Gender differences in gastrointestinal, biopsychosocial and healthcare-seeking behaviors in Chinese patients with irritable bowel syndrome predominant with diarrhea.

BACKGROUND: Evidences of comparison of sex difference in Chinese irritable bowel syndrome (IBS) patients were few. We aim to compare gender difference in the biopsychosocial characteristics of Chinese patients of IBS predominant with diarrhea (IBS-D). METHODS: IBS-D patients meeting Rome III criteria were enrolled. We administered IBS symptom questionnaires, evaluation of psychological status (HAMD and HAMA scales) and IBS quality of life (IBS-QOL), dietary habits, healthcare seeking behaviors, and compared biopsychosocial characteristics between male and female patients. RESULTS: Four hundred and ninety patients were enrolled including 299 males and 191 females. More female patients reported abdominal pain associated with defecation (84.3% vs. 74.9%, P = 0.014) while males reported more abdominal discomfort (39.8% vs. 26.7%, P = 0.003). Females had higher IBS symptom score (9.7 ± 1.7 vs. 9.4 ± 1.4, P = 0.025) and more of females had severe abdominal pain/discomfort (17.8% vs. 12.4%, P = 0.013) while there were no significant differences of other bowel symptoms. Females reported higher incidence of comorbid anxiety state (64.9% vs. 52.8%, P = 0.008) and depression state (35.6% vs. 19.7%, P < 0.001) than males. Female patients also had lower IBS-QOL score (70.2 ± 20.4 vs. 75.1 ± 16.8, P = 0.028) and more frequent consultations, as well as less response for dietary modification than males. CONCLUSIONS: Chinese female patients with IBS-D had more prominent psychosocial disorders compared to male patients and their abdominal symptoms had minor differences.

Shared decision-making improving efficacy in diarrhoea-dominant irritable bowel syndrome in Chinese outpatient setting: protocol of a prospective, randomised controlled trial.

INTRODUCTION: Diarrhoea-dominant irritable bowel syndrome (IBS-D) is a disorder with multiple pathogenesis; many people with IBS-D may have psychosocial issues which can make assessment and treatment more difficult. Routine treatment procedure might not always achieve the desired outcome. Therefore, patients may not be satisfied with the conventional experience and would like to be more involved in clinical decision-making. A shared decision-making (SDM) model, that requires patient participation, has been demonstrated to have a powerful effect on the diagnosis and treatment of other diseases, which improves patients' compliance, satisfaction, thus refining the clinical outcome. However, there is no corresponding evidence in IBS-D. Herein, we hope to verify the effect of SDM through clinical studies, and we anticipate that SDM can improve the therapeutic effect in patients with IBS-D. METHODS: The study is a prospective, randomised, single-centre trial. 166 IBS-D outpatients who attend Peking Union Medical College Hospital will be allocated into routine treatment group and SDM group. The primary endpoint is the severity of bowel symptoms, measured by the IBS symptom severity scale. Secondary endpoints include impact of disease and quality of life, negative psychology and the evaluation of diagnosis and treatment process. ETHICS AND DISSEMINATION: Ethical approval has been obtained from the research ethics committee of Peking Union Medical College Hospital (I-23PJ470). This protocol has been approved by Chinese Clinical Trial Register (ChiCTR2300073681) in July 2023. The results of this trial will be published in an open-access way and disseminated among gastrointestinal physicians. TRIAL REGISTRATION NUMBER: Chinese Clinical Trial Register (ChiCTR2300073681).

Cognition of abdominal pain and abdominal discomfort in Chinese patients with irritable bowel syndrome with diarrhea.

