FGF15 promotes hepatic NPC1L1 degradation in lithogenic diet-fed mice.

BACKGROUND: Cholesterol gallstone disease (CGD) is accompanied by biliary cholesterol supersaturation. Hepatic Niemann-Pick C1-like 1 (NPC1L1), which is present in humans but not in wild-type (WT) mice, promotes hepatocyte cholesterol uptake and decreases biliary cholesterol supersaturation. In contrast, intestinal NPC1L1 promotes intestinal cholesterol absorption, increasing biliary cholesterol supersaturation. Ezetimibe (EZE) can inhibit both hepatic and intestinal NPC1L1. However, whether hepatic NPC1L1 can affect CGD progress remains unknown. METHODS: Mice expressing hepatic NPC1L1 (NPC1L1hepatic-OE mice) were generated using Adeno-associated viruses (AAV) gene delivery. The protein level and function of hepatic NPC1L1 were examined under chow diet, high fat-cholesterol diet (HFCD), and lithogenic diet (LD) feeding. Gallstone formation rates were examined with or without EZE treatment. Fibroblast growth factor 15 (FGF15) treatment and inhibition of fibroblast growth factor receptor 4 (FGFR4) were applied to verify the mechanism of hepatic NPC1L1 degradation. RESULTS: The HFCD-fed NPC1L1hepatic-OE mice retained the biliary cholesterol desaturation function of hepatic NPC1L1, whereas EZE treatment decreased biliary cholesterol saturation and did not cause CGD. The ubiquitination and degradation of hepatic NPC1L1 were discovered in LD-fed NPC1L1hepatic-OE mice. Treatment of FGF15 during HFCD feeding and inhibition of FGFR4 during LD feeding could affect the protein level and function of hepatic NPC1L1. CONCLUSIONS: LD induces the ubiquitination and degradation of hepatic NPC1L1 via the FGF15-FGFR4 pathway. EZE may act as an effective preventative agent for CGD.

Biliary microbiota and mucin 4 impact the calcification of cholesterol gallstones.

BACKGROUND: Cholesterol gallstones account for over 80% of gallstones, and the pathogenesis of gallstone formation involves genetic and environmental factors. However, data on the evolution of cholesterol gallstones with various densities are limited. This study aimed to determine the roles of microbiota and mucins on the formation of calcified cholesterol gallstones in patients with cholelithiasis. METHODS: Paired gallbladder tissues and bile specimens were obtained from cholelithiasis patients who were categorized into the isodense group and calcified group according to the density of gallstones. The relative abundance of microbiota in gallbladder tissues was detected. Immunohistochemistry and enzyme-linked immunosorbent assay were performed to detect the expression levels of MUC1, MUC2, MUC3a, MUC3b, MUC4, MUC5ac and MUC5b in gallbladder tissues and bile. The correlation of microbiota abundance with MUC4 expression was evaluated by linear regression. RESULTS: A total of 23 patients with gallbladder stones were included. The density of gallstones in the isodense group was significantly lower than that of the calcified group (34.20 ± 1.50 vs. 109.40 ± 3.84 HU, P < 0.0001). Compared to the isodense group, the calcified group showed a higher abundance of gram-positive bacteria at the fundus, in the body and neck of gallbladder tissues. The concentrations of MUC1, MUC2, MUC3a, MUC3b, MUC5ac and MUC5b in the epithelial cells of gallbladder tissues showed no difference between the two groups, while the concentrations of MUC4 were significantly higher in the calcified group than that in the isodense group at the fundus (15.49 ± 0.69 vs. 10.23 ± 0.54 ng/mL, P < 0.05), in the body (14.54 ± 0.94 vs. 11.87 ± 0.85 ng/mL, P < 0.05) as well as in the neck (14.77 ± 1.04 vs. 10.85 ± 0.72 ng/mL, P < 0.05) of gallbladder tissues. Moreover, the abundance of bacteria was positively correlated with the expression of MUC4 (r = 0.569, P < 0.05) in the calcified group. CONCLUSIONS: This study showed the potential clinical relevance among biliary microbiota, mucins and calcified gallstones in patients with gallstones. Gram-positive microbiota and MUC4 may be positively associated with the calcification of cholesterol gallstones.

