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Loss-of-function mutations of microRNA-142-3p promote ASH1L expression to induce immune evasion and hepatocellular carcinoma progression

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World Journal of gastroenterology 2025年第1期31卷 126-145页

作者： Xing-Hui Yu Yan Xie Jian Yu Kun-Ning Zhang Zhou-Bo Guo Di Wang Zhao-Xian Li Wei-Qi Zhang Yu-Ying Tan Li Zhang Wen-Tao Jiang School of Medicine Nankai UniversityTianjin 300192China Tianjin Key Laboratory of Molecular Diagnosis and Treatment of liver Cancer Tianjin First Center HospitalTianjin 300192China department of liver transplantation Tianjin First Center HospitalTianjin 300192China First Central Clinical School Tianjin Medical UniversityTianjin 300192China

BACKGROUND Hepatocellular carcinoma(HCC)has been a pervasive malignancy throughout the world with elevated *** therapeutic targets are beneficial to treat and predict the ***,the exact molecular mechanisms leading to the progression of HCC are still *** has shown that the microRNA-142-3p level decreases in HCC,whereas bioinformatics analysis of the cancer genome atlas database shows the ASH1L expression increased among liver tumor *** this paper,we will explore the effects and mechanisms of microRNA-142-3p and ASH1L affect the prognosis of HCC patients and HCC cell bioactivity,and the association between *** To investigate the effects and mechanisms of microRNA-142-3p and ASH1L on the HCC cell bioactivity and prognosis of HCC *** In this study,we grouped HCC patients according to their immunohistochemistry results of ASH1L with pathological tissues,and retrospectively analyzed the prognosis of HCC ***,explored the roles and mechanisms of microRNA-142-3p and ASH1L by cellular and animal experiments,which involved the following experimental methods:Immunohistochemical staining,western blot,quantitative real-time-polymerase chain reaction,flow cytometric analysis,tumor xenografts in nude mice,*** statistical methods involved in this study contained t-test,one-way analysis of variance,theχ^(2)test,the Kaplan-Meier approach and the log-rank *** In this study,we found that HCC patients with high expression of ASH1L possess a more recurrence rate as well as a decreased overall survival ***1L promotes the tumorigenicity of HCC and microRNA-142-3p exhibits reduced expression in HCC tissues and interacts with ASH1L through targeting the ASH1L 3′untranslated ***,microRNA-142-3p promotes apoptosis and inhibits proliferation,invasion,and migration of HCC cell lines in vitro via *** the exploration mechanism,we found ASH1L may promote an immunosuppressive mi

关键词： Hepatocellular carcinoma MicroRNA-142-3p ASH1L Immune evasion Tumor immune microenvironment Apoptosis

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Redefining endoluminal biliary drainage:Challenges and innovations in endosonography-guided techniques

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World Journal of gastroenterology 2025年第1期31卷 146-151页

作者： Marcel Razpotnik department of gastroenterology and Hepatology Campus Virchow/Campus MitteCharitéBerlinBerlin 10117Germany

Endoscopic retrograde cholangiopancreatography is considered the gold standard for treating benign and malignant biliary ***,its use in complex biliary obstructions is *** the past decades,therapeutic endosonography(EUS)and emerging technologies such as lumen-apposing metal stents have enabled endoscopic treatment of conditions previously requiring nonendoscopic or surgical *** show that EUS-guided choledochoduodenostomy is a reliable alternative to endoscopic retrograde cholangiopancreatography in the treatment of distal malignant biliary obstructions and can be considered a primary drainage modality in centers with adequate *** malignant hilar biliary obstructions,draining at least 50%of viable liver tissue often requires combining different *** treatment strategy in these patients should be individualized,depending on the Bismuth classification,patient physical status,and intended systemic *** to the lack of evidence,general recommendations cannot be made for EUS-guided hepaticoduodenostomy or combined procedures with transhepatic bridging *** novel techniques should be limited to selected palliative cases where conventional methods have failed and conducted within clinical trials to generate evidence before broader application.

