Consensus on endoscopic anterior fundoplication with MUSE for gastroesophageal reflux disease / 中华消化杂志

Endoscopic anterior fundoplication with the MUSE is an endoscopic therapy that combines ultrasound and endoscopic anti-reflux technology for moderate to severe gastroesophageal reflux disease. Training and learning procedures are required to obtain qualifications for this endoscopic therapy before clinical operations. At present, there is limited high-quality evidence-based medical evidence on MUSE treatment, and lack of expert consensus or guidance for training and the standard of MUSE therapy procedure. This consensus is based on the published literature, and formulated by experts with MUSE clinical experience in China, to provide guidance for the training and clinical standard operation of this technique.

Progress in Research on Esophageal Motility Disorders / 胃肠病学

With the alterations of social operation and lifestyle, the clinical problems related to esophagus have increased and changed greatly. Due to the innovation and progression of high - resolution manometry and endoscopy techniques, as well as the achievements of basic research and clinical practice related to duodenal inflammation, intestinal microbiota, leaky gut syndrome and gut - brain interaction, the understanding of esophageal motility disorders has been gradually improved though more doubts have also been raised. This article reviewed the clinical manifestations, pathogenesis, diagnosis and treatment of primary esophageal motility disorders.

A New Beginning of the Understanding and Management of Gastroparesis / 胃肠病学

With the rapid progress of exploration of basic and clinical gastroenterology, the understanding of gut-brain axis, interaction of metabolism-neuroimmunity-intestinal microecology leading to gastrointestinal inflammation and regulatory mechanism of enteric nervous system had significantly changed the recognition of definition, clinical manifestation, diagnosis and management of gastroparesis. In this article, the implications of these changes for the clinical practice of gastroparesis were reviewed and prospected.

Interaction Between Circadian Rhythms and Gut-brain Axis / 胃肠病学

The gastrointestinal tract connect with brain by many methods, such as the vagus nerve, neuroactive monoamine neuromodulators, immune system, intestinal microbiota and microbial metabolites. Circadian rhythms are 24 hours patterns of behavior, such as light-dark cycle, hormones secretion, cell movement and so on. This article reviewed the interactions between circadian rhythms and gut-brain axis through gut motility, gut microbiota, immunity and colorectal cancer.

Experts' Opinion on Rational Use of Dopamine D / 胃肠病学

Gastrointestinal motility disorder is one of the key pathophysiological mechanisms of functional gastrointestinal disorders (FGIDs). The prokinetics, dopamine D

Stress Causes Dyspepsia via Macrophage-mediated Duodenal Inflammation / 胃肠病学

Background: Epidemiological evidence revealed that stress is the causative factor of dyspeptic symptoms. It has been documented that duodenal inflammation is one of the key mechanisms of dyspepsia, and macrophage is crucial for inflammation. Aims: To determine whether patients with functional dyspepsia (FD) comorbid psychological stress have duodenal inflammation. Furthermore, to identify whether macrophage is involved in the mechanisms of stress-related duodenal inflammation by using water avoidance stress (WAS)animal model. Methods: Duodenal inflammation was observed and compared between FD patients with psychological factors and asymptomatic healthy controls. WAS mouse model with 1 h stress daily for 10 days was used to evaluate the duodenal inflammation at different time points to describe its dynamic changes. The role of macrophage in the development of duodenal inflammation was determined in an interventional study, in which the resident macrophages were depleted by clodronate liposomes. In both clinical and animal studies, the severity of duodenal inflammation was assessed by HE staining and immunocyte counts, the macrophage infiltration was detected by immunohistochemistry, and the expression of inflammatory cytokines was detected by real-time PCR. Results: FD patients with psychological factors developed severe duodenal inflammation in comparison with the healthy controls (immunocytes/HPF: 138.91±7.13 vs. 81.44±23.60, P<0.000 1). At the same time, the expressions of proinflammatory cytokines (IL-1β, TNF-α, and IL-17A) were increased, while the expressions of anti-inflammatory cytokines (IL-10 and TGF-β) were decreased (all P<0.05). In WAS mouse model, a dynamic change in duodenal inflammation which peaked on day 5 was observed, and the changes of macrophage infiltrating in the duodenal tissue were consistent with the duodenal inflammation. Clodronate liposomes pretreatment could effectively deplete macrophages, protected the WAS mouse model against duodenal inflammation (immunocytes/HPF: 75.10±4.08 vs. 202.43±5.18, P<0.001), with a marked reduction of the expressions of proinflammatory cytokines (IL-1β, TNF-α, and IL-8), and a marked elevation of the expression of anti-inflammatory cytokine IL-10 (all P<0.05). Conclusions: Psychological stress may lead to dyspeptic symptoms via macrophage-mediated duodenal inflammation.