Increased risk of herpes zoster infection in patients with inflammatory bowel disease: a meta-analysis of cohort studies.

Previous studies have shown increased risk of herpes zoster (HZ) infection in patients with inflammatory bowel disease (IBD). The aim of this study is to better characterize this possible association by conducting a meta-analysis. A comprehensive search of relevant literature until April 30, 2019, was performed. Data on HZ infection and medications in patients with IBD and controls were extracted. The relative risk (RR) and 95% confidence interval (CI) were calculated. Subgroup analyses were performed to assess the source of heterogeneity. Seven cohort studies were included that involved more than 1,000,000 participants. The RR of HZ infection in patients with Crohn's disease (CD) compared with non-CD patients was 1.74 (95% CI 1.57-1.92, p < 0.001). The pooled RR of HZ infection in patients with ulcerative colitis (UC) compared with non-UC was 1.40 (95% CI 1.31-1.50, p < 0.001). Subgroup analyses revealed that age, race, and publication year contribute to heterogeneity. We also found that steroid users were at increased risk of HZ in CD (OR = 1.78, 95% CI 1.10-2.88). Steroid users and anti-TNFα users were at increased risk of HZ in UC, with RRs of 1.99 (95% CI 1.64-2.42) and 2.29 (95% CI 1.52-3.45), respectively. Begg's test and Egger's test suggested no publication bias. There was a 74% increased risk of HZ infection in patients with CD and 40% increased risk of HZ infection in patients with UC compared with that in non-IBD. IBD patients with high risk of HZ infection may benefit from an HZ vaccine.

Nuclear Receptors in the Pathogenesis and Management of Inflammatory Bowel Disease.

Nuclear receptors (NRs) are ligand-dependent transcription factors that regulate the transcription of target genes. Previous epidemiological and genetic studies have documented the association of NRs with the risk of inflammatory bowel disease (IBD). Although the mechanisms of action of NRs in IBD have not been fully established, accumulating evidence has demonstrated that NRs play complicated roles in regulating intestinal immunity, mucosal barriers, and intestinal flora. As one of the first-line medications for the treatment of IBD, 5-aminosalicylic acid (5-ASA) activates peroxisome proliferator-activated receptor gamma (PPARγ) to attenuate colitis. The protective roles of rifaximin and rifampicin partly depend on promoting pregnane X receptor (PXR) expression. The aims of this review are to discuss the roles of several important NRs, such as PPARγ, PXR, vitamin D receptor (VDR), farnesoid X receptor (FXR), and RAR-related orphan receptor gammat (RORγt), in the pathogenesis of IBD and management strategies based on targeting these receptors.

Hepatitis C Virus Infection Is Positively Associated with Gallstones in Liver Cirrhosis.

AIM: To elucidate the prevalence and risk factors of gallstone disease (GD) among patients with liver disease and explore their association with the aetiology and severity of hepatic injury. METHODS: We analysed 4,832 subjects of hepatic injury induced by one of the following aetiologies: hepatitis B virus (HBV) infection, hepatitis C virus (HCV) infection, excessive alcohol consumption. The risk factors significantly associated with GD were analysed using stepwise logistic regression analysis, the influence of aetiology and severity of liver disease on the prevalence of GD were assessed by multiple logistic regression analysis adjusting for confounding factors. RESULTS: Three thousand forty eight patients were of positive HBV surface antigen alone with a prevalence of GD of 18.6%, 526 were tested as positive Anti-HCV alone with a prevalence of GD of 22.4%, and 1,258 were identified with excessive alcohol consumption patterns with a prevalence of GD of 13.5%. In each aetiological category, the prevalence of GD increased by age. Stepwise logistic regression analysis showed that age, female, low-density lipoprotein-cholesterol (LDL-Cho), family history of GD, HBV infection, HCV infection, chronic hepatitis and cirrhosis were independent factors associated with GD. After adjusting for age, LDL-Cho and family history of GD, the prevalence of gallstone disease was significantly associated with HCV-related cirrhosis in both genders, HBV-related cirrhosis in males and alcohol-related cirrhosis in females compared with patients with less severe liver disease [corrected]. After adjusting for gender, age, LDL-Cho and family history of GD, patients with HCV-related cirrhosis (OR 2.66, 95% CI 1.49-3.84) but not HBV-related cirrhosis (OR 1.52, 95% CI 0.73-1.82) were more likely to have GD compared with alcohol-related cirrhosis. CONCLUSION: HCV infection is positively associated with gallstone formation especially in those with cirrhosis patients.

