Secondary Prophylaxis of Cirrhotic Gastric Variceal Bleeding: Addition of Non-Selective Beta-Blockers to Endoscopic Combined Treatment.

Background: It remains unclear whether the addition of non-selective beta-blockers (NSBB) provides further benefit after combined use of tissue adhesive and endoscopic variceal ligation for bleeding gastroesophageal varices.

Objective: This is the first cohort study comparing the secondary prophylactic efficacy of adding NSBB to combined endoscopic treatment in cirrhotic patients with gastric varices (without inclusion of isolated gastric varices [IGVs], which are rare in patients with cirrhosis without splanchnic thrombosis).

Methods: We retrospectively analyzed two matched large cohorts of cirrhotic patients with gastric varices who received combined endoscopic treatment and were assigned to receive NSBB treatment or not as secondary prophylaxis.

GSDMD-Dependent Neutrophil Extracellular Traps Mediate Portal Vein Thrombosis and Associated Fibrosis in Cirrhosis.

Portal vein thrombosis (PVT) is a challenging and controversial complication of cirrhosis. Experimental models that reproduce cirrhotic PVT and effective pharmacological therapies are limited. We aimed to investigate the nature course and mechanisms of PVT in cirrhosis.

Atf3-mediated metabolic reprogramming in hepatic macrophage orchestrates metabolic dysfunction-associated steatohepatitis.

Metabolic dysfunction-associated steatohepatitis (MASH) is regulated by complex interplay between the macrophages and surrounding cells in the liver. Here, we show that Atf3 regulates glucose-fatty acid cycle in macrophages attenuates hepatocyte steatosis, and fibrogenesis in hepatic stellate cells (HSCs). Overexpression of Atf3 in macrophages protects against the development of MASH in Western diet-fed mice, whereas Atf3 ablation has the opposite effect.

TET2-STAT3-CXCL5 nexus promotes neutrophil lipid transfer to fuel lung adeno-to-squamous transition.

Phenotypic plasticity is a rising cancer hallmark, and lung adeno-to-squamous transition (AST) triggered by LKB1 inactivation is significantly associated with drug resistance. Mechanistic insights into AST are urgently needed to identify therapeutic vulnerability in LKB1-deficient lung cancer. Here, we find that ten-eleven translocation (TET)-mediated DNA demethylation is elevated during AST in KrasLSL-G12D/+; Lkb1L/L (KL) mice, and knockout of individual Tet genes reveals that Tet2 is required for squamous transition.

Increased Factor VIII Activity Is Predictive of the Occurrence of Portal Vein Thrombosis in Cirrhosis.

Background:  The aim of this study was to identify the role of factor VIII (FVIII) in portal vein thrombosis (PVT) occurrence in cirrhotic patients with gastroesophageal variceal bleeding.

Methods:  A total of 453 cirrhotic patients with gastroesophageal varices were enrolled. Computed tomography was performed at baseline and patients were divided into PVT and non-PVT groups ( = 131 vs.

Platelet-derived TGF-β1 is related to portal vein thrombosis in cirrhosis by promoting hypercoagulability and endothelial dysfunction.

Background: Portal vein thrombosis (PVT) is a serious complication of cirrhosis accompanied by unclear pathogenesis. Transforming growth factor-beta (TGF-β) has been implicated in atherosclerosis and venous thrombosis whereas study regarding its part in PVT is lacking. The aim of this study was to explore the role of cytokine TGF-β1 in PVT and the potential mechanism.

Characteristics of myeloproliferative neoplasm-associated portal hypertension and endoscopic management of variceal bleeding.

Background: Myeloproliferative neoplasms (MPNs) are a rare yet important clinical cause of portal hypertension, which may cause recurrent gastroesophageal variceal bleeding (GVB). MPN-associated variceal bleeding lacks specific guidelines and clinical consensus and desiderates cohort studies. We performed a multicenter retrospective study to investigate the efficacy of endoscopic management of bleeding in MPNs.

ALK fusion promotes metabolic reprogramming of cancer cells by transcriptionally upregulating PFKFB3.

Anaplastic lymphoma kinase (ALK), a receptor tyrosine kinase of the insulin receptor kinase subfamily, is activated in multiple cancer types through translocation or overexpression. Although several generations of ALK tyrosine kinase inhibitors (TKIs) have been developed for clinic use, drug resistance remains a major challenge. In this study, by quantitative proteomic approach, we identified the glycolytic regulatory enzyme, 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3), as a new target of ALK.

UPLC-MS/MS-Based Serum Metabolomics Signature as Biomarkers of Esophagogastric Variceal Bleeding in Patients With Cirrhosis.

: Esophagogastric variceal bleeding (EVB) is a common and ominous complication of cirrhosis and represents the degree of portal hypertension progression and cirrhosis decompensation, desiderating the investigation into sensitive and specific markers for early detection and prediction. The purpose of this study is to characterize unique metabolites in serum of cirrhotic EVB patients and identify potential noninvasive biomarkers for detecting and assessing risk of variceal bleeding and cirrhosis progression through metabolomics-based approaches and explore possible pathophysiological mechanisms. : We used ultra-performance liquid chromatography coupled to tandem mass spectrometry (UPLC-MS/MS) to profile serum metabolomes.

Elevated nuclear localization of glycolytic enzyme TPI1 promotes lung adenocarcinoma and enhances chemoresistance.

Increased glycolysis is a hallmark of tumor, which can provide tumor cells with energy and building blocks to promote cell proliferation. Recent studies have shown that not only the expression of glycolytic genes but also their subcellular localization undergoes a variety of changes to promote development of different types of tumors. In this study, we performed a comprehensive analysis of glycolysis and gluconeogenesis genes based on data from TCGA to identify those with significant tumor-promoting potential across 14 types of tumors.

CBFB-MYH11 Fusion Sequesters RUNX1 in Cytoplasm to Prevent DNMT3A Recruitment to Target Genes in AML.

A growing number of human diseases have been found to be associated with aberrant DNA methylation, including cancer. Mutations targeting genes encoding DNA methyltransferase (DNMT), TET family of DNA demethylases, and isocitrate dehydrogenase (IDH1, IDH2) that produce TET inhibitory metabolite, 2-hyoxyglutarate (2-HG), are found in more than half of acute myeloid leukemia (AML). To gain new insights into the regulation of DNA de/methylation and consequence of its alteration in cancer development, we searched for genes which are mutated in a manner that is linked with gene mutations involved in DNA de/methylation in multiple cancer types.