Vagal Transient Receptor Potential Ankyrin 1 Mediates Stress-exacerbated Visceral Mechanonociception After Antral Cold Exposure

BACKGROUND/AIMS: Abdominal pain can be evoked or exacerbated after gastrointestinal cold stimulation in some patients with diarrhea-predominant irritable bowel syndrome (IBS-D), indicating a low temperature-induced sensitization of visceral perception. We investigated the role of vagal transient receptor potential ankyrin 1 (TRPA1, a cold-sensing ion channel) in cold-aggravated visceral mechanonociception in a stress-induced IBS animal model. METHODS: TRPA1 expression was examined in antral biopsies of healthy controls and IBS-D patients. Abdominal symptoms were assessed before and after warm or cold water intake. The visceromotor response (VMR) to colorectal distention (CRD) following intra-antral infusion of cold saline was measured in animals undergoing sham or chronic water avoidance stress. TRPA1 expression, extracellular signal-regulated protein kinase 1/2 (ERK1/2) phosphorylation, and neuronal calcium influx in vagal afferents were assessed. RESULTS: Compared to healthy controls, IBS-D patients displayed elevated antral TRPA1 expression, which was associated with symptom scores after cold (4°C) water intake. Intra-antral infusion of cold saline increased VMR to CRD in naive rats, an effect dependent on vagal afferents. In stressed rats, this effect was greatly enhanced. Functional blockade and gene deletion of TRPA1 abolished the cold effect on visceral nociception. TRPA1 expression in vagal (but not spinal) afferents increased after stress. Moreover, the cold-induced, TRPA1-dependent ERK1/2 activation and calcium influx in nodose neurons were more robust in stressed rats. CONCLUSIONS: Stress-exaggerated visceral mechanonociception after antral cold exposure may involve up-regulation of TRPA1 expression and function on vagal afferents. Our findings reveal a novel mechanism for abnormal gastrointestinal cold sensing in IBS.

Advances in Study on Role of Psychological Factors in Ulcerative Colitis / 胃肠病学

Ulcerative colitis(UC)is a chronic non-specific inflammatory disease involving colon and rectum. The etiology and pathogenesis of UC are not yet fully defined. Multiple enteroscopy,and drug therapy such as steroid and immunosuppressant,can cause adverse effects on psychology in UC patients. It is found that psychological disorder is a risk factor of UC. It can affect the quality of life and social function of UC patients,reduce the treatment compliance,prolong the course of disease,and ultimately results in poor prognosis. This article reviewed the advances in study on role of psychological factors in UC.

IgG4-related Disease in Digestive System / 胃肠病学

Immunoglobulin G4-related disease (IgG4-RD) is an immune-mediated fibroinflammatory disorder which can occur in different organs.It is characterized by massive IgG4 + lymphocytes and plasma cells infiltration,which leads to visceral enlargement,thickening or tubercle formation,and tends to form mass lesions.Most of the patients with IgG4-RD are associated with elevated levels of serum and tissue IgG4.This article reviewed the pathogenesis,clinical manifestations,diagnosis,treatment and prognosis of IgG4-RD in digestive system.

