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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 In an effort to identify further published, unpublished and ongoing trials we searched ongoing trials registers, reference lists and relevant conference proceedings, and contacted authors and pharmaceutical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.


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.


Wu W.M.,Chinese PLA General Hospital
Journal of digestive diseases | Year: 2014

Bacteria are sparsely distributed in the stomach due to the gastric microbicidal barrier. Several innate defenses (low pH, migrating motor complex and the entero-salivary circulation of nitrate) as well as external factors (diet, Helicobacter pylori infection, proton pump inhibitors, antibiotics and stomach diseases) have been shown to influence significantly the microbiota composition in the stomach. In recent years new culture-independent technologies have allowed the investigation of the cross talk that occurs between hosts and stomach-associated microflora, which helps us to understand the role of gastric bacterial flora in the gastrointestinal microbiological system, both in physiological and pathological conditions. Here, we reviewed the literatures related to this topic and set the stage for future developments of the field. © 2013 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and Wiley Publishing Asia Pty Ltd.


Dai W.,Chinese PLA General Hospital
Cephalalgia : an international journal of headache | Year: 2013

Nummular headache, or coin-shaped cephalagia, is defined as a mild to moderate, pressure-like pain that is felt exclusively in a circumscribed area. More than 200 cases of nummular headache have been reported since it was defined in 2002, but the pathogenesis remains unclear. A patient with nummular headache who had the symptomatic area of his scalp removed but suffered headache reappearance was reported. All published cases of nummular headache in the English literature were reviewed and analyzed for demographic and clinical features, image and laboratory findings, and response to treatment. The patient with nummular headache had the symptomatic area of the scalp removed but suffered reappearance of headache in another area that overlapped with the former one. The literature review showed that nummular headache was a chronic, mild to severe, pressure-like pain with a circular or elliptical shape of 1-10 cm in diameter. The parietal region was the most affected region. Exacerbations and sensory disturbances in the affected area were reported in 43% and 56% of cases, respectively. Observational data suggested botulinum toxin type A (BoNTA) and gabapentin may be beneficial. Our case and evidence from the literature review support the peripheral mechanism of nummular headache. Nummular headache might be a local pain disorder stemming from terminal branches of a sensory nerve and could induce peripheral sensitization in one or several primary sensory neurons.


Background With a well-developed strategy of acute graft-versus-host disease (aGVHD) prophylaxis, the prognosis of allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients who develop aGVHD has improved considerably. Meanwhile, transfusion-associated GVHD (TA-GVHD) can be fatal. Recent advancements in immune cellular therapy are being adopted in clinical practice, although many concerns including TA-GVHD remain. This report describes a 64-year-old male non-HSCT candidate diagnosed with acute myeloid leukemia who had received decitabine followed by an infusion of granulocyte-colony- stimulating factor-primed peripheral blood stem cells (G-PBSCs) from his daughter, who carried haploidentical human leukocyte antigen. The patient developed aGVHD on the 20th day after infusion. Study Design and Methods This study is a single case report of a non-HSCT candidate who developed skin aGVHD with mild clinical course after decitabine and G-PBSCs combination. The clinical course, chimerism, and aGVHD pathology studies are detailed. Results Compared with conventional aGVHD in allo-HSCT recipients and TA-aGVHD, the presentation of this case followed a self-limited clinical course without marrow aplasia or severe progression. However, the patient eventually died of leukemia without a significant graft-versus-leukemia effect. Conclusion First, the results demonstrate the existence of aGVHD in elderly non-HSCT candidates receiving adoptive cellular immune therapy. Second, aGVHD occurring under these conditions is probably a unique entity of aGVHD compared to TA-aGVHD and the conventional pattern in allo-HSCT recipients with respect to clinical course and prognosis. © 2013 American Association of Blood Banks.


