EBD is a safe and effective modality for the treatment of benign esophageal stricture after ESD for early esophageal neoplasms.

Background Transcriptional regulators are seminal players in the onset and progression of prostate cancer. However, clarification of their underlying regulatory circuits and mechanisms demands considerable effort. Methods Integrated analyses were performed on genomic, transcriptomic, and clinicopathological profiles of primary prostate cancer and transcription factor-binding profiles, which included estimating transcription factor activity, identifying transcription factors of prognostic values, and discovering cis - and trans -regulations by long noncoding RNAs. Interactions between transcription factors and long noncoding RNAs were validated by RNA immunoprecipitation quantitative PCR. RNA interference assays were performed to explore roles of the selected transcription regulators. Findings Sixteen transcription factors, namely, ETS1, ARID4B, KLF12, GMEB1, HBP1, MXI1, MYC, MAX, PGR, BCL11A, AR, KLF4, SRF, HIF1A, EHF, and ATOH1, were jointly identified as a prognostic signature. Candidate long noncoding RNAs interplaying with the prognostic signature constituent transcription factors were further discovered. Their interactions were randomly checked, and many of them were experimentally proved. Transcription regulation by MYC and its long noncoding RNA partner AL590617.2 was further validated on their candidate targets. Moreover, the regulatory network governed by the transcription factors and their interacting long noncoding RNA partners is illustrated and stored in our LNCTRN database ( https://navy.shinyapps.io/lnctrn ). Interpretation The prognostic signature constituent transcription factors and their interacting long noncoding RNAs may represent promising biomarkers and/or therapeutic targets for prostate cancer. Furthermore, the computational framework proposed in the present study can be utilized to explore critical transcriptional regulators in other types of cancer. Funding This work was supported by National Natural Science Foundation of China and Fudan University.

High‐frequency electrosurgery has been widely applied in digestive endoscopy with constantly expanding indications. However, high‐frequency electrosurgery may cause possible complications such as hemorrhage or perforation during or after the procedure, of which endoscopists must be cautious. Digestive endoscopists must have a firm grasp of the principles of high‐frequency electrosurgery as well as its safety issues so as to improve the safety of its clinical application. To this end, experts in gastroenterology and hepatology, digestive endoscopy, surgery, nursing and other related fields were invited to draft a consensus on the clinical application of high‐frequency electrosurgery in digestive endoscopy based on relevant domestic and international literatures and their experiences.

No abstract

Age-related macular degeneration (AMD) is a chronic and progressive macular degeneration disease, which can also lead to serious visual loss. In our research, we aim to efficiently identify biomarkers relevant for AMD diagnosis. We collected the gene expression data of retinal segmented epithelium (RPE) and retina tissues of GSE29801 and GSE135092 and performed differential expression analysis. The differentially expressed genes (DEGs) related to the RPE and retina in the two sets of data were identified and enriched by intersection analysis. A PPI network was constructed for intersection genes, and the top 20 genes with the largest connectivity in the network were selected as candidate genes. The LASSO model was used to identify key genes from candidate genes, and the nomogram and ROC curve were used to evaluate the diagnostic ability of key genes. We identified 464 intersection genes associated with RPE and 509 intersection genes associated with retina. The TGF-beta signaling pathway was enriched by RPE-related DEGs, while oxidative phosphorylation was enriched by retina-related DEGs. Among the candidate genes of RPE, the LASSO model identified 7 key genes. MAPK1 and LUM can predict the clinical diagnosis of AMD. Among the candidate genes of retina, the LASSO model identified four key genes. PTPN11 has the highest predictive diagnostic value. The results suggest that the imbalance mechanism of RPE in AMD may be related to the TGF-beta signaling pathway, and the imbalance mechanism of the retina may be related to oxidative phosphorylation. MAPK1 and LUM are potential diagnostic markers of RPE, and PTPN11 is a potential diagnostic marker of the retina. Also, our results provide a theoretical basis for better understanding the molecular mechanisms of AMD onset and treatment in the future.

No abstract

Background In patients with chronic kidney disease (CKD), vascular calcification (VC) is common and is associated with a higher risk of all-cause mortality. Shh, one ligand for Hedgehog (Hh) signaling, participates in osteogenesis and several cardiovascular diseases. However, it remains unclear whether Shh is implicated in the development of VC. Methods 2.6 mM inorganic phosphorus was used to induce vascular smooth muscle cells (VSMCs) calcification. Mice were fed with adenine diet supplement with 1.2% phosphorus to induce VC. Results Shh was decreased in VSMCs exposed to inorganic phosphorus, calcified arteries in mice fed with an adenine diet, as well as radial arteries from patients with CKD presenting vascular calcification (VC). Overexpression of Shh inhibited VSMCs ostosteoblastic differentiation and calcification, whereas its silencing accelerated these processes. Likewise, mice treated with SAG (Hh signaling agonist) showed alleviated VC. And mice treated with CPN (Hh signaling antagonist) exhibited severe VC. Additionally, overexpression of Gli2 significantly reversed the pro-calcification effect of Shh silencing on VSMCs, suggesting that Shh inhibited VC via Gli2. Mechanistically, Gli2 interacted with Runx2 and promoted its ubiquitin proteasomal degradation, therefore protecting against VC. Of interest, the pro-degradation effect of Gli2 on Runx2 was independent of Smurf1 and Cullin4B. Conclusions Our study provided deeper insight to the pathogenesis of VC and Shh might be a novel potential target for VC treatment.