关键词： Endoscopic biliary drainage Interventional endosonography Lumen-apposing metal stent Malignant hilar biliary obstruction Malignant distal biliary obstruction

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Portal biliopathy

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World Journal of gastroenterology 2012年第43期18卷 6177-6182页

作者： Somnath Chattopadhyay Samiran Nundy department of surgical gastroenterology and liver transplantation Sir Ganga Ram Hospital New Delhi 110060 India

Biliary ductal changes are a common radiological finding in patients with portal hypertension, however only a small percentage of patients (5%-30%) develop symptomatic bile duct obstruction. The exact pathogenesis is not clear, but an involvement of factors such as bile duct compression by venous collaterals, ischemia, and infection is accepted by most authors. Although endoscopic retrograde cholangiopancrea- tography was used to define and diagnose this condition, magnetic resonance cholangiopancreatography is currently the investigation of choice for diagnosing this condition. Treatment is indicated only for symptomatic cases. Portosystemic shunts are the treatment of choice for symptomatic portal biliopathy. In the majority of patients, the changes caused by biliopathy resolve after shunt surgery, however, 15%-20% patients require a subsequent bilio-enteric bypass or endoscopic management for persistent biliopathy. There is a role for endoscopic therapy in patients with bile duct stones, cholangitis or when portosystemic shunt surgery is not feasible.

关键词： Pseudosclerosing cholangitis Non cirrhotic portal fibrosis Extrahepatic portal venous obstruction Proximal lienorenal shunt Biliary obstruction Portal cavernoma

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Is bactibilia a predictor of poor outcome of pancreaticoduodenectomy?

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Hepatobiliary & Pancreatic Diseases International 2010年第1期9卷 65-68页

作者： Sivanpillay Mahadevan Sivaraj Velayutham Vimalraj Palanichamy Saravanaboopathy Shanmugasundaram Rajendran Sathyanesan Jeswanth Palaniappan Ravichandran Rosy Vennilla Rajagopalan Surendran Institute of surgical gastroenterology and liver transplantation New Gastroenterology BlockGovernment Stanley Medical College Hospital

BACKGROUND:Although bile infection has been proposed to increase infective complications following pancreaticoduodenectomy,its association with infective complications and non-infective complications like pancreatic fistula is still ***:Seventy-six patients who had undergone pancreaticoduodenectomy between July 2007 and December 2008 were included in a prospective database and their data *** all patients intraoperative bile from the bile duct was ***,intra-operative,and post-operative variables were recorded and ***:Bile culture showed positive growth in 35 patients and negative growth in *** patients in the positive group underwent ERCP and *** patients with a positive bile culture had a higher incidence of infective complications including intra-abdominal abscess (n=8),wound infection (n=27),bacteremia (n=10),and renal insufficiency (n=9).There was no increase in the rate of non-infective complications of pancreaticoduodenectomy including pancreatic fistula (n=7),delayed gastric emptying (n=9),and post-operative hemorrhage (n=3).The hospital stay was significantly prolonged in the patients with a positive bile culture (P=0.0002).CONCLUSIONS:Pre-operative biliary drainage is significantly associated with bile infection,and bile infection increases the overall rates of infective complications and renal *** of the high incidence of complications is associated with infected bile,routine intra-operative bile culture is recommended in patients undergoing ***-operative prophylaxis is dependent on sensitivity of cases to perioperative antibiotics and intraoperative bile culture *** of its significant association with infected bile,biliary stenting should be used in strictly selected cases.

关键词： bactibilia Whipples pancreaticoduodenectomy perioperative outcomes

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Summary of the current guidelines for managing iatrogenic colorectal perforations and the evolving role of endoluminal vacuum therapy

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World Journal of Clinical Cases 2025年第6期13卷 1-8页

作者： Ahmed Tawheed Ibrahim Halil Bahcecioglu Mehmet Yalniz Mubin Ozercan Ali Cagri Oral Mohamed El-Kassas department of Endemic Medicine Faculty of MedicineHelwan UniversityCairo 11795Egypt department of gastroenterology Firat UniversityElazig 23119Türkiye liver Disease Research Center College of MedicineKing Saud UniversityRiyadh 7805Saudi Arabia

Colonoscopy represents a safe procedure that is widely used in medical practice either to diagnose or treat various gastrointestinal *** the last few years,the incidence rate of perforations in colonoscopic procedures has increased,especially in therapeutic *** recent advancements in endoscopic techniques and gastrointestinal tumoral resection procedures such as endoscopic mucosal resection,endoscopic full-thickness resection,and endoscopic submucosal dissection(ESD)could be a risk factor for this increased *** incidence rate of mortality of serious colonoscopic perforations is 7.1%.The management plan for these perforations starts with conservative treatment in mild cases,endoscopic closure,and surgical management in severe ***,endoluminal vacuum therapy was found to be effective in the management of colorectal perforations and this has been reported in multiple case *** editorial provides an overview of the current guidelines for the management of iatrogenic colorectal *** insights are from the perspectives of endoscopists and *** also present a management algorithm based on the guidelines of the European Society of Gastrointestinal Endoscopy,the American Gastroenterological Association,and the World Society of Emergency *** also discussed in brief the use of endoluminal vacuum therapy in colorectal perforations.

