Huimin Chen

The study on the role of inflammatory cells and mediators in post-infectious functional dyspepsia

Abstract Objective. Functional dyspepsia is a common gastrointestinal disorder. The pathogenesis of functional dyspepsia remains unclear. Functional dyspepsia may begin after a bout of gastroenteritis (post-infectious functional dyspepsia) or de novo (nonspecific functional dyspepsia). The aim of this study was to investigate the prevalence and probable mechanisms of post-infectious functional dyspepsia. Material and methods. Functional dyspepsia patients with a history of unsanitary food intake and acute gastroenteritis 6-12 months ago were enrolled. 13C-UBT confirmed absence of H. pylori infection. Controls consisted of healthy nondyspeptic volunteers and patients with nonspecific functional dyspepsia. Gastric biopsies were used for routine histology, immunohistochemistry, electron microscopy, ELISA, HPLC assays and Western blot examination. Results. Eighty-five subjects were entered including 35 with post-infectious functional dyspepsia, 30 with nonspecific functional dyspepsia, and 20 healthy controls. The number of mast cells in post-infectious functional dyspepsia and nonspecific functional dyspepsia were significantly greater than that in healthy controls. The number of enterochromaffin cells (ECs) in post-infectious functional dyspepsia was significantly higher than those in nonspecific functional dyspepsia or in healthy controls. The number of mast cells and ECs increased with the density of chronic inflammatory cells. The release of histamine and 5-hydroxytryptamine from gastric mucosa of post-infectious functional dyspepsia patients was significantly greater than those from nonspecific functional dyspepsia or healthy controls. Tryptase protein expression was higher in post-infectious functional dyspepsia and nonspecific functional dyspepsia than in healthy controls. The histological score of chronic gastric inflammation was greater in post-infectious functional dyspepsia versus patients with nonspecific functional dyspepsia or healthy controls. Electron microscopy showed secreting granules in the cytoplasm of both mast cells and ECs. The number of activated mast cells and Ecs at a distance of < 5 μm of nerve fibers were significantly greater in post-infectious functional dyspepsia versus nonspecific functional dyspepsia or controls. Conclusions. Dyspepsia may occur after an acute onset of gastroenteritis in a part of patients. Potent chemicals derived from mast cells and ECs, including histamine, tryptase and 5-hydroxytryptamine may be involved in the pathogenesis of post-infectious functional dyspepsia.

A Prospective Study on Evaluating the Diagnostic Yield of Video Capsule Endoscopy Followed by Directed Double-Balloon Enteroscopy in Patients with Obscure Gastrointestinal Bleeding

AimsVideo capsule endoscopy (VCE) and double-balloon enteroscopy (DBE) are two novel methods for examining the small bowel and could be complementary to each other. The aim of the present study is to prospectively evaluate the diagnostic yield of VCE followed by a directed DBE in patients with obscure gastrointestinal (GI) bleeding.MethodsPatients with obscure gastrointestinal bleeding for a complete VCE examination were involved in the study. DBE was recommended after a negative or indeterminate finding of VCE. The diagnostic and follow-up data were collected for analysis.ResultsA total of 190 patients with a complete VCE examination were enrolled in the study. The overall positive detection rate for small-bowel disease in the VCE group was 86.8% (165/190), while 63.7% (121/190) patients were definitely diagnosed. Fifty-one patients with indeterminate (44 cases) and negative (seven cases) findings of first VCE underwent DBE procedures. A total of 18 patients with negative VCE findings refused the further examination. DBE demonstrated a positive finding in 66.7% (34/51) patients, 33 from indeterminate group and one from the negative group. Following an unrevealing DBE, at surgical follow-up, three further negative DBE procedures were documented. The overall diagnostic yield was 88.9%, including 121 diagnoses made by VCE alone and 48 by both VCE and DBE (confirmed at surgery or other treatments). The negative predictive value (NPV) and positive predictive value (PPV) of DBE in indeterminate VCE were 81.8 and 100%, respectively.ConclusionsCapsule endoscopy followed by directed double-balloon enteroscopy is a good strategy for investigating the causes of obscure GI bleeding and especially in confirming indeterminate and negative findings from VCE.

