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Liu J.,Chinese PLA General Hospital
Cochrane database of systematic reviews (Online) | Year: 2013

Gamma aminobutyric acid (GABA) receptor agonists have been shown to have a neuroprotectant effect in reducing infarct size and improving functional outcome in animal models of cerebral ischemia. However, the sedation effects of GABA receptor agonists have limited their wider application in acute stroke patients due to the potential risk of stupor. To determine the efficacy and safety of GABA receptor agonists in the treatment of acute stroke. We searched the Cochrane Stroke Group Trials Register (January 2012), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2012, Issue 1), MEDLINE (1949 to March 2012), EMBASE (1980 to March 2012), CINAHL (1982 to March 2012), AMED (1985 to March 2012) and 11 Chinese databases (March 2012). In an effort to identify further published, unpublished and ongoing trials we searched ongoing trials registers, reference lists and relevant conference proceedings, and contacted authors and pharmaceutical companies. We included randomized controlled trials (RCTs) investigating GABA receptor agonists versus placebo for acute stroke patients (within 12 hours after stroke onset), with the outcomes of death or dependency, functional independence and adverse events. Two review authors independently screened the titles and abstracts of identified records, selected studies for inclusion, extracted eligible data, cross-checked the data for accuracy and assessed the methodological quality. We included five trials with 3838 patients. The methodological quality of the included trials was generally good, with low risk of bias. Four trials measured death and dependency at three months in chlormethiazole versus placebo without significant difference (risk ratio (RR) 1.03, 95% confidence interval (CI) 0.95 to 1.11). One trial measured this outcome between diazepam and placebo (RR 0.94, 95% CI 0.82 to 1.07). In the subgroup analysis of total anterior circulation syndrome (TACS), a higher percentage of functional independence was found in the chlormethiazole group (RR 1.33, 95% CI 1.09 to 1.64). The frequent adverse events related to chlormethiazole were somnolence (RR 4.56, 95% CI 3.50 to 5.95) and rhinitis (RR 4.75, 95% CI 2.67 to 8.46). This review does not provide the evidence to support the use of GABA receptor agonists (chlormethiazole or diazepam) for the treatment of patients with acute ischemic or hemorrhagic stroke. Chlormethiazole appeared to be beneficial in improving functional independence in patients with TACS according to the subgroup analysis, but this result must be interpreted with great caution. More well-designed RCTs with large samples of TACS would be required for further confirmation. However, somnolence and rhinitis are frequent adverse events related to chlormethiazole. Source


Liu J.,Chinese PLA General Hospital
Cochrane database of systematic reviews (Online) | Year: 2013

The treatment baclofen can rapidly reduce symptoms of severe alcohol withdrawal syndrome (AWS) in alcoholic patients, with a significant reduction in the cost. Baclofen is easy to manage, and rare euphoria, craving and other pleasant effects are reported by patients treated with baclofen. To assess the efficacy and safety of baclofen for patients with AWS. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library (October 2012), MEDLINE (1966 to October 2012), EMBASE (1980 to October 2012) and CINAHL (1982 to October 2012). We also searched registers of ongoing trials, for example ClinicalTrials.gov, Controlled-trials.com, EUDRACT, etc. At the same time, we handsearched the references quoted in the identified trials, and contacted researchers, pharmaceutical companies and relevant trial authors seeking information about unpublished or uncompleted trials. All searches included the non-English language literature. All randomized controlled clinical trials (RCTs) evaluating baclofen versus placebo or any other treatment for patients with AWS. Uncontrolled, non-randomized or quasi-randomized trials were excluded. Both parallel group and cross-over design were included. Two review authors independently assessed references retrieved for possible inclusion. All disagreements were resolved by an independent party. Study authors were contacted for additional information. Adverse effects information was collected from the trials. We identified a total of 113 references from all electronic databases searched excluding duplicates. After screening of titles and abstracts, full papers of 10 studies were obtained and assessed for eligibility. Finally, two RCTs with 81 participants were eligible according to the inclusion criteria. Regarding the efficacy, one study suggested that both baclofen and diazepam significantly decreased the Clinical Institute Withdrawal Assessment of Alcohol Scale Revised (CIWA-Ar) score, without any significant difference between the two interventions. The other study showed no significant difference in CIWA-Ar score between baclofen and placebo but a significantly decreased dependence on high-dose benzodiazepines with baclofen compared to placebo. Meanwhile, only one study reported the safety outcomes and there were no side effects in either the baclofen or diazepam groups. The evidence for recommending baclofen for AWS is insufficient. More well designed RCTs are needed to prove its efficacy and safety. Source


