1. To investigate Genkwa Flos hepatotoxicity, a cell metabolomics strategy combined with serum pharmacology was performed on human HL-7702 liver cells in this study.
2. Firstly, cell viability and biochemical indicators were determined and the cell morphology was observed to confirm the cell injury and develop a cell hepatotoxicity model. Then, with the help of cell metabolomics based on UPLC-MS, the Genkwa Flos group samples were completely separated from the blank group samples in the score plots and seven upregulated as well as two down-regulated putative biomarkers in the loading plot were identified and confirmed. Besides, two signal molecules and four enzymes involved in biosynthesis pathway of lysophosphatidylcholine and the sphingosine kinase/sphingosine-1-phosphate pathway were determined to investigate the relationship between Genkwa Flos hepatotoxicity and these two classic pathways. Finally, the metabolic pathways related to specific biomarkers and two classic metabolic pathways were analyzed to explain the possible mechanism of Genkwa Flos hepatotoxicity.
3. Based on the results, lipid peroxidation and oxidative stress, phospholipase A2/lysophosphatidylcholine pathway, the disturbance of sphingosine-1-phosphate metabolic profile centered on sphingosine kinase/sphingosine-1-phosphate pathway and fatty acid metabolism might be critical participators in the progression of liver injury induced by Genkwa Flos. 相似文献
BackgroundThe purpose of the study was to evaluate the efficacy and safety of stereotactic body radiotherapy (SBRT) for centrally located, primary non–small-cell lung cancer (NSCLC).Materials and MethodsSystematic search of 4 databases (PubMed, MEDLINE, EMBASE, and Cochrane Library) was performed for literature published until May 9, 2018. Primary (overall survival [OS] and local control [LC] rates) and secondary (Grade ≥3 toxicity) endpoints were reported.ResultsThirteen studies encompassing 599 patients with central NSCLCs were included. Median values of T1 tumor proportion, tumor size, and median survival were 55.3% (range, 0%-75%), 3.3 (range, 2.1-4.1) cm, and 26 (range, 14-68.9) months, respectively. Pooled rates of 1-, 2-, and 3-year OS rates were 84.3% (95% confidence interval [CI], 75.7-90.3), 64.0% (95% CI, 52.9-72.2), and 50.5% (95% CI, 39.4-61.5), respectively. Pooled rates of 1-, 2-, and 3-year LC rates were 89.4% (95% CI, 80.8-94.4), 82.2% (95% CI, 71.7-89.4), and 72.2% (95% CI, 55.0-84.7), respectively. Pooled rate of Grade ≥3 complication was 12.0% (95% CI, 7.3-19.0). Meta-regression analyses showed significant positive relationships between biologically equivalent dose using an α/β of 10 Gy in the linear quadratic model (BED10Gy) and 1- and 2-year LC rates (P < .001 and P < .001), and 1- and 2-year OS rates (P = .0178 and P = .032), and Grade ≥3 complication rate (P = .0029). In subgroup comparisons between BED10Gy <100 Gy versus ≥100 Gy, 1- and 2-year LC rates were significantly different but not for OS and Grade ≥3 complication rates.ConclusionOur results suggests that SBRT is potent for tumor control in central NSCLC, although complications should be further minimized through optimization of dose-fractionation scheme and accurate planning. Using BED10Gy ≥100 Gy yielded higher LC rates, and dose escalation was related to OS, LC, and complications. 相似文献
Objective: Several biologic therapies are available for the treatment of mild-to-moderate Crohn’s disease (CD). This network meta-analysis (NMA) aimed to assess the comparative efficacy of ustekinumab, adalimumab, vedolizumab and infliximab in the maintenance of clinical response and remission after 1?year of treatment.
Methods: A systematic literature search was performed to identify relevant randomized controlled trials (RCTs). Key outcomes of interest were clinical response (CD activity index [CDAI] reduction of 100 points; CDAI-100) and remission (CDAI score under 150 points; CDAI < 150). A treatment sequence Bayesian NMA was conducted to account for the re-randomization of patients based on different clinical definitions, the lack of similarity of the common comparator for each trial and the full treatment pathway from the induction phase onwards.
Results: Thirteen RCTs were identified. Ustekinumab 90?mg q8w was associated with statistically significant improvement in clinical response relative to placebo and vedolizumab 300?mg. For clinical remission, ustekinumab 90?mg q8w was associated with statistically significant improvement relative to placebo and vedolizumab 300?mg q8w. Findings from sub-population analyses had similar results but were not statistically significant.
Conclusions: The NMA suggest that ustekinumab is associated with the highest likelihood of reaching response or remission at 1?year compared with placebo, adalimumab and vedolizumab. Results should be interpreted with caution because this is a novel methodology; however, the treatment sequence analysis may be the most methodologically sound analysis to derive estimates of comparative efficacy in CD in the absence of head-to-head evidence. 相似文献
IntroductionLung cancer is the leading cause of cancer-death worldwide. The U.S. Preventative Services Task Force (USPTSF) approved screening for current or former smokers aged 55–80 based on the results of the National Lung Screening trial (NLST). Following the NLST, new evidence has emerged from clinical trials and updates to previous trials prior to the anticipated update to the USPSTF guideline. We review the new evidence on lung cancer screening with low dose computed tomography (LDCT) and the surgical implications.MethodsA review of new literature was performed pertaining to lung cancer screening since implementation of UPSTF guidelines. Articles for inclusion were identified by both authors’, then search of the Pubmed and Cochrane database was performed from January 1st, 2013 through February 4th, 2020 using the MeSH search terms: “lung cancer”; “screening”; “low dose CT”. The results of these studies are summarized.ResultsWe identified multiple prospective randomized control trials and meta-analysis since the NLST supporting lung cancer-specific mortality with screening. We identified new nodule classification systems and the development of risk-models which may reduce false positive rates and identify high risk patients not currently eligible for screening. Finally, we discussed the surgical implications of screening.ConclusionNew data supports NLST findings and show ongoing benefit to LDCT for lung cancer screening. Standardized LDCT screening classification has been shown to reduce harm and lower false positive rates. Further study is needed regarding use of risk-modeling. Screening will require an increase in the thoracic workforce to accommodate the amount of surgically operable cancers. 相似文献