Role of vascular endothelial growth factor in angiodysplasia: an interventional study with thalidomide.

Background and Aim:  The pathogenesis of angiodysplasia is still not fully understood and effective therapy is not available. Thalidomide was reported to be effective in the treatment of angiodysplasia, but the mechanisms underlying its activity are, as yet, unknown. We aimed to investigate the expression of vascular endothelial growth factor (VEGF) in angiodysplasia tissues, and the role of hypoxia‐inducible factor‐1α (HIF‐1α) and basic fibroblast growth factor (bFGF) on VEGF expression in human umbilical vein endothelial cells (HUVEC). Additionally, we aimed to study the role of thalidomide in these parameters.

TNF-α-induced CXCL8 production by A549 cells: Involvement of the non-neuronal cholinergic system

It was recently suggested that the non-neuronal cholinergic system has a regulatory role in pulmonary inflammation. We investigated this systems involvement in the control of cytokine production by the A549 human alveolar epithelial cell line. CXCL8 and acetylcholine (ACh) concentrations were measured using ELISA and LC-MS/MS, respectively. The mRNA expression of muscarinic receptor (MR) subtypes was determined using RT-PCR. In A549 cells, TNF-α increased the release of CXCL8 and ACh and the expression of the subtype 3 MR (M3R). Furthermore, TNF-α-induced CXCL8 secretion was (i) inhibited by the MR antagonist tiotropium and the M3R antagonist 4-DAMP and (ii) enhanced by the M1/M3R agonist pilocarpine and the cholinesterase inhibitor physostigmine. Taken as a whole, these results suggest that ACh release by A549 cells enhances TNF-α-induced CXCL8 secretion through activation of the M3R. Western blot analysis revealed that pilocarpine and physostigmine enhanced the TNF-α-induced phosphorylation of ERK1/2 and p38 MAPK and the degradation of IκBα. Inhibition of these pathways with specific inhibitors abrogated the pilocarpine-induced CXCL8 release. Our results suggest that the TNF-α-induced secretion of CXCL8 in A549 cells is regulated by the release of ACh, the latters binding to the M3R and the downstream activation of NF-κB and the ERK1/2 and p38 MAPK signaling pathways. Our findings suggest that MR antagonists may have anti-inflammatory effects by preventing pro-inflammatory events driven by endogenous, non-neuronal ACh.

Up-regulation of KCa3.1 promotes human airway smooth muscle cell phenotypic modulation

Airway smooth muscle (ASM) cell phenotype modulation, characterized by reversible switching between contractile and proliferative phenotypes, is considered to contribute to proliferative diseases such as allergic asthma and chronic obstructive pulmonary disease (COPD). KCa3.1 has been suggested to be involved in regulating ASM cell activation, proliferation, and migration. However, little is known regarding the exact role of KCa3.1 in ASM cell phenotypic modulation. To elucidate the role of KCa3.1 in regulating ASM cell phenotypic modulation, we investigated the effects of KCa3.1 channels on ASM contractile marker protein expression, proliferation and migration of primary human bronchial smooth muscle (BSM) cells. We found that PDGF increased KCa3.1 channel expression in BSM cells with a concomitant marked decrease in the expression of contractile phenotypic marker proteins including smooth muscle myosin heavy chain (SMMHC), smooth muscle α-actin (α-SMA), myocardin and KCa1.1. These changes were significantly attenuated by the KCa3.1 blocker, TRAM-34, or gene silencing of KCa3.1. Pharmacological blockade or gene silencing of KCa3.1 also suppressed PDGF-induced human BSM cell migration and proliferation accompanied by a decrease in intracellular free Ca(2+) levels as a consequence of membrane depolarization, resulting in a reduction in cyclin D1 level and cell cycle arrest at G0-G1 phase. Additionally, PDGF-induced up-regulation of KCa3.1 and down-regulation of BSM contractile marker proteins were regulated by the ERK inhibitor U0126 and the AKT inhibitor LY294002. These findings highlight a novel role for the KCa3.1 channel in human BSM cell phenotypic modulation and provide a potential target for therapeutic intervention for proliferative airway diseases.

