Background: This study was performed to systematically evaluate the accuracy of magnetic resonance elastography (MRE) in staging of liver fibrosis in non-alcoholic fatty liver disease (NAFLD). Methods: PUBMED, EMBASE, Web of Science, CNKI, Cochrane Library database were searched from January 2008 to December 2018 for studies related to MRE in the diagnosis of NAFLD liver fibrosis. The quality of the included literature was assessed by Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool. The pooled sensitivity, the pooled specificity, and area under the receiver operating characteristic curve (AUROC) value was performed by STATA 14.0 software. Results: A total of 12 studies were included, involving 910 patients. The pooled sensitivity and specificity of each group were 0.77 (95%CI 0.69-0.83) and 0.90 (95%CI 0.83-0.94) for F ≥ 1 (mild liver fibrosis), 0.87 (95%CI 0.74-0.94) and 0.86 (95%CI 0.71-0.94) for F ≥ 2 (significant liver fibrosis), 0.89 (95%CI 0.81-0.94) and 0.84 (95%CI 0.63-0.94) for F ≥ 3(severe liver fibrosis), 0.94 (95%CI 0.85-0.98) and 0.75 (95%CI 0.35-0.94) for F ≥ 4 (early cirrhosis), respectively. The area under the summary receiver operating characteristic (SROC) curve was 0.89, 0.93, 0.93, and 0.95, respectively. Conclusions: MRE has high accuracy in the diagnosis of hepatic fibrosis staging in patients with NAFLD.
Background & Aims Most targeted therapies against cancer are designed to block growth factor–stimulated oncogenic growth. However, response rates are low, and resistance to therapy is high. One mechanism might relate to the ability of tumor cells to induce growth factor–independent proliferation (GFIP). This project aims to understand how (1) cancer cells preferentially derive a major growth advantage by using critical metabolic products of glucose, such as phosphoenolpyruvate (PEP), to drive proliferation and (2) esophageal squamous cell carcinoma (ESCC) cells, but not esophageal adenocarcinoma cells, can induce GFIP by using glycolysis to activate phosphohistidine (poHis)-mediated signaling through focal adhesion kinase (FAK). Methods The hypothesis to be tested is that ESCC GFIP induced by glucose is facilitated by PEP-mediated histidine phosphorylation (poHis) of FAK, leading to the possibility that ESCC progression can be targeted by blocking poHis signaling . Biochemical, molecular biological, and in vivo experiments including bromodeoxyuridine/5-ethynyl-2′-deoxyuridine labeling, radioisotope tracing, CRISPR gene editing, and analysis of signaling gene sets in human cancer tissues and xenograft models were performed to define the mechanisms underlying ESCC GFIP. Results Glucose promotes growth factor–independent DNA replication and accumulation of PEP in ESCC cells. PEP is the direct phospho-donor to poHis58-FAK within a known “HG” motif for histidine phosphorylation. Glucose-induced poHis58 promotes growth factor–independent FAK-mediated proliferation. Furthermore, glucose activates phosphatidylinositol-3′-kinase/AKT via poHis58-FAK signaling. Non-phosphorylatable His58A-FAK reduces xenograft growth. Conclusions Glucose induces ESCC, but not esophageal adenocarcinoma GFIP via PEP-His58-FAK-AKT signaling. ESCC progression is controlled by actionable growth factor–independent, glucose-induced pathways that regulate proliferation through novel histidine phosphorylation of FAK.
Background Although hundreds of risk loci for Crohn’s disease (CD) have been identified, the underlying pathogenesis of CD remains unclear. Recently, evidence has shown that aberrant gene expression in colon tissues of CD patients is associated with the progression of CD. We reasoned that post-transcriptional regulation, especially alternative splicing (AS), may also play important roles in the pathogenesis of CD. Methods We re-analyzed public mRNA-seq data from the NCBI GEO dataset (GSE66207) and identified approximately 3000 unique AS events in CD patients compared to healthy controls. Results “Lysine degradation” and “Sphingolipid metabolism” were the two most enriched AS events in CD patients. In a validation study, we also sequenced eight subjects and demonstrated that key genes that were previously linked to CD, such as IRF1 and STAT3, also had significant AS events in CD. Conclusion Our study provided a landscape of AS events in CD, especially as the first study focused on a Chinese cohort. Our data suggest that dysregulation of AS may be a new mechanism that contributes to the pathogenesis of CD.
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