Lu Y.,Chinese PLA General Hospital
Molecular & cellular proteomics : MCP | Year: 2012

Anti-Thy1 nephritis is a well-established experimental mesangial proliferative nephritis model. Exploring the molecular mechanisms of pathophysiology in anti-Thy1 nephritis may elucidate the pathogeneses of mesangial proliferation. We examined the roles and acting mechanisms of differentially expressed proteins (DEPs) by bioinformatics analysis of glomeruli proteomic profiles during the course of anti-Thy1 nephritis. In total, 108 DEPs were found by two-dimensional fluorescence difference gel electrophoresis (2D-DIGE), and 40 DEPs were identified by matrix-assisted laser desorption ionization/time of flight and liquid chromatography-MS. DEPs were classified into five clusters (Clusters 1-5), according to their expression trends using Cluster 3.0 software, involved in regulating biological processes such as the stress response, cell proliferation, apoptosis, energy metabolism, transport, and the actin cytoskeleton. The expression patterns of ten DEPs, distributed across five clusters, including AKR1A1, AGAT, ATP6V1B2, HIBADH, MDH1, MPST, NIT2, PRDX6, PSMB7, and TPI1, were validated by Western blotting. Based on Western blotting and immunohistochemistry, we also found that the DEP FHL2, which was primarily expressed in the mesangial region, was down-regulated on days 3 and 5, and up-regulated on day 10. In vitro, we found that FHL2 overexpression induced mesangial cell proliferation by increasing the number of S-phase cells and decreasing G2/M-phase cells, whereas inhibiting FHL2 had the opposite effect. This study explored novel DEPs and their expression patterns during anti-Thy1 nephritis, and elucidated FHL2's effect on mesangial cell proliferation. These results will contribute to our understanding of the pathogenesis of mesangial proliferation. Source


Wang X.,Chinese PLA General Hospital
Current Molecular Medicine | Year: 2015

Cell-in-cell, a phenomenon characterized by one or more viable cells entering actively into another cell, was observed more than a century and has only attracted more attention in recent years and is becoming a new hot topic in the biological field, owing its biological significance in evolutionary as well as physiological and pathological relevance in development, homeostasis and diseases. In this paper we focus on the diversity, evolutionary conservatism and clinical implication of cell-in-cell as well as latest opinions on the research strategies. Based on the findings from our laboratory and other research groups three working models of cell-in-cell are also proposed. © 2015 Bentham Science Publishers. Source


Midazolam is a benzodiazepine derivative drug that has powerful anxiolytic, amnestic, hypnotic, and sedative properties. The cytoprotective effect of midazolam on brain astrocytes is poorly understood. This study aimed to investigate the cytoprotective effect of midazolam on astrocytes exposed to corticosterone, a stress-produced glucocorticoid. We found that midazolam stimulated pregnenolone and progesterone secretion in astrocytes in a dose-dependent manner. Midazolam protected astrocytes from corticosterone-induced damages in a dose-dependent manner. In addition, we demonstrated that progesterone reduced corticosterone-induced damages. Finally, we applied trilostane, an inhibitor of 3β-hydroxysteroid dehydrogenase, to inhibit pregnenolone metabolism and found that pretreatment with trilostane significantly inhibited the cytoprotective effect of midazolam on corticosterone-induced cytotoxicity in rat astrocytes in a dose-dependent manner. Taken together, these results demonstrate that midazolam has cytoprotective effect on astrocytes. This is, at least partially, derived from midazolam-induced steroidogenesis including progesterone and downstream products in astrocytes. Our data provide new insights into the cytoprotective effect of midazolam. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved. Source

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