Inadequate gastric preparation and its associated factors for magnetically controlled capsule endoscopy.

Goals: To explore factors associated with inadequate gastric preparation for MCE. Background: Factors associated with inadequate gastric preparation for magnetically controlled capsule endoscopy (MCE) remains unclear. Study: Data of patients who underwent MCE from June 2021 to July 2022 were prospectively collected. The gastric cleanliness score (GCS) of the six stomach regions (gastric cardia, fundus, body, angulus, antrum, and pylorus) was recorded. Patients with GCS score ≥18 were defined as the adequate preparation. Factors related to inadequate gastric preparation were analyzed using a logistic regression model with estimated odds ratios (OR). Results: The mean GCS score of 211 patients was 17.01 ± 2.82. In the multivariable analysis, proton pump inhibitor (PPI) use (OR 3.57; 95% CI 1.69-7.95; p < 0.01) and premedication time after administering simethicone <30 min (OR 2.86; 95% CI 1.10-7.39; p = 0.03) were independent risk factors for inadequate gastric preparation. Comparing the gastric cleanliness of different locations, the median GCS of the lower stomach [10.00, IQR (9.50, 11.00)] was significantly higher than that of the upper stomach [7.00, IQR (6.00, 8.00)] (p <0.001). Conclusion: PPI use and inadequate premedication time (<30 min) may reduce the quality of gastric preparation for MCE. The type, dose, duration of medication, and discontinuation time of PPIs was well worth further exploration. Appropriate control of the type and time of premedication may be the key to improving overall gastric cleanliness.

Screening for upper gastrointestinal cancers with magnetically controlled capsule gastroscopy: a feasibility study.

BACKGROUND: The medical consortium is an intensive and disease-specific association that integrates tertiary public hospitals and medical examination centers in China. We aimed to evaluate the feasibility of the medical consortium for screening upper gastrointestinal (GI) cancers (MCSC) by magnetically controlled capsule gastroscopy (MCCG). METHODS: 6627 asymptomatic subjects underwent MCCG as part of health check-ups in the MCSC between March and November 2018. Relevant clinical data were collected and analyzed. RESULTS: The MCSC detected 32 patients with upper GI cancer (0.48 %) confirmed by pathology. The detection rate of early gastric cancer was 16.67 % (4 /24). Gastric polyps, ulcers, and submucosal tumors were found in 15.54 %, 3.76 %, and 3.17 % of subjects, respectively. The whole GI preparation and operation process were well tolerated. CONCLUSIONS: The MCSC was a feasible model for upper GI cancer screening, especially for asymptomatic subjects. Further prospective studies with better operational quality control are warranted.

Colonic mucosal N-methyl-D-aspartate receptor mediated visceral hypersensitivity in a mouse model of irritable bowel syndrome.

OBJECTIVE: The aim of this study was to investigate whether colonic mucosal N-methyl-D-aspartate receptor (NMDAR) participates in visceral hypersensitivity in irritable bowel syndrome (IBS). METHODS: C57BL/6 mice were administered intrarectally with trinitrobenzenesulfonic acid (TNBS) for the establishment of an IBS-like visceral hypersensitivity model. Those received an equivalent volume of 50% ethanol were regarded as the controls. Abdominal withdrawal reflex (AWR) scores in response to colorectal distention (CRD) were used to assess visceral sensitivity. NMDAR levels in the colonic mucosa were detected by both immunohistochemistry and Western blot. The concentrations of glutamate and ammonia in the feces of the mice were measured. Changes in visceral sensitivity after the intracolonic administration of ammonia or NMDAR antagonist were recorded. RESULTS: The established IBS-like mouse model of visceral hypersensitivity showed no evident inflammation in the colon. NMDAR levels in the colonic mucosa of the IBS-like mice were significantly higher compared with the controls, and were positively associated with AWR scores. The glutamate level in the feces of the TNBS-treated mice was similar to that of the controls, although the ammonia level was significantly higher. Intracolonic administration of ammonia induced visceral hypersensitivity in mice, which was repressed by pretreatment with NMDAR antagonist MK801. CONCLUSIONS: Overexpressed NMDAR in the colonic mucosa may participate in the pathogenesis of visceral hypersensitivity in IBS. Our study identifies the effect of ammonia in the colonic lumen on NMDAR in the colonic mucosa as a potential novel targeted mechanism for IBS treatment.

