Beckermarkussen4057

Introduction Considering the physique of the Japanese population, the standard daily vancomycin dose of 2 g/day and doses ≥ 3 g/day are high in terms of dose per body weight. Studies have reported that administering high-dose vancomycin to achieve a high target trough concentration has been associated with nephrotoxicity. The risk of high-dose vancomycin-associated nephrotoxicity is believed to be exceptionally high for Japanese patients because of their relatively low body weights, but data on the population is lacking. In this retrospective study, we aimed to evaluate risk factors associated with nephrotoxicity in Japanese patients treated with vancomycin. Methods We examined the medical records of 107 Japanese patients who received vancomycin (3 to 4 g/day). They were divided into two groups based on the presence or absence of nephrotoxicity, and their demographics and clinical characteristics were compared. Results The incidence of nephrotoxicity in patients receiving high-dose vancomycin was 13%. Age (≥ 60 years) and concurrent use of piperacillin/tazobactam were independent risk factors for vancomycin-associated nephrotoxicity (P = 0.027 and 0.017, respectively). Conclusions We conclude that the nephrotoxicity risk of high-dose vancomycin in Japanese patients is not excessively high when administered within the confines of a therapeutic drug-monitoring program. However, special care must be taken with patients who are older or on concurrent piperacillin/tazobactam therapy.Early administration of edaravone for acute ischemic stroke patients (AIS) receiving intravenous thrombolysis (IVT) has a potential neuroprotective effect. This study aimed to estimate the safety and efficacy of edaravone for AIS patients receiving IVT. We searched PubMed, Embase, Cochrane Library and Chinese Databases (CNKI database, Weipu database, and Wanfang database) for randomized controlled trials (RCT) from the inception of the database to 20 July 2020. Efficacy outcome was reduced National Institutes of Health Stroke Scale (NIHSS) score before and after treatment. Safety outcomes were intracranial hemorrhage (ICH) and mortality. Review Manager 5.3 and Stata 14.0 was used to perform the meta-analysis. A total of 1877 AIS patients from 17 studies were included, 939 (50.03%) patients received edaravone combined with alteplase treatment. Compared with alteplase alone, combined treatment reduced the NIHSS score (MD=3.95,95% CI 2.92-4.99, I² = 92%) and ICH (OR=0.44,95% CI 0.29-0.66, I² =0%) during hospitalization. There was no significant association between combined treatment and mortality during follow-up (OR=0.43,95% CI 0.13-1.42, I² =0%). Conclusions Edaravone combined with alteplase seems to be safe and effective for AIS patients' short term outcomes.Cholestatic liver fibrosis occurs in liver injuries accompanied by inflammation, which develops into cirrhosis if not effectively treated in early stage. The aim of the study is to explore the effect of fenofibrate on liver fibrosis in chronic cholestatic mice. In this study, wild-type (WT) and Pparα-null (KO) mice were dosed alpha-naphthylisothiocyanate (ANIT) diet to induce chronic cholestasis. Induced liver fibrosis was determined by pathological biomarkers. Then fenofibrate 25 mg/kg was orally administrated to mice twice/day for 14 days. Serum and liver samples were collected for analysis of biochemistry and fibrosis. In WT mice, cholestatic biomarkers were increased by 5-8-fold and the expression of tissue inhibitors of metalloproteinases 1 (TIMP-1), Monocyte chemoattractant protein 1 (MCP-1), Collagen protein I (Collagen I) was increased by more than 10-fold. Fenofibrate significantly downgraded the biochemical and fibrotic biomarkers. In Western blot analysis, levels of collagenI and alpha-smooth muscle actin (α-SMA) were strongly inhibited by fenofibrate. In KO mice, liver fibrosis was induced successfully, but no improvement after fenofibrate treatment was observed. These data showed low-dose fenofibrate reverses cholestatic liver fibrosis in WT mice but not in KO mice, suggesting the dependence of therapeutic action on peroxisome proliferator-activated receptor alpha (PPARα). The study offers an additional therapeutic strategy for cholestatic liver fibrosis in practice.Pulmonary fibrosis (PF) is a severe chronic disease. Although astragaloside IV (ASV) is known to have therapeutic effects on PF, the therapeutic targets of ASV require further study. This study was designed to elucidate the regulatory effect of ASV on PF via NLRP3. PF was triggered by transforming growth factor-β (TGF-β) in vitro. The relative activity of TGF-β was measured by luciferase reporter assay. Protein levels were determined by western blotting assay. The NLRP3 expression was analyzed using immunofluorescence analysis. mRNA levels were detected by qRT-PCR. MTT assay was performed to determine cell viability. Wound healing and transwell assays were conducted to investigate cell migration and invasion. We found that ASV markedly suppressed TGF-β activity, Smad2/3 and NLRP3 protein expression levels. ASV inhibited cell viability, migration and invasion ability. Moreover, ASV mediated downregulation of N-cadherin and Snail and upregulation of E-cadherin, which further suppressed the epithelial-mesenchymal transition (EMT). However, overexpression of NLRP3 reversed the effects of ASV and promoted Collagen I, Collagen II and α-SMA protein expressions. In conclusion, ASV efficiently retarded PF progress via suppressing NLRP3 expression in vitro.Ibrutinib is an irreversible inhibitor of Bruton's tyrosine kinase and has proven to be an effective agent for B-cell-mediated hematological malignancies, including multiple myeloma (MM). Several clinical trials of ibrutinib treatment combined with dexamethasone (DXMS) for relapsed MM have demonstrated high response rates, however, the mechanism still remains unclear. CID-44246499 In this study, we explored the therapeutic effect and mechanism of ibrutinib combined with DXMS on MM in vitro and vivo. The apoptosis of MM cell lines and mononuclear cells from MM patients' bone marrow induced by ibrutinib combined with DXMS was detected by flow cytometry and the expression of apoptosis-related proteins were detected by Western blot. A mice MM model was established to verify the therapeutic effect of ibrutinib combined with DXMS on MM. We found that ibrutinib combined with DXMS increased the apoptosis of MM cell lines through the PI3K/PARP pathway, significantly reduced CD38 expression in MM cells from patients in vitro, and reduced tumor size and increased the survival time in mice model.