Ten-Day Vonoprazan-Amoxicillin Dual Therapy vs Standard 14-Day Bismuth-Based Quadruple Therapy for First-Line Helicobacter pylori Eradication: A Multicenter Randomized Clinical Trial.

INTRODUCTION: Whether 10-day short-course vonoprazan-amoxicillin dual therapy (VA-dual) is noninferior to the standard 14-day bismuth-based quadruple therapy (B-quadruple) against Helicobacter pylori eradication has not been determined. This trial aimed to compare the eradication rate, adverse events, and compliance of 10-day VA-dual regimen with standard 14-day B-quadruple regimen as first-line H. pylori treatment. METHODS: This prospective randomized clinical trial was performed at 3 institutions in eastern China. A total of 314 treatment-naive, H. pylori -infected patients were randomly assigned in a 1:1 ratio to either 10-day VA-dual group or 14-day B-quadruple group. Eradication success was determined by 13 C-urea breath test at least 4 weeks after treatment. Eradication rates, adverse events, and compliance were compared between groups. RESULTS: Eradication rates of VA-dual and B-quadruple groups were 86.0% and 89.2% ( P = 0.389), respectively, by intention-to-treat (ITT) analysis; 88.2% and 91.5% ( P = 0.338), respectively, by modified ITT analysis; and 90.8% and 91.3% ( P = 0.884), respectively, by per-protocol (PP) analysis. The efficacy of the VA-dual remained noninferior to B-quadruple therapy in all ITT, modified ITT, and PP analyses. The incidence of adverse events in the VA-dual group was significantly lower compared with that in the B-quadruple group ( P < 0.001). Poor compliance contributed to eradication failure in the VA-dual group ( P < 0.001), while not in the B-quadruple group ( P = 0.110). DISCUSSION: The 10-day VA-dual therapy provided satisfactory eradication rates of >90% (PP analysis) and lower rates of adverse events compared with standard 14-day B-quadruple therapy as first-line H. pylori therapy. TRAIL REGISTRATION NUMBER: ChiCTR2300070100.

Fatty liver is associated with significant liver inflammation and increases the burden of advanced fibrosis in chronic HBV infection.

BACKGROUND: Concurrent non-alcoholic fatty liver disease (NAFLD) is common in patients with chronic HBV infection. But the impact of fatty liver on the histologic progression of HBV infection remains controversial. METHODS: Consecutive HBV-infected patients who underwent liver biopsy between 2016 and 2021 were included. Alcohol consumption and other types of viral hepatitis were excluded. All biopsies were scored for grading and staging by Scheuer's score, and the steatosis was scored as an estimate of the percentage of liver parenchyma replaced by fat. Logistic regression analyses were applied to assess the associated factors for significant liver inflammation (G ≥ 2), significant fibrosis (S ≥ 2) and advanced fibrosis (S ≥ 3). RESULTS: Among the 871 HBV-infected patients, hepatic steatosis was prevalent in 255 patients (29.28%). Significant liver inflammation was present in 461 patients (52.93%). Significant fibrosis was observed in 527 patients (60.51%), while advanced liver fibrosis was observed in 171 patients (19.63%). Patients with concomitant NAFLD were more likely to have significant liver inflammation and advanced fibrosis. Fatty liver was an independent risk factor for significant liver inflammation (OR: 2.117, 95% CI: 1.500-2.988), but it could not predict the development of fibrosis. Especially, in HBV-infected patients with persistent normal ALT (immune tolerant and inactive carrier phase), the presence of significant liver inflammation was higher in NAFLD than those without NAFLD. The prevalence of advanced liver fibrosis was higher in NAFLD than non-NAFLD only in the immune tolerant phase, while NAFLD did not increase fibrosis burden in other stages of HBV infection. We developed a predictive model for significant liver inflammation with the area under receiver operating characteristic curve (AUROC) of 0.825, and a model for significant fibrosis with the AUROC of 0.760. CONCLUSIONS: NAFLD is independently associated with significant liver inflammation, and increases the burden of advanced liver fibrosis in HBV-infected patients. The influence of NAFLD on the degree of liver inflammation and fibrosis is different in distinct clinical phases of chronic HBV infection.

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.

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.

Current status of Helicobacter pylori eradication and risk factors for eradication failure.