Therapeutic effect of endoscopic anterior fundoplication by MUSETM in thirteen patients with gastroesophageal reflux disease / 中华消化杂志

Objective To evaluate the efficacy and safety of endoscopic anterior fundoplication by the MUSETM endoscopic stapling device in gastroesophageal reflux disease (GERD).Methods From March to November 2017,in the Department of Gastroenterology of Chinese PLA General Hospital in Beijing,The First People's Hospital Affiliated to Shanghai Jiao Tong University and Renji Hospital Affiliated to Shanghai Jiao Tong University School of Medicine,thirteen GERD patients who underwent the endoscopic anterior fundoplication by the MUSETM system were enrolled.The GERD health related quality of life questionnaire (GERD-HRQL) score,satisfaction of symptomatic control,questionnaire for gastroesophageal reflux disease (GERD-Q) score,the degree of esophagitis,condition of gastroesophageal flap valve,medicine administration and side effects were compared before and after the operation.Paired t test and Wilcoxon rank sum test were performed for statistical analysis.Results The total GERD-HRQL score decreased from 23 points (14 to 36 points) before operation when proton pump inhibitor (PPI) was stopped for seven days to 3 points (0 to 21 points) at three months after operation and 1 point (0 to 18 points) at six months after operation;and the differences were statistically significant (Z=-3.111 and -3.183,both P＜0.01).Among 13 patients,the GERD-HRQL score of 11 patients decreased over 50 ％ after operation.The heartburn score decreased from 21 points (13 to 29 points) before operation when PPI was stopped for seven days to 0 point (0 to 17 points) at three months after operation and 0 point (0 to 16 points) at six months after operation;and the differences were statistically significant (Z=-3.113 and -3.182,both P＜0.01).Among 13 patients,assessment of symptom control at three months after operation of seven patients were satisfactory,four patients were mostly satisfactory and two patients were unsatisfactory;assessment of symptom control at six months after operation of nine patients were satisfactory,four patients were mostly satisfactory;and the satisfaction rate were both higher than that before operation,and the differences were statistically significant (x2=16.235 and 25.159,both P＜0.01).The total GERD-Q score reduced from 13 points (8 to 17 points) before operation to 6 points (3 to 11 points) at three months after operation and 6 points (6 to 13 points) at six months after operation (Z=-3.192 and-3.066,both P＜0.01).DeMeester score decreased from 38.40 points (20.20 to 255.30 points) to 11.10 points (1.10 to 46.20 points) at six months after operation;and the percent of total time of esophageal pH＜4 reduced from 10％ (5％ to 75％) to 3％ (0 to 13％) at six months after operation;the difference was statistically significant (Z=-3.181 and-3.180,both P=0.001).There was no significant difference in esophageal motility changes before and after treatment (all P ＞ 0.05).The number of patients without esophagitis increased from three before treatment to eight after treatment.Additionally,the number of patients whose gastroesophageal flap valve was less than grade Ⅱ increased from three before operation to 11 at six months after operation.The patients were followed up for six months,among 13 patients,10 patients were completely deprived of PPI,one patient was reduced over 50％,and two patients were treated with less than 50％ reduction.All 13 patients had mild tolerable abdominal pain and sore throat within 48 hours after operation.No other adverse reactions were observed.Conclusion The endoscopic anterior fundoplication by the MUSETM is a safe and effective treatment for GERD.

Platelet Count/Spleen Diameter Ratio for Prediction of Esophageal Varices in Patients with HBV-related Cirrhosis: A Clinical Study / 胃肠病学

Background: Esophageal variceal bleeding is a clinical emergency and the major cause of death in patients with liver cirrhosis.Aims: To assess the value of platelet count (PC)/spleen diameter (SD) ratio in predicting the presence of esophageal varices (EV) in patients with HBV-related cirrhosis in China.Methods: A total of 91 consecutive HBV-related cirrhosis patients with EV from Aug.2013 to Dec.2015 at Renji Hospital (South Campus),School of Medicine,Shanghai Jiao Tong University were enrolled.Thirty-two HBV-related cirrhosis patients without EV were enrolled as controls.Upper gastrointestinal endoscopy,routine laboratory examinations and abdominal ultrasonography were performed and the related parameters were collected.Binary Logistic regression analysis was carried out to identify independent risk factors associated with EV.ROC curve was used to evaluate the predictive performance of PC/SD ratio for the presence of EV.Results: The PC/SD ratio was significantly lower in EV group than in non-EV group (538.2±327.0 vs.1 105.9±426.6,P=0.001).Binary Logistic regression analysis showed that the PC/SD ratio was independently associated with the presence of EV (OR=57.29,95％ CI: 15～214,P=0.000).In ROC curve analysis,the area under the curve (AUC) of PC/SD ratio in predicting the presence of EV was 0.853;the optimal cutoff value was 842,and the sensitivity,specificity,positive predictive value and negative predictive value were 85.7％,75.0％,90.7％,and 64.9％,respectively.Conclusions: PC/SD ratio can be used as a non-invasive tool for prediction of the presence of EV in patients with HBV-related cirrhosis.It may reduce the number of unnecessary endoscopy.