Ablation Induced by Single- and Multiple-Femtosecond Laser Pulses in Lithium Niobate

We present results on the surface-damage threshold of lithium niobate after single-and multiple-femtosecond laser pulse irradiation at the pulse duration of 80 fs, with a 800-nm wavelength, and a repetition rate of 1 kHz. The surface-ablation threshold was found to decrease significantly with an increase in the pulse number applied to the surface until reaching an almost constant level due to an incubation effect, which is attributed to the laser-induced defect formation. The threshold of lithium niobate under a single shot is found to be 2.82 J/cm2, and the threshold fluence for an infinite number of pulses Fth(∞) converges to a common value of 0.52 ± 0.06 J/cm2 for N > 80. The results have the potential for application in laser micromachining and the fabrication of related optical devices and applications in frequency conversion by a femtosecond laser in lithium niobate.

A novel modality for the estimation of the enteroscope insertion depth during double-balloon enteroscopy

BACKGROUND Until now, the insertion depth of the enteroscope during double-balloon enteroscopy (DBE) could only be estimated. However, the currently available methods have limitations, and development of newer, simple, and accurate modalities is needed. OBJECTIVE To evaluate the accuracy of a novel method for evaluation of enteroscope insertion depth during DBE. DESIGN Prospective, single-center cohort study. SETTING Tertiary referral university hospital. PATIENTS Fifty-one patients who had lesions found during 41 antegrade and 10 retrograde DBEs and treated by surgery were enrolled in this study. INTERVENTIONS The length of the ligament of Treitz/ileocecal valve lesion was estimated by adding the forward enteroscope length during each cycle of passage and by calculating the overtube insertion length (every 5 cm of overtube advancement means 40 cm of enteroscope advancement based on preliminary observations) during DBE, respectively, and was evaluated at surgery. MAIN OUTCOME MEASUREMENTS The length from the ligament of Treitz/ileocecal valve to the lesion. RESULTS Surgical evaluation was used as the standard. Regardless of insertion route, the mean difference from surgery in evaluation of enteroscope insertion length between using the enteroscope method and the overtube method was 19 cm (range 0-50 cm) and 17 cm (range 0-60 cm), respectively (P > .05). LIMITATIONS Small number of patients with a case series study design. CONCLUSIONS Calculating the length of the overtube passage is accurate, and it is simple to estimate the insertion depth of the enteroscope during DBE, which is useful in clinical practice.

Rabeprazole Combined with Hydrotalcite is Effective for Patients with Bile Reflux Gastritis after Cholecystectomy

BACKGROUND Regardless of surgical technique, patients who have undergone cholecystectomy appear to be predisposed to the development of bile reflux gastritis. OBJECTIVE To assess the efficacy of rabeprazole and hydrotalcite in patients with bile reflux gastritis after cholecystectomy. METHODS Postcholecystectomy patients with bile reflux gastritis confirmed by endoscopy and 24 h gastric bilirubin monitoring were randomly assigned to one of four eight-week treatments: observation (group A), rabeprazole alone (group B), hydrotalcite alone (group C) and rabeprazole in combination with hydrotalcite (group D). Endoscopy and 24 h gastric bilirubin monitoring were repeated in all patients after treatment. Dyspeptic symptoms of abdominal pain, bloating, heartburn, bitter taste, endoscopic and histological finding, and biliary reflux were evaluated before and after treatment. RESULTS After administering medication, patient symptoms in groups B, C and D were relieved - most significantly in group D (P<0.05). There were no significant differences in endoscopic hyperemia and histological inflammation among the groups (P>0.05). However, histological activity, the number of reflux episodes and the number of reflux episodes lasting longer than 5 min were significantly decreased only in group D (P<0.05). The total per cent of bilirubin absorption (value of 0.14 units or greater) time was decreased in groups B, C and D, and most significantly in group D (P<0.05). CONCLUSION Rabeprazole combined with hydrotalcite is an effective therapeutic option in the treatment of patients with bile reflux gastritis after cholecystectomy.