关键词： Colon Rectum Iatrogenic colonic perforation Colonoscopy Guidelines Endovacuum Endolumical vacuum therapy Endoscopic management

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New insights into the coagulopathy of liver disease and liver transplantation

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World Journal of gastroenterology 2006年第48期12卷 7725-7736页

作者： M Senzolo P Burra E Cholongitas AK Burroughs gastroenterology Department of Surgical and Gastroenterological Sciences University Hospital of Padua Padua ItalyLiver Transplantation and Hepatobiliary Unit Royal Free Hospital London United Kingdom gastroenterology Department of Surgical and Gastroenterological Sciences University Hospital of Padua Padua Italy liver transplantation and Hepatobiliary Unit Royal Free Hospital London United Kingdom

The liver is an essential player in the pathway of coagulation in both primary and secondary haernostasis. Only yon Willebrand factor is not synthetised by the liver, thus liver failure is associated with impairment of coagulation. However, recently it has been shown that the delicate balance between pro and antithrornbotic factors synthetised by the liver might be reset to a lower level in patients with chronic liver disease. Therefore, these patients might not be really anticoagulated in stable condition and bleeding may be caused only when additional factors, such as infections, supervene. Portal hypertension plays an important role in coagulopathy in liver disease, reducing the number of circulating platelets, but platelet function and secretion of thrornbopoietin have been also shown to be impaired in patients with liver disease. Vitamin K deficiency may coexist, so that abnormal clotting factors are produced due to lack of gamma carboxylation. Moreover during liver failure, there is a reduced capacity to clear activated haernostatic proteins and protein inhibitor complexes from the circulation. Usually therapy for coagulation disorders in liver disease is needed only during bleeding or before invasive procedures. When end stage liver disease occurs, liver transplantation is the only treatment available, which can restore normal haemostasis, and correct genetic clotting defects, such as haemophilia or factor V Leiden mutation. During liver transplantation haemorrage may occur due to the pre-existing hypocoagulable state, the collateral circulation caused by portal hypertension and increased fibrinolysis which occurs during this surgery.

关键词： Coagulation Cirrhosis liver transplantation

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Veno occlusive disease: Update on clinical management

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World Journal of gastroenterology 2007年第29期13卷 3918-3924页

作者： M Senzolo G Germani E Cholongitas P Burra AK Burroughs gastroenterology Department of Surgical and Gastroenterological Sciences University Hospital of Padua Padua Italy liver transplantation and Hepatobiliary Unit Royal Free Hospital London United Kingdom

Hepatic veno-occlusive disease is a clinical syndrome characterized by hepatomegaly, ascites, weight gain and jaundice, due to sinusoidal congestion which can be caused by alkaloid ingestion, but the most frequent cause is haematopoietic stem cell transplantation （STC） and is also seen after solid organ transplantation. The incidence of veno occlusive disease （VOD） after STC ranges from 0 to 70%, but is decreasing. Survival is good when VOD is a mild form, but when it is severe and associated with an increase of hepatic venous pressure gradient 〉 20 mmHg, and mortality is about 90%. Prevention remains the best therapeutic strategy, by using non-myeloablative conditioning regimens before STC. Prophylactic administration of ursodeoxycholic add, being an antioxidant and antiapoptotic agent, can have some benefit in reducing overall mortality. Defibrotide, which has pro-fibrinolytic and antithrombotic properties, is the most effective therapy; decompression of the sinusoids by a b-ansjugular intrahepatic portosystemic shunt （TIPS） can be tried, especially to treat VOD after liver transplantation and when multiorgan failure （HOF） is not present. liver transplantation can be the last option, but can not be considered a standard rescue therapy, because usually the concomitant presence of multiorgan failure contraindicates this procedure.

关键词： Veno occlusive disease Defibrotide Transjugular intrahepatic portosystemic shunt liver transplantation

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A gist of gastrointestinal stromal tumors: A review

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World Journal of Gastrointestinal Oncology 2013年第6期5卷 102-112页

作者： Ashwin Rammohan Jeswanth Sathyanesan Kamalakannan Rajendran Anbalagan Pitchaimuthu Senthil-Kumar Perumal UP Srinivasan Ravi Ramasamy Ravichandran Palaniappan Manoharan Govindan The Institute of surgical gastroenterology and liver transplantation Centre for GI Bleed Division of HPB Diseases Stanley Medical College Hospital

