Risk assessment model constructed by differentially expressed lncRNAs for the prognosis of glioma.

A risk assessment model was constructed using differentially expressed long non­coding (lnc)RNAs for the prognosis of glioma. Transcriptome sequencing of the lncRNAs and mRNAs from glioma samples were obtained from the TCGA database. The samples were divided into bad and good prognosis groups based on survival time, then differently expressed lncRNAs between these two groups were screened using DEseq and edgeR packages. Multivariate Cox regression analysis was performed to establish a risk assessment system according to the weighted regression coefficient of lncRNA expression. Survival analysis and receiver operating characteristic curve were conducted for the risk assessment model. Furthermore, the co­expression network of the screened lncRNAs was constructed, followed by the functional enrichment analysis for associated genes. A total of 117 lncRNAs were screened using edgeR and DEseq packages. Among all differently expressed lncRNAs, five lncRNAs (RP3­503A6, LINC00940, RP11­453M23, AC009411 and CDRT7) were identified to establish the risk assessment model. The risk assessment model demonstrated a good prognostic function with high area under the curve values in the training, validation and entire sets. The risk score was certified as an independent prognostic factor for gliomas. Multiple genes were screened to be co­expressed with these five lncRNAs. Functional enrichment analysis demonstrated that they were involved in cytoskeleton, adhesion and Janus kinase/signal transducer and activator of transcription signaling pathway­associated processes. The present study established a risk assessment model integrating five significantly different expressed lncRNAs, which may help to assess the prognosis of patients with glioma with increased accuracy.

A novel scoring system for gastric cancer risk assessment based on the expression of three CLIP4 DNA methylation-associated genes.

Gastric cancer (GC) is the fifth most common cancer and the third leading cause of cancer-associated mortality worldwide. In the current study, comprehensive bioinformatic analyses were performed to develop a novel scoring system for GC risk assessment based on CAP-Gly domain containing linker protein family member 4 (CLIP4) DNA methylation status. Two GC datasets with methylation sequencing information and mRNA expression profiling were downloaded from the The Cancer Genome Atlas and Gene Expression Omnibus databases. Differentially expressed genes (DEGs) between the CLIP4 hypermethylation and CLIP4 hypomethylation groups were screened using the limma package in R 3.3.1, and survival analysis of these DEGs was performed using the survival package. A risk scoring system was established via regression factor-weighted gene expression based on linear combination to screen the most important genes associated with CLIP4 methylation and prognosis. Genes associated with high/low-risk value were selected using the limma package. Functional enrichment analysis of the top 500 DEGs that positively and negatively associated with risk values was performed using DAVID 6.8 online and the gene set enrichment analysis (GSEA) software. In total, 35 genes were identified to be that significantly associated with prognosis and CLIP4 DNA methylation, and three prognostic signature genes, claudin-11 (CLDN11), apolipoprotein D (APOD), and chordin like 1 (CHRDL1), were used to establish a risk assessment system. The prognostic scoring system exhibited efficiency in classifying patients with different prognoses, where the low-risk groups had significantly longer overall survival times than those in the high-risk groups. CLDN11, APOD and CHRDL1 exhibited reduced expression in the hypermethylation and low-risk groups compare with the hypomethylation and high-risk groups, respectively. Multivariate Cox analysis indicated that risk value could be used as an independent prognostic factor. In functional analysis, six functional gene ontology terms and five GSEA pathways were associated with CLDN11, APOD and CHRDL1. The results established the credibility of the scoring system in this study. Additionally, these three genes, which were significantly associated with CLIP4 DNA methylation and GC risk assessment, were identified as potential prognostic biomarkers.

Midazolam and propofol used alone or sequentially for long-term sedation in critically ill, mechanically ventilated patients: a prospective, randomized study.

INTRODUCTION: Midazolam and propofol used alone for long-term sedation are associated with adverse effects. Sequential use may reduce the adverse effects, and lead to faster recovery, earlier extubation and lower costs. This study evaluates the effects, safety, and cost of midazolam, propofol, and their sequential use for long-term sedation in critically ill mechanically ventilated patients. METHODS: A total of 135 patients who required mechanical ventilation for >3 days were randomly assigned to receive midazolam (group M), propofol (group P), or sequential use of both (group M-P). In group M-P, midazolam was switched to propofol until the patients passed the spontaneous breathing trial (SBT) safety screen. The primary endpoints included recovery time, extubation time and mechanical ventilation time. The secondary endpoints were pharmaceutical cost, total cost of ICU stay, and recollection to mechanical ventilation-related events. RESULTS: The incidence of agitation following cessation of sedation in group M-P was lower than group M (19.4% versus 48.7%, P = 0.01). The mean percentage of adequate sedation and duration of sedation were similar in the three groups. The recovery time, extubation time and mechanical ventilation time of group M were 58.0 (interquartile range (IQR), 39.0) hours, 45.0 (IQR, 24.5) hours, and 192.0 (IQR, 124.0) hours, respectively; these were significantly longer than the other groups, while they were similar between the other two groups. In the treatment-received analysis, ICU duration was longer in group M than group M-P (P = 0.016). Using an intention-to-treat analysis and a treatment-received analysis, respectively, the pharmaceutical cost of group M-P was lower than group P (P <0.01) and its ICU cost was lower than group M (P <0.01; P = 0.015). The proportion of group M-P with unbearable memory of the uncomfortable events was lower than in group M (11.7% versus 25.0%, P <0.01), while the proportion with no memory was similar (P >0.05). The incidence of hypotension in group M-P was lower than group (P = 0.01). CONCLUSION: Sequential use of midazolam and propofol was a safe and effective sedation protocol, with higher clinical effectiveness and better cost-benefit ratio than midazolam or propofol used alone, for long-term sedation of critically ill mechanically ventilated patients. TRIAL REGISTRATION: Current Controlled Trials ISRCTN01173443. Registered 25 February 2014.