BACKGROUND: The Helicobacter pylori (H. pylori) eradication rate is decreasing in the general population of China. AIM: To evaluate the H. pylori eradication status in real-world clinical practice and to explore factors related to eradication failure. METHODS: Patients with H. pylori infection who were treated with standard 14-d quadruple therapy and received a test of cure at a provincial medical institution between June 2018 and May 2019 were enrolled. Demographic and clinical data were recorded. Eradication rates were calculated and compared between regimens and subgroups. Multivariate analysis was performed to identify predictors of eradication failure. RESULTS: Of 2610 patients enrolled, eradication was successful in 1999 (76.6%) patients. Amoxicillin-containing quadruple regimens showed a higher eradication rate than other quadruple therapy regimens (83.0% vs 69.0%, P < 0.001). The quadruple therapy containing amoxicillin plus clarithromycin achieved the highest eradication rate (83.5%). Primary therapy had a higher eradication rate than rescue therapy (78.3% vs 66.5%, P < 0.001). In rescue therapy, the amoxicillin- and furazolidone-containing regimens achieved the highest eradication rate (80.8%). Esomeprazole-containing regimens showed a higher eradication rate than those containing other proton pump inhibitors (81.8% vs 74.9%, P = 0.001). Multivariate regression analysis found that older age, prior therapy, and use of omeprazole or pantoprazole were associated with an increased risk of eradication failure. CONCLUSION: The total eradication rate is 76.6%. Amoxicillin-containing regimens are superior to other regimens. Age, prior therapy, and use of omeprazole or pantoprazole are independent risk factors for eradication failure.

Association between Serum Uric Acid to HDL-Cholesterol Ratio and Nonalcoholic Fatty Liver Disease in Lean Chinese Adults.

METHODS: A cross-sectional study was performed among 6285 lean Chinese adults (body mass index < 24 kg/m2) who took their annual health checkups. NAFLD was diagnosed based on hepatic ultrasound examination, with exclusion of other etiologies. RESULTS: Of 6285 lean participants enrolled, 654 NAFLD cases were diagnosed. The overall NAFLD prevalence was 10.41%, and the prevalence was 15.45% and 7.16% in men and women, respectively. UHR was significantly higher in NAFLD patients than in controls (14.25 ± 5.33% versus 10.09 ± 4.23%, P < 0.001). UHR quintiles were positively associated with NAFLD prevalence, which was 1.91% in the first UHR quintile and increased to 3.58%, 7.81%, 14.17%, and 24.54% in the second, third, fourth, and fifth quintile groups, respectively (P < 0.001 for trend). Multivariate logistic regression analysis showed that UHR was independently associated with an increased risk of NAFLD (odds ratio: 1.105; 95% CI: 1.076-1.134; P < 0.001). Sensitivity analysis showed that UHR remained significantly associated with NAFLD in lean participants with normal range of serum uric acid and HDL-cholesterol levels. CONCLUSIONS: UHR was significantly associated with NAFLD and may serve as a novel and reliable marker for NAFLD in lean adults.

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.

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.

Olfactomedin-4 in digestive diseases: A mini-review.

Olfactomedin-4 (OLFM4, GW112, hGC-1) is a glycoprotein belonging to the olfactomedin family. The expression of OLFM4 is strong in the small intestine, colon and prostate, and moderate in the stomach and bone marrow. Previous studies have revealed that OLFM4 is closely associated with many digestive diseases. Up-regulation of OLFM4 has been detected in the Helicobacter pylori (H. pylori)-infected gastric mucosa, inflammatory bowel disease tissue and gastrointestinal malignancies, including gastric cancer, colorectal cancer, pancreatic cancer and gallbladder cancer. Down-regulation of OLFM4 has also been detected in some cases, such as in poorly differentiated, advanced-stage and metastatic tumors. Studies using OLFM4-deficient mouse models have revealed that OLFM4 acts as a negative regulator of H. pylori-specific immune responses and plays an important role in mucosal defense in inflammatory bowel disease. Patients with OLFM4-positive gastric cancer or colorectal cancer have a better survival rate than OLFM4-negative patients. However, the prognosis is worse in pancreatic cancer patients with high levels of expression of OLFM4. The NF-κB, Notch and Wnt signaling pathways are involved in the regulation of OLFM4 expression in digestive diseases, and its role in pathogenesis is associated with anti-inflammation, apoptosis, cell adhesion and proliferation. OLFM4 may serve as a potential specific diagnostic marker and a therapeutic target in digestive diseases. Further studies are required to explore the clinical value of OLFM4.

Endoscopic Ultrasonography in the Diagnosis and Treatment Strategy Choice of Esophageal Leiomyoma.