BACKGROUND: In Asia, the proportion of patients with irritable bowel syndrome (IBS) with abdominal discomfort alone is significantly higher than that in western countries. The purposes of this study are to understand the cognition of abdominal pain and abdominal discomfort in Chinese patients with IBS and to compare the clinical characteristics of patients with abdominal pain alone and with abdominal discomfort alone. METHODS: Patients with IBS with diarrhea (IBS-D) who met the Rome III diagnostic criteria and had episodes of at least one day/week were consecutively enrolled. The cognition of abdominal pain and abdominal discomfort were investigated through face-to-face unstructured interview. Patients were divided into a pain group and a discomfort group according to the cognition interviews, then the characteristics and severity of symptoms (IBS symptom severity scale, IBS-SSS), IBS quality of life (IBS-QOL) and psychological state were compared between groups. RESULTS: A total of 88 patients with IBS-D were enrolled. Most of the patients with self-reported abdominal pain described their pain as spasm/cramping; patients with self-reported abdominal discomfort had as many as 24 different descriptions of discomfort. Most patients having abdominal pain and discomfort could accurately distinguish the two symptoms. The degree of abdominal pain in the pain group was higher than abdominal discomfort in the discomfort group (P = 0.002). There was no significant difference in IBS-SSS, extra-intestinal pain, IBS-QOL, and psychological state between the two groups. CONCLUSIONS: For Chinese patients with IBS-D, abdominal pain and abdominal discomfort are two different symptoms, but they have similar clinical features. TRIAL REGISTRATION: ChiCTR, ChiCTR1900028082. Registered 11 December 2019 - Retrospectively registered, http://www.chictr.org.cn .

Sera anti-neuronal antibodies in patients with irritable bowel syndrome and their correlations with clinical profiles.

BACKGROUND: Immune factors were involved in the pathophysiology of irritable bowel syndrome (IBS). The aim of the study was to test anti-neuronal antibodies in sera of IBS patients and demonstrate their correlations with IBS profiles and psychological disorders. METHODS: Patients with IBS met Rome III criteria and excluded organic diseases were enrolled. Controls included healthy subjects (HS), slow transit functional constipation, autoimmune diseases, and so on. Indirect immunofluorescence with monkey cerebellum and small intestine as substrates was used to detect anti-neuronal antibodies including anti-cerebral neuronal antibodies (ACNA) and anti-enteric neuronal antibodies (AENA). RESULTS: A total of 293 IBS patients, 100 HS and 153 disease controls were included in this study. The ACNA positive rate of IBS patients was significantly higher than HS (14% vs. 6%, p = 0.033). The positive rate of ACNA was significantly lower than AENA (14.0% vs. 76.8%, p = 0.028) in IBS patients. The prevalence of headache and sleeping disorder were higher in ACNA-positive IBS patients than ACNA-negative IBS patients (61% vs. 42.9%, p = 0.03; 75.6% vs. 57.1%, p = 0.03, respectively). Among IBS patients, ACNA and AENA were both negative in 21.8% patients, ACNA negative and AENA positive in 64.2% patients, and ACNA and AENA were both positive in 12.6% patients. There were no significant differences of intestinal symptoms among the three groups, while the prevalence of headache (64.9% vs. 37.5% and 44.7%, p = 0.03) and sleeping disorder (78.4% vs. 50.0% and 59.6%, p = 0.02) were higher in patients with both ACNA and AENA positive than patients with both ACNA and AENA negative, patients with ACNA negative and AENA positive. There were no significant differences of the prevalence of depression and anxiety, HAMD, and HAMA scores among the three groups. CONCLUSIONS AND INFERENCES: Anti-neuronal antibodies in sera of IBS patients were mainly targeted to enteric neurons and in a small part to cerebral neurons. ACNA were closely related to headache and sleeping disorder but unrelated to intestinal symptoms, depression, or anxiety of IBS patients.

Multiple rather than specific autoantibodies were identified in irritable bowel syndrome with HuProt™ proteome microarray.

