Background and aimsGastric intestinal metaplasia (IM) is common in the gastric epithelium of patients with chronic atrophic gastritis. CDX2 activation in IM is driven by reflux of bile acids and ...following chronic inflammation. But the mechanism underlying how bile acids activate CDX2 in gastric epithelium has not been fully explored.MethodsWe performed microRNA (miRNA) and messenger RNA (mRNA) profiling using microarray in cells treated with bile acids. Data integration of the miRNA/mRNA profiles with gene ontology (GO) analysis and bioinformatics was performed to detect potential miRNA-mRNA regulatory circuits. Transfection of gastric cancer cell lines with miRNA mimics and inhibitors was used to evaluate their effects on the expression of candidate targets and functions. Immunohistochemistry and in situhybridisation were used to detect the expression of selected miRNAs and their targets in IM tissue microarrays.ResultsWe demonstrate a bile acids-triggered pathway involving upregulation of miR-92a-1–5p and suppression of its target FOXD1 in gastric cells. We first found that miR-92a-1–5p was increased in IM tissues and induced by bile acids. Moreover, miR-92a-1–5p was found to activate CDX2 and downstream intestinal markers by targeting FOXD1/FOXJ1 axis and modulating activation of nuclear factor kappa B (NF-κB) pathway. Furthermore, these effects were found to be clinical relevant, as high miR-92a-1–5p levels were correlated with low FOXD1 levels and high CDX2 levels in IM tissues.ConclusionThese findings suggest a miR-92a-1–5p/FOXD1/NF-κB/CDX2 regulatory axis plays key roles in the generation of IM phenotype from gastric cells. Suppression of miR-92a-1–5p and restoration of FOXD1 may be a preventive approach for gastric IM in patients with bile regurgitation.
Summary Acute upper gastrointestinal bleeding is a common medical emergency worldwide, a major cause of which are bleeding peptic ulcers. Endoscopic treatment and acid suppression with proton-pump ...inhibitors are cornerstones in the management of the disease, and both treatments have been shown to reduce mortality. The role of emergency surgery continues to diminish. In specialised centres, radiological intervention is increasingly used in patients with severe and recurrent bleeding who do not respond to endoscopic treatment. Despite these advances, mortality from the disorder has remained at around 10%. The disease often occurs in elderly patients with frequent comorbidities who use antiplatelet agents, non-steroidal anti-inflammatory drugs, and anticoagulants. The management of such patients, especially those at high cardiothrombotic risk who are on anticoagulants, is a challenge for clinicians. We summarise the published scientific literature about the management of patients with bleeding peptic ulcers, identify directions for future clinical research, and suggest how mortality can be reduced.
The MYC oncogene is overexpressed in hepatocellular carcinoma (HCC) and has been associated with widespread microRNA (miRNA) repression; however, the underlying mechanisms are largely unknown. Here, ...we report that the c‐Myc oncogenic transcription factor physically interacts with enhancer of zeste homolog 2 (EZH2), a core enzymatic unit of polycomb repressive complex 2 (PRC2). Furthermore, miR‐101, an important tumor‐suppressive miRNA in human hepatocarcinomas, is epigenetically repressed by PRC2 complex in a c‐Myc‐mediated manner. miR‐101, in turn, inhibits the expression of two subunits of PRC2 (EZH2 and EED), thus creating a double‐negative feedback loop that regulates the process of hepatocarcinogenesis. Restoration of miR‐101 expression suppresses multiple malignant phenotypes of HCC cells by coordinate repression of a cohort of oncogenes, including STMN1, JUNB, and CXCR7, and further increases expression of endogenous miR‐101 by inhibition of PRC2 activation. In addition, co‐overexpression of c‐Myc and EZH2 in HCC samples was closely associated with lower expression of miR‐101 (P < 0.0001) and poorer prognosis of HCC patients (P < 0.01). Conclusions: c‐Myc collaborates with EZH2‐containing PRC2 complex in silencing tumor‐suppressive miRNAs during hepatocarcinogenesis and provides promising therapeutic candidates for human HCC. (Hepatology 2014;59:1850–1863)
