± 2.37 ),and the difference was statistical significant ( P ＜0.01 ).Conclusions Special siRNA could block the expression of special gene,and Lck specific siRNA could block the activation and differentiation of T cells and reduce the secretion of inflammatory cytokines in asthmatic mice.

ObjectiveUsing the technology of siRNA to inhibit the gene expression of no-receptor　tyrosine protein kinase Lck in T cells of asthmatic mice,and to study the therapeutic effect of Lck specific　siRNA in asthmatic mice.MethodsReceptor tyrosine protein kinase Lck specific siRNA fragments were　taken from chemosynthesis.In vivo-jetPEITM was used to transfect the siRNA into mice body through tail　vein injection.The mice were killed 48 hours later,and the levels of IL-4,IL-17 in bronchoalveolar lavage　fluid (BALF) were detected with respondent ELISA kits.The change of inflammatory histopathology in lung　was observed with H.E.staining.The expression of Lck in lung was detected with immunohistochemistry　(IHC),and the level of Lck in lung tissue homogenate was detected with Western Blot.Results Compared with asthmatic group[ (234.68 ± 11.15 ) pg/ml,( 96.76 ± 8.28 ) pg/ml],the levels of IL-4,IL-17　[ (234.68 ± 11.15)pg/ml,(96.76 ±8.28) pg/ml] in the BALF of siRNA interference group decreased,　and the inflammation in the lung relieved.IHC indicated that the expression of Lck in lung decreased and　the level of Lck in lung tissue homogenate decreased ( P ＜ 0.05 ).Conclusions Lck specific siRNA　could reduce the level of IL-4,IL-17 in the lung tissues of asthmatic mice,and relieve the inflammatory reaction in lung.

Objective To investigate the effects of trichostatin A(TSA)on the mice model of collagen induced arthritis(CIA).Methods Mice model of rheumatoid arthritis(RA)was induced in DBA/1 mice with type Ⅱ collagen.Paws were scored for histological severity of arthritis.The severity of inflammation of mouse joint was evaluated by histological examination.Real-time PGR was used to determine the cytokine mRNA expression.Cytokine production was measured by ELISA from serum,spleen cell culture or dendritic cell and T cell co-culture supematant.T cell proliferation was examined by MTT method.Results TSA can significantly suppress the severity of the arthritis in CIA.IFN-γ was elevated in CIA mice,but was inhibited significantly by TSA introduced either at the same time with immunization or at the onset of manifestation of arthritis.Collagen specific T cell proliferation was significantly suppressed by introduction of TSA.Increased level of IL-4 by T cells was observed in TSA treated group compared to that of control group.Conclusion IL-4 level was increased and played a critical role in the protective effects of TSA in CIA.TSA suppresses the progress of CIA by regulates the balance of Th1/Th2 differentiation.

Objective To construct profiles of health status based upon physical,mental and social support items in adult twins of Qingdao.Methods Grade of Membership(GoM) model was applied to a set of 31 indicators to construct ideal profiles.Results Four health profiles were identified: pure type Ⅰ(healthy),pure type Ⅱ(personality disorders),pure type Ⅲ(psychological symptoms) and pure type Ⅳ(physiological symptoms).The most frequently occurring combination in this population was profile Ⅰ,Ⅱ,Ⅳ(14.74%),followed by profile Ⅰ,Ⅱ,Ⅲ,Ⅳ(13.44%),and then type Ⅰ(11.08%).Only 13.56% of subjects fell completely into one single pure type.Conclusions One healthy type and three non-healthy types are determined.Most individuals exhibit some of the characteristics of two or more types,holding partial membership in multiple categories.