Immune activation and several autoantibodies might be involved in the pathophysiology of irritable bowel syndrome (IBS). We aimed to identify serum biomarkers for IBS by HuProt™ microarray. IBS patients met Rome III criteria were enrolled. Control groups included healthy controls (HCs) and disease controls (DCs). In stage I, we profiled sera from IBS and control groups with HuProt™ microarrays. Based on significant different proteins in stage I, IBS focused microarrays were constructed and validated in a larger cohort in stage II, then decision tree models were generated to establish a combination of biomarkers. In stage III, 4 purified proteins were verified by ELISA. Finally, we analyzed the correlation of autoantibodies with symptoms. In stage I, we identified 47 significant different proteins including 8 autoantibodies of IgG, 2 of IgA between IBS and HCs; 13 autoantibodies of IgG, 13 of IgA between IBS and DCs. In stage II, we found the positive rates of 14 IgG and IgA autoantibodies in IBS were significantly higher than HCs. Five autoantibodies of IgG and 7 IgA were comprehensively involved in differentiating IBS and HCs with the sensitivity and specificity to diagnose IBS as 40%-46.7% and 79.4%-86.3%. The median optical density value of ELAVL4 (IgG) and PIGP (IgA) were significantly higher in IBS than HCs. Parts of autoantibodies above were related to IBS symptoms. We found a combination of autoantibodies to differentiate IBS with HCs, but no specific autoantibodies could serve as serum biomarkers for IBS.

Ethnic differences in genetic polymorphism associated with irritable bowel syndrome.

Genetic polymorphism is associated with irritable bowel syndrome (IBS) in terms of susceptibility and clinical manifestations. Previous studies have shown that genetic polymorphism might play a key role in the onset and progression of IBS by modulating components of its pathogenesis such as the gut-brain axis, gastrointestinal motility, inflammatory activity, and immune status. Although underlying pathophysiological mechanisms have not been fully clarified, the potential ethnic differences that are present in worldwide genetic studies of IBS deserve attention. This review surveyed numerous studies focusing on IBS-associated single nucleotide polymorphisms, and investigated the ethnic disparities revealed by them. The results demonstrate the need for more attention on ethnic factors in IBS-related genetic studies. Taking ethnic backgrounds into accounts and placing emphasis on disparities potentially ascribed to ethnicity could help lay a solid and generalized foundation for transcultural, multi-ethnic, or secondary analyses in IBS, for example, a meta-analysis. Broader genetic studies considering ethnic factors are greatly needed to obtain a better understanding of the pathophysiological mechanisms of IBS and to improve the prevention, intervention, and treatment of this disease.

Dissecting expression profiles of gastric precancerous lesions and early gastric cancer to explore crucial molecules in intestinal-type gastric cancer tumorigenesis.

Intestinal-type gastric cancer (IGC) has a clear and multistep histological evolution. No studies have comprehensively explored gastric tumorigenesis from inflammation through low-grade intraepithelial neoplasia (LGIN) and high-grade intraepithelial neoplasia (HGIN) to early gastric cancer (EGC). We sought to investigate the characteristics participating in IGC tumorigenesis and identify related prognostic information within the process. RNA expression profiles of 94 gastroscopic biopsies from 47 patients, including gastric precancerous lesions (GPL: LGIN and HGIN), EGC, and paired controls, were detected by Agilent Microarray. During IGC tumorigenesis from LGIN through HGIN to EGC, the number of activity-changed tumor hallmarks increased. LGIN and HGIN had similar expression profiles when compared to EGC. We observed an increase in the stemness of gastric epithelial cells in LGIN, HGIN, and EGC, and we found 27 consistent genes that might contribute to dedifferentiation, including five driver genes. Remarkably, we perceived that the immune microenvironment was more active in EGC than in GPL, especially in the infiltration of lymphocytes and macrophages. We identified a five-gene signature from the gastric tumorigenesis process that could independently predict the overall survival and disease-free survival of GC patients (log-rank test: p < 0.0001), and the robustness was verified in an independent cohort (n > 300) and by comparing with two established prognostic signatures in GC. In conclusion, during IGC tumorigenesis, cancer-like changes occur in LGIN and accumulate in HGIN and EGC. The immune microenvironment is more active in EGC than in LGIN and HGIN. The identified signature from the tumorigenesis process has robust prognostic significance for GC patients. © 2020 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.

Clinical characteristics of cytomegalovirus gastritis: A retrospective study from a tertiary medical center.