MicroRNA-129 Inhibits Gastric Cancer Cells Proliferation and Invasion by Targeting HMGA2 / 胃肠病学

Background:More and more evidences suggest that microRNA plays an important role in the development of gastric cancer (GC).Expression of miR-129 in GC tissues is found abnormal, however, the mechanism of miR-129 in cell proliferation and invasion is still undefined.Aims:To investigate the expression of miR-129 in GC tissue and GC cell lines and the mechanism of miR-129 in proliferation and invasion of SGC-7901 cells.Methods:Eighty-two GC tissues and corresponding paracancerous tissues were collected, human gastric epithelial cell line and different GC cell lines were cultured, qPCR was conducted to assess miR-129 expression.SGC-7901 cells were transfected with miR-129 mimic or miR-NC, and then were transfected with overexpressed HMGA2 plasmid.Colony formation assay was used to detect cell proliferation ability, and Transwell chamber was used to assess cell invasion ability.Pearson correlation analysis was used to analyze the correlation between miR-129 and HMGA2 mRNA expression.Luciferase assay was performed to determine the activity of luciferase.mRNA and protein expressions of miR-129, HMGA2 were determined by qPCR and Western blotting, respectively.Results:Compared with paracancerous tissues, expression of miR-129 was significantly decreased in GC tissues (P<0.05);when compared with human gastric epithelial cells, expression of miR-129 was significantly decreased in GC cell lines (P<0.05).Compared with miR-NC group, proliferation and invasion abilities of SGC-7901 cells were inhibited in miR-129 mimic group (P<0.05).HMGA2 mRNA expression in GC tissues was significantly upregulated (P<0.05), and was negatively correlated with miR-129 expression (r=-0.543 9, P<0.01).Luciferase activity in wild-type miR-129 mimic group was significantly lower than that in miR-NC group (P<0.05);mRNA and protein expressions of HMGA2 were decreased after transfection with miR-129 mimic (P<0.05).Compared with miR-129+vector group, proliferation and invasion of SGC-7901 cells were significantly increased in miR-129 mimic+HMGA2 group (P<0.05).Conclusions:The expression of miR-129 is decreased in GC tissue and cells;miR-129 inhibits SGC-7901 cells proliferation and invasion by negatively regulating HMGA2.

Integrative Psycho-gastrointestinal Thinking and Strategies in the Practice of Management of Inflammatory Bowel Disease / 胃肠病学

Treatment for inflammatory bowel disease (IBD)is becoming a great challenge in clinical practice. Currently,treatment strategies are focused on attenuation of intestinal inflammation and autoimmune reactivity as well as surgical therapy. However,these measures cannot prevent the progression of pathophysiological process in quite a number of patients. The understanding of brain-gut interaction in the pathogenesis of IBD has shed light on the treatment of this disease. This review article discussed the importance of integrative psycho-gastrointestinal thinking and strategies targeting on the intestinal inflammation-associated psychological factors,neuroimmune abnormalities,and intestinal microbiota in the management of IBD in clinical practice.

Integrative Psycho-gastrointestinal Thinking and Strategies in the Practice of Management of Inflammatory Bowel Disease / 胃肠病学

Treatment for inflammatory bowel disease (IBD)is becoming a great challenge in clinical practice. Currently,treatment strategies are focused on attenuation of intestinal inflammation and autoimmune reactivity as well as surgical therapy. However,these measures cannot prevent the progression of pathophysiological process in quite a number of patients. The understanding of brain-gut interaction in the pathogenesis of IBD has shed light on the treatment of this disease. This review article discussed the importance of integrative psycho-gastrointestinal thinking and strategies targeting on the intestinal inflammation-associated psychological factors,neuroimmune abnormalities,and intestinal microbiota in the management of IBD in clinical practice.