Gastrointestinal stromal tumors (GISTs) have been recognized as a biologically distinctive tumor type, different from smooth muscle and neural tumors of the gastrointestinal tract (GIT). They constitute the majority of gastrointestinal mesenchymal tumors of the GIT and are known to be refractory to conventional chemotherapy or radiation. They are defined and diagnosed by the expression of a proto-oncogene protein detected by immunohistochemistry which serves as a crucial diagnostic and therapeutic target. The identification of these mutations has resulted in a better understanding of their oncogenic mechanisms. The remarkable antitumor effects of the molecular inhibitor imatinib have necessitated accurate diagnosis of GIST and their distinction from other gastrointestinal mes-enchymal tumors. Both traditional and minimally invasive surgery are used to remove these tumors with minimal morbidity and excellent perioperative outcomes. The revolutionary use of specific, molecularlytargeted therapies, such as imatinib mesylate, reduces the frequency of disease recurrence when used as an adjuvant following complete resection. Neoadjuvant treatment with these agents appears to stabilize disease in the majority of patients and may reduce the extent of surgical resection required for subsequent complete tumor removal. The important interplay between the molecular genetics of GIST and responses to targeted therapeutics serves as a model for the study of targeted therapies in other solid tumors. This review summarizes our current knowledge and recent advances regarding the histogenesis, pathology, molecular biology, the basis for the novel targeted cancer therapy and current evidence based management of these unique tumors.

关键词： Gastrointestinal stromal tumors c-KIT Imatinib mesylate Surgery Review

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Successful Resection in a Case of Hepatocellular Carcinoma Masquerading as Hilar Cholangiocarcinoma: A Case Report

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Journal of Clinical and Translational Hepatology 2018年第4期6卷 442-446页

作者： Prakriti Gupta Shashi Dhawan Vivek Mangla Siddharth Mehrotra Shailendra Lalwani Naimish N Mehta Samiran Nundy department of Pathology Sir Ganga Ram HospitalNew DelhiIndia department of surgical gastroenterology and liver transplantation Sir Ganga Ram HospitalNew DelhiIndia

Obstructive jaundice in the setting of a hilar mass raises strong suspicion of a cholangiocarcinoma,with diagnosis usually made on ***,when present in patients with hepatocellular carcinoma,is mostly related to underlying liver disease(***)and only rarely to diffuse tumor infiltration of liver parenchyma or hilar *** report here the good outcome of a 67 year-old patient who presented with obstructive jaundice,underwent surgery and was given a diagnosis of hepatocellular carcinoma,which was made only at histopathological examination of resected specimen.

关键词： Obstructive jaundice Hepatocellular carcinoma Cholangiocarcinoma

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Management of hepatitis C infection before and after liver transplantation

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World Journal of gastroenterology 2015年第15期21卷 4447-4456页

作者： Stefano Fagiuoli Roberto Ravasio Maria Grazia Lucà Anna Baldan Silvia Pecere Alessandro Vitale Luisa Pasulo gastroenterology and Transplant Hepatology Papa Giovanni XXIII Hospital PHarm ES Milano liver transplantation and Hepatobiliary surgical Unit Padua University Hospital

Chronic hepatitis C(CHC) is the most common indication for liver transplantation(LT). Aggressive treatment of hepatitis C virus(HCV) infection before cirrhosis development or decompensation may reduce LT need and risk of HCV recurrence post-LT. Factors associated with increased HCV risk or severity of recurrence include older age, immunosuppression, HCV genotype 1 and high viral load at LT. HCV recurrence post-LT leads to accelerated liver disease and cirrhosis development with reduced graft and patient survival. Currently, interferon(IFN)-based regimens can be used in dualagent regimens with ribavirin, in triple-agent antiviral strategies with direct-acting antivirals(e.g., protease inhibitors telaprevir or boceprevir), or before transplant in compensated patients to reduce HCV viral load to prevent or reduce the risk of post-LT recurrence and complications; they cannot be used in patients with decompensated cirrhosis. IFN-based regimens are used in less than half of HCV-infected patients waiting for LT due to extremely low efficacy and poor tolerability. However, antiviral therapy is indicated after LT in patients with histologically confirmed CHC despite tolerability issues. Improvements in side effect management have increased survival in patients achieving therapeutic targets. HCV treatment pre- and post-LT results in significant health care costs especially when lack of efficacy leads to disease worsening, although studies have shown sofosbuvir treatment before LT vs conventional post-LT dual antiviral is cost effective. The suboptimal efficacy and tolerability of IFN-based therapies, plus the significant economic burden, means the need for effective and well tolerated IFN-free antiHCV therapy for pre- and post-LT remains high.

关键词： Hepatitis C virus Orthotopic liver trans plantation Interferon-free treatment Decompensated cirrhosis Chronic hepatitis C

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