Cytomegalovirus (CMV) gastritis is a rare opportunistic infection with diverse clinical manifestations. Our study aimed to investigate the clinical features of Chinese patients with CMV gastritis.Six inpatients diagnosed with CMV gastritis were retrospectively enrolled, based on the finding of inclusion bodies in routine hematoxylin and eosin staining or positive anti-CMV monoclonal antibodies under immunohistochemistry in the gastric biopsy. Data, including demographics, diagnostic measurements, and medications, were collected.Abdominal pain was the most frequently reported symptom, occurring in 4 patients. Five patients were immunocompromised with associated underlying diseases, and 3 patients had decreased leukocyte differentiation antigen 4 positive (CD4) T lymphocyte counts. Only 3 patients had either positive cytomegalovirus (CMV)-immunoglobulin (Ig) M or increased copies of CMV-DNA peripherally. All patients had gastric lesions in the antrum of the stomach, including ulcers or erosions observed by gastroscopy. All patients received ganciclovir by intravenous injection (IV) as the first line anti-CMV therapy, and attained complete (4) or partial remission (2) during the follow-up.CMV gastritis should be taken into consideration in patients with immunocompromised status who have abdominal pain, nausea, or vomiting. Gastroscopy and necessary biopsy are the major diagnostic methods for CMV gastritis. Early diagnosis leads to a better prognosis for these patients.

Phase III, randomised, double-blind, multicentre study to evaluate the efficacy and safety of vonoprazan compared with lansoprazole in Asian patients with erosive oesophagitis.

OBJECTIVE: To establish the non-inferior efficacy of vonoprazan versus lansoprazole in the treatment of Asian patients with erosive oesophagitis (EO). DESIGN: In this phase III, double-blind, multicentre study, patients with endoscopically confirmed EO were randomised 1:1 to receive vonoprazan 20 mg or lansoprazole 30 mg, once daily for up to 8 weeks. The primary endpoint was EO healing rate at 8 weeks. The secondary endpoints were EO healing rates at 2 and 4 weeks. Safety endpoints included treatment-emergent adverse events (TEAEs). RESULTS: In the vonoprazan (n=238) and lansoprazole (n=230) arms, 8-week EO healing rates were 92.4% and 91.3%, respectively (difference 1.1% (95% CI -3.822% to 6.087%)). The respective 2-week EO healing rates were 75.0% and 67.8% (difference 7.2% (95% CI -1.054% to 15.371%)), and the respective 4-week EO healing rates were 85.3% and 83.5% (difference 1.8% (95% CI -4.763% to 8.395%)). In patients with baseline Los Angeles classification grade C/D, 2-week, 4-week and 8-week EO healing rates were higher with vonoprazan versus lansoprazole (2 weeks: 62.2% vs 51.5%, difference 10.6% (95% CI -5.708% to 27.002%); 4 weeks: 73.3% vs 67.2%, difference 6.2% (95% CI -8.884 to 21.223); and 8 weeks: 84.0% vs 80.6%, difference 3.4% (95% CI -9.187% to 15.993%)). Overall, EO healing rates appeared higher with vonoprazan versus lansoprazole. TEAE rates were 38.1% and 36.6% in the vonoprazan and lansoprazole group, respectively. CONCLUSION: Our findings demonstrate the non-inferior efficacy of vonoprazan versus lansoprazole in terms of EO healing rate at 8 weeks in this population. Safety outcomes were similar in the two treatment arms. TRIAL REGISTRATION NUMBER: NCT02388724.

Natural history of gastroesophageal reflux: A prospective cohort study in a stratified, randomized population in Beijing.

OBJECTIVE: To explore the natural history of and risk factors for gastroesophageal reflux (GER) in a prospective cohort in Beijing, China. METHODS: We selected adult participants using a stratified randomized method and performed initial surveys in 1996 and the current survey in 2008. Well-trained investigators administered the survey questionnaire using face-to-face interviews. Reflux symptoms were evaluated by their intensity and frequency. GER was defined as heartburn, acid reflux, and food regurgitation at least once a week, and monthly reflux was defined as at least one of the above symptoms occurring 1-3 days per month. RESULTS: The resurvey response rate was 47.8% (1189/2486). Over 12 years, 66.9% of the respondents remained unchanged, and one-third changed, with a GER new onset rate of 7.0 per 1000 person-years and a GER disappearance rate of 64.6 per 1000 person-years. This kept the GER prevalence stable at 8.2% to 9.5% (P = 0.28). GER and monthly reflux exhibited significant differences in their tendency to persist or become aggravated to GER (22.4% vs 11.9%, P = 0.02). Participants who initially had single, mild to moderate, daily GER were more likely to recover from reflux over time. Participants with persistent and aggravated GER had more severe heartburn and acid reflux than those with new-onset GER in the current survey. Multiple logistic regression analysis showed that emotional depression is a risk factor for GER aggravation (odds ratio 3.52, 95% confidence interval 1.43-8.67, P = 0.006). CONCLUSION: The initial symptom profile of reflux determines the outcome of GER over time.

