MicroRNA-376b-3p ameliorates nonalcoholic fatty liver disease by targeting FGFR1 and regulating lipid oxidation in hepatocytes.

AIMS: Nonalcoholic fatty liver disease (NAFLD) is a common chronic liver disease whose molecular mechanisms remain unclear. This study aimed to explore the role and mechanisms of microRNA-376b-3p in NAFLD. MATERIALS AND METHODS: We used a microarray to reveal hepatic microRNA expression profiles and validated their expression in cellular and mouse models via qRT-PCR. In vitro, the expression of microRNA-376b-3p was increased by a microRNA-376b-3p mimic and decreased by a microRNA-376b-3p inhibitor. The role and potential mechanisms of microRNA-376b-3p in NAFLD were investigated in mice injected with lentiviral vectors before high-fat diet (HFD) feeding, and the direct target gene was explored using a dual-luciferase reporter gene assay and confirmed by Western blotting. KEY FINDINGS: Microarray analysis and subsequent validation showed that the expression of microRNA-376b-3p was downregulated by nearly 90 % in the livers of HFD-fed mice and by >50 % in free fatty acid-stimulated hepatocytes. Overexpression of microRNA-376b-3p markedly ameliorated hepatic lipid accumulation, which was attributable to an increase in fatty acid oxidation. Conversely, inhibition of miR-376b-3p exhibited the opposite effects. The luciferase reporter assay indicated that Fgfr1 is a direct target gene of miR-376b-3p. Fgfr1 intervention eliminated the effect of miR-376b-3p on the lipid oxidation pathway and hepatocyte steatosis, which suggests that miR-376b-3p regulates fatty acid oxidation by targeting Fgfr1 to influence NAFLD development. SIGNIFICANCE: miR-376b-3p was downregulated in NAFLD and has a novel regulatory role in lipid oxidation through a miR-376b-3p-Fgfr1-dependent mechanism. Thus, miR-376b-3p may serve as a potential diagnostic marker or therapeutic target for NAFLD.

Metabolic dysfunction is associated with steatosis but no other histologic features in nonalcoholic fatty liver disease.

BACKGROUND: Recently, nonalcoholic fatty liver disease (NAFLD) has been renamed metabolic-associated fatty liver disease (MAFLD). Based on the definition for MAFLD, a group of non-obese and metabolically healthy individuals with fatty liver are excluded from the newly proposed nomenclature. AIM: To analyze the histologic features in the MAFLD and non-MAFLD subgroups of NAFLD. METHODS: Eighty-three patients with biopsy-proven NAFLD were separated into MAFLD and non-MAFLD groups. The diagnosis of MAFLD was established as hepatic steatosis along with obesity/diabetes or evidence of metabolic dysfunction. The histologic features were compared according to different metabolic disorders and liver enzyme levels. RESULTS: MAFLD individuals had a higher NAFLD activity score (P = 0.002) and higher severity of hepatic steatosis (42.6% Grade 1, 42.6% Grade 2, and 14.8% Grade 3 in MAFLD; 81.8% Grade 1, 13.6% Grade 2, and 4.5% Grade 3 in non-MAFLD; P = 0.007) than the non-MAFLD group. Lobular and portal inflammation, hepatic ballooning, fibrosis grade, and the presence of nonalcoholic steatohepatitis (NASH) and significant fibrosis were comparable between the two groups. The higher the liver enzyme levels, the more severe the grades of hepatic steatosis (75.0% Grade 1 and 25.0% Grade 2 in normal liver function; 56.6% Grade 1, 39.6% Grade 2, and 3.8% Grade 3 in increased liver enzyme levels; 27.8% Grade 1, 27.8% Grade 2, and 44.4% Grade 3 in liver injury; P < 0.001). Patients with liver injury (alanine aminotransferase > 3 × upper limit of normal) presented a higher severity of hepatocellular ballooning (P = 0.021). Moreover, the grade of steatosis correlated significantly with hepatocellular ballooning degree (r = 0.338, P = 0.002) and the presence of NASH (r = 0.466, P < 0.001). CONCLUSION: Metabolic dysfunction is associated with hepatic steatosis but no other histologic features in NAFLD. Further research is needed to assess the dynamic histologic characteristics in NAFLD based on the presence or absence of metabolic disorders.

