T-cell acute lymphoblastic leukemia (T-ALL) is a highly aggressive hematologic malignancy with a poor prognosis, despite advancements in treatment. Many patients struggle with relapse or refractory disease. Investigating the role of the super-enhancer (SE) regulated gene ubiquitin-specific protease 20 (USP20) in T-ALL could enhance targeted therapies and improve clinical outcomes. Analysis of histone H3 lysine 27 acetylation (H3K27ac) chromatin immunoprecipitation sequencing (ChIP-seq) data from six T-ALL cell lines and seven pediatric samples identified USP20 as an SE-regulated driver gene. Utilizing the Cancer Cell Line Encyclopedia (CCLE) and BloodSpot databases, it was found that USP20 is specifically highly expressed in T-ALL. Knocking down USP20 with short hairpin RNA (shRNA) increased apoptosis and inhibited proliferation in T-ALL cells. In vivo studies showed that USP20 knockdown reduced tumor growth and improved survival. The USP20 inhibitor GSK2643943A demonstrated similar anti-tumor effects. Mass spectrometry, RNA-Seq, and immunoprecipitation revealed that USP20 interacted with hypoxia-inducible factor 1 subunit alpha (HIF1A) and stabilized it by deubiquitination. Cleavage under targets and tagmentation (CUT&Tag) results indicated that USP20 co-localized with HIF1A, jointly modulating target genes in T-ALL. This study identifies USP20 as a therapeutic target in T-ALL and suggests GSK2643943A as a potential treatment strategy.

Background:The morbidity of ulcerative colitis(UC)is high,and is easily recurrent.A number of systematic review/meta-analysis have explored the efficacy and safety of fecal microbiota transplantation(FMT)in the treatment of UC with varying conclusions,however,the quality of these studies has not yet been adequately assessed.Aims:To overview the systematic review/meta-analysis of FMT for UC.Methods:Systematic review/meta-analysis of FMT in the treatment of UC were retrieved from PubMed,Cochrane Library,Embase,Web of Science,CNKI,CBM,Wanfang,VIP and other databases from the date of database establishment to May 2023,while gray literatures were searched and experts were consulted.Literature screening and extract information were performed by two researchers.The PRISMA checklist,AMSTAR-2 tool was used to assess the reporting quality and methodological quality,respectively,as well as to grade the quality of evidence for outcome measurements based on the GRADE system.Results:Seventeen systematic review/meta-analysis were finally included.The original studies included randomized controlled trials and observational studies.Most of the studies drew positive conclusions about the efficacy and safety of FMT in the treatment of UC.The PRISMA checklist score was 12.5-22.5,and the mean score was 17.68.Three studies reported relative completeness;ten had some deficiencies;and four had relatively serious report deficiencies.AMSTAR-2 tool showed that two were of intermediate quality,three were of low quality,and twelve were of very low quality.GRADE system ratings showed that six of the eight outcome measurements were of intermediate quality and two were of low quality.Conclusions:FMT may be a safe and effective treatment for UC,but the quality of the current evidence is low and users of clinical evidence need to treat the above evidence with caution.

Background:Ulcerative colitis(UC)is highly prevalent and recurrent.A number of systematic review/meta-analysis have explored the efficacy and safety of fecal microbiota transplantation(FMT)in the treatment of UC with varying conclusions,however,the quality of these studies has not yet been adequately assessed.Aims:To overview of systematic review/meta-analysis of FMT for UC.Methods:Systematic review/meta-analysis of FMT for the treatment of UC were retrieved from PubMed,Cochrane Library,Embase,Web of Science,CNKI,CBM,Wanfang,VIP and other databases from the date of database establishment to May 2023,while gray literature was searched manually and experts were consulted.Literature screening and extract information were performed by two researchers.The PRISMA checklist,AMSTAR-2 tool was used to assess the reporting quality and methodological quality,respectively,as well as to grade the quality of evidence for outcome measurements based on the GRADE system.Results:Seventeen systematic review/meta-analysis were finally included.The original studies included randomized controlled trials and observational studies.Most of the studies drew positive conclusions about the effectiveness and safety of FMT in the treatment of UC,but some of them only made inferences about possible effectiveness.The PRISMA checklist score was 12-22.5,and the mean score was 17.68.Four studies(23.5%)reported relative completeness;nine(52.9%)had some deficiencies;and four(23.5%)had relatively serious information deficiencies.AMSTAR-2 score showed that two were of intermediate quality,three were of low quality,and twelve were of very low quality.GRADE ratings showed that five of the eight outcome measurements were of intermediate quality and three were of low quality.Conclusions:FMT may be a safe and effective treatment for UC,but the quality of the current evidence is low and users of clinical evidence need to treat the above evidence with caution.

Carvedilol is a new non-selective beta blocker, and studies have proven that the effect of carvedilol in receptor blocking is 2-4 times that of propranolol. Carvedilol is widely used in the treatment of heart failure. However, there are still controversies over its effect in reducing portal pressure and preventing esophageal variceal bleeding. This article analyzes and compares the clinical application of carvedilol, propranolol, and endoscopic variceal ligation in the prevention and treatment of bleeding and summarizes the pharmacological action, clinical effect, dose, and adverse reactions of carvedilol. It is pointed out that carvedilol can significantly improve hemodynamic disorder caused by portal hypertension and thus may become a new drug for the prevention and treatment of esophageal variceal bleeding.