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 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 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 compare the regional leptomeningeal (rLMC) scale scores,Miteff scale scores and Tan scale scores to provide the clinical basis for selecting collateral circulation evaluation methods.Methods One hundred and fifteen patients with acute ischemic stroke,admitted to our hospital from August 2013 to February 2017 were chosen in our study.The rLMC scale,Miteff scale,and Tan scale were used to evaluate the collateral circulations of each patient.The credibility and validity of these 3 scales were compared.Modified Rankin scale (mRS) scores at 3 months were followed by 0-2 for good prognosis and 3-6 for poor prognosis.Binary Logistic regression analysis was used to determine the independent prognostic factors of ischemic stroke.Receiver operating characteristic (ROC) curve was used to compare the predictive values of the 3 scales for prognoses of ischemic stroke.Results Intra-observer agreement of the 3 scales from the highest to the lowest was rLMC scale (Kappa=0.871),Tan scale (Kappa=0.842),and Miteff scale (Kappa=0.752).The test-retest reliability of the 3 scales from the highest to the lowest was rLMC scale (Kappa=0.879),Tan scale (Kappa=0.826),and Miteffscale (Kappa=0.775).The validity of the 3 scales from the highest to the lowest was rLMC scale (rs=0.690),Tan scale (rs=0.680),and Miteff scale (rs=0.650).Univariable and multivariable analyses showed that the results of collateral circulation defined by rLMC scale (OR=1.325,95％CI=1.048-1.675,P=0.019),Tan scale (OR=2.938,95％CI=1.115-7.744,P=0.029) and Miteff scale (OR=2.698,95％CI=1.050-6.931,P=0.039) were associated with prognoses of acute ischemic stroke.ROC curve showed that the area under the curve of rLMC scale,Tan scale,and Miteff scale was 0.848,0.799,and 0.759,respectively;there were significant differences among the 3 scoring methods in the area under the curve (P＜0.05),indicating the predictive values of the three to the prognoses:rLMC scale＞Tan scale＞Miteff scale.Conclusions As compared with Miteff scale and Tan scale,rLMC scale has high intra-observer agreement and validity,and is reliable but complicated.The results of collateral circulation defined by these 3 scoring methods are associated with the prognoses of acute ischemic stroke.

Neonatal necrotizing enterocolitis(NEC) is a common critical disease of the digestive system in neonatal period.In severe case,it may even endanger the lives of newborn.The mechanism of NEC is complex and uncertain.Neonatal infection is one of the most important aspects of the mechanism.The immature digestive system,intestinal barrier structure and function in premature infants,the innate defects of intestinal immunity and the abnormal intestinal bacterial colonization can lead to a high incidence of NEC in premature infants.Currently,there is limited specific treatment.It will benefit for reducing incidence of NEC if prevention is targeted on the found of risk factors.

BACKGROUND:Although vitamin C has an anti-oxidation role and can promote cell proliferation, there is a lack of research about the promoting effect of vitamin C on the proliferation of adipose-derived stem cells under high glucose conditions and the related molecular mechanisms.OBJECTIVE:To explore the promoting effect of vitamin C on the proliferation adipose-derived stem cells treated by the high glucose and the related molecular mechanisms.METHODS:Passage 3 human adipose-derived stem cells were cultured under high glucose conditions and then treated with different concentrations of vitamin C (0, 100, 150, 200, 250, 300 μmol/L). Cells cultured under low glucose conditions acted as controls. The expression levels of p-ERK and p-AKT proteins were detected by western blot. MTT method was used to choose the optimal concentration and time of vitamin C for all the subsequent tests. Human adipose-derived stem cells cultured under high glucose conditions were divided into four groups, and cells in blank control group had no treatment. Cells in the other three groups were treated with the optimal concentration of vitamin C (vitamin C group), LY294002+the optimal concentration of vitamin C (LY294002 group), or U0126+the optimal concentration of vitamin C (U0126 group) for 48 hours.EdU staining assay was used to detect the cell proliferation of human adipose-derived stem cells.RESULTS AND CONCLUSION:(1) Cell counting kit detection:We found that high glucose reduced the proliferation of human adipose-derived stem cells, and vitamin C promoted the proliferation of these cells. The best concentration of vitamin C was 200 μmol/L and the optimal effect time was 48 hours. (2) Western blot detection:Compared with the 0 μmol/L vitamin C group, the level of p-ERK in the 200 μmol/L vitamin C group was upregulated significantly (P < 0.01),while no significant expression change in p-AKT protein was found in control, 0 and 200 μmol/L vitamin C groups.(3) EdU test:the number of EdU positive cells was significantly higher in the vitamin C, LY294002, and control groups compared with the blank control group (P < 0.01). Moreover, compared with the vitamin C group, the EdU positive cells in the U0126 group were decreased significantly in number (P < 0.01). In conclusion, the ERK/MAPK signaling pathway is involved in the promotion effect of vitamin C on the proliferation of human adipose-derived stem cells under high glucose conditions.