Esophageal Mucosal Autograft for Preventing Stricture After Widespread Endoscopic Submucosal Dissection of Superficial Esophageal Lesions.

BACKGROUND: Although esophageal mucosal autograft prevents esophageal stricture after widespread endoscopic submucosal dissec- tion and has been reported as a new technique, it is relatively unproven in clinical practice. This prospective study was conducted to evaluate our experience using esophageal mucosal autograft to prevent strictures after widespread endoscopic submucosal dissection in patients with widespread superficial esophageal lesions. METHODS: Between October 2017 and June 2018, 15 patients with widespread superficial esophageal lesions were consecutively treated with widespread endoscopic submucosal dissection and then underwent esophageal mucosal autograft. The main outcomes measured included esophageal epithelialization and esophageal stricture. RESULTS: The median longitudinal diameter of the widespread superficial esophageal lesions was 5.2 cm. All 15 patients were success- fully treated with widespread endoscopic submucosal dissection and esophageal mucosal autograft, and the median procedural time was 182 minutes. During follow-up (median, 23 months), esophageal epithelialization was found in 13 patients (86.7%), and 7 patients experienced esophageal stricture (46.7%). In those 7 patients, the esophageal strictures were successfully relieved after endoscopic bal- loon dilation or endoscopic radial incision. No complications related to endoscopic balloon dilation/endoscopic radial incision occurred. Additionally, local recurrence was found in 1 patient with poorly differentiated squamous cell carcinoma, and further surgical resection was performed. CONCLUSIONS: Esophageal mucosal autograft appears to be an efficient approach to reconstructing local esophageal epithelium and might have a potential role in preventing esophageal stricture after widespread endoscopic submucosal dissection. However, as a new technique, it needs more improvement to enhance its role in preventing esophageal stricture after widespread endoscopic submucosal dissection.

Chinese Consensus Report on Family-Based Helicobacter pylori Infection Control and Management (2021 Edition).

OBJECTIVE: Helicobacter pylori infection is mostly a family-based infectious disease. To facilitate its prevention and management, a national consensus meeting was held to review current evidence and propose strategies for population-wide and family-based H. pylori infection control and management to reduce the related disease burden. METHODS: Fifty-seven experts from 41 major universities and institutions in 20 provinces/regions of mainland China were invited to review evidence and modify statements using Delphi process and grading of recommendations assessment, development and evaluation system. The consensus level was defined as ≥80% for agreement on the proposed statements. RESULTS: Experts discussed and modified the original 23 statements on family-based H. pylori infection transmission, control and management, and reached consensus on 16 statements. The final report consists of three parts: (1) H. pylori infection and transmission among family members, (2) prevention and management of H. pylori infection in children and elderly people within households, and (3) strategies for prevention and management of H. pylori infection for family members. In addition to the 'test-and-treat' and 'screen-and-treat' strategies, this consensus also introduced a novel third 'family-based H. pylori infection control and management' strategy to prevent its intrafamilial transmission and development of related diseases. CONCLUSION: H. pylori is transmissible from person to person, and among family members. A family-based H. pylori prevention and eradication strategy would be a suitable approach to prevent its intra-familial transmission and related diseases. The notion and practice would be beneficial not only for Chinese residents but also valuable as a reference for other highly infected areas.

Antibiotic Resistance of Helicobacter pylori Isolated from Patients after Partial Gastrectomy: A Retrospective Study.

