LncRNA-Gm9795 promotes inflammation in non-alcoholic steatohepatitis via NF-[Formula: see text]B/JNK pathway by endoplasmic reticulum stress.

BACKGROUND: Non-alcoholic steatohepatitis (NASH) is a key stage in leading development of non-alcoholic simple fatty liver (NAFL) into cirrhosis and even liver cancer. This study aimed at exploring the lncRNAs expression profile in NASH and the biological function of a novel LncRNA-gm9795. METHODS: Microarray analysis was performed to compare the expression profiles of lncRNAs in the liver of NASH, NAFLD and normal mice (5 mice for each group). Methionine-choline-deficient Medium (MCD) with Lipopolysaccharide (LPS) or palmitic acid (PA)were used to built NASH cell models. The role and mechanism of LncRNA-gm9795 in NASH were explored by knocking down or over-expressing its expression. RESULTS: A total of 381 lncRNAs were found to be not only highly expressed in NAFLD, but also is going to go even higher in NASH. A novel LncRNA-gm9795 was significantly highly expressed in liver tissues of NASH animal models and NASH cell models. By staining with Nile red, we found that gm9795 did not affect the fat accumulation of NASH. However, gm9795 in NASH cell models significantly promoted the expression of TNF [Formula: see text], IL-6, IL-1[Formula: see text], the important inflammatory mediators in NASH. At the same time, we found that gm9795 upregulated the key molecules in endoplasmic reticulum stress (ERS), while NF-[Formula: see text]B/JNK pathways were also activated. When ERS activator Thapsigargin (TG) was introduced in cells with Ggm9757 si-RNA, NF-[Formula: see text]B and JNK pathways were activated. Conversely, ERS inhibitor Tauroursodeoxycholic acid (TUDCA) inhibited NF-kB and JNK pathways in cells with gm9795 overexpression plasmid. CONCLUSION: LncRNA-gm9795 promotes inflammatory response in NASH through NF-kB and JNK pathways by ERS, which might provide theoretical basis for revealing the pathogenesis of NASH and discovering new therapeutic targets.

Risk factors associated with the detection and missed diagnosis of colorectal flat adenoma: a Chinese multicenter observational study.

OBJECTIVES: Flat colorectal adenomas have a high risk of malignancy; however, their detection is often difficult due to their flat morphology. In this retrospective, large-scale study, we investigated the prevalence and characteristics of flat adenomas in a population in China. METHODS: We analyzed the data collected for 16951 consecutive patients who underwent colonoscopy at four participating hospitals between September 2013 and September 2015. All colonoscopies were performed without magnification. RESULTS: Among the 1,6951 patients, 2938 (17.3%) had adenoma and 796 (4.7%) had flat adenomas. The detection of flat adenoma showed a weak correlation with the detection of adenoma (r = 0.666). Multivariable logistic regression analysis revealed the following independent factors influencing the detection of flat adenomas: patient-related factors of age, presence of warning symptoms, history of adenomas and bowel preparation as well as endoscopist-related factors of endoscopist's level of proficiency, number of colonoscopy operators and withdrawal time. CONCLUSIONS: The prevalence of flat adenomas in our study on Chinese patients was consistent with that reported from other countries. Factors conducive to the detection of flat adenomas were patient age of > 60 years, warning symptoms, history of adenoma, good bowel preparation, experienced endoscopist, single-operator colonoscopy and colonoscopy withdrawal time of >6 min.

A novel quality scoring system for the evaluation of individual colonoscopy: A multicenter retrospective study.

BACKGROUND AND AIM: It is essential to develop a novel evaluation system for the quality of individual colonoscopy and provide guidelines on whether and when to follow up the patient after the initial colonoscopy. This study aimed to establish and validate a scoring system for the quality of individual colonoscopy in terms of the adenoma miss rate (AMR). METHODS: Patients undergoing two consecutive colonoscopies within 90 days between 2009 and 2011 from different levels of hospitals in China were enrolled into this study. Potential risk factors for adenoma miss at the individual colonoscopy in a cohort of patients were evaluated in univariate and multivariate analyses. Corresponding scores for the procedure-related factors were generated based on their weights, and a scoring system was established and then validated by correlating the system with AMR. RESULTS: A total of 2093 patients were enrolled. Procedure-related factors at the individual colonoscopy (including bowel preparation and imaging methods), doctor experience, retroflexion, and withdrawal time were identified to be independent risk factors, and each of these factors was scored from 0 to 3. Then, a novel scoring system for the quality of individual colonoscopy (ranging from 0 to 9) was established, which was closely correlated with the AMRs in the establishment (adjusted R(2) = 0.845) and validation databases (adjusted R(2) = 0.733). CONCLUSIONS: The developed and validated evaluation system, consisting of procedure-related independent factors, successfully assesses the quality of individual colonoscopy in terms of AMRs.

