Two investigators (X.W. and Y.D.) independently searched PubMed and Embase for prospective studies examining the association between cholesterol and the risk of hemorrhagic stroke. Three main categories of cholesterol, including TC, high-density lipoprotein Background and Purpose-Cholesterol levels are inconsistently associated with the risk of hemorrhagic stroke. The purpose of this study is to assess their relationships using a meta-analytic approach. Methods-We searched PubMed and Embase for pertinent articles published in English. Only prospective studies that reported effect estimates with 95% confidential intervals (CIs) of hemorrhagic stroke for ≥3 categories of cholesterol levels, for high and low comparison, or for per 1 mmol/L increment of cholesterol concentrations were included. We used the random-effects model to pool the study-specific results. Results-Twenty-three prospective studies were included, totaling 1 430 141 participants with 7960 (5.6%) hemorrhagic strokes. In high versus low analysis, the summary relative risk of hemorrhagic stroke was 0.

BackgroundIn traumatic brain injury (TBI), the appropriate timing and route of feeding, and the efficacy of immune-enhancing formulae have not been well established. We performed this meta-analysis aiming to compare the effects of different nutritional support modalities on clinical outcomes of TBI patients.MethodsWe systematically searched Pubmed, Embase, and the Cochrane Library until October, 2012. All randomized controlled trials (RCTs) and non-randomized prospective studies (NPSs) that compared the effects of different routes, timings, or formulae of feeding on outcomes in TBI patients were selected. The primary outcomes included mortality and poor outcome. The secondary outcomes included the length of hospital stay, the length of ventilation days, and the rate of infectious or feeding-related complications.Findings13 RCTs and 3 NPSs were included. The pooled data demonstrated that, compared with delayed feeding, early feeding was associated with a significant reduction in the rate of mortality (relative risk [RR] = 0.35; 95% CI, 0.24–0.50), poor outcome (RR = 0.70; 95% CI, 0.54–0.91), and infectious complications (RR = 0.77; 95% CI, 0.59–0.99). Compared with enteral nutrition, parenteral nutrition showed a slight trend of reduction in the rate of mortality (RR = 0.61; 95% CI, 0.34–1.09), poor outcome (RR = 0.73; 95% CI, 0.51–1.04), and infectious complications (RR = 0.89; 95% CI, 0.66–1.22), whereas without statistical significances. The immune-enhancing formula was associated with a significant reduction in infection rate compared with the standard formula (RR = 0.54; 95% CI, 0.35–0.82). Small-bowel feeding was found to be with a decreasing rate of pneumonia compared with nasogastric feeding (RR = 0.41; 95% CI, 0.22–0.76).ConclusionAfter TBI, early initiation of nutrition is recommended. It appears that parenteral nutrition is superior to enteral nutrition in improving outcomes. Our results lend support to the use of small-bowel feeding and immune-enhancing formulae in reducing infectious complications.

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Hepatocellular carcinoma (HCC) is generally acknowledged as the most common primary malignant tumor, and it is known to be resistant to conventional chemotherapy. Wentilactone B (WB), a tetranorditerpenoid derivative extracted from the marine algae-derived endophytic fungus Aspergillus wentii EN-48, has been shown to trigger apoptosis and inhibit metastasis in HCC cell lines. However, the mechanisms of its antitumor activity remain to be elucidated. We report here that WB could significantly induce cell cycle arrest at G2 phase and mitochondrial-related apoptosis, accompanying the accumulation of reactive oxygen species (ROS). Additionally, treatment with WB induced phosphorylation of extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), but not p38 MAP kinase. Among the pathway inhibitors examined, only SP600125 (JNK inhibitor) markedly reversedWB-induced apoptosis, and only U0126 (ERK inhibitor) significantly blocked WB-triggered G2 phase arrest. We also found that WB treatment increased both Ras and Raf activation, and transfection of cells with dominant-negative Ras (RasN17) abolishedWB-induced apoptosis and G2 phase arrest in SMMC-7721 cells. Furthermore, the results of inverse docking (INVDOCK) analysis suggested that WB could bind to Ras–GTP, and the direct binding affinity was also confirmed by surface plasmon resonance (SPR). Finally, in vivo, WB suppressed tumor growth in mouse xenograft models. Taken together, these results indicate that WB induced G2/M phase arrest and apoptosis in human hepatoma SMMC-7721 cells via the Ras/Raf/ERK and Ras/Raf/JNK signaling pathways, and this agent may be a potentially useful compound for developing anticancer agents for HCC.

BackgroundModafinil is a novel wake-promoting agent approved by the FDA ameliorating excessive daytime sleepiness (EDS) in three disorders: narcolepsy, shift work sleep disorder and obstructive sleep apnea. Existing trials of modafinil for fatigue and EDS associated with neurological disorders provided inconsistent results. This meta-analysis was aimed to assess drug safety and effects of modafinil on fatigue and EDS associated with neurological disorders.MethodsA comprehensive literature review was conducted in order to identify published studies assessing the effects of modafinil on fatigue and EDS associated with neurological disorders. Primary outcomes included fatigue and EDS. Secondary outcomes included depression and adverse effects.FindingsTen randomized controlled trials were identified including 4 studies of Parkinson’s disease (PD), 3 of multiple sclerosis (MS), 2 of traumatic brain injury (TBI) and 1 of post-polio syndrome (PPS). A total of 535 patients were enrolled. Our results suggested a therapeutic effect of modafinil on fatigue in TBI (MD -0.82 95% CI -1.54 - -0.11 p=0.02, I2=0%), while a beneficial effect of modafinil on fatigue was not confirmed in the pooled studies of PD or MS. Treatment results demonstrated a clear beneficial effect of modafinil on EDS in patients with PD (MD -2.45 95% CI -4.00 - -0.91 p=0.002 I2=14%), but not with MS and TBI. No difference was seen between modafinil and placebo treatments in patients with PPS. Modafinil seemed to have no therapeutic effect on depression. Adverse events were similar between modafinil and placebo groups except that more patients were found with insomnia and nausea in modafinil group.ConclusionsExisting trials of modafinil for fatigue and EDS associated with PD, MS, TBI and PPS provided inconsistent results. The majority of the studies had small sample sizes. Modafinil is not yet sufficient to be recommended for these medical conditions until solid data are available.