Misdiagnosis of hemangioma of left triangular ligament of the liver as gastric submucosal stromal tumor: Two case reports.

BACKGROUND: Extragastric lesions are typically not misdiagnosed as gastric submucosal tumor (SMT). However, we encountered two rare cases where extrinsic lesions were misdiagnosed as gastric SMTs. CASE SUMMARY: We describe two cases of gastric SMT-like protrusions initially misdiagnosed as gastric SMTs by the abdominal contrast-enhanced computed tomography (CT) and endoscopic ultrasound (EUS). Based on the CT and EUS findings, the patients underwent gastroscopy; however, no tumor was identified after incising the gastric wall. Subsequent surgical exploration revealed no gastric lesions in both patients, but a mass was found in the left triangular ligament of the liver. The patients underwent laparoscopic tumor resection, and the postoperative diagnosis was hepatic hemangiomas. CONCLUSION: During EUS procedures, scanning across different layers and at varying degrees of gastric cavity distension, coupled with meticulous image analysis, has the potential to mitigate the likelihood of such misdiagnoses.

Endoscopic ultrasound-guided lauromacrogol injection for treatment of colorectal cavernous hemangioma: Two case reports.

BACKGROUND: Colorectal cavernous hemangioma is a rare vascular malformation resulting in recurrent lower gastrointestinal hemorrhage, and can be misinterpreted as colitis. Surgical resection is currently the mainstay of treatment, with an emphasis on sphincter preservation. CASE SUMMARY: We present details of two young patients with a history of persistent hematochezia diagnosed with colorectal cavernous hemangioma by endoscopic ultrasound (EUS). Cavernous hemangioma was relieved by several EUS-guided lauromacrogol injections and the patients achieved favorable clinical prognosis. CONCLUSION: Multiple sequential EUS-guided injections of lauromacrogol is a safe, effective, cost-efficient, and minimally invasive alternative for colorectal cavernous hemangioma.

Effect of hepatic NPC1L1 on cholesterol gallstone disease and its mechanism.

Cholesterol gallstone disease (CGD) is associated with bile cholesterol supersaturation. The Niemann-Pick C1-like 1 (NPC1L1), the inhibitory target of ezetimibe (EZE), is a critical sterol transporter of cholesterol absorption. Intestinal NPC1L1 facilitates the absorption of cholesterol, whereas hepatic NPC1L1 promotes cholesterol uptake by hepatocytes and reduces bile cholesterol supersaturation. The potential of hepatic NPC1L1 to prevent CGD has yet to be established due to its absence in the mice model. In this study, we generated mice expressing hepatic NPC1L1 using adeno-associated virus (AAV) gene delivery. The biliary cholesterol saturations and gallstone formations were explored under chow diet and lithogenic diet (LD) with or without EZE treatment. The long-term (8-week) LD-fed AAV-mNPC1L1 mice exhibited no significant differences in biliary cholesterol saturation and gallstone formation compared to WT mice. EZE effectively prevented CGD in both WT and AAV-mNPC1L1 mice. Mechanistically, prolonged LD feeding induced the degradation of hepatic NPC1L1, whereas short-term (2-week) LD feeding preserved the expression of hepatic NPC1L1. In conclusion, our findings suggest that hepatic NPC1L1 is unable to prevent CGD, whereas EZE functions as an efficient bile cholesterol desaturator during CGD development.

Esophageal bronchogenic cyst excised by endoscopic submucosal tunnel dissection: A case report.