OBJECTIVES:: Esophageal leiomyoma is the most common benign tumor of the esophagus, and it originates from mesenchymal tissue. This study analyzed the clinicopathological characteristics of esophageal leiomyoma and aimed to evaluate the role of endoscopic ultrasonography in the diagnosis and treatment selection for these lesions. METHODS:: Two hundred and twenty-five patients who had suspected esophageal leiomyomas in endoscopic ultrasonography were enrolled at the Endoscopy Center of The First Affiliated Hospital, Zhejiang University from January 1st, 2009 to May 31th, 2015. The main outcomes included the demographic and morphological characteristics, symptoms, comparisons of diagnosis and treatment methods, adverse events, and prognosis. RESULTS:: One hundred and sixty-seven patients were diagnosed as having an esophageal leiomyoma by pathological examination. The mean patient age was 50.57±9.983 years. In total, 62.9% of the lesions originated from the muscularis mucosa, and the others originated from the muscularis propria. The median distance to the incisors was 30±12 cm. The median diameter was 0.72±0.99 cm. As determined by endoscopic ultrasonography, most existing leiomyomas were homogeneous, endophytic, and spherical. The leiomyomas from the muscularis mucosa were smaller than those from the muscularis propria and much closer to the incisors (p<0.05). SMA (smooth muscle antibody) (97.2%) and desmin (94.5%) were positive in the majority of patients. In terms of treatments, patients preferred endoscopic therapies, which led to less adverse events (e.g., intraoperative bleeding, local infection, pleural effusion) than surgical operations (p<0.05). The superficial leiomyomas presented less adverse events and better recovery (p<0.05) than deep leiomyomas. CONCLUSION:: Endoscopic ultrasonography has demonstrated high accuracy in the diagnosis of esophageal leiomyomas and provides great support in selecting treatments; however, EUS cannot completely avoid misdiagnosis, so combining it with other examinations may be a good strategy to solve this problem.

Endoscopic Ultrasonography in the Diagnosis and Treatment Strategy Choice of Esophageal Leiomyoma

OBJECTIVES: Esophageal leiomyoma is the most common benign tumor of the esophagus, and it originates from mesenchymal tissue. This study analyzed the clinicopathological characteristics of esophageal leiomyoma and aimed to evaluate the role of endoscopic ultrasonography in the diagnosis and treatment selection for these lesions. METHODS: Two hundred and twenty-five patients who had suspected esophageal leiomyomas in endoscopic ultrasonography were enrolled at the Endoscopy Center of The First Affiliated Hospital, Zhejiang University from January 1st, 2009 to May 31th, 2015. The main outcomes included the demographic and morphological characteristics, symptoms, comparisons of diagnosis and treatment methods, adverse events, and prognosis. RESULTS: One hundred and sixty-seven patients were diagnosed as having an esophageal leiomyoma by pathological examination. The mean patient age was 50.57±9.983 years. In total, 62.9% of the lesions originated from the muscularis mucosa, and the others originated from the muscularis propria. The median distance to the incisors was 30±12 cm. The median diameter was 0.72±0.99 cm. As determined by endoscopic ultrasonography, most existing leiomyomas were homogeneous, endophytic, and spherical. The leiomyomas from the muscularis mucosa were smaller than those from the muscularis propria and much closer to the incisors (p<0.05). SMA (smooth muscle antibody) (97.2%) and desmin (94.5%) were positive in the majority of patients. In terms of treatments, patients preferred endoscopic therapies, which led to less adverse events (e.g., intraoperative bleeding, local infection, pleural effusion) than surgical operations (p<0.05). The superficial leiomyomas presented less adverse events and better recovery (p<0.05) than deep leiomyomas. CONCLUSION: Endoscopic ultrasonography has demonstrated high accuracy in the diagnosis of esophageal leiomyomas and provides great support in selecting treatments; however, EUS cannot completely avoid misdiagnosis, so combining it with other examinations may be a good strategy to solve this problem.

Association between serum α-L-fucosidase and non-alcoholic fatty liver disease: Cross-sectional study.