CNTNAP3 Copy Number Variation and its Significance in Crohn's Disease / 胃肠病学

DNA copy number variation is an important pathogenic factor of human diseases and might be involved in the pathogenesis and pathological process of inflammatory bowel disease (IBD).Aims: To investigate the copy number variation of CNTNAP3 gene and its significance in Crohn''s disease (CD).Methods: A total of 101 active CD patients admitted from Jul.2009 to Dec.2010 at Renji Hospital, School of Medicine, Shanghai Jiao Tong University were enrolled.Eighty healthy subjects were served as controls.Peripheral blood or intestinal mucosa samples of CD patients were collected, and the copy number variation of CNTNAP3 gene was screened and validated by array-based comparative genomic hybridization (aCGH, n=8) and real-time PCR (n=93);expression of CNTNAP3 encoding protein was determined by ELISA (n=55).Results: A large fragment copy number amplification was revealed by aCGH at chromosome 9p13 region (including CNTNAP3 gene) in untreated CD patients.Real-time PCR confirmed that the copy number of CNTNAP3 gene was amplified in peripheral blood of CD patients, especially steroid-naive patients as compared with the normal controls (208 616.4±126 984.7 and 233 453.3±113 520.8 vs.161 750.2 ±53 940.3, P0.05).Furthermore, the plasma CNTNAP3 level in CD patients with amplified copy number was not correlated with the simplified endoscopic score for CD (P>0.05).Conclusions: Copy number amplification of CNTNAP3 gene might be involved in the pathogenesis of CD in Chinese population.Glucocorticoid treatment and smoking might affect the copy number variation of CNTNAP3 gene.Plasma CNTNAP3 level cannot discriminate CD patients from healthy subjects.Conclusions of this study needs to be further demonstrated and discussed.

Interleukin-17 Promotes Activation of Human Hepatic Stellate Cells and Collagen Expression / 胃肠病学

Background:Activation of hepatic stellate cells( HSCs)plays a pivotal role in development of liver fibrosis. Interleukin-17(IL-17)is the most important effector of T helper 17(Th17)cells that causes inflammatory cell infiltration and tissue damage. Preliminary studies showed that the number of IL-17-positive cells in liver tissue was positively correlated with the severity of liver fibrosis in patients with chronic hepatitis B and autoimmune hepatitis. However,the mechanism of IL-17 in liver fibrosis is not yet clarified. Aims:To investigate the effect of IL-17 on activation of human HSC cell line LX2 and collagen expression. Methods:Human HSC cell line LX2 was treated with different concentrations of IL-17. Viability of LX2 cells was measured by CCK-8 assay. mRNA expressions of α-smooth muscle actin(α-SMA), type Ⅰ collagen(Col-Ⅰ)and Col-Ⅲ were determined by real-time PCR. Protein expressions of α-SMA、Col-Ⅰ and Col-Ⅲ were detected by immunofluorescence. Results: Viability of LX2 cells increased with the increase of IL-17 concentration,but no significant differences were seen between any two groups(P > 0. 05). mRNA expressions of α-SMA, Col-Ⅰ and Col-Ⅲ in IL-17 treatment group(100 ng/ mL)were significantly higher than those in blank control group(P <0. 05). With the increase of IL-17 concentration,protein expressions of α-SMA,Col-Ⅰ and Col-Ⅲ gradually increased. Conclusions:IL-17 can promote the activation of HSCs and expressions of Col-Ⅰ and Col-Ⅲ,thereby contributing to the development of liver fibrosis.

Percutaneous Transhepatic Variceal Embolization Combined with Partial Splenic Embolization for Treatment of Esophagogastric Variceal Bleeding in Patients with Liver Cirrhosis / 胃肠病学