BDNF contributes to IBS-like colonic hypersensitivity via activating the enteroglia-nerve unit.

The over-expressed colonic brain-derived neurotrophic factor (BDNF) has been reported to be associated with abdominal pain in patients with irritable bowel syndrome (IBS). However, the neuropathological mechanism is unclear. We here investigated the involvement of enteroglial cells (EGCs) and enteric nerves in IBS-like visceral hypersensitivity. We showed that glial fibrillary acidic protein (GFAP), tyrosine receptor kinase B (TrkB) and substance P (SP) were significantly increased in the colonic mucosa of IBS patients. The upregulation of those proteins was also observed in the colon of mice with visceral hypersensitivity, but not in the colon of BDNF(+/-) mice. Functionally, TrkB or EGC inhibitors, or BDNF knockdown significantly suppressed visceral hypersensitivity in mice. Using the EGC cell line, we found that recombinant human BDNF (r-HuBDNF) could directly activate EGCs via the TrkB-phospholipase Cγ1 pathway, thereby inducing a significant upregulation of SP. Moreover, supernatants from r-HuBDNF-activated EGC culture medium, rather than r-HuBDNF alone, triggered markedly augmented discharges in isolated intestinal mesenteric afferent nerves. r-HuBDNF alone could cause mesenteric afferent mechanical hypersensitivity independently, and this effect was synergistically enhanced by activated EGCs. We conclude that EGC-enteric nerve unit may be involved in IBS-like visceral hypersensitivity, and this process is likely initiated by BDNF-TrkB pathway activation.

Increased production of BDNF in colonic epithelial cells induced by fecal supernatants from diarrheic IBS patients.

Colonic brain-derived neurotrophic factor (BDNF) plays an essential role in pathogenesis of abdominal pain in diarrhea-predominant irritable bowel syndrome (IBS-D), but regulation on its expression remains unclear. We investigated the role of fecal supernatants (FSN) from IBS-D patients on regulating BDNF expression in colonic epithelial cells of human and mice. Using human Caco-2 cells, we found that IBS-D FSN significantly increased BDNF mRNA and protein levels compared to control FSN, which were remarkably suppressed by the serine protease inhibitor. To further explore the potential mechanisms, we investigated the impact of protease-activated receptor-2 (PAR-2) on BDNF expression. We found a significant increase in PAR-2 expression in Caco-2 after IBS-D FSN stimulation. Knockdown of PAR-2 significantly inhibited IBS-D FSN-induced upregulation of BDNF. Moreover, we found that phosphorylation of p38 MAPK, not NF-κB p65, contributed to PAR-2-mediated BDNF overexpression. To confirm these results, we intracolonically infused IBS-D or control FSN in mice and found that IBS-D FSN significantly elevated colonic BDNF and visceral hypersensitivity in mice, which were both suppressed by the inhibitor of serine protease or antagonist of PAR-2. Together, our data indicate that activation of PAR-2 signaling by IBS-D FSN promotes expression of colonic BDNF, thereby contributing to IBS-like visceral hypersensitivity.

Increased gap density predicts weakness of the epithelial barrier in vivo by confocal laser endomicroscopy in indomethacin-induced enteropathy.