Objective To evaluate the protective effect of Bletilla striata polysaccharide ( BSPS) on immunological and chemical liver injury in mice. Methods Thirty Kunming male mice were randomly divided into five groups, including the normal control group,model control group,and low-,middle-,and high-dose BSPS groups (n=6 each).Tail vein injection of ConA was carried out to establish the ConA-induced liver injury model.After different treatments,all the animals were sacrificed,and the plasma levels of ALT and AST were tested.Additionally,sixty Kunming male mice were randomly divided into six groups,including the normal control group,model control group,silymarin group,and low-,middle-,and high-dose BSPS groups (n=10 each).Tail vein injection of CCl4 was performed to establish the CCl4-induced acute liver injury model.After different treatments,the plasma levels of ALT and GSH were tested.The effects of BSPS on the weights of the liver and spleen were examined. Results The levels of ALT and AST were reduced in BSPS-treated mice when compared with those experiencing only ConA-induced liver injury ( model control group) ,and significant difference was found between the middle-and high-dose BSPS groups and the model control group (P<0.01,P<0.05).The weights of the liver and spleen and the level of ALT were reduced in BSPS-treated mice as compared with those with only CCl4-induced acute liver injury (model control group),while the level of GSH was significantly increased in middle-and high-dose BSPS groups (P<0.05). Conclusion BSPS at low,middle,and high doses can prevent against the ConA-induced immunological liver injury and CCl4-induced acute liver injury in mice.

Objective To summarize the clinical features and possible impacts of Goodpasture's syndrome in pregnancy on the pulmonary and kidney of the newborn and the mothers. Methods One patient diagnosed Goodpasture's syndrome in pregnancy hospitalized in Peking Union Medical College Hospital on August 23 in 2011 delivered a neonate with bullae of lung. And literatures including 8 cases of pregnancy complicated by Goodpasture's syndrome worldwide through Medline were reviewed. Results (1) Case report:one 31-year-old women presented with acute renal failure at 30+6 weeks of gestation and delivered a male infant with birth weight 1 900 g by caesarean section at 31+1 weeks of gestation. Diagnosis was confirmed as Goodpasture's syndrome with anti-glomerular basement membrane(GBM) antibodies in serum and renal biopsy after delivery. Then she was treated with methylprednisolone, cyclophosphamide, plasmapheresis and dialysis. The neonate showed the lung bullae in the right middle lobe and bilateral intraventricular hemorrhage but renal function was transient normal with anti-GBM as 113.1 EU/ml. The baby was treated by glucocorticoid for two months and clinical symptoms were improved. Anti-GBM antibodies and chest CT showed normal. After been followed up for two years, the baby was normal. (2) Literatures review:the main manifestations of Goodpasture's syndrome in pregnancy were malignant hypertension and renal failure but respiratory symptoms were not obvious. Treated with plasmapheresis, hematodialysis and glucocorticoid maybe have good effects. Most cases had premature delivery. Neonatal anti-GBM antibodies coming from mothers could result to cerebral, renal and pulmonary injury which could be treated by glucocorticoid. Conclusions The Clinical features of pregnancy complicating the Goodpasture's syndrome are malignant hypertension and renal failure. Diagnosis was depended on positive anti-GBM antibodies and renal pathological changes and treatment were depended on plasmapheresis, hematodialysis and glucocorticoid. Neonatal cerebral, renal and pulmonary injury resulting from anti-GBM antibodies coming from mothers should be followed up, and glucocorticoid should be taken if necessary.