Berberine Inhibits Nod-Like Receptor Family Pyrin Domain Containing 3 Inflammasome Activation and Pyroptosis in Nonalcoholic Steatohepatitis via the ROS/TXNIP Axis.

Berberine (BBR), an isoquinoline alkaloid originating from herbal plants, has been deemed beneficial for non-alcoholic fatty liver disease. Increasing evidence has demonstrated that Nod-like receptor family pyrin domain containing 3 (NLRP3) inflammasome activation and the subsequent pyroptosis contribute to the progression of non-alcoholic steatohepatitis (NASH). However, whether BBR impacts NLRP3 inflammasome activation and pyroptosis in NASH and the potential mechanism remains unclear. In the current study, we found that BBR significantly decreased lipid accumulation, ameliorated reactive oxygen species (ROS) and lipid peroxides, Tumor necrosis factor alpha (TNF-α) expression, and phosphorylation of Nuclear factor kappa B (NF-κB) p65 both in vivo and in vitro. In particular, BBR significantly inhibited NLRP3 expression, caspase-1 activity, and the pyroptosis executor, GSDMD-N, expression. In addition, BBR displayed similar inhibitory effects on NLRP3 inflammasome and pyroptosis with a decrease in ROS levels and TXNIP expression as N-acetyl-cysteine, a ROS scavenger, did. Whereas, the inhibitory effect of BBR on ROS, TXNIP expression, NLRP3 inflammasome activation and pyroptosis could be reversed by H2O2 in AML12 cells. This study demonstrates that BBR's inhibitory effect on NLRP3 inflammasome activation and pyroptosis may be mediated by ROS/TXNIP axis in vitro for the first time. Our findings suggest BBR is a potential candidate for the treatment of NASH.

Determination of withdrawal times in individualized opportunistic screening colonoscopies.

To investigate effects of bowel preparation, experience level of colonoscopists, and colonoscopy withdrawal time (CWT) on the quality of an individual opportunistic screening colonoscopy, according to adenoma detection rate (ADR).Data were retrospectively analyzed from opportunistic screening colonoscopies (n = 16,951) at 4 hospitals of various care levels in China.The ADR positively correlated with the experience level of the colonoscopist. The individualized CWT varied, depending on the quality of bowel preparation and the number of colonoscopies performed previously by the colonoscopist. In a setting of adequate bowel preparation, the mean CWT decreased with the increased experience of the colonoscopist. With poor and inadequate bowel preparation, no colonoscopist at any level of experience could obtain a satisfactory ADR.For adequately prepared colonoscopies, minimum CWTs have been determined. Repeat colonoscopy is strongly recommended for patients with poor bowel preparation, regardless of the colonoscopist's experience.

Association between patient characteristics and magnetically controlled capsule endoscopy findings.

Background/Aim: Magnetically-controlled capsule endoscopy (MCE) is a potential option for the evaluation of gastric diseases in cases that are unsuited for conventional endoscopy, avoiding discomfort, sedation, and related complications. This retrospective study investigated associations between MCE findings and patient gender, age, and inpatient/outpatient status. Patients and Methods: The data of 580 consecutive patients who underwent MCE from 2015 to 2016 were analyzed. Data included age, gender, indication for MCE, inpatient/outpatient status, overall coverage of gastric anatomical landmarks, and comorbid conditions. Results: Compared with outpatients, inpatients had a higher rate of overall significant MCE findings (P = 0.014), polyp (P = 0.03), and ulceration (P = 0.003). MCE findings of the inpatient men and women were similar. Considering all patients, the percentage with ulceration was significantly higher in men than in women (P = 0.004), and men were younger (P < 0.001). Compared with younger patients, those aged ≥60 years had significantly higher rates of overall significant findings, mainly polyp and angiodysplasia. Conclusions: Compared with outpatients, the inpatients showed higher overall significant findings. Men undergoing MCE were younger than the women, and more likely to have ulcerations. Older patients, whether outpatient or inpatient, had higher rates of significant findings, mainly polyp and angiodysplasia.

LncRNA-AK012226 Is Involved in Fat Accumulation in db/db Mice Fatty Liver and Non-alcoholic Fatty Liver Disease Cell Model.