Sera with anti-enteric neuronal antibodies from patients with irritable bowel syndrome promote apoptosis in myenteric neurons of guinea pigs and human SH-Sy5Y cells.

BACKGROUND: Sera anti-enteric neuronal antibodies (AENA), neuronal inflammation, and degeneration in myenteric plexus in patients with irritable bowel syndrome (IBS) were reported. Effects of sera AENA in patients with IBS are unclear. METHODS: Patients with IBS met Rome III criteria were enrolled. Controls included healthy subjects (HS) and patients with slow transit functional constipation, inflammatory bowel disease, chronic intestinal pseudo-obstruction, and autoimmune diseases. Indirect immunofluorescence was used to detect AENA. Anti-enteric neuronal antibodies intensities were termed as "1" = weak fluorescence (mild positive); "2" = moderate fluorescence (moderate positive); "3" = very high fluorescence (intensive positive). Intensities of ≥1 were defined as positive and ≥2 were defined as obvious positive. Cultured myenteric neurons of small intestine from guinea pigs and human SH-Sy5Y cells were incubated with fetal bovine serum (FBS), HS sera, or IBS sera with or without AENA. Indirect immunofluorescence with anti-PGP9.5/DAPI/anti-active caspase-3 or TUNEL, Western blot, and flow cytometry were used to detect apoptosis. KEY RESULTS: Overall, 293 patients with IBS were enrolled (41.7 ± 11.5 years). AENA-positive and obvious positive rates in IBS were higher than HS (76.8% vs 33%; 43.7% vs 7%; all P < 0.001). Myenteric neurons incubated with AENA moderate or intensive positive IBS sera showed higher rates of anti-active caspase-3 and TUNEL-positive cells than HS or FBS (20% ± 7.3% and 35% ± 13.3% vs 4.3% ± 1.5% and 0.9% ± 0.4%, respectively; 6.2% ± 2.0% and 10.2% ± 4.6% vs 1.3% ± 1.9% and 0.5%±0.5%, respectively; all P < 0.05). Human SH-Sy5Y cells incubated with AENA moderate or intensive positive IBS sera showed increased cleaved caspase-3 and Bax expression and decreased Bcl-2 expression. Flow cytometry showed apoptosis rates of these two groups were higher than that of AENA mild positive, negative, HS, and FBS (7.6%±0.8% and 10.7%±1.3% vs 5.0%±0.8%, 3.8%±0.3%, 3.4%±0.2% and, 2.8%±0.2%, P < 0.05). CONCLUSIONS AND INFERENCES: The AENA obvious positive rate in patients with IBS was higher than HS, and sera with higher levels of AENA promoted neuronal apoptosis. AENA-mediated neuropathy might exist in a subset of patients with IBS.

[Values of Different Laboratory Diagnostic Approaches for Tuberculous Peritonitis].

Objective To evaluate the diagnostic accuracy of different laboratory approaches for tuberculous peritonitis(TP).Methods The clinical data of patients with suspected TP who were mainly manifested as ascites in Peking Union Medical College Hospital from January 2014 to June 2017 were retrospectively analyzed. Ascites samples were tested with different diagnostic approaches,including acid fast stain,culture for mycobacterium,real-time polymerase chain reaction for identifying DNA of mycobacterium tuberculosis,and T-cell spot of tuberculosis test(T-SPOT.TB). Results Totally 163 cases aged 15-84 years [mean±SD:(50±17)years] with complete data were enrolled,among whom 82(50.3%) were males and 81(49.7%) were females. Finally,27 patients were confirmed as TP,which was excluded in the other 136 cases. The sensitivity and specificity of ascites acid fast stain were 0% and 100%,respectively,followed by ascites culture for mycobacterium(21.74% and 100%),real-time polymerase chain reaction for DNA of mycobacterium tuberculosis in ascites(18.52% and 100%),T-SPOT.TB on ascites(95.42% and 61.90%),and T-SPOT.TB on peripheral blood(76.19% and 80.18%). Conclusion The diagnosis of tuberculous peritonitis remains challenging because of the limitations of the currently available diagnostic tests. Diagnosis should also be based on clinical manifestations and auxiliary examinations.