BACKGROUND AND AIMS: The intestinal epithelial barrier plays an important role in the pathogenesis of non-steroidal anti-inflammatory drug-induced enteropathy, and its disruption is often associated with increased cell shedding. The purpose of this report is to observe the gap density in indomethacin-induced small intestinal damage by confocal laser endomicroscopy (CLE) and to investigate the mechanisms involved in this process and how mucosal protectants improve intestinal epithelial barrier dysfunction. CLE is expected to provide a new way for evaluating non-steroidal anti-inflammatory drugs-induced enteropathy in humans and assessing drug efficacy. METHODS: Using the new technique of CLE, we established a method to evaluate, in real time, intestinal damage after the administration of indomethacin in Wistar rats by investigating the gap density in the small intestine. The mucosal protectant teprenone and acid-suppressant rabeprazole were then given by gavage before and after the administration of indomethacin, and the mechanisms affecting the intestinal epithelial barrier were investigated. RESULTS: Using CLE, gaps could be clearly observed and easily distinguished from goblet cells. Gap density was increased after the administration of indomethacin. During this process, the expression of tumor necrosis factor-α, nuclear factor-κB, and caspase-3 was up-regulated and the expression of tight junctions was down-regulated, which led to the damage of the epithelial barrier. Teprenone and rabeprazole could intervene in this pathway and protect the integrity of the epithelial barrier. CONCLUSIONS: CLE can be objective, accurate, and real time in investigating gap density. Teprenone and rabeprazole can prevent indomethacin-induced intestinal lesions and protect the epithelial barrier by intervening in the tumor necrosis factor-α pathway. Gap density was expected to be an indicator of evaluating intestinal inflammation and drug efficacy.

A school-based study with Rome III criteria on the prevalence of functional gastrointestinal disorders in Chinese college and university students.

BACKGROUND: Functional gastrointestinal disorders, including functional dyspepsia, irritable bowel syndrome and functional constipation are very common worldwide. OBJECTIVE: This research aims to estimate the prevalence and associated factors involved in functional gastrointestinal disorders in Chinese college and university students using the Rome III criteria. METHODS: A total of 5000 students from Shandong University in China were asked in January-May 2012 to complete questionnaires, including the Rome III questionnaire, hospital anxiety and depression scale, and negative life events scale. RESULTS: Based on the 4638 students who completed the questionnaire, the prevalence of functional dyspepsia, irritable bowel syndrome and functional constipation in college and university students of North China worked out to be 9.25%, 8.34% and 5.45% respectively. They were more frequent in female students. The factors of anxiety (OR 1.07; 95% CI 0.99 to 1.16, P=0.002<0.05) and depression (OR 0.55; 95% CI 0.15 to 1.05, P=0.045<0.05) indicated a high risk of causing irritable bowel syndrome. CONCLUSION: Functional dyspepsia, irritable bowel syndrome and functional constipation were common in college and university students of North China. Psychological disorders such as anxiety and depression provide significant risk factors for irritable bowel syndrome patients.

Brain-derived neurotrophic factor enhances the contraction of intestinal muscle strips induced by SP and CGRP in mice.

BACKGROUND AND AIMS: Brain-derived neurotrophic factor (BDNF) has been found in the intestinal tract of a variety of species. Its effects on visceral hyperalgesia have been examined to some degree, but limited studies have focused on gut motility. The aim of the present study was to investigate the effects of BDNF on gut motility of mice. METHODS: Longitudinal muscle (LM) strips were prepared from mice ileum and distal colon. The motility of gut was evaluated by the contraction of LM strips, which was recorded by a polyphisograph in vitro. Firstly, the roles of substance P (SP), calcitonin gene-related peptide (CGRP), and acetylcholine (ACh) on the contraction of LM strips were clarified. Then the exogenous BDNF was administered, and the alterations of SP/CGRP/ACh-induced contractions of the muscle strips were explored. Finally, heterozygous BDNF(+/-) mice and antibody of TrkB were introduced to investigate the role of endogenous BDNF on the SP/CGRP/ACh-induced gut motility. KEY RESULTS: SP (10(-8)-10(-6) mol L(-1)), CGRP (10(-8)-10(-7) mol L(-1)) and ACh (10(-8)-10(-6) mol L(-1)) dose-dependently caused the contraction of LM strips from ileum and distal colon, while the excitatory effect of CGRP was preceded by a transient inhibition. But 10(-6) mol L(-1) CGRP inhibited the contraction of LM strips. Pretreatment with exogenous BDNF (10(-8) mol L(-1)) remarkably enhanced the contraction of LM strips induced by SP (10(-9)-10(-7) mol L(-1)) and CGRP (10(-8)-10(-9) mol L(-1)). However, exogenous BDNF couldn't affect the contraction induced by ACh (10(-9)-10(-7) mol L(-1)). The excitatory effects of SP (10(-8)-10(-6) mol L(-1)) and CGRP (10(-8)-10(-7) mol L(-1)) on the contractions of LM strips from ileum and distal colon were significantly attenuated in BDNF(+/-) mice compared with those in BDNF(+/+) mice, while no difference of the effects of ACh (10(-8)-10(-6) mol L(-1)) on LM strips was observed between BDNF(+/-) mice and BDNF(+/+) mice. The monoclonal antibody of TrkB (TrkB-Ab) dramatically attenuated the excitatory effects of SP and CGRP on the contractions of LM strips, without affecting the excitatory effects of ACh. CONCLUSIONS AND INFERENCES: These data clarified the excitatory effects of SP, ACh and bilateral effects of CGRP on gut motility of mice and confirmed an essential role of BDNF on accelerating gut motility by enhancing the excitatory effects of SP/CGRP.