Peroxisome proliferator-activated receptor gamma (PPAR-γ) agonists are insulin-sensitising drugs used for the treatment of insulin resistance. In addition to lowing glucose in diabetes, these drugs may also protect against hyperlipidaemia and arteriosclerosis, which are risk factors for stroke. To assess the efficacy and safety of PPAR-γ agonists in the secondary prevention of stroke and related vascular events for people with stroke or transient ischaemic attack (TIA). We searched the Cochrane Stroke Group Trials Register (August 2013), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2013, Issue 9), MEDLINE (1949 to October 2013), EMBASE (1980 to October 2013), CINAHL (1982 to October 2013), AMED (1985 to October 2013) and 11 Chinese databases (October 2013). 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. There were no language restrictions. We included randomised controlled trials (RCTs) evaluating PPAR-γ agonists versus placebo for the secondary prevention of stroke and related vascular events in people with stroke or TIA, with the outcomes of recurrent stroke, vascular events 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 identified four eligible studies with 1163 participants; only one study had a low risk of bias for all domains. The participants in different studies were heterogeneous. The number of participants with recurrent stroke was evaluated in two studies, where PPAR-γ agonists reduced the recurrence of stroke compared with placebo (risk ratio (RR) 0.52, 95% confidence interval (CI) 0.34 to 0.80). PPAR-γ agonists given over a mean duration of 34.5 months in a single trial were found to reduce a composite outcome of total events of cardiovascular death, non-fatal myocardial infarction or non-fatal stroke (RR 0.73, 95% CI 0.54 to 0.99). Data on additional composite outcomes reflecting serious adverse events (all-cause death and other major vascular events; all-cause mortality, non-fatal myocardial infarction or non-fatal stroke) were similar although the confidence intervals were wider and the effects were not statistically significant. In addition, two studies respectively measured insulin sensitivity and the ubiquitin-proteasome activity in carotid plaques with significant differences in these outcomes between PPAR-γ agonists and placebo. None of the studies reported the number of participants with disability due to vascular events or improvement in quality of life. Three RCTs reported information about adverse events. Frequent adverse events included oedema, cardiac failure and anaemia. Evidence that adverse events occurred more frequently in participants treated with PPAR-γ agonists when compared with placebo was imprecise and inconsistent (risk difference (RD) 10%, 95% CI -8% to 28%, I2 = 86%). PPAR-γ agonists were demonstrated to reduce recurrent stroke and total events of cardiovascular death, non-fatal myocardial infarction or non-fatal stroke, and improve insulin sensitivity and the stabilisation of carotid plaques. There is evidence of limited quality that they are well-tolerated. However, the conclusions should be interpreted with caution considering the small number and the quality of the included studies. In future, well-designed, double-blind RCTs with large samples are required to test the efficacy and safety of PPAR-γ agonists in the secondary prevention of stroke and related vascular events in people with stroke or TIA.


Patent
Chinese PLA General Hospital | Date: 2015-10-26

The present invention relates to a compound of Formula I, or an isomer, pharmaceutically acceptable salt and solvate of the compound, and to a composition comprising the compound of Formula I, or the isomer, pharmaceutically acceptable salt and solvate thereof, and a pharmaceutically acceptable carrier, excipient or diluents. The present invention also relates to use of the compound of Formula I, or the isomer, pharmaceutically acceptable salt and solvate thereof for combating apoptosis, preventing or treating a disease or disorder associated with apoptosis; and especially use for protecting cardiomyocyte, and for preventing or treating a disease or disorder associated with cardiomyocyte apoptosis.


Patent
Chinese PLA General Hospital | Date: 2013-03-27

The present invention relates to a compound of Formula I, or an isomer, pharmaceutically acceptable salt and solvate thereof; the present invention also relates to a composition comprising a compound of Formula I, or an isomer, pharmaceutically acceptable salt and solvate thereof, and a pharmaceutically acceptable carrier, excipient or diluents. The present invention also relates to use of a compound of Formula I, or an isomer, pharmaceutically acceptable salt and solvate thereof for combating apoptosis, preventing or treating a disease or disorder associated with apoptosis; especially use for protecting cardiomyocyte, preventing or treating a disease or disorder associated with cardiomyocyte apoptosis.


The present invention relates to an acrylamide compound of Formula I, or an isomer, pharmaceutically acceptable salt and solvate thereof, to a composition comprising the compound or an isomer, pharmaceutically acceptable salt and solvate thereof, and a pharmaceutically acceptable carrier, excipient or diluent, and to a use of the compound or the composition for prophylaxis and/or treatment of a disease or disorder associated with cardiomyocyte apoptosis


Patent
Chinese PLA General Hospital | Date: 2013-03-20

The present invention relates to a compound of Formula I, or an isomer, pharmaceutically acceptable salt and solvate thereof. The present invention also relates to a composition comprising a compound of Formula I, or an isomer, pharmaceutically acceptable salt and solvate thereof, and a pharmaceutically acceptable carrier, excipient or diluents. Further, the present invention relates to use of a compound of Formula I, or an isomer, pharmaceutically acceptable salt and solvate thereof for anti-apoptosis, preventing or treating a disease or disorder associated with apoptosis; especially useful for protecting cardiomyocyte, preventing or treating a disease or disorder associated with cardiomyocyte apoptosis.

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