AIM: To explore the association between serum α-L-fucosidase (AFU) and non-alcoholic fatty liver disease (NAFLD). METHODS: A total of 16473 individuals (9456 men and 7017 women) were included in the current study, who presented for a health examination at the First Affiliated Hospital of Zhejiang University School of Medicine in 2014. The baseline characteristics of the cohort were compared by NAFLD status. Linear regression analysis and stepwise multiple regression analysis were applied to assess the risk factors for NAFLD. Receiver operating characteristic curve was used to determine the sensitivity and specificity of AFU in the diagnosis of NAFLD. RESULTS: The prevalence rates of NAFLD and metabolic syndrome (MetS) were 38.0% and 25.4%, respectively. The NAFLD group had significantly higher AFU levels than the non-NAFLD group (28.7 ± 7.9 U/L vs 26.0 ± 7.3 U/L, P < 0.001) and the prevalence rate of NAFLD increased with progressively higher serum AFU levels. AFU was positively correlated with MetS and its five components: central obesity, hypertriglyceridemia, low high-density lipoprotein cholesterol, and elevated blood pressure and fasting glucose. Stepwise multiple logistic regression analysis showed that AFU was associated with an increased risk of NAFLD (OR = 1.009, 95%CI: 1.003-1.014, P < 0.001). The best cut-off value of AFU for the diagnosis of NAFLD was 27.5 U/L. The area under the curve (diagnostic efficacy index) was 0.606. The sensitivity and specificity were 54.6% and 61.8%, respectively. CONCLUSION: AFU level is significantly associated with NAFLD, and elevated AFU level is an independent risk factor for NAFLD.

Is gallstone disease associated with inflammatory bowel diseases? A meta-analysis.

OBJECTIVE: To investigate the association between inflammatory bowel disease (IBD) and gallstone disease (GD) by performing a meta-analysis. METHODS: PubMed, Medline, Embase, Web of Science and the Cochrane Library were searched for relevant articles published between January 1980 and February 2015. All statistical analyses were performed using STATA 12.0. A fixed-effects model was adopted; heterogeneity was evaluated by χ(2) test and I(2) statistic; publication bias was assessed by Begg's and Egger's tests. RESULTS: Five studies qualified for inclusion in the meta-analysis. Patients with IBD had a significantly higher prevalence of GD than those in the control group [odds ratio (OR) 1.72, 95% confidence interval (CI) 1.40-2.12, P < 0.0001]. Subgroup analyses showed a significantly higher prevalence of GD in patients with Crohn's disease (CD) (OR 2.05, 95% CI 1.61-2.63, P < 0.0001). However, no significant difference in the prevalence of GD was observed between patients with ulcerative colitis (UC) and controls (OR 1.12, 95% CI 0.75-1.68, P = 0.585). Studies from Italy, Sweden and the UK revealed a higher prevalence of GD in patients with IBD. No heterogeneity (I(2) = 25.2%, P = 0.228) or publication bias was observed in our meta-analysis (Begg's test, P = 0.711; Egger's test, P = 0.805). CONCLUSIONS: Our meta-analysis suggests there is a trend towards higher prevalence of GD in IBD patients, and especially in patients with CD. More rigorous, large-scale multi-center studies are required to investigate the association between GD and IBD.

Screening for pancreatic cancer in familial high-risk individuals: A systematic review.

AIM: To analyze the benefits and harms of pancreatic cancer screening in familial high-risk individuals (HRIs). METHODS: Studies were identified by searching PubMed, EBSCO, ClinicalTrials.gov and the Cochrane database from database inception to June 2014. We also obtained papers from the reference lists of pertinent studies and systematic reviews. English-language trials and observational studies were searched. The key words used as search terms were "screening" and "surveillance". Cost-effectiveness, diagnostic rate, survival rate, mortality and adverse events were the outcomes of interest. Age, sex, lifestyle and other confounding factors were also considered. However, anticipating only a few of these studies, we also included observational studies with or without control groups. We also included studies concerning the anxiety associated with pancreatic cancer risk and other psychological changes in familial HRIs. We extracted details on study design, objectives, population characteristics, inclusion criteria, year of enrollment, method of screening, adjusted and unadjusted mortality, cost-effectiveness and adverse events from the included studies. Studies were assessed using the Reporting of Observational studies in Epidemiology (STROBE) checklist. RESULTS: Sixteen studies on pancreatic cancer screening were included. Five studies included control groups, nine were observational studies without control groups, and the other two studies investigated the worry associated with pancreatic cancer risk. We found that pancreatic cancer screening resulted in a high curative resection rate (60% vs 25%, P = 0.011), longer median survival time (14.5 mo vs 4 mo, P < 0.001), and higher 3-year survival rate (20% vs 15.0%, P = 0.624). We also found that familial HRIs had a higher diagnostic rate of pancreatic tumors than controls (34% vs 7.2%, P < 0.001). In patients who underwent regular physical examinations, more stage I pancreatic cancers were observed (19% vs 2.6%, P = 0.001). In addition, endoscopic ultrasonography, which was the main means of detection, diagnosed 64.3% of pancreatic cancers. In comparison, endoscopic retrograde cannulation of the pancreas, magnetic resonance imaging, and computed tomography diagnosed 28.6%, 42.9%, and 21.4%, respectively. For mass lesions, instant surgery was recommended because of the beneficial effects of post-operative chemotherapy. However, in patients with intraductal papillary mucinous neoplasms, we did not find a significant difference in outcome between surgery and follow-up without treatment. Moreover, pancreatic cancer screening in familial HRIs had a greater perceived risk of pancreatic cancer (P < 0.0001), higher levels of anxiety regarding pancreatic cancer (P < 0.0001), and increased economic burden. CONCLUSION: Pancreatic cancer screening in familial HRIs is associated with a higher detection rate and longer survival, although screening may influence psychological function and increase the economic burden.

