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The aim of this study was to explore the pathogenesis of chronic cough caused by non-acid reflux. Seven patients with chronic cough due to non-acid reflux, 12 patients with chronic cough due to acid reflux, 10 patients with gastro-oesophageal reflux disease without cough and 12 healthy volunteers were recruited for the study. All subjects underwent oesophageal multi-channel intraluminal impedance measurements combined with pH monitoring, and assessment of cough reflex sensitivity to capsaicin and induced sputum cytology. The concentrations of substance P, mast cell tryptase, prostaglandin D2 and histamine in induced sputum were measured by ELISA. Cough threshold C2 and C5 did not differ between patients with chronic cough due to non-acid or acid reflux, but the values were significantly lower than those for patients with gastro-oesophageal reflux disease without cough and healthy volunteers. Weakly acidic reflux episodes were obviously more frequent in patients with chronic cough due to non-acid reflux than in the other three groups. Sputum substance P and mast cell tryptase concentrations were remarkably increased in patients with chronic cough, but were similar for those with cough due to non-acid or acid reflux. There were significant inverse correlations between substance P levels and cough threshold C2 or C5 in patients with cough due to non-acid or acid reflux, and between mast cell tryptase levels and cough threshold C2 in patients with cough due to acid reflux. Chronic cough due to non-acid reflux may be related to cough reflex hypersensitivity caused by neurogenic airway inflammation and mast cell activation, in which weakly acidic reflux is possibly a major factor. Chronic cough due to non-acid reflux may be related to cough reflex hypersensitivity caused by neurogenic airway inflammation and mast cell activation, in which weakly acidic reflux is possibly a major factor. [ABSTRACT FROM AUTHOR]

Ten–eleven translocation 3 (TET3) participates in tumorigenesis and malignant transformation by mediating DNA demethylation and specific gene activation in malignances. This study aims to elucidate its molecular function and regulatory mechanism in esophageal squamous cell carcinoma (ESCC). Stable ESCC cells that infected with TET3 overexpression (OE) and knockdown lentiviral vector had been established. The biological behaviors and molecular mechanism of TET3 were demonstrated by cell biology experiments in vitro and in vivo. Tissues from patients with ESCC were used to demonstrate the clinical value of TET3. Our findings revealed that TET3 is highly expressed in ESCC tissues and related to poor prognosis of patients with ESCC. OE of TET3 presented a significant effect on proliferation, metastatic potential, and spheroid formation of ESCC cells by activating the PI3K/AKT/ GSK3β/β-catenin axis. Knockdown of TET3 could remarkably reverse these malignant phenotypes. Patients with ESCC with high TET3 expression resulted in a shorter overall survival (OS) and disease-free survival. Based on the multivariate analysis, TET3 could be an independent favorable factor for predicting OS and recurrence. The high expression of TET3 not only aggravates malignant behaviors in vitro and in vivo but also becomes a novel biomarker for clinical monitoring and individualized precision treatment for patients with ESCC. [ABSTRACT FROM AUTHOR]

Background & Aims: There is still considerable controversy surrounding the relationship between fatigue of endoscopists and the quality of colonoscopy. The aim of this study is to comprehensively explore the association between fatigue and adenoma detection rate (ADR) and cecal intubation rate (CIR). Methods: The mixed effects logistic regression model was used to explore the relationship between fatiguerelated factors including procedure order, session of procedures and the day of week and ADR as well as CIR. Results: When controlling for confounders, the day of week (Monday as reference, Friday, p=0.022; weekends, p=0.015) and session of procedures (P<0.001) were significantly associated with ADR while procedure order (<5 as reference, 6-10, p<0.001; >10, p=0.001) and session of procedures (p=0.004) were independent predictors for CIR. Additionally, there was a significant downward trend on ADR and CIR with the approaching of weekends (p=0.005) and increasing procedure orders (p<0.001), respectively. In the subgroup analysis stratified by gender, age and workload intensity, significant lower ADR was found in the afternoon in all subgroups (male, p<0.001; female, p=0.005; <40 years, p<0.001; ≥40 years, p=0.020; intensity<50 per month, p=0.017; intensity≥50 per month, p<0.001) but the downward trend on ADR as the week progressed was only found in endoscopists with male gender (p=0.011), age<40 (p=0.027) and high workload intensity (p=0.003). Moreover, a significant downward trend on CIR as the procedure order increased was found in all subgroups except endoscopists with age≥40 (male, p=0.005; female, p<0.001; <40 years, p<0.001; intensity<50 per month, p=0.001; intensity≥50 per month, p<0.001). Conclusions: Colonoscopies in the afternoon will affect ADR negatively while increasing procedure order will cause a lower CIR. Importantly, the significant negative influence of Friday and weekends on ADR was first discovered in this study. Moreover, endoscopists with female gender and advanced age (≥40) but not high workload intensity showed superiority in resistance of fatigue caused by the end of the week and increasing daily procedures. [ABSTRACT FROM AUTHOR]