BACKGROUND: Esophageal bronchogenic cyst (EBC) is a rare congenital disease that is difficult to diagnose preoperatively, and treatment remains controversial. CASE SUMMARY: We report a 53-year-old Chinese woman hospitalized in our hospital following the discovery of a submucosal protruding mass of the esophagus by upper endoscopy. A preliminary diagnosis of EBC was made by endoscopic ultrasonography (EUS), and treatment was accomplished by endoscopic submucosal tunnel dissection (ESTD). The pathological results verified the diagnosis. No scar changes or cystic lesion within the original lesion were found under EUS after a 3-mo follow-up. CONCLUSION: EUS is valuable for the preliminary diagnosis of EBC and surveillance. ESTD is a safe and effective treatment for EBC. Further evaluation of complications and long-term follow-ups are required.

Diagnosis and Treatment of Duodenal Gastrointestinal Stromal Tumors.

OBJECTIVES: The diagnostic value of different noninvasive diagnostic modalities and the endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) reliability of duodenal gastrointestinal stromal tumors (GISTs) are ambiguous in the present studies. METHODS: Patients with a histopathological diagnosis of the primary duodenal GISTs between the years 2008 and 2018 were analyzed. Data on the treatment and clinicopathological features were recorded. Furthermore, the computed tomography (CT)/magnetic resonance imaging (MRI), EUS, and EUS-FNA results were collected and compared. RESULTS: A total of 142 patients were enrolled into the study. In all patients, the most common symptom was gastrointestinal bleeding (44.4%), followed by abdominal pain and bloating (27.5%). Duodenal GISTs were mostly located in the second duodenal portion (52.1%), followed by the first portion (19.0%). EUS had significantly higher sensitivity and positive predictive values than CT or MRI (P = 0.047 and P = 0.005, respectively). The EUS-FNA sensitivity of duodenal GISTs was also significantly higher than the conventional endoscopic biopsy (73.3% vs 33.3%, P = 0.006). A total of 131 patients underwent surgery, including limited resection or pancreaticoduodenectomy. The tumor size and postoperative complication rates were higher in patients who underwent pancreaticoduodenectomy (P = 0.001 and P < 0.001, respectively). DISCUSSION: The diagnostic value of EUS is significantly higher than that of CT and MRI for duodenal GISTs. The EUS-FNA can provide a histological diagnosis of duodenal GISTs in most cases.

Ectopic pancreas in the ileum: An unusual condition and our experience.

BACKGROUND: Ectopic pancreas in the ileum, including lesions within Meckel diverticulum, can cause severe manifestations and complications; yet, it was seldom reported in English literature. AIM: This study aimed to raise awareness and provide information for better clinical management of this rare yet serious condition. METHODS: A total of 1713 cases of small bowel resection were performed in our hospital between 2009 and 2018, among which 10 cases of ileac ectopic pancreas were identified. A comprehensive retrospective review of the 10 cases was taken. RESULTS: Five lesions were located in the ileum wall and 5 were within Meckel diverticulum. Two lesions within Meckel diverticulum were incidental; the remaining 8 lesions were all associated with abdominal pain, gastrointestinal bleeding, and anemia. Of the 5 patients with lesions in the ileum wall, computed tomography uniformly revealed ileoileal intussusceptions with masses as lead points. Capsule endoscopies were performed in 6 cases, of which 3 showed positive findings. Double-balloon enteroscopy was conducted in one case and revealed an ileal diverticulum. Therapeutically, the offending bowel segments were removed, and intussusceptions were restored except for one case in which diverticulectomy was applied. No relapse or sequela was observed in the follow-up. CONCLUSIONS: Ileac ectopic pancreas can be seen in the ileum wall or Meckel diverticulum. The majority of the lesions found in clinical practice present with abdominal pain, gastrointestinal bleeding, and anemia. Lesions in the ileum wall often cause ileoileal intussusception. Computed tomography, capsule endoscopy, and double-balloon enteroscopy are helpful preoperative examinations. Segmental small bowel resection is the treatment of choice.

Quantitative Proteomic Analysis Reveals the Deregulation of Nicotinamide Adenine Dinucleotide Metabolism and CD38 in Inflammatory Bowel Disease.