Background:Esophagogastric variceal bleeding is a severe and commonly seen complication of portal hypertension in patients with liver cirrhosis. Prevention of rebleeding remains an important issue in the management of patients suffered from the disease. Aims:To evaluate the efficacy and safety of percutaneous transhepatic variceal embolization(PTVE) combined with partial splenic embolization(PSE)for treatment of esophagogastric variceal bleeding in patients with liver cirrhosis. Methods:Ten liver cirrhosis patients with esophagogastric variceal bleeding were prospectively selected and treated by PTVE combined with PSE. The blood flow of portal system was measured by Doppler ultrasonography pre- and post-operatively;meanwhile peripheral blood cells were counted. A 1-2-year follow-up was carried out and the rebleeding and procedure-related complications were recorded. Results:The postoperative inner diameter of main portal vein,as well as the blood flow velocity of main portal vein and splenic vein were significantly reduced as compared with those before operation(P < 0. 05). Three months after operation,the peripheral white blood cell and platelet were still significantly higher than those before operation(P < 0. 05). During 1-year follow-up,rebleeding appeared in 2 patients,one of them was found having main portal vein thrombosis developed,and was treated by endoscopic esophageal variceal ligation because the gastric varices was not as evident as ever. The rebleeding rate and incidence of portal system thrombosis after the PTVE-PSE procedure was 20. 0% and 10. 0%,respectively. Conclusions:PTVE combined with PSE seemed efficient for alleviating portal hypertension,and might be recommended as a safe and effective interventional therapy for liver cirrhosis patients with esophagogastric variceal bleeding.

Advances in Study on Intestinal Apical Sodium-dependent Bile Acid Transporter and Related Diseases / 胃肠病学

Bile acids play critical roles in the solubilization and absorption of lipids. The ileal apical sodium-dependent bile acid transporter( ASBT)located at the enterocyte brush border is responsible for the reuptake of bile acids and the maintenance of bile acid homeostasis. Recently,great success has been made in understanding the relationship between ASBT and intestinal inflammation,tumorigenesis,secretion,motility,sensation,gut microbiota,and gut-liver axis in addition to its expression regulation,which implicates ASBT as a contributor of some gastrointestinal diseases and a promising new therapeutic target for these diseases. In this review article,the advances in study on above-mentioned issues were summarized.

Value of Serum Pepsinogen Detection in Warning Gastric Cancer and Evaluating Gastric Mucosa Function / 胃肠病学

Serum pepsinogen(PG)is an effective marker for evaluating gastric mucosa function and can be used as a supplement for screening and early diagnosis of gastric cancer. Recently,serum PG has become a hot spot of study in portal hypertensive gastropathy and functional dyspepsia. Serum PG detection is a noninvasive,simple and low cost investigation method with marked clinical value. This article reviewed the value of serum PG detection in warning gastric cancer and evaluating gastric mucosa function.

Meta-analysis of the effect of flupentixol and melitracen combined with conventional medicine on irritable bowel syndrome / 中华消化杂志

Objective To evaluate the efficacy difference between flupentixol and melitracen combined with conventional medicine and conventional drug alone in the treatment of irritable bowel syndrome (IBS).Methods Studies on flupentixol and melitracen combined with conventional medicine (pinaverium bromide and trimebutine maleate) and conventional medicine alone in the treatment of IBS were collected and reviewed through searching the Chinese Academic Journals Full-text Database,Chinese VIP Full-text Database and PubMed database.After that,the test for homogeneity and the combined effect test were estimated. Results A total of 12 clinical studies on flupentixol and melitracen combined with conventional medicine for four to twelve weeks in the treatment of IBS were collected six studies indicated the homogeneity test of flupentixol and melitracen combined with pinaverium bromide (x2 =1.90,df=5,P=0.86,I2 =0).For the fixed-effect model,the odds ratio was 7.92 and 95％ CI was between 4.85 and 12.95,which suggested the combined therapy was better.The other six studies indicated the homogeneity test of flupentixol and melitracen combined with trimebutine maleate (x2 =5.60,df=5,P =0.35,I2 =10.6 ％).For the fixed-effect model,the odds ratio was 5.91 and 95％ CI was between 4.06 and 8.61,which suggested the combined therapy was better.After merging the 12 studies it indicated the homogeneity test of flupentixol and melitracen combined with conventional medicine (x2 =8.40,df =11,P =0.68,I2 =0).For the fixed effect model,the odds ratio was 6.63 and 95％ CI was between 4.92 and 8.93.Conclusion The efficacy of flupentixol and melitracen combined with conventional medicine in the treatment of IBS was better than that of conventional medicine alone,however,still more high quality trials are needed for further confirmation.