Background/Aims: Early adverse life events (EALs) are relevant to irritable bowel syndrome in adulthood. Maternal separation (MS), as one of the EALs, has proved to induce visceral hypersensitivity in adult rats. However, the effect of MS on visceral hypersensitvity from the post-weaning period to adulthood remains unknown. Methods: One hundred and ten neonatal Sprague-Dawley rats were randomly divided into 2 groups: rats in the MS group were exposed to 3 hours daily MS on postnatal day (PND) 2-14; the normal control (NC) group remained undisturbed. Visceral sensitivity was determined by measuring the visceromotor response to colorectal distention on PND21, 35, and 56. Anxiety-like behaviors were measured by the open field test. Results: Compared with NC rats, MS rats showed significant visceral hypersensitivity from the post-weaning period to adult. The proportion of visceral hypersensitive rats decreased with age from 87.5% to 70.0% in the female MS group and from 90.0% to 66.7% in the male MS group. The relative VMR ratio of MS and NC on PND21 was higher than PND35 and PND56. MS rats showed decreased ability of movement and exploration to the novel environment in the post-weaning period, obesity in the prepubertal period, and more anxietylike behaviors in adulthood. Conclusions: MS can significantly affect visceral sensitivity and behaviors of rats in different age stages, especially in the post-weaning period. Visceral hypersensitivity of MS rats is more pronounced in the post-weaning period and slightly restored in adults. Thus, visceral hypersensitivity in the post-weaning period might play a more meaningful pathophysiologic role in the formation of adult irritable bowel syndrome. [ABSTRACT FROM AUTHOR]

Background/Aims. Patients with type II diabetes mellitus (DM) were known to have higher prevalence of gastroesophageal reflux disease (GERD) in the Western countries, but data on the impact of GERD on DM patients in our country are scarce. The aim of this study was to evaluate the prevalence of GERD in type II DM patients in Shanghai, China, and to explore its possible risk factors. Methods. 775 type II DM cases were randomly collected. Reflux Disease Questionnaire (RDQ) was used to check the presence of GERD. Patients' characteristics, laboratory data, face-to-face interview, nerve conduction study, and needle electromyogram (EMG) test were analyzed. Results. 16% patients were found with typical GERD symptoms. Pathophysiological factors such as peripheral neuropathy, metabolism syndrome, and obesity were found to have no significant differences between GERD and nonGERD type II DM patients in the present study. Conclusion. The prevalence of GERD in type II DM patients is higher than that in adult inhabitants in Shanghai, China. No difference in pathophysiological factors, such as peripheral neuropathy, and metabolism syndrome was found in DM-GERD patients, suggesting that further study and efforts are needed to explore deeper the potential risk factors for the high prevalence rate of GERD in DM patients. [ABSTRACT FROM AUTHOR]

Background: Abnormal processing of esophageal sensation at the level of the central nervous system has been proven to be involved in gastroesophageal reflux disease (GERD). However, most studies were focused on the possible functions of perceptual processing related network during task status, little attention has been paid to default mode network, which has been manifested to be important in the pathogenesis of many diseases. In our study, we compared the brain activity characteristic in GERD patients with the healthy subjects (HS) at baseline, looking for whether activities of default mode network were abnormal in GERD patients and attempting to identify their possible roles in GERD. In present study, fractional amplitude of low-frequency fluctuation was adopted to detect the brain activities at baseline. Group-level analyses were conducted by one-sample t test within groups (voxel thresholds were p < 0.001 and cluster level >42, corrected P < 0.05) and independent-samples t test between groups (p < 0.01 and cluster level >90, corrected P < 0.05) using SPM5. Results: The predominant activity area in both groups mainly located in default mode network such as medial superior frontal gyrus, precuneus, posterior cingulate gyrus, etc. However, the activities of precuneus and posterior cingulate gyrus were significantly lower in GERD patients than those in the HS. Conclusions: The activities of precuneus and posterior cingulate gyrus of default mode network in GERD patients were significantly lower compared to the HS, suggesting abnormal activities of brain regions in default mode network may be involved in pathophysiology of GERD symptom generation. [ABSTRACT FROM AUTHOR]

Gastroesophageal reflux disease is a diversity disease that affects life quality of people in the world. Due to the complicated pathogenesis and variations in clinical manifestations, there is still no true gold standard for GERD diagnosis, and it is still difficult to diagnose this disease in some patients. The proton pump inhibitor's diagnostic test (the PPI test) is noninvasive, of low cost, tied to treatment, and widely accepted. Our aim is to evaluate the diagnostic significance of coapplying a rabeprazole test with the SF-36 for GERD in this study. Our study shows that the SF-36 in combination with the rabeprazole test can screen GERD patients and increase the sensitivity and specificity of GERD diagnosis through reference to the change in SF-36 score before and after the treatment (65 in the trial). [ABSTRACT FROM AUTHOR]