Inflammatory bowel disease (IBD) has become a major health challenge worldwide. However, the precise etiological and pathophysiological factors involved in IBD remain unclear. Proteomics can be used for large-scale protein identification analysis. In the current study, using tandem mass tag- (TMT-) based shotgun proteomics, proteomic differences between intestinal tissue from health controls, patients with Crohn's disease (CD), and patients with ulcerative colitis (UC) were compared. Proteins with fold change >2 or <0.5 and P value < 0.05 between groups were considered differentially expressed. ProteinAtlas was used to analyze the tissue specificity of differentially expressed proteins (DEPs). Reactome pathway analysis was applied to cluster functional pathways. A total of 4786 proteins were identified, with 59 proteins showing higher levels and 43 showing lower levels in patients with IBD than in controls. Seventeen proteins, including angiotensin converting enzyme 2 (ACE2) and angiotensin converting enzyme 1 (ACE), showed higher levels in CD than in UC. Several novel proteins such as CD38, chitinase 3-like 1 (CHI3L1), olfactomedin 4 (OLFM4), and intelectin 1 were screened out between patients with IBD and controls. When proteins with fold change >1.2 or <0.84 and P value < 0.05 between groups were considered differentially expressed, the expression of 10 proteins, including CD38, involved in the nicotinamide adenine dinucleotide (NAD) metabolism and signaling pathway showed significant changes in IBD. Using the NCBI GEO database, we confirmed increased CD38 mRNA expression in patients with UC and in mouse colitis models. Protein CD38 expression was higher in CD and UC than in normal controls. CD38 expression was higher in inflamed tissues than in noninflamed tissues, and CD38 was located in F4/80-positive cells. Our study may provide novel insights into the molecular pathogenesis of IBD. Further studies are required on the role of NAD metabolism and CD38 in intestinal inflammation.

Effectiveness of mesalazine to treat irritable bowel syndrome: A meta-analysis.

AIM: Accumulating evidence has explored the effect of mesalazine on irritable bowel syndrome (IBS). However, these studies remain inconsistent. Thus, a meta-analysis was conducted to estimate the role of mesalazine on IBS. METHODS: PubMed, Medline, Embase, Web of Science, and the Cochrane Library Database were searched for all relevant randomized, controlled, blinded trials on mesalazine in patients with IBS between January 1980 and October 2018. All statistical analyses were performed using Revman 5.3 software. A fixed-effects model was adopted, 95% confidence intervals for SMD was calculated. Heterogeneity was evaluated by χ test and I statistic. RESULTS: Five studies involving 387 participants were finally included in this meta-analysis. The results showed that the SMD for clinical efficacy on abdominal pain in IBS patients treated with mesalazine in comparison to placebo was 0.19 (95% CI = -0.01 to 0.39, P = .06), which was statistically non-significant but clinically important. For beneficial effect of abdominal bloating, the SMD was 0.05 (95% CI = -0.20 to 0.30, P = .70), which was statistically non-significant. In regard to clinical efficacy on defecation frequency per day, the results revealed that the SMD was 0.29 (95% CI = -0.14 to 0.73, P = .18), which was statistically non-significant but clinically important. As for beneficial effect of general well-being, we found that the SMD was 0.41 (95% CI = -0.75 to 1.58, P = .49), which was statistically non-significant. With respect to stool consistency, the SMD was 0.01 (95% CI = -0.31 to 0.33, P = .96), which was statistically non-significant. For the effect of defecation urgency severity in IBS patients treated with mesalazine in comparison to placebo, we detected a surprising result with an SMD of 0.54 (95% CI = 0.05-1.04, P = .03), which was statistically significant. There was no significant difference between mesalazine group and placebo group on total mucosal immune cell counts of the patients with IBS with an SMD of -1.64 (95% CI = -6.17 to 2.89, P = .48) and there was also no significant difference in adverse reactions between two groups with an SMD of 1.05 (95% CI = 0.76-1.46 P = .77). CONCLUSION: Mesalazine is not superior to placebo in relieving clinical symptoms of abdominal pain, abdominal bloating, and general well-being of IBS and has no advantage of reducing defecation frequency per day and immune cell infiltration and improving stool consistency though without adverse reactions of mesalazine compared with placebo. For defecation urgency severity, placebo is even superior to mesalazine for IBS patients. Thus, mesalazine might be a cost burden to patients without providing good effectiveness. In view of the small sample size of the current study and the differences in every experimental designs, this study has high heterogeneity and requires subsequent verification.