Instances of obesity and related metabolic abnormalities are increasing across the world. Non-alcoholic fatty liver disease (NAFLD) is a common disorder in obese people and is becoming the leading cause of hepatocellular carcinoma. Recently, long non-coding RNAs (lncRNAs) have been proven to play remarkable roles in numerous biological processes and human diseases, including NAFLD. However, the function of lncRNA in NAFLD pathogenesis remains largely unknown. The aim of this study was to explore the lncRNA expression profile in NAFLD mice and to identify novel lncRNAs involved in the pathogenesis of NAFLD. We performed microarray analysis to compare the expression profiles of lncRNAs and mRNAs in the liver of diabetic db/db mice with NAFLD and normal mice. A total of 3360 lncRNAs (2048 up-regulated and 1312 down-regulated) and 2685 mRNAs (1195 up-regulated and 1490 down-regulated) were found to be differentially expressed between the NAFLD and control groups. Real-time PCR validation of five differentially expressed lncRNAs in the liver samples was consistent with the microarray results. Besides, the up-regulated lncRNA, AK012226, was also significantly increased in an NCTC1469 NAFLD cellular model. Thus, the up-regulated lncRNA, AK012226, was chosen for subsequent studies. A co-expression network of AK012226-mRNAs was constructed and bioinformatic analysis of these co-expressed mRNAs indicated that they were enriched in the PPAR signaling pathway. Furthermore, Nile red staining and flow cytometry analysis revealed that knockdown of AK012226 by siRNA significantly reduced the lipid accumulation in the NCTC1469 cells treated with free fatty acids. In conclusion, the present study identifies the dysregulated lncRNAs and mRNAs involved in NAFLD, and in particular, a novel lncRNA, AK012226, was identified to be associated with lipid accumulation in NAFLD.

The evaluation of the OMOM capsule endoscopy with similar pictures elimination mode.

BACKGROUND AND OBJECTIVE: The reading of capsule endoscopy (CE) is time-consuming. Thus, several time-saving features have been added to the CE software by different CE companies. However, the similar pictures elimination mode in the OMOM capsule endoscopy software has not been evaluated yet. Our aim is to evaluate the sensitivity and specificity of the similar pictures elimination mode. METHODS: We retrospectively studied 200 consecutive capsule endoscopy procedures in Nanfang Hospital between April 2012 and July 2012, among which 52 cases were excluded for poor bowel preparation, failure to reach the colon or data missing. All images of the small-bowel were re-evaluated with four different reading modes (conventional mode and three levels of similar pictures elimination mode) by four experienced endoscopists. Then, the reading time, the number of detected lesions, κ value, sensitivity and specificity were compared between 4 methods. RESULTS: The mean reading time with levels I to III, respectively, was significantly shorter than with conventional mode (P<0.001, conventional mode 33.25min, level I 24.90min, level II 20.54min, level III 14.96min). The sensitivity between conventional mode and level I were similar (93.8% vs. 87.7%, P=0.073), while the sensitivity of levels II and III was significantly lower than conventional mode (77.8% vs. 93.8%, 70% vs. 93.8%, respectively). The specificity between all 4 modes were similar (100% for conventional mode, 98.5% for levels I to III). CONCLUSIONS: Level I reading mode was as efficient as the conventional mode and less time-consuming. Its sensitivity and specificity were similar compared with the conventional mode.

Risk factors associated with missed colorectal flat adenoma: a multicenter retrospective tandem colonoscopy study.

AIM: To determine the miss rate for colorectal flat adenomas during colonoscopy and the risk factors. METHODS: Flat adenomas are frequently missed during colonoscopy. However, the risk factors that influence their miss rates are unclear. This was a multicenter, retrospective study in which patients diagnosed with colorectal adenomas at a diagnostic colonoscopy and followed within 3 mo by a second therapeutic colonoscopy were pooled out from the established database. The "per-patient" and "per-adenoma" adenoma miss rates (AMR) for overall adenomas and flat adenomas, and patient-, adenoma-, and procedure-related risk factors potentially associated with the "per-adenoma" AMR for flat adenomas were determined. RESULTS: Chromoscopy and high-definition colonoscopy were not taken under consideration in the study. Among 2093 patients with colorectal adenomas, 691 (33.0%) were diagnosed with flat adenomas, 514 with concomitant protruding adenomas and 177 without. The "per-patient" AMR for flat adenomas was 43.3% (299/691); the rates were 54.3% and 11.3%, respectively, for those with protruding adenomas and those without (OR = 9.320, 95%CI: 5.672-15.314, χ (2) = 99.084, P < 0.001). The "per-adenoma" AMR for flat adenomas was 44.3% (406/916). In multivariate analysis, older age, presence of concomitant protruding adenomas, poor bowel preparation, smaller adenoma size, location at the right colon, insufficient experience of the colonoscopist, and withdrawal time < 6 min were associated with an increased "per-adenoma" AMR for flat adenomas. The AMR for flat adenomas was moderately correlated with that for overall adenomas (r = 0.516, P < 0.0001). The AMR for flat adenomas during colonoscopy was high. CONCLUSION: Patient's age, concomitant protruding adenomas, bowel preparation, size and location of adenomas, proficiency of the colonoscopist, and withdrawal time are factors affecting the "per-adenoma" AMR for flat adenomas.