Brain-derived neurotrophic factor contributes to abdominal pain in irritable bowel syndrome.

OBJECTIVE: Brain-derived neurotrophic factor (BDNF), a member of the neurotrophin family, may play a critical role in many chronic pain conditions. The possible involvement of BDNF in the altered gut sensation in patients with irritable bowel syndrome (IBS) was investigated in the present study. METHODS: Rectosigmoid biopsies were collected from 40 patients with IBS fulfilling the Rome II criteria and 21 healthy controls. Abdominal pain was quantified by a validated questionnaire. The presence of BDNF and nerve fibres in the mucosa was assessed by immunohistochemistry. The structure of mucosal nerve fibres was assessed by transmission electron microscopy. Mucosal BDNF release was measured by ELISA and correlated with abdominal pain scores. Animal studies using BDNF(+/-) mice were carried out to evaluate visceral sensitivity, mucosal nerve fibre density and ultrastructural changes. Alterations of visceral sensitivity and TrkB expression in dorsal root ganglia were examined in BDNF(+/+) mice following different doses of BDNF administration. RESULTS: Biopsies from patients with IBS revealed a significant upregulation of BDNF (p=0.003), as compared with controls. Total nerve fibres were also substantially increased in patients with IBS. Electron microscopy showed ultrastructural damage on the mucosal nerve fibres (eg, swollen mitochondria and nerve axons). Elevated BDNF release was significantly correlated with the abdominal pain scores. Meanwhile, abdominal withdrawal reflex scores to colorectal distension and mucosal protein gene product 9.5 immunoreactivity were significantly lowered in BDNF(+/-) than in BDNF(+/+) mice. Electron microscopy showed degenerative changes on the mucosal nerve fibres in BDNF(+/-) mice. Exogenous BDNF induced an obvious dose-dependent increase in TrkB expression in dorsal root ganglia and dose-dependent decrease in threshold pressure in BDNF(+/+) mice. CONCLUSIONS: The increased expression of BDNF in colonic mucosa, together with the structural alterations of mucosal innervation, may contribute to the visceral hyperalgesia in IBS.

[Characteristics of SRAP marker in detecting polymorphism of cucumber genome].

When SRAP (Sequence-Related Amplified Polymorphism) marker was used in constructing genetic map and analyzing QTL for high temperature resistance in cucumber (Cucumis sativus L.), it exhibited certain characteristics in detecting genomic polymorphism. When each forward primer was combined with different reverse primers, the number of primer combinations that produced polymorphism ranged from five to eight. When each reverse primer was in combination with different forward primers, the number of polymorphic primer combinations ranged from two to eleven. The reverse primers SA4 or EM6 produced identical polymorphic bands when combined with all the forward primers tested. These bands might be amplified by the reverse primers. The polymorphic bands amplified from OD3ME11 co-segregated in the F2 population. The utilization of these characteristics in our research was discussed.