Esophageal squamous cell carcinoma (ESCC) is a deadly disease. To identify key genes in esophageal squamous cell carcinoma, we followed a strategy utilizing the laiurger microarray dataset (GSE38129) as the training set and another independent microarray dataset (GSE20347) as the validation set. Following quality control, differentially expressed genes (DEGs) were obtained using R software. Functional enrichment analysis was performed using DAVID database and the DEG co-expression network was established with Weighted Gene Co-Expression Network Analysis (WGCNA) and visualized by Cytoscape. The prognosis-related hub genes were then identified by Kaplan-Meier analysis based on the TCGA database. A total of 188 DEGs were obtained; 88 up-regulated genes and 100 down-regulated. The up-regulated DEGs were significantly associated with extracellular matrix organization and disassembly while down-regulated DEGs were significantly related to keratinocyte differentiation. Blue and turquoise co-expression modules were established and 18 hub genes were identified. The blue module was associated with mitotic nuclear division, cell division and mitotic cytokinesis and the turquoise module was associated with collagen catabolic process, extracellular matrix organization and keratinocyte differentiation. We established that the TPX2, CDK1 and CEP55 blue module hub genes were associated with relapse-free survival, and our overall results not only identify key genes but also provide potential novel biomarkers for ESCC diagnosis and treatment.

PurposeEsophageal adenocarcinoma (EAC) is the most common type of esophageal cancer in Western countries. It is usually detected at an advanced stage and has a poor prognosis. The aim of this study was to identify key genes and miRNAs in EAC.MethodsThe mRNA microarray data sets GSE1420, GSE26886, and GSE92396 and miRNA data set GSE16456 were downloaded from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) and differentially expressed miRNAs (DEMs) were obtained using R software. Functional enrichment analysis was performed using the DAVID database. A protein–protein interaction (PPI) network and functional modules were established using the STRING database and visualized by Cytoscape. The targets of the DEMs were predicted using the miRecords database, and overlapping genes between DEGs and targets were identified. The prognosis-related overlapping genes were identified using Kaplan–Meier analysis and Cox proportional hazard analysis based on The Cancer Genome Atlas (TCGA) database. The differential expression of these prognosis-related genes was validated using the expression matrix in the TCGA database.ResultsSeven hundred and fifteen DEGs were obtained, consisting of 313 upregulated and 402 downregulated genes. The PPI network consisted of 281 nodes; 683 edges were constructed and 3 functional modules were established. Forty-four overlapping genes and 56 miRNA– mRNA pairs were identified. Five genes, FAM46A, RAB15, SLC20A1, IL1A, and ACSL1, were associated with overall survival or relapse-free survival. FAM46A and IL1A were found to be independent prognostic indicators for overall survival, and FAM46A, RAB15, and SLC20A1 were considered independent prognostic indicators for relapse-free survival. Among them, the overexpression of RAB15 and SLC20A1 and lower expression of ACSL1 were also identified in EAC tissues based on the expression matrix in the TCGA database.ConclusionThese prognosis-related genes and differentially expressed miRNA have provided potential biomarkers for EAC diagnosis and treatment.

Esophageal adenocarcinoma (EAC) is the predominant pathological subtype of esophageal cancer in Europe and the USA. The present bioinformatics study analyzed a high-throughput sequencing dataset, GSE94869, to determine differentially expressed genes (DEGs) in order to identify key genes, biological processes and pathways associated with EAC. Functional enrichment analysis was performed using the Database for Annotation Visualization and Integrated Discovery. The co-expression network of the DEGs was established using Weighted Gene Co-Expression Network Analysis and visualized using Cytoscape. A Kaplan-Meier analysis based on The Cancer Genome Atlas (TCGA) database was used to identify prognosis-associated genes. Univariate and multivariate Cox proportional hazard models were used to identify genes with a prognostic value regarding relapse-free survival (RFS), while validation of the differential expression of prognosis-associated genes was performed using a box plot based on data from TCGA and another microarray dataset, GSE26886. A total of 130 DEGs, comprising 82 upregulated and 48 downregulated genes, were identified. The upregulated DEGs were significantly associated with extracellular matrix organization, disassembly, and the phosphoinositide-3 kinase/AKT, Rap1 and Ras signaling pathways, while the downregulated genes were associated with the Wnt signalling pathway. Subsequently, two co-expression modules were established and 20 hub genes were identified. The blue module was associated with the Rap1 signaling pathway, while the turquoise module was associated with the Ras and Rap1 signaling pathways. Among them, methyltransferase like 7B (METTL7B) was associated with RFS. Furthermore, the overexpression of METTL7B in EAC was successfully validated using data from TCGA and GSE26886. The present study identified key genes and provides potential biomarkers for the diagnosis and treatment of EAC.