BACKGROUND: To determine the prevalence of Helicobacter pylori infection and the antibiotic susceptibility of H. pylori in patients after partial gastrectomy. METHODS: Patients who underwent gastroscopy from January 2009 to November 2017 and had a history of partial gastrectomy were retrospectively enrolled in the remnant stomach group. Contemporary non-gastrectomized patients with an endoscopic diagnosis of chronic gastritis were enrolled in the non-operated stomach group. The detection of H. pylori infection was performed by culture and histology. The in vitro antimicrobial susceptibility was examined by the agar dilution method on strains from gastric biopsies. RESULTS: In this study, a total of 728 gastrectomized and 5035 non-gastrectomized patients were included. There was a significantly lower prevalence of H. pylori infection in the gastric-remnant patients (8.65%) than in the non-gastrectomized patients (17.76%) (P < .001) with the diagnostic method of culture. In the gastric-remnant patients, the H. pylori strains had resistance rates to metronidazole, clarithromycin, levofloxacin, amoxicillin, and furazolidone of 100%, 20.63%, 22.22%, 0%, and 0%, respectively. In the nongastrectomized patients, H. pylori resistance to metronidazole, clarithromycin, levofloxacin, amoxicillin, and furazolidone was 90.49%, 24.61%, 21.70%, 0.22%, and 0.11%, respectively. Gastric-remnant patients had a significantly higher metronidazole resistance rate than non-gastrectomized patients (P = .005). Moreover, no significant changes in the resistance to 5 antibiotics were observed among the gastric-remnant patients from different age, gender, and surgical indication groups. CONCLUSION: Patients after partial gastrectomy showed a lower prevalence of H. pylori infection. Gastric-remnant patients were more likely to harbor metronidazole-resistant H. pylori strains.

A novel model for predicting fatty liver disease by means of an artificial neural network.

BACKGROUND: The artificial neural network (ANN) emerged recently as a potent diagnostic tool, especially for complicated systemic diseases. This study aimed to establish a diagnostic model for the recognition of fatty liver disease (FLD) by virtue of the ANN. METHODS: A total of 7,396 pairs of gender- and age-matched subjects who underwent health check-ups at the First Affiliated Hospital, College of Medicine, Zhejiang University (Hangzhou, China) were enrolled to establish the ANN model. Indices available in health check-up reports were utilized as potential input variables. The performance of our model was evaluated through a receiver-operating characteristic (ROC) curve analysis. Other outcome measures included diagnostic accuracy, sensitivity, specificity, Cohen's k coefficient, Brier score, and Hosmer-Lemeshow test. The Fatty Liver Index (FLI) and the Hepatic Steatosis Index (HSI), retrained using our training-group data with its original designated input variables, were used as comparisons in the capability of FLD diagnosis. RESULTS: Eight variables (age, gender, body mass index, alanine aminotransferase, aspartate aminotransferase, uric acid, total triglyceride, and fasting plasma glucose) were eventually adopted as input nodes of the ANN model. By applying a cut-off point of 0.51, the area under ROC curves of our ANN model in predicting FLD in the testing group was 0.908 [95% confidence interval (CI), 0.901-0.915]-significantly higher (P < 0.05) than that of the FLI model (0.881, 95% CI, 0.872-0.891) and that of the HSI model (0.885; 95% CI, 0.877-0.893). Our ANN model exhibited higher diagnostic accuracy, better concordance with ultrasonography results, and superior capability of calibration than the FLI model and the HSI model. CONCLUSIONS: Our ANN system showed good capability in the diagnosis of FLD. It is anticipated that our ANN model will be of both clinical and epidemiological use in the future.

Construction of a convolutional neural network classifier developed by computed tomography images for pancreatic cancer diagnosis.

BACKGROUND: Efforts should be made to develop a deep-learning diagnosis system to distinguish pancreatic cancer from benign tissue due to the high morbidity of pancreatic cancer. AIM: To identify pancreatic cancer in computed tomography (CT) images automatically by constructing a convolutional neural network (CNN) classifier. METHODS: A CNN model was constructed using a dataset of 3494 CT images obtained from 222 patients with pathologically confirmed pancreatic cancer and 3751 CT images from 190 patients with normal pancreas from June 2017 to June 2018. We established three datasets from these images according to the image phases, evaluated the approach in terms of binary classification (i.e., cancer or not) and ternary classification (i.e., no cancer, cancer at tail/body, cancer at head/neck of the pancreas) using 10-fold cross validation, and measured the effectiveness of the model with regard to the accuracy, sensitivity, and specificity. RESULTS: The overall diagnostic accuracy of the trained binary classifier was 95.47%, 95.76%, 95.15% on the plain scan, arterial phase, and venous phase, respectively. The sensitivity was 91.58%, 94.08%, 92.28% on three phases, with no significant differences (χ 2 = 0.914, P = 0.633). Considering that the plain phase had same sensitivity, easier access, and lower radiation compared with arterial phase and venous phase , it is more sufficient for the binary classifier. Its accuracy on plain scans was 95.47%, sensitivity was 91.58%, and specificity was 98.27%. The CNN and board-certified gastroenterologists achieved higher accuracies than trainees on plain scan diagnosis (χ 2 = 21.534, P < 0.001; χ 2 = 9.524, P < 0.05; respectively). However, the difference between CNN and gastroenterologists was not significant (χ 2 = 0.759, P = 0.384). In the trained ternary classifier, the overall diagnostic accuracy of the ternary classifier CNN was 82.06%, 79.06%, and 78.80% on plain phase, arterial phase, and venous phase, respectively. The sensitivity scores for detecting cancers in the tail were 52.51%, 41.10% and, 36.03%, while sensitivity for cancers in the head was 46.21%, 85.24% and 72.87% on three phases, respectively. Difference in sensitivity for cancers in the head among the three phases was significant (χ 2 = 16.651, P < 0.001), with arterial phase having the highest sensitivity. CONCLUSION: We proposed a deep learning-based pancreatic cancer classifier trained on medium-sized datasets of CT images. It was suitable for screening purposes in pancreatic cancer detection.

Adipose-derived mesenchymal stem cells alleviate TNBS-induced colitis in rats by influencing intestinal epithelial cell regeneration, Wnt signaling, and T cell immunity.

BACKGROUND: Conventional Crohn's disease (CD) treatments are supportive rather than curative and have serious side effects. Adipose-derived mesenchymal stem cells (ADSCs) have been gradually applied to treat various diseases. The therapeutic effect and underlying mechanism of ADSCs on CD are still not clear. AIM: To investigate the effect of ADSC administration on CD and explore the potential mechanisms. METHODS: Wistar rats were administered with 2,4,6-trinitrobenzene sulfonic acid (TNBS) to establish a rat model of CD, followed by tail injections of green fluorescent protein (GFP)-modified ADSCs. Flow cytometry, qRT-PCR, and Western blot were used to detect changes in the Wnt signaling pathway, T cell subtypes, and their related cytokines. RESULTS: The isolated cells showed the characteristics of ADSCs, including spindle-shaped morphology, high expression of CD29, CD44, and CD90, low expression of CD34 and CD45, and osteogenic/adipogenic ability. ADSC therapy markedly reduced disease activity index and ameliorated colitis severity in the TNBS-induced rat model of CD. Furthermore, serum anti-sacchromyces cerevisiae antibody and p-anti-neutrophil cytoplasmic antibody levels were significantly reduced in ADSC-treated rats. Mechanistically, the GFP-ADSCs were colocalized with intestinal epithelial cells (IECs) in the CD rat model. GFP-ADSC delivery significantly antagonized TNBS-induced increased canonical Wnt pathway expression, decreased noncanonical Wnt signaling pathway expression, and increased apoptosis rates and protein level of cleaved caspase-3 in rats. In addition, ADSCs attenuated TNBS-induced abnormal inflammatory cytokine production, disturbed T cell subtypes, and their related markers in rats. CONCLUSION: Successfully isolated ADSCs show therapeutic effects in CD by regulating IEC proliferation, the Wnt signaling pathway, and T cell immunity.

Development of a validated Chinese version of the inflammatory bowel disease disability index.

OBJECTIVE: The inflammatory bowel disease disability index (IBD-DI) has been used to evaluate functional status for patients with inflammatory bowel diseases (IBD). The study aimed to develop a reliable Chinese version of IBD-DI (C-IBD-DI). METHODS: Consecutive patients with IBD and healthy controls were recruited from June 2016 to July 2017 in the First Affiliated Hospital, College of Medicine, Zhejiang University (Hangzhou, Zhejiang Province, China) to complete an inflammatory bowel disease questionnaire-32 (IBDQ-32), Hamilton's anxiety rating scale (HAMA) and Hamilton's depression rating scale-24 items (HAMD-24). The validation process included item reduction, reliability and validity tests. RESULTS: Altogether 122 patients with IBD completed the validation process. Factor analysis reduced the C-IBD-DI to 13 items. Cronbach's α coefficient was 0.90. The C-IBD-DI scores were correlated with IBDQ-32 score (r = -0.79, P < 0.001), HAMA (r = 0.78, P < 0.001) and HAMD-24 (r = 0.81, P < 0.001). The total score of C-IBD-DI was significantly higher in patients with active IBD than in those in remission. The intraclass correlation coefficient was 0.83 in the stable IBD group, representing a good test-retest reliability. Those with improved disease activity had a significantly lower C-IBD-DI score at the follow-up visit than at baseline. Patients with IBD had worse disability levels and quality of life than the controls, and were more likely to be anxious and depressed, especially those with active IBD. CONCLUSIONS: The validated C-IBD-DI comprising 13 questions has highly acceptable reliability and validity. Multicenter studies including large sample sizes are needed to further confirm our results.

Allyl isothiocyanate ameliorates lipid accumulation and inflammation in nonalcoholic fatty liver disease via the Sirt1/AMPK and NF-κB signaling pathways.

BACKGROUND: Allyl isothiocyanate (AITC), a classic anti-inflammatory and antitumorigenic agent, was recently identified as a potential treatment for obesity and insulin resistance. However, little is known about its direct impact on the liver. AIM: To investigate the effect and underlying mechanism of AITC in nonalcoholic fatty liver disease (commonly referred to as NAFLD). METHODS: To establish a mouse and cellular model of NAFLD, C57BL/6 mice were fed a high fat diet (HFD) for 8 wk, and AML-12 cells were treated with 200 µM palmitate acid for 24 h. For AITC treatment, mice were administered AITC (100 mg/kg/d) orally and AML-12 cells were treated with AITC (20 µmol/L). RESULTS: AITC significantly ameliorated HFD-induced weight gain, hepatic lipid accumulation and inflammation in vivo. Furthermore, serum alanine aminotransferase and aspartate aminotransferase levels were markedly reduced in AITC-treated mice. Mechanistically, AITC significantly downregulated the protein levels of sterol regulatory element-binding protein 1 (SREBP1) and its lipogenesis target genes and upregulated the levels of proteins involved in fatty acid ß-oxidation, as well as the upstream mediators Sirtuin 1 (Sirt1) and AMP-activated protein kinase α (AMPKα), in the livers of HFD-fed mice. AITC also attenuated the nuclear factor kappa B (NF-κB) signaling pathway. Consistently, AITC relieved palmitate acid-induced lipid accumulation and inflammation in AML-12 cells in vitro through the Sirt1/AMPK and NF-κB signaling pathways. Importantly, further studies showed that the curative effect of AITC on lipid accumulation was abolished by siRNA-mediated knockdown of either Sirt1 or AMPKα in AML-12 cells. CONCLUSION: AITC significantly ameliorates hepatic steatosis and inflammation by activating the Sirt1/AMPK pathway and inhibiting the NF-κB pathway. Therefore, AITC is a potential therapeutic agent for NAFLD.

The Role of Dietary Energy and Macronutrients Intake in Prevalence of Irritable Bowel Syndromes.

BACKGROUND: Irritable bowel syndrome (IBS) is a chronic gastrointestinal disorder characterized by abdominal pain and altered bowel habits in the absence of any detectable organic illnesses. Interest in the effect of dietary opponents to the IBS pathogenesis has been increased in recent years. This study aims to review previous studies to determine the relationship between IBS prevalence in community and dietary energy and macronutrients intakes according to the national nutrition surveys. METHODS: A literature search was conducted in PubMed and EMBASE to September, 2018, to identify population-based studies that reported the prevalence of IBS. Daily energy intake, daily carbohydrates, and protein and fat percent contribution to energy intake (%) were obtained from study population-based national nutrition survey. The correlations of prevalence of IBS and dietary intakes were obtained by Spearman coefficient or Pearson coefficient. RESULTS: Global prevalence of IBS was 11.7%. There was no correlation between overall prevalence of IBS of individual countries and national energy intake (P = 0.785), protein proportion (P = 0.063), carbohydrates proportion (P = 0.505), or fat proportion (P = 0.384) according to the years when the studies were conducted. No correlations were detected between dietary intake and male or female IBS prevalence. Interestingly, protein proportion was positively correlated with the prevalence of IBS in Rome III criteria (r = 0.569). CONCLUSION: Our findings demonstrate that dietary energy and macronutrients intake do not play a direct role in prevalence of IBS. However, IBS diagnostic criteria seem to have a bias on the correlation between prevalence of IBS and dietary intake. Further studies are needed to confirm the correlation between prevalence of IBS and specific dietary intake.

A Zero-Valent Pd/Fe Loaded and Nanofibrillated Cellulose-Reinforced Carboxymethyl Cellulose Hydrogel for Dechlorination of 2,4,6-Trichlorophenol.

A full-cellulose derived hydrogel, composed of carboxymethyl cellulose (CMC) and nanofibrillated cellulose (NFC), was successfully manufactured and immobilized with Pd/Fe bimetallic nanoparticles for the dechlorination of 2,4,6-trichlorophenol. The NFC-reinforced CMC hydrogels with or without loading of bimetallic nanoparticles were characterized by Fourier transform infrared spectroscopy, Transmission electron microscopy, Scanning electron microscopy-energy dispersive X-ray, and X-ray diffraction analyses. The effect of amounts of NFC on the loading capacity of Pd/Fe, mechanical properties and specific Brunauer-Emmett-Teller surface areas of NFC-reinforced CMC hydrogel was also investigated. The experimental results showed that Pd/Fe bimetallic nanoparticles were dispersed and fixed in the hydrogel matrix with the nanosize spherical shape. The hydrogel would protect the Pd/Fe nanoparticles from oxidation, and thus providing long-term stability in comparison with only NFC-coated Pd/Fe nanoparticles. The hydrogel loaded with Pd/Fe nanoparticles, as a soft material catalytic system, was investigated to dechlorinate 2,4,6-trichlorophenol and was found to be very effective.

Application of Machine Learning Techniques for Clinical Predictive Modeling: A Cross-Sectional Study on Nonalcoholic Fatty Liver Disease in China.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases. Machine learning techniques were introduced to evaluate the optimal predictive clinical model of NAFLD. METHODS: A cross-sectional study was performed with subjects who attended a health examination at the First Affiliated Hospital, Zhejiang University. Questionnaires, laboratory tests, physical examinations, and liver ultrasonography were employed. Machine learning techniques were then implemented using the open source software Weka. The tasks included feature selection and classification. Feature selection techniques built a screening model by removing the redundant features. Classification was used to build a prediction model, which was evaluated by the F-measure. 11 state-of-the-art machine learning techniques were investigated. RESULTS: Among the 10,508 enrolled subjects, 2,522 (24%) met the diagnostic criteria of NAFLD. By leveraging a set of statistical testing techniques, BMI, triglycerides, gamma-glutamyl transpeptidase (γGT), the serum alanine aminotransferase (ALT), and uric acid were the top 5 features contributing to NAFLD. A 10-fold cross-validation was used in the classification. According to the results, the Bayesian network model demonstrated the best performance from among the 11 different techniques. It achieved accuracy, specificity, sensitivity, and F-measure scores of up to 83%, 0.878, 0.675, and 0.655, respectively. Compared with logistic regression, the Bayesian network model improves the F-measure score by 9.17%. CONCLUSION: Novel machine learning techniques may have screening and predictive value for NAFLD.

Determination of lysine content based on an in situ pretreatment and headspace gas chromatographic measurement technique.

This work reports on a simple method for the determination of lysine content by an in situ sample pretreatment and headspace gas chromatographic measurement (HS-GC) technique, based on carbon dioxide (CO2) formation from the pretreatment reaction (between lysine and ninhydrin solution) in a closed vial. It was observed that complete lysine conversion to CO2 could be achieved within 60 min at 60 °C in a phosphate buffer medium (pH = 4.0), with a minimum molar ratio of ninhydrin/lysine of 16. The results showed that the method had a good precision (RSD < 5.23%) and accuracy (within 6.80%), compared to the results measured by a reference method (ninhydrin spectroscopic method). Due to the feature of in situ sample pretreatment and headspace measurement, the present method becomes very simple and particularly suitable to be used for batch sample analysis in lysine-related research and applications. Graphical abstract The flow path of the reaction and HS-GC measurement for the lysine analysis.

Gastric xanthelasma and metabolic disorders: A large retrospective study among Chinese population.

AIM: To gain knowledge of xanthelasma, a large population-based study was conducted. METHODS: Patients who underwent upper gastrointestinal endoscopy at the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China during Jan 2009 to Nov 2016 were included. General characteristics as well as clinical data were collected, including blood routine, serum biochemical analysis, endoscopic findinds, histological evaluation and comorbiditie. Statistical analyses was performed using SPSS 20.0 software for Windows (IBM Inc., Chicago, IL, United States) using Student's t-test, Mann-Whitney U test, χ2 test, univariable and multivariable logistic analysis. 2-tailed P value less than 0.05 was considered to be statistically significant. RESULTS: A total of 176006 endoscopies were retrieved and we included 1370 xanthelasma participants (703 men, 667 women) in this study. Prevalence of xanthelasma was 0.78% with average age of 56.6 ± 11.2 years. Chief complaint of xanthelasma consisted abdominal pain (24.2%), up-abdominal discomfort (14.1%), abdominal distention (10.1%), dyspepsia (9.1%), et al. Most xanthelasma occurred as single lesion in gastric antrum. Xanthelasma patients witnessed higher Helicobacter pylori (H. pylori) infection rate, more of other gastric lesions including atrophy, intestinal metaplasia and dysplasia (P < 0.01). In xanthelasma patients, serum carcinoembryonic antigen, triglyceride, fasting glucose, neutrophil, neutrophil-to-lymphocyte ratio were significantly higher, and high density lipoprotein-cholesterol, lymphocyte was lower (P < 0.05). Xanthelasma accompanied with more fatty liver disease and hepatic cyst, but fewer gallbladder polyp (P < 0.05). In logistic regression, it revealed that fasting plasma glucose (OR = 3.347, 1.170-9.575, P < 0.05), neutrophil (OR = 1.617, 1.003-2.605, P < 0.05), and carcinoembryonic antigen (OR = 2.011, 1.236-3.271, P < 0.01) were all independent risk factors in xanthelasma. CONCLUSION: Current study described a large xanthelasma cohort in Chinese population, revealed its relationship with H. pylori infection, carcinogenesis, metabolic dysfunction and inflammation as well.

Gastric cancer-derived heat shock protein-gp96 peptide complex enhances dendritic cell activation.

AIM: To investigate the role of heat shock protein (HSP)-glycoprotein (gp)96 in dendritic cells (DCs) and lymphocytes induction in gastric cancer (GC). METHODS: Human GC cell lines KATOIII, MKN-28 and SGC-7901 were infected with adenovirus gp96 at a multiplicity of infection of 100. gp96-GC antigen peptide complexes were purified. MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay, lactate dehydrogenase (LDH) release assay and enzyme-linked immunosorbent assay were used to determine allo-reactive T cell stimulation, natural killer (NK) cell activity and expression of cytokines (such as interleukin (IL)-10, IL-12, interferon (IFN)-γ and tumor necrosis factor (TNF)-α), respectively. Effect of cytotoxic T lymphocyte (CTL) on DCs incubated with HSP-gp96 was also evaluated by LDH release. All assays were performed in triplicate and the average values were reported. Comparison between groups was conducted using Student's t test. RESULTS: T cells incubated with HSP-gp96 exhibited a marked increase in proliferation in a dose-dependent manner (P < 0.05). NK cell activity after gp96-GC peptide complex treatment was significantly higher than that after antigen peptide treatment (P < 0.05). The activity of CTLs incubated with DCs from three GC cells lines was obviously higher than that stimulated by GC antigen at ratios of 50: 1, 25: 1, 10: 1, and 5: 1 (P < 0.05). Furthermore, the secretion of TNF-α, IL-10, IL-12 (P70) and IFN-γ markedly increased after incubation with HSP-gp96 (P < 0.05). CONCLUSION: HSP-gp96 promotes T cell response, enhances DC antigen presentation and induces cytokine secretion, as well. HSP-gp96 has potential as immunotherapy for elimination of residual GC cells.

Effect of miR-146 targeted HDMCP up-regulation in the pathogenesis of nonalcoholic steatohepatitis.

BACKGROUNDS/AIMS: Mitochondrial dysfunction plays an important role inthe pathogenesis of nonalcoholic steatohepatitis (NASH), where uncoupling protein (UCP) is actively involved. We previously reported the uncoupling activity of HDMCP and its role in liver steatosis. We now aim to investigate the degree and therapeutic effect of HDMCP in NASH and the regulatory role of miR-146 on HDMCP. METHODS: NASH animal model was established by feeding BALB/c mice with MCD diet while L02 cell was cultured with high concentration of fatty acid (HFFA) for 72h to mimic the steatosis and inflammation of NASH in-vitro appearance. The steatosis level was assessed by H-E/oil-red staining and serum/supernatant marker detection. The inflammation activity was evaluated by levels of Hepatic activity index, transwell, apoptosis degree (TUNEL/flow cytometry) and serum/supernatant marker. HDMCP level was detected by western blot and miRNA expression was tested by qRT-PCR. NASH severity change was recorded after RNA interference while the regulatory role of miR-146 on HDMCP was confirmed by dual luciferase report system. The H2O2 and ATP levels were measured for mechanism exploration. RESULTS: Increased HDMCP expression was identified in NASH animal model and HFFA-72h cultured L02 cell. Moreover, under regulation of miR-146, NASH alleviation was achieved after HDMCP downregulation in both in vivo and in vitro, according to the declination of steatosis and inflammation related markers. Though H2O2 and ATP levels were increased and decreased in NASH models, HDMCP down regulation both increased their levels. CONCLUSIONS: The miR-146-HDMCP-ATP/H2O2 pathway may provide novel mechanism and treatment option for NASH.

Clinical guidelines of non-alcoholic fatty liver disease: A systematic review.

AIM: To perform a systematic review to grade guidelines and present recommendations for clinical management of non-alcoholic fatty liver disease (NAFLD). METHODS: A database search was conducted on PubMed for guidelines published before May 2016, supplemented by reviewing relevant websites. The Appraisal of Guidelines for Research and Evaluation (ARGEE) Instrument II was a tool designed to appraise the methodological rigor and transparency in which a clinical guideline is developed and it is used internationally. It was used to appraise the quality of guidelines in this study. The inclusion criteria include: clinical NAFLD guidelines for adults, published in English, and released by governmental agencies or key organizations. RESULTS: Eleven guidelines were included in this study. Since 2007, guidelines have been released in Asia (3 in China, 1 in South Korea, and 1 in Japan), Europe (1 in Italy), America (1 in United States and 1 in Chile) and three international agencies [European associations joint, Asia-Pacific Working Party and World Gastroenterology Organization (WGO)]. Using the ARGEE II instrument, we found US 2012 and Europe 2016 had the highest scores, especially in the areas of rigor of development and applicability. Additionally, Italy 2010 and Korea 2013 also presented comprehensive content, rigorous procedures and good applicability. And WGO 2014 offered various algorithms for clinical practice. Lastly, a practical algorithm for the clinical management was developed, based on the recommended guidelines. CONCLUSION: This is the first systematic review of NAFLD guidelines. It may yield insights for physicians and policy-makers in the development and application of guidelines.