OBJECTIVE:To study the antitumor activity of Anthopleura xanthogrammica crude extract on human lung cancer SPC-A1 cells in vitro. METHODS:A. xanthogrammica crude extract obtained by the methods of repeated freezing and thawing,ac-etone precipitation. After treated with crude extract 0(blank control),0.625,1.25 and 2.5 mg/ml for 24,48 and 72 h,the activity of SPC-A1 cells were measured by MTT assay. The growth inhibition rate and IC50 were also calculated. 24 h later,the morphologi-cal changes of SPC-A1 cells were observed by HE staining and AO/EB fluorescence staining. RESULTS:MTT assay showed that A. xanthogrammica crude extract has significant inhibitory effect on the proliferation of human lung cancer SPC-A1 cells;with the increasing of the concentration and the extension of the time,the inhibitory rate was increased. Its 24 h,48 h ,72 h IC50 were 1.81,1.32 and 1.18 mg/ml. HE staining and AO/EB staining appeared obvious morphological changes of apoptosis that cell mor-phology narrowed,vacuoles arose in the cytoplasm,karyopyknosis and part of nuclear disappearance occurred. CONCLUSIONS:A. xanthogrammica crude extract has an inhibitory effect on the proliferation of human lung cancer SPC-A1 cells.

Objective　To explore the expression of Cav-1 mRNA,S100A4 mRNA and CD31 in prostate cancer (PCa) and their correlation with tumor metastasis and patient survival rate.　Methods PCa specimens (n =42) and adjacent tissue specimens ( n =12 ) from radical prostatectomy were obtained from January 2004 to May 2006.The mean age of patient was 71.6 ± 7.6 years ( range 58 - 86 years).According to Gleason scores,prostatectomy specimens were stratified into≤6 (n =17),7 (n =12) and ≥8( n =13 ) groups.Patients were classified as clinical stage T1 ( n =16),stage T2 ( n =9 ),stage T3 ( n =11 )and stage T4 (n =6).Patients were divided into PCa with bone metastasis (n =8 ) and PCa without bone metastasis ( n =34).Preoperative PSA levels of the patients were stratified into three groups: ＜ 4 ( n =4)μg/L,4-10 (n=10)μg/Land ＞10 μg/L (n=28).12 adjacent tissues 1 -2 cm away from tumor or another lobe of prostate were microscopically verified without cancer cells and were tested for comparison.The expression of Cav-1 mRNA and S100A4 mRNA were detected by Situ hybridization in 42 PCa specimens and 12 adjacent tissues and using CD31 for marking vascular endothelial cells,the tumor microvascular density (MVD) was counted.The correlation of Cav-1 mRNA,S100A4 mRNA and CD31 expression was analyzed in combination.with clinical and pathological fcatures including Gleason score,TNM staging,PSA values and bone metastasis.　Results　The positive expression rate of Cav-1 mRNA in PCa was 35.7％　( 15/42),while it was 0％ (0/12) in controls,P ＜0.05.The positive expression rate of S100A4 mRNA in PCa was 47.6％ (20/42),while it was 8.3％ (1/12) in controls,P ＜0.05.The positive expression rate of Cav-1 mRNA in PCa was positively correlated with Gleason score,TNM stage and bone metastasis.The positive expression rate of S100A4 mRNA in PCa was positively correlated with TNM stage and bone metastasis.The average MVD in patients of negative expression of Cav-1 mRNA was (62.8 ± 10.4)/mm2,and the average -MVD in patients of positive expression of Cav-1 mRNA was (83.5 ±6.7 )/mm2,P ＜ 0.05.While the average MVD in patients of negative expression of S100A4 mRNA was (63.3 ± 12.0)/mm2,and the average MVD in patients of positive expression of S100A4 mRNA was (77.9 ± 11.0)/mm2,P ＜ 0.05.The 5-year survival rate in patients with positive Cav-1 mRNA expression was significantly lower than that of with negative expression (46.7％ versus 85.2％,P ＜ 0.05 ),while the 5-year survival rate in the patients with positive expression of S100A4 mRNA was significantly lower than that of with negative expression (50.0％ versus 90.9％,P ＜ 0.05 ).　Conclusions　The positive Cav-1 mRNA and S100A4 mRNA expression,increased MVD are positively correlated with PCa progression and bone metastasis. Furthermore,Cav-1 and S100A4 in PCa may promote angiogenesis and cause tumor cells to bone metastases,which can reduce survival rate of patients.