Comparative study on two colonic bowel preparations for patients with chronic constipation

Objective. To determine the efficacy, tolerance, and safety of oral sodium phosphate compared with polyethylene glycol in patients with chronic constipation. Material and methods. From May 2007 to October 2007, 100 patients with chronic constipation were prospectively randomized into two groups for colonoscopy. Group A (n=49) received sodium phosphate before colonoscopy, while Group B (n=51) received polyethylene glycol. During the same period, another 50 patients in Group C with normal defecation function were enrolled and received the polyethylene glycol preparation. Patients with intestinal stenosis found by colonoscopy were excluded. The quality of preparation was assessed by the endoscopist, who was blinded to the types of bowel preparation. Laboratory examinations including hematocrit, serum phosphorous, serum calcium, blood urea nitrogen, and serum creatinine were carried out in Groups A and B before and after preparation. A questionnaire was used to assess adverse effects and patients’ tolerance to the bowel preparation. Results. Two patients in Group A with a diagnosis of malignant tumor detected by colonoscopy were excluded. The baseline parameters, including weight, age, gender, endoscopic diagnosis, or constipation status, were homogeneously distributed in the three groups. It was shown that the quality of preparation in Group B was poorer than that in Group C (p<0.05). Compared with Group B, Group A showed better quality of preparation, a smaller amount of intestinal air bubble, and a higher number of defecations after taking the medicine (p<0.05 for all). There were no significant differences in acceptance of the two preparations and the prevalence of adverse effects. Transient hyperphosphatasemia was noted in four patients in Group A, but neither clinical symptoms nor hypocalcemia was observed. Conclusions. Based on our preliminary study, in the preparation of patients with chronic constipation for colonoscopy, sodium phosphate is just as well tolerated and safe as a standard polyethylene glycol preparation and might provide a better quality of bowel preparation.

Bleeding recurrence in patients with gastrointestinal vascular malformation after thalidomide.

Abstract Thalidomide may be used for the treatment of gastrointestinal vascular malformation (GIVM), but the long-term response and adverse effects are unknown. Aim to study the recurrence rate of GIVM bleeding after thalidomide treatment, the response to treatment, and the adverse effects. This was a retrospective study of 80 patients with GIVM treated with thalidomide between November 2003 and November 2013. Patients received a course of 100 mg/day of thalidomide for 4 months and were followed up for at least 1 year. The response rate during follow-up, the recurrence rate after the 1st course of treatment, and the rate of retreatment were assessed. Comorbidities, the need for blood transfusion, yearly bleeding episodes, hemoglobin levels, hospitalization after thalidomide treatment, and the rate of adverse effects were also examined. The overall response rate during follow-up was 79.5% (62/78). The recurrence rate was 21.0% after the 1st course of thalidomide. The response rate of retreatment was 100%. After thalidomide treatment, yearly blood transfusion amounts, yearly bleeding episodes, and yearly hospitalization numbers were significantly decreased, while hemoglobin levels were significantly increased (P < 0.001). Adverse effects were observed in 60.0% (48/80) of the patients. Serious adverse effects were reported in 31.3% (25/80). The overall response rate was 76.7% (23/30) in 30 patients with comorbidities, while the rate was 78.0% (39/50) in patients without comorbidities (P = 0.55). The rate of serious adverse effects was similar between the comorbidities (33.3%) and no-comorbidities groups (30.0%) (P = 0.76). Thalidomide showed a good response rate and low adverse effect rate in patients with recurrent gastrointestinal bleeding due to GIVM.