Serum proteome profiles to differentiate Crohn disease from intestinal tuberculosis and primary intestinal lymphoma: A pilot study.

The differential diagnosis of Crohn disease (CD) from intestinal tuberculosis (ITB) and primary intestinal lymphoma (PIL) is challenging in patients who exhibit atypical clinical characteristics. The aim of the present study was to explore the serum proteome profiles of CD, PIL and ITB and to identify their differentiations.Treatment-naïve patients with CD (n = 10), PIL (n = 10) and ITB (n = 10) were enrolled in the present study. Differentially expressed proteins (DEPs) in patient serum samples were compared between groups using tandem mass tag labeled proteomic technology. A principal component analysis (PCA) plot and volcano maps were also visualized. Functional pathway analysis was performed using Reactome. The Area under the Curve (AUC) was calculated for each DEP.A total of 818 proteins were identified through proteomic quantification. Among them, 108 DEPs were identified to be differentiated between CD and ITB, 105 proteins between CD and PIL and 55 proteins between ITB and PIL. The proteome from the three groups was distinguishable in the PCA plot. The results revealed that 19, 12, and 10 proteins (AUC ≥ 0.95) were differentially expressed between CD and PIL, CD and ITB, and PIL and ITB, respectively. Among these DEPs, tumor necrosis factor ligand superfamily member 13 was higher in CD than in ITB and PIL. Peroxiredoxin-5, T-complex protein 1 subunit Gamma, CutA, and Fibulin-5 were increased in CD and PIL when compared with ITB. The levels of fibrinogen chains were also significantly higher in patients with PIL compared with CD.The current study demonstrated that serum proteome was distinguishable among patients with CD, PIL, and ITB. The identified proteins may assist in the clinical differentiation among them.

Tenascin-C Is Increased in Inflammatory Bowel Disease and Is Associated with response to Infliximab Therapy.

Tenascin-C (TNC) is an extracellular matrix glycoprotein expressed in response to inflammation and tissue damage. The role of TNC in patients with inflammatory bowel disease (IBD) is not well understood. In this study, we analyzed the expression of TNC in the inflamed mucosa of patients with ulcerative colitis (UC) and Crohn's disease (CD). Serum TNC levels were determined by the enzyme-linked immunosorbent assay (ELISA), and the levels of TNC in patients with different disease activities were compared. The expression of TNC was derived from a GEO dataset. THP-1 cells were stimulated with TNC to evaluate the proinflammatory role of TNC. We found higher TNC expression in the inflamed mucosa of patients with UC and CD compared with normal controls (NCs). TNC was mainly expressed in the stromal area of the intestinal mucosa. The median serum levels of TNC were significantly higher in UC (median 74.1 ng/ml, range 42.6-102.1 ng/ml) and CD (median 59.2 ng/ml, range 44.0-80.9 ng/ml). We also found that serum TNC levels were correlated with Mayo scores in UC and Crohn's disease activity index (CDAI) in CD. Through GSE14580, we demonstrated that patients who were nonresponsive to infliximab treatment had higher mucosal TNC mRNA expression. High TNC mRNA expression in the inflamed intestinal mucosa was associated with poor response to infliximab therapy in patients with UC. Furthermore, THP-1 cells stimulated with TNC showed increased expression of IL-6, but not TNF-α, IL-8, MCP-1, or IL-1ß. Thus, increased TNC levels may participate in the pathogenesis of IBD and may serve as a biomarker for disease activity and response to treatment with infliximab.

Correction: Exploration of Serum Proteomic Profiling and Diagnostic Model That Differentiate Crohn's Disease and Intestinal Tuberculosis.

[This corrects the article DOI: 10.1371/journal.pone.0167109.].

Association between Helicobacter pylori infection and nonalcoholic fatty liver disease: a systemic review and meta-analysis.

