SUMMARYThe role of natural killer (NK) cells in controlling hepatitis C virus (HCV) infection and replication has not been fully delineated. We examined NK cell-mediated noncytolytic effect on full cycle HCV infection of human hepatocytes. Human hepatocytes (Huh7.5.1 cells) co-cultured with NK cells or treated with supernatants (SN) from NK cells cultures had significantly lower levels of HCV RNA and protein than control cells. This NK cell-mediated anti-HCV activity could be largely abolished by antibody to interferon-gamma (IFN-γ). The investigation of the mechanisms for NK cell-mediated anti-HCV activity showed that NK SN-treated hepatocytes expressed higher levels of IFN-α/β than the control cells. NK SN also enhanced IFN regulatory factor-3 and 7 expression in the hepatocytes. In addition, NK SN enhanced the expression of signal transducer and activator of transcription 1 and 2, the nuclear factors that are essential for the activation of IFN-mediated antiviral pathways. These data provide direct evidence at cellular and molecular levels that NK cells have a key role in suppressing HCV infection of and replication in human hepatocytes.
Background Inadequate bowel preparation is associated with a decrease in adenoma detection rate (ADR). A deep learning-based bowel preparation assessment system based on the Boston bowel preparation scale (BBPS) has been previously established to calculate the automatic BBPS (e-BBPS) score (ranging 0-20). The aims of this study were to investigate whether there was a statistically inverse relationship between the e-BBPS score and the ADR, and to determine the threshold of e-BBPS score for adequate bowel preparation in colonoscopy screening.
MethodsIn this prospective, observational study, we trained and internally validated the e-BBPS system using retrospective colonoscopy images and videos from the Endoscopy Center of Wuhan University, annotated by endoscopists. We externally validated the system using colonoscopy images and videos from the First People's Hospital of Yichang and the Third Hospital of Wuhan. To prospectively validate the system, we recruited consecutive patients at Renmin Hospital of Wuhan University aged between 18 and 75 years undergoing colonoscopy. The exclusion criteria included: contraindication to colonoscopy, family polyposis syndrome, inflammatory bowel disease, history of surgery for colorectal or colorectal cancer, known or suspected bowel obstruction or perforation, patients who were pregnant or lactating, inability to receive caecal intubation, and lumen obstruction. We did colonoscopy procedures and collected withdrawal videos, which were reviewed and the e-BBPS system was applied to all colon segments. The primary outcome of this study was ADR, defined as the proportion of patients with one or more conventional adenomas detected during colonoscopy. We calculated the ADR of each e-BBPS score and did a correlation analysis using Spearman analysis.Findings From May 11 to Aug 10, 2020, 616 patients underwent screening colonoscopies, which evaluated. There was a significant inverse correlation between the e-BBPS score and ADR (Spearman's rank -0•976, p<0•010). The ADR for the e-BBPS scores 1-8 was 28•57%,
BackgroundCD4+ memory T cells are an important component of the tumor microenvironment (TME) and affect tumor occurrence and progression. Nevertheless, there has been no systematic analysis of the effect of CD4+ memory T cells in gastric cancer (GC).MethodsThree datasets obtained from microarray and the corresponding clinical data of GC patients were retrieved and downloaded from the Gene Expression Omnibus (GEO) database. We uploaded the normalize gene expression data with standard annotation to the CIBERSORT web portal for evaluating the proportion of immune cells in the GC samples. The WGCNA was performed to identify the modules the CD4+ memory T cell related module (CD4+ MTRM) which was most significantly associated with CD4+ memory T cell. Univariate Cox analysis was used to screen prognostic CD4+ memory T cell-related genes (CD4+ MTRGs) in CD4+ MTRM. LASSO analysis and multivariate Cox analysis were then performed to construct a prognostic gene signature whose effect was evaluated by Kaplan-Meier curves and receiver operating characteristic (ROC), Harrell’s concordance index (C-index), and decision curve analyses (DCA). A prognostic nomogram was finally established based on the CD4+ MTRGs.ResultWe observed that a high abundance of CD4+ memory T cells was associated with better survival in GC patients. CD4+ MTRM was used to stratify GC patients into three clusters by unsupervised clustering analysis and ten CD4+ MTRGs were identified. Overall survival, five immune checkpoint genes and 17 types of immunocytes were observed to be significantly different among the three clusters. A ten-CD4+ MTRG signature was constructed to predict GC patient prognosis. The ten-CD4+ MTRG signature could divide GC patients into high- and low-risk groups with distinct OS rates. Multivariate Cox analysis suggested that the ten-CD4+ MTRG signature was an independent risk factor in GC. A nomogram incorporating this signature and clinical variables was established, and the C-index was 0.73 (95% CI: 0.697–0.763). Calibration curves and DCA presented high credibility for the OS nomogram.ConclusionWe identified three molecule subtypes, ten CD4+ MTRGs, and generated a prognostic nomogram that reliably predicts OS in GC. These findings have implications for precise prognosis prediction and individualized targeted therapy.
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