AIM:To compare the liver transplantation-free(LTF)survival rates between patients who underwent transjugular intrahepatic portosystemic shunts(TIPS)and those who underwent paracentesis by an updated ...meta-analysis that pools the effects of both number of deaths and time to death.METHODS:MEDLINE,EMBASE,and the Cochrane Library were searched from the inception to October2012.LTF survival,liver transplantation,liver diseaserelated death,non-liver disease-related death,recurrent ascites,hepatic encephalopathy(HE)and severe HE,and hepatorenal syndrome were assessed as outcomes.LTF survival was estimated using a HR with a95%CI.Other outcomes were estimated using OR with95%CIs.Sensitivity analyses were performed to assess the effects of potential outliers in the studies according to the risk of bias and the study characteristics.RESULTS:Six randomized controlled trials with 390patients were included.In comparison to paracentesis,TIPS significantly improved LTF survival(HR=0.61,95%CI:0.46-0.82,P<0.001).TIPS also significantly decreased liver disease-related death(OR=0.62,95%CI:0.39-0.98,P=0.04),recurrent ascites(OR=0.15,95%CI:0.09-0.24,P<0.001)and hepatorenal syndrome(OR=0.32,95%CI:0.12-0.86,P=0.02).However,TIPS increased the risk of HE(OR=2.95,95%CI:1.87-4.66,P=0.02)and severe HE(OR=2.18,95%CI:1.27-3.76,P=0.005).CONCLUSION:TIPS significantly improved the LTF survival of cirrhotic patients with refractory ascites and decreased the risk of recurrent ascites and hepatorenal syndrome with the cost of increased risk of HE compared with paracentesis.Further studies are warranted to validate the survival benefit of TIPS in clinical practice settings.
Abstract Background Infliximab revolutionized the treatment paradigm of Crohn's disease (CD), but did not reduce the need for surgery. The impact of biologic agents on surgical complication rates ...remains debated. The aim of this study was to determine the effect of preoperative infliximab use on early postoperative complications in patients with CD undergoing abdominal surgery. Method PubMed and Embase databases were searched to identify comparative studies that investigated postsurgical morbidity in CD patients receiving infliximab preoperatively with those not on infliximab. We used meta-analysis with random-effects model to calculate the pooled odds ratios (ORs) with 95% confidence intervals (CIs) for total complication rate as well as major, minor, infectious, and non-infectious complications. Results A total of 18 studies involving 5769 patients included in this systematic review. There was significant association between infliximab therapy prior to surgery and total (OR = 1.45, 95% CI 1.04–2.02; 13 studies, 2538 patients), infectious (OR = 1.47, 95% CI 1.08–1.99; 10 studies, 2116 patients) and non-infectious (OR = 2.29, 95% CI 1.14–4.61; 3 studies, 729 patients) postoperative complications respectively. There was no significant disparity in the major (OR = 1.39, 95% CI 0.85–2.27; 9 studies, 3696 patients) and minor (OR = 1.39, 95% CI 0.57–3.40; 5 studies, 753 patients) complication rates between infliximab and control groups. No publication bias was detected. Conclusion Preoperative infliximab use modestly increases the risk of total early postoperative complications, and particularly infectious complications in CD patients.
Currently, nonselective β-blockers(NSBBs) are commonly used for the prevention of variceal bleeding in liver cirrhosis. The beneficial effects of NSBBs are primarily attributed to the reduction in ...cardiac output by blockade of β1 receptors and vasoconstriction of the splanchnic circulation by the blockade of β2 receptors. The prognostic value of occlusive portal vein thrombosis(PVT) in cirrhotic patients has been increasingly recognized. The most important risk factor for the development of PVT in liver cirrhosis is the decreased portal vein inflow velocity. Collectively, we propose that the use of NSBBs potentially increases the development of portal vein thrombosis by reducing portal vein inflow velocity. The hypothesis should be confirmed by prospective cohort studies, in which cirrhotic patients without prior PVT treated with and without NSBBs are enrolled, and the development of PVT during followup is compared between the two groups. Additionally,subgroup analyses should be performed according to the dosage of NSBBs and the reduction of portal inflow velocity after use of NSBBs.
The current work aimed to examine the rates of and risk factors for mortality and readmission after heart failure (HF).
A systematic search was carried out in PubMed, the Cochrane Library, and EMBASE ...to identify eligible reports. The random-effects model was utilized to evaluate the pooled results.
A total of 27 studies with 515,238 participants were finally meta-analysed. The HF patients had an average age of 76.3 years, with 51% of the sample being male, in the pooled analysis.
The outcome measures were 30-day and 1-year readmission rates, mortality, and risk factors for readmission and mortality.