Although clinical studies have shown possible links of Helicobacter pylori infection with the development of nonalcoholic fatty liver disease (NAFLD), the results remain controversial. The aim of this meta-analysis is to investigate the association between H. pylori infection and NAFLD. A comprehensive search of relevant studies was performed up to November 2018. Data on H. pylori infection in NAFLD patients and controls were extracted. Odds ratio (OR) and 95% confidence interval (CI) were calculated using a random-effects model. Twelve studies involving 27 400 NAFLD patients and 60 347 controls were included. The pooled overall OR of H. pylori infection in NAFLD patients compared with controls was 1.36 (95% CI: 1.22-1.53, I=89.6%, P=0.000). Meta-regression and subgroup analysis showed that the sample size and the case-control ratio may have accounted for some of the heterogeneity. When stratified by publication year, the diagnostic method used for H. pylori, and Newcastle-Ottawa Scale scores, the OR remained significant. However, possible publication bias was observed. Of the 12 studies, six had carried out multivariable analysis after adjusting for potential confounders. The pooled results from these studies still indicated a higher risk of NAFLD in patients infected with H. pylori (OR=1.17, 95% CI: 1.01-1.36, I=72.4%, P=0.003). There is a 36% increased risk of NAFLD in patients with H. pylori infection. Further studies are warranted to investigate whether eradication of H. pylori is useful in the prevention and treatment of NAFLD.

Exploration of Serum Proteomic Profiling and Diagnostic Model That Differentiate Crohn's Disease and Intestinal Tuberculosis.

AIM: To explore the diagnostic models of Crohn's disease (CD), Intestinal tuberculosis (ITB) and the differential diagnostic model between CD and ITB by analyzing serum proteome profiles. METHODS: Serum proteome profiles from 30 CD patients, 21 ITB patients and 30 healthy controls (HCs) were analyzed by using weak cationic magnetic beads combined with MALDI-TOF-MS technique to detect the differentially expressed proteins of serum samples. Three groups were made and compared accordingly: group of CD patients and HCs, group of ITB patients and HCs, group of CD patients and ITB patients. Wilcoxon rank sum test was used to screen the ten most differentiated protein peaks (P < 0.05). Genetic algorithm combining with support vector machine (SVM) was utilized to establish the optimal diagnostic models for CD, ITB and the optimal differential diagnostic model between CD and ITB. The predictive effects of these models were evaluated by Leave one out (LOO) cross validation method. RESULTS: There were 236 protein peaks differently expressed between group of CD patients and HCs, 305 protein peaks differently expressed between group of ITB patients and HCs, 332 protein peaks differently expressed between group of CD patients and ITB patients. Ten most differentially expressed peaks were screened out between three groups respectively (P < 0.05) to establish diagnostic models and differential diagnostic model. A diagnostic model comprising of four protein peaks (M/Z 4964, 3029, 2833, 2900) can well distinguish CD patients and HCs, with a specificity and sensitivity of 96.7% and 96.7% respectively. A diagnostic model comprising four protein peaks (M/Z 3030, 2105, 2545, 4210) can well distinguish ITB patients and HCs, with a specificity and sensitivity of 93.3% and 95.2% respectively. A differential diagnostic model comprising three potential biomarkers protein peaks (M/Z 4267, 4223, 1541) can well distinguish CD patients and ITB patients, with a specificity and sensitivity of 76.2% and 80.0% respectively. Among the eleven protein peaks from the diagnostic models and differential diagnostic model, two have been successfully purified and identified, Those two peaks were M/Z 2900 from the diagnostic model between CD and HCs and M/Z 1541 from the differential diagnostic model between CD and ITB. M/Z 2900 was identified as appetite peptide, M/Z 1541 was identified as Lysyl oxidase-like 2 (LOXL-2). CONCLUSION: The differently expressed protein peaks analyzed by serum proteome with weak cationic magnetic beads combined MALDI-TOF-MS technique can effectively distinguish CD patients and HCs, ITB patients and HCs, CD patients and ITB patients. The diagnostic model between CD patients and HCs consisting of four protein peaks (M/Z 4964, 3029, 2833, 2900), the diagnostic model between ITB patients and HCs comprising four protein peaks (M/Z 3030, 2105, 2545, 4210) and the differential diagnostic model between CD patients and ITB patients comprising three protein peaks (M/Z 4267, 4223, 1541) had high specificity and sensitivity and can contribute to diagnoses of CD, ITB and the differential diagnosis between CD and ITB. Two proteins from the diagnostic model of CD and the differential diagnostic model between CD and ITB were identified. Further experiments are required using a larger cohort of samples.