PDIA3 Knockdown Exacerbates Free Fatty Acid-Induced Hepatocyte Steatosis and Apoptosis.

Nonalcoholic fatty liver disease (NAFLD) has emerged as one of the most common chronic liver disease over the past decades. Endoplasmic reticulum stress (ERS) plays a pivotal role during the development of NAFLD. This study aims to analyze the potential role of protein disulfide isomerase A3 precursor (PDIA3), one of the ER chaperones, in free fatty acid-induced cell model of NAFLD. Human liver L02 cell line was treated with sodium palmitate for 24 hours, which developed severe intracellular lipid accumulation. The increased protein level of PDIA3 was detected via immunoblotting analysis in the fat loaded cell models of NAFLD. siRNA-mediated knockdown of PDIA3 in L02 cells not only increased the cellular lipid accumulation, but also exacerbated hepatocytes apoptosis induced by sodium palmitate. Further investigation revealed that knockdown of PDIA3 up-regulated protein expression of fatty acid synthase (FAS), a key enzyme involved in fatty acid synthesis. PDIA3 knockdown also up-regulated key molecules of ERS pathway, including glucose-regulated protein 78 (GRP78), phospho-PKR-like ER kinase (p-PERK), and C/EBP homologous protein (CHOP). Our results suggested that ER chaperone PDIA3 plays a pivotal role in FFA-induced hepatocyte steatosis and apoptosis.

Association between polymorphism of dopamine D2 receptor genes and therapeutic effect of domperidone in functional dyspepsia.

BACKGROUND/AIMS: Functional dyspepsia (FD) is a common gastrointestinal disease, for which domperidone is one of the most commonly used drugs. This study aimed to investigate the potential causes of the varying therapeutic effects of domperidone among FD patients. MATERIALS AND METHODS: The effects of domperidone therapy in patients with FD were evaluated using a clinical symptom score combined with real-time ultrasonography examination of antral motor index. Single nucleotide polymorphism (SNP) of the dopamine D2 receptor genes 141C Ins/Del, A-241G, and TaqI, were analyzed by ligase detection reaction. RESULTS: The results of real-time ultrasonography correlated with clinical symptom scores. Single nucleotide polymorphism analysis of dopamine D2 receptor TaqI gene showed that the genotype frequencies of "C/C", "C/T", and "T/T" in the effective group were 51.35%, 31.08%, and 17.57%, respectively; the allele frequencies were 66.89% and 33.11%. In the ineffective group, the genotype frequencies of "C/C", "C/T", and "T/T" were 17.81%, 52.05%, and 30.14%, respectively; and the allele frequencies were 43.84% and 56.16%. The difference was statistically different between the two groups (p<0.01). CONCLUSION: Clinical symptom scores combined with real-time ultrasonography is effective in evaluating the therapeutic effect of domperidone in patients with functional dyspepsia. The therapeutic effect of domperidone in these patients was associated with polymorphism of dopamine D2 receptor TaqI gene.

Association between serum alpha-fetoprotein levels and fatty liver disease: a cross-sectional study.

AIM: To investigate the association between serum alpha-fetoprotein (AFP) levels and fatty liver disease (FLD) in a Chinese population. METHODS: A cross-sectional study was performed among subjects who presented for a health examination at the First Affiliated Hospital, College of Medicine, Zhejiang University in 2013. FLD was diagnosed based on an ultrasonography examination. Serum AFP levels were measured with a chemiluminescence immunoassay. RESULTS: Of the 9800 subjects enrolled, 2601 were diagnosed with FLD. Subjects with FLD had higher serum AFP levels than those without the disease. Subjects with high serum AFP levels had a higher prevalence of FLD, metabolic syndrome, and its components. Univariate logistic analysis showed that elevated serum AFP levels were associated with an increased risk of FLD (OR = 1.057, 95%CI: 1.031-1.084). However, after adjusting for covariates, AFP no longer remained significantly associated with the risk factors for FLD. CONCLUSION: Our results suggest that serum AFP levels are significantly associated with FLD and that AFP acts as a cofactor, but not as an independent factor, for FLD.