The effect sizes for readmission and mortality were estimated as the mean and 95% confidence interval (CI). The estimated 30-day and 1-year all-cause readmission rates were 0.19 (95% CI 0.14-0.23) and 0.53 (95% CI 0.46-0.59), respectively, while the all-cause mortality rates were 0.14 (95% CI 0.10-0.18) and 0.29 (95% CI 0.25-0.33), respectively. Comorbidities were highly prevalent in individuals with HF.
Heart failure hospitalization is followed by high readmission and mortality rates.
Nowadays,transjugular intrahepatic portosystemic shunt(TIPS)has become a mainstay treatment option for the management of portal hypertension-related complications in liver cirrhosis.Accumulated ...evidence has shown that its indications are being gradually expanded.Notwithstanding,less attention has been paid for the selection of an appropriate stent during a TIPS procedure.Herein,we attempt to review the current evidence regarding the diameter,type,brand,and position of TIPS stents.Several following recommendations may be considered in the clinical practice:(1)a 10-mm stent may be more effective than an 8-mm stent for the management of portal hypertension,and may be superior to a 12-mm stent for the improvement of survival and shunt patency;(2)covered stents are superior to bare stents for reducing the development of shunt dysfunction;(3)if available,Viatorr stent-grafts may be recommended due to a higher rate of shunt patency;and(4)the placement of a TIPS stent in the left portal vein branch may be more reasonable for decreasingthe development of hepatic encephalopathy.However,given relatively low quality of evidence,prospective well-designed studies should be warranted to further confirm these recommendations.
AIM:To evaluate the frequency of use of various treatment modalities for Budd-Chiari syndrome(BCS)in China by conducting a preliminary survey of relevant literature.METHODS:All papers regarding the ...treatment of BCS in Chinese patients were identified by searching PubMed,Chinese Scientific and Technological Journal,and China National Knowledge Infrastructure databases.Data regarding the number of BCS patients treated with different treatment modalities over time were collected.The proportions of BCS patients undergoing various treatment modalities were calculated.RESULTS:Overall,300 of 3005 papers initially retrieved were included.These papers included 23352BCS patients treated with different treatment modalities.The treatment modalities include surgery(n=8625),interventional treatment(n=13940),surgery combined with interventional treatment(n=363),medical therapy(n=277),other treatments(n=91),and no treatment(n=56).After 2005,the number of BCS patients treated with surgery was drastically decreased,but the number of BCS patients who underwent interventional treatment was almost maintained.Shunt surgery was the most common type of surgery(n=3610).Liver transplantation was rarely employed(n=2).Balloon angioplasty with or without stenting was the most common type of interventional treatment(n=13747).Transjugular intrahepatic portosystemic shunt was rarely employed(n=81).CONCLUSION:Selection of treatment modalities for BCS might be different between China and Western countries.Further work should be necessary to establish a unanimous therapeutic strategy for BCS in China.
Although tamoxifen (TAM), a selective estrogen receptor modulator, has been widely used in the treatment of hormone-responsive breast cancer, its estrogen-like effect increases the risk of ...endometrial cancer. However, the molecular mechanisms of TAM-induced endometrial carcinoma still remain unclear. In this report, we explored the role of microRNAs (miRNAs) in TAM-induced epithelial-mesenchymal transition (EMT) in ECC-1 and Ishikawa endometrial cancer cell lines and found miR-200 is involved in this process via the regulation of c-Myc. When treated with TAM, ECC-1 and Ishikawa cells were characterized by higher invasiveness and motility and underwent EMT. miR-200, a miRNA family with tumor suppressive functions in a wide range of cancers, was found reduced in response to TAM treatment. Consistent with zinc finger E-box binding homeobox 2, which was confirmed as a direct target of miR-200b in endometrial cancer cell lines, some other key factors of EMT such as Snail and N-cadherin increased, whereas E-cadherin decreased in the TAM-treated cells, contributing to TAM-induced EMT in these endometrial cancer cells. In addition, we showed that c-Myc directly binds to and represses the promoter of miR-200 miRNAs, and its up-regulation in TAM-treated endometrial cancer cells leads to the down-regulation of miR-200 and eventually to EMT. Collectively, our data suggest that TAM can repress the miR-200 family and induce EMT via the up-regulation of c-Myc in endometrial cancer cells. These findings describe a possible mechanism of TAM-induced EMT in endometrial cancer and provide a potential new therapeutic strategy for it.
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