The current study aims to investigate the significance of N 6-methyladenosine (m 6 A) methylationrelated genes in the clinical prognosis of hepatocellular carcinoma (HCC) using bioinformatics analyses based on The Cancer Genome Atlas (TCGA) database. Transcriptome data and corresponding clinical data on m 6 A methylation-related genes (including 15 genes) were obtained from TCGA database. Differential expression of 15 genes was identified. Survival curves of subgroups based on m 6 A methylation-related gene expression levels were plotted. We selected potential predictive genes and analyzed their prognostic values using bioinformatics methods. Eleven genes (METTL3,
Objective
To assess the efficacy and safety of peripherally acting mu-opioid receptor antagonists (PAMORAs) for the treatment of opioid-induced constipation (OIC).
Methods
Randomized controlled trials (RCTs) were searched for OIC therapy comparing PAMORAs with placebo. Both a pairwise and network meta-analysis were performed. The surface under the cumulative ranking area (SUCRA) was used to determine the efficacy and safety of OIC treatment using different PAMORAs.
Results
The primary target outcome was a response that achieves an average of three or more bowel movements (BMs) per week. In the network meta-analysis, four PAMORAs (naldemedine, naloxone, methylnaltrexone, and alvimopan) showed a better BM response than the placebo. Naldemedine was ranked first (odds ratio [OR] = 2.8, 95% credible interval [CrI] = 2–4.5, SUCRA = 89.42%), followed by naloxone (OR = 2.9, 95% CrI = 1.6–5.3, SUCRA = 87.44%), alvimopan (OR = 2.2, 95% CrI = 1.3–3.5, SUCRA = 68.02%), and methylnaltrexone (OR = 1.7, 95% CrI = 1.0–2.8, SUCRA = 46.09%). There were no significant differences in safety found between the PAMORAs and the placebo.
Conclusions
We found that PAMORAs are effective and can be safely used for the treatment of OIC. In network meta-analysis, naldemedine and naloxone appear to be the most effective PAMORAs for the treatment of OIC.
Background
In our previous study it was found that CENPL was overexpressed in hepatocellular carcinoma and significantly predicted patient's prognosis. However, the expression and prognostic value of CENPL in other gastrointestinal tumors remain unknown. Therefore, we investigated the expression and prognostic value of CENPL in esophageal carcinoma (ESCA), stomach adenocarcinoma (STAD), pancreatic adenocarcinoma (PAAD), colon adenocarcinoma (COAD) and rectum adenocarcinoma (READ).
Methods
In this study, Oncomine, GEPIA, OncoLnc, TIMER, cBioPortal, miRWalk and ENCORI databases were used to analyze the level of CENPL mRNA, prognostic value and potential regulatory mechanism of CENPL mRNA in tumors. The CENPL expression and clinicopathological data regarding PAAD were from the UCSC Xena database and univariate and multivariate Cox regression analyses were performed using R (Version 3.6.3). Immunohistochemical staining was used to verify the expression of CENPL protein in clinical specimens. Cytoscape (Version: 3.7.2) was used to visualize microRNA (miRNA) that potentially regulates CENPL.
Results
Gene differential expression analysis showed that CENPL mRNA was significantly overexpressed in ESCA, STAD, PAAD, COAD and READ (p < 0.01). The overexpression of CENPL mRNA was significantly correlated with the poor prognosis of PAAD patients (p < 0.05). However, there was no significant correlation between the level of CENPL mRNA and the prognosis of ESCA, STAD, COAD and READ patients (p > 0.05). Univariate and multivariate Cox regression analyses suggested that CENPL was a prognostic risk factor for PAAD. The mutation rate of CENPL in PAAD was 2.2% (17/850). There was no significant correlation between the CENPL expression and the infiltration levels of immune cells in PAAD (|Cor|< 0.5). Immunohistochemical staining showed that CENPL was overexpressed in 42% (11/26) of PAAD specimens, which was significantly higher compared with that in the normal tissues. The expression of miR-340-3p and miR-484 in PAAD were significantly lower than in the normal tissues (p < 0.05) and PAAD patients with lower expression of miR-340-3p had poorer prognosis (p < 0.05).
Conclusion
CENPL potentially regulated by miR-340-3p, is overexpressed in PAAD and predicts patient’s prognosis, suggestive of a diagnostic and prognostic value in PAAD patients.
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