Purpose. To explore the effect of sedation on the quality of colonoscopy. Methods. The data collected from the Digestive Endoscopy Center of Shanghai Tongji Hospital from March 2012 to June 2019 were retrospectively analyzed. The rate of sedation and quality metrics of colonoscopy such as adenoma detection rate (ADR) and cecal intubation rate (CIR) were calculated. The logistic regression model was used to explore the relationship between sedation and quality metrics of colonoscopy. The interaction effects between experience of endoscopists and sedation on quality of colonoscopy was also investigated in subgroups stratified by total number of colonoscopies during career using the logistic regression model. Results. A total of 63,417 colonoscopies including 11,417 colonoscopies without sedation and 52,000 colonoscopies with sedation were enrolled in our study. The proportion of colonoscopy with sedation was 82.0%. The ADR and CIR were all significantly higher in cases with sedation compared with cases without sedation (ADR, 22.5% vs. 17.0%, p < 0.001 ; CIR, 94.7% vs. 91.2%, p < 0.001 ). Multivariate analysis showed that the sedation was an independent factor associated with adenoma detection ( OR = 1.448 , 95% CI: 1.372~1.529, p < 0.001 ) and cecal intubation ( OR = 1.560 , 95% CI: 1.446~1.683, p < 0.001 ). A total of 14 endoscopists with complete colonoscopy data in our database and corresponding 20,949 colonoscopies data were enrolled for further analysis. The logistic regression model yielded a similar result that sedation was an independent factor on adenoma detection and cecal intubation when the factor, experience of endoscopists, was also entered into the model as a confounder (adenoma detection, OR = 1.408 , 95% CI: 1.333~1.487, p < 0.001 ; cecal intubation, OR = 1.601 , 95% CI: 1.482-1.729, p < 0.001 ). Conclusion. Colonoscopy with sedation has a positive effect on ADR and CIR in all endoscopists with different experience of colonoscopy, which makes the quality of colonoscopy better.

Early adverse life events (EALs), such as maternal separation (MS), can cause visceral hypersensitivity, which is thought to be a key pathophysiological mechanism of irritable bowel syndrome (IBS). Previous studies mainly focused on EALs-induced visceral hypersensitivity in adulthood but did not consider that it may have occurred in the preadult period. We previously found that rats who experienced MS suffered from visceral hypersensitivity starting from the post-weaning period. Moreover, the hippocampus is considered to be critical in regulating the formation of visceral hypersensitivity induced by MS. But the underlying mechanisms throughout different life periods are unclear. In this study, behavioral tests, RNA-seq, lentiviral interference, and molecular biology techniques were applied to investigate the molecular mechanism in the hippocampus underlying MS-induced long-lasting visceral hypersensitivity. It was found that both visceral sensitivity and anxiety-like behaviors were significantly increased in MS rats in post-weaning, prepubertal, and adult periods, especially in the prepubertal period. Subsequently, RNA-seq targeting the hippocampus identified that the expression level of Netrin-1 was significantly increased in all periods, which was further confirmed by quantitative real-time PCR and Western blot. Knocking-down hippocampal Netrin-1 in the post-weaning period by lentivirus interference alleviated visceral hypersensitivity and anxiety-like behaviors of MS rats in the later phase of life. In addition, deleted in colorectal cancer (DCC), instead of neogenin-1(Neo-1) or uncoordinated (UNC5), was proved to be the specific functional receptor of Netrin-1 in regulating visceral hypersensitivity, whose upregulation may result in the most severe symptoms in the prepubertal period. Furthermore, the activation of the Netrin-1/DCC pathway could enhance long-term potentiation (LTP) in the hippocampus, probably via recruitment of the AMPA receptor subunit GluA1, which finally resulted in the formation of visceral hypersensitivity. These novel findings suggest that long-lasting over-expression of Netrin-1 can mediate visceral hypersensitivity and anxiety disorder from the post-weaning period to adulthood by activating DCC/GluA1 pathway in the hippocampus. Moreover, early intervention of Netrin-1 in the post-weaning period could lead to significant symptom relief afterward, which provides evidence that the Netrin-1/DCC/GluA1 signaling pathway may be a potential therapeutic target for the treatment of visceral hypersensitivity in clinics.

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Prestressed composite concrete pipe (PCCP) has been widely used in water-transmission line and has been proven with many advantages over pure concrete or steel pipes, such as high performance with relatively low cost for materials as well as simplified installation and construction process. Recent efforts have been made to enable the PCCP structure suitable for pipe jacking method so as to replace the conventional cut and cover method. In this way, the construction time, disturbance to nearby structures, and the cost can be greatly reduced. In this paper, we present the full-scale experimental and numerical studies of PCCP and the evaluation of fracture and delamination behaviour of the structure when it is used with pipe jacking construction method subjected to various jacking forces and ground conditions.