Empirical treatment of outpatients with gastroesophageal reflux disease with proton pump inhibitors: A survey of Chinese patients (the ENLIGHT Study).

BACKGROUND AND AIM: Empirical proton pump inhibitor (PPI) treatment is recommended as a diagnostic indicator for gastroesophageal reflux disease (GERD) and as a therapy for symptomatic control, with responses generally seen within 4 weeks. However, there are no real-world data assessing the effectiveness of short-term empirical treatment with PPIs in patients with GERD in China. METHODS: The ENLIGHT study was a multicenter, prospective, observational study conducted in China. The primary outcome was the overall response rate after 4 weeks' empirical treatment with PPIs. Adult patients aged between 18 and 65 years of age, with a gastroesophageal reflux disease questionnaire score of ≥ 8, prescribed empirical PPI treatment by their physicians and with no planned endoscopy were eligible to participate. Statistical analyses were primarily descriptive. RESULTS: Overall, 987 patients were eligible to participate and were included in the full analysis set (FAS); 707 patients were included in the per protocol set. In the FAS, esomeprazole was received by 57.1% of patients and was the most commonly used PPI. After 4-week treatment, 71.1% (95% confidence interval [CI], 67.9% to 74.2%) of patients were considered responders to PPI. The response rate at the end of 2-week PPI treatment reached 57.0% (95% CI, 52.5% to 61.7%). The median time to response was 13 days (95% CI, 12 to 15). Response rates at 2 and 4 weeks of the per protocol set were similar to those of the FAS. CONCLUSIONS: Short-term empirical PPI treatment can provide an effective relief of GERD symptoms in most Chinese patients in real-world practice.

Predictors of healthcare-seeking behavior among Chinese patients with irritable bowel syndrome.

AIM: To analyze predictors of healthcare-seeking behavior among Chinese patients with irritable bowel syndrome (IBS) and their satisfaction with medical care. METHODS: Participating patients met IBS Rome III criteria (excluding those with organic diseases) and were enrolled in an IBS database in a tertiary university hospital. Participants completed IBS questionnaires in face-to-face interviews. The questionnaires covered intestinal and extra-intestinal symptoms, medical consultations, colonoscopy, medications, and self-reported response to medications during the whole disease course and in the past year. Univariate associations and multivariate logistic regression were used to identify predictors for frequent healthcare-seeking behavior (≥ 3 times/year), frequent colonoscopies (≥ 2 times/year), long-term medications, and poor satisfaction with medical care. RESULTS: In total, 516 patients (293 males, 223 females) were included. Participants' average age was 43.2 ± 11.8 years. Before study enrollment, 55.2% had received medical consultations for IBS symptoms. Ordinary abdominal pain/discomfort (non-defecation) was an independent predictor for healthcare-seeking behavior (OR = 2.07, 95%CI: 1.31-3.27). Frequent colonoscopies were reported by 14.7% of patients (3.1 ± 1.4 times per year). Sensation of incomplete evacuation was an independent predictor for frequent colonoscopies (OR = 2.76, 95%CI: 1.35-5.67). During the whole disease course, 89% of patients took medications for IBS symptoms, and 14.7% reported they were satisfied with medical care. Patients with anxiety were more likely to report dissatisfaction with medical care (OR = 2.08, 95%CI: 1.20-3.59). In the past year, patients with severe (OR = 1.74, 95%CI: 1.06-2.82) and persistent (OR = 1.66, 95%CI: 1.01-2.72) IBS symptoms sought medical care more frequently. CONCLUSION: Chinese patients with IBS present high rates of frequent healthcare-seeking behavior, colonoscopies, and medications, and low satisfaction with medical care. Intestinal symptoms are major predictors for healthcare-seeking behavior.

Isomalto-oligosaccharides ameliorate visceral hyperalgesia with repair damage of ileal epithelial ultrastructure in rats.

BACKGROUND: Treatment of irritable bowel syndrome (IBS) with probiotics has achieved effectiveness to a certain extent. Whether prebiotics will work is still unclear. This study aimed to investigate the therapeutic effects of the prebiotic isomalto-oligosaccharides (IMO) on visceral hypersensitivity (VHS) in rats and to explore potential mechanism. METHODS: Water avoidance stress (WAS) was used to induce VHS in rats. The score for the abdominal withdrawal reflex (AWR) was determined while colorectal distension and compared between VHS group and control group in order to validate VHS preparation. Rats with VHS were then divided into an IMO-treated group (intragastric 5% IMO, 2 mL/d, 14 days) and a water-control group (intragastric water). After treatment, AWR score and intestinal transit rate (ITR) were determined, stool culture was performed, the ultrastructure of the ileum epithelium was observed with scanning electron microscopy (SEM), and serum cytokines were measured. RESULTS: WAS significantly increased AWR score responding to colorectal distension, and lowered the pain threshold. IMO treatment improved VHS with a reduction in AWR score on graded colorectal distension and an increase in pain threshold. SEM showed damages on the ileal epithelial ultrastructure in VHS rats, which was attenuated by IMO treatment. ITR, fecal microbiota and serum cytokine levels were comparable among control group, water-control group, and IMO-treated rats. CONCLUSION: In this randomized placebo-controlled study, the results showed that IMO ameliorated WAS-induced visceral hyperalgesia in rats, this effect may be attributed to the repair of damages on intestinal epithelial ultrastructure.

Clinical and Laboratory Diagnosis of Intestinal Tuberculosis.

BACKGROUND: Tuberculosis (TB) remains a worldwide problem. Intestinal TB (ITB) constitutes a major public health problem in developing countries and has been associated with significant morbidity and mortality. The aim of this study was to characterize the clinical, radiological, endoscopic, and pathological features of ITB and to define the strategy for establishing the diagnosis. METHODS: A retrospective study (from January 2000 to June 2015) was carried out in Peking Union Medical College Hospital and all hospitalized cases were diagnosed as ITB during the study period were included. The relevant clinical information, laboratory results, microbiological, and radiological investigations were recorded. RESULTS: Of the 85 cases, 61 cases (71.8%) were ranged from 20 to 50 years. The ileocecal region was involved in about 83.5% (71/85) of patients. About 41.2% (35/85) of patients had co-existing extra ITB, especially active pulmonary TB. Abdominal pain (82.4%) was the most common presenting symptom followed by weight loss (72.9%) and fever (64.7%). Both T-cell spot of TB test (T-SPOT.TB) and purified protein derivatives (PPD) tests were performed in 26 patients: 20 (76.9%) positive T-SPOT.TB and 13 (50.0%) positive PPD were detected, with a statistical significant difference (P = 0.046). Twenty cases (23.5%) were histopathology and/or pathogen confirmed TB; 27 cases (31.8%) were diagnosed by clinical manifestation consistent with ITB and evidence of active extra ITB; 38 cases (44.7%) were diagnosed by good response to diagnostic anti-TB therapy. CONCLUSIONS: ITB is difficult to diagnose even with modern medical techniques due to its nonspecific clinical and laboratory features. At present, combination of clinical, endoscopic, radiological, and pathological features continues to be the key to the diagnosis of ITB.

Changes in Enteric Neurons of Small Intestine in a Rat Model of Irritable Bowel Syndrome with Diarrhea.

BACKGROUND/AIMS: Physical and/or emotional stresses are important factors in the exacerbation of symptoms in irritable bowel syndrome (IBS). Several lines of evidence support that a major impact of stress on the gastrointestinal tract occurs via the enteric nervous system. We aimed to evaluate histological changes in the submucosal plexus (SMP) and myenteric plexus (MP) of the distal ileum in concert with the intestinal motor function in a rat model of IBS with diarrhea. METHODS: The rat model was induced by heterotypic chronic and acute stress (CAS). The intestinal transit was measured by administering powdered carbon by gastric gavage. Double immunohistochemical fluorescence staining with whole-mount preparations of SMP and MP of enteric nervous system was used to assess changes in expression of choline acetyltransferase, vasoactive intestinal peptide, or nitric oxide synthase in relation to the pan neuronal marker, anti-Hu. RESULTS: The intestinal transit ratio increased significantly from control values of 50.8% to 60.6% in the CAS group. The numbers of enteric ganglia and neurons in the SMP were increased in the CAS group. The proportions of choline acetyltransferase- and vasoactive intestinal peptide-immunoreactive neurons in the SMP were increased (82.1 ± 4.3% vs. 76.0 ± 5.0%, P = 0.021; 40.5 ± 5.9% vs 28.9 ± 3.7%, P = 0.001), while nitric oxide synthase-immunoreactive neurons in the MP were decreased compared with controls (23.3 ± 4.5% vs 32.4 ± 4.5%, P = 0.002). CONCLUSIONS: These morphological changes in enteric neurons to CAS might contribute to the dysfunction in motility and secretion in IBS with diarrhea.

[Esophageal motility abnormalities and their impact on esophageal acid exposure in patients with gastroesophageal reflux disease].

OBJECTIVE: To identify the characteristics of esophageal motility abnormalities in patients with gastroesophageal reflux disease (GERD) and its influence on esophageal acid exposure. METHODS: Patients with typical reflux symptoms and diagnosis of reflux esophagitis (RE) or non-erosive reflux disease (NERD), and healthy subject were enrolled in this prospective controlled study. The esophageal manometry and esophageal 26 hours pH monitoring were performed. GERD patients were divided into 3 groups according to their esophageal motility abnormalities: ① low lower esophageal sphincter pressure (LESP) group, ② ineffective esophageal motivation (IEM) group, ③ IEM and low LESP group. Esophageal acid exposure was analyzed among different groups. RESULTS: A total of 27 GERD patients (15 RE, 12 NERD) and 10 healthy subjects were enrolled in this study. The esophageal motility abnormalities in GERD patients mainly presented as the decrease of LESP and distal esophageal body pressure. The proportion of 3 kinds of esophageal motility abnormalities has significant difference between RE and NERD patients (P = 0.017). In IEM and low LESP group, all patients suffered from RE, with the total number of acid exposure, the total acid exposure time and the acid exposure time in fasting higher than those in low LESP group [98.0 (63.3, 282.8) times vs 41.0 (25.0, 82.0) times, P = 0.029; 11.7% (4.1%, 30.0%) vs 2.2% (1.4%, 9.6%), P = 0.045; 2.6% (0.9%, 4.9%) vs 0.0 (0.0, 1.2%), P = 0.015]. CONCLUSIONS: Esophageal motility abnormalities in GERD patients are characterized as low LESP and IEM in distal esophagus. The coexistence of low LESP and IEM exacerbates esophageal acid exposure, which might explain the mechanism of esophageal mucosal injury in RE patients.

Magnifying narrow-band imaging endoscopy is superior in diagnosis of early gastric cancer.

AIM: To evaluate the diagnostic effectiveness of white light endoscopy, magnifying endoscopy (ME), and magnifying narrow-band imaging endoscopy (ME-NBI) in detecting early gastric cancer (EGC). METHODS: From March 2010 to June 2012, a total of 3616 patients received screening for gastric cancer by magnifying endoscopy. There were 3675 focal gastric lesions detected using conventional high definition white light endoscopy (HD-WLE) in four different referential hospitals that were recruited for further investigation using ME and ME-NBI. The images obtained from HD-WLE, ME, and ME-NBI were reviewed by four experienced endoscopists to evaluate their diagnostic effectiveness for EGC. The diagnosis of cancerous and non-cancerous lesions was conducted by evaluating the microvascular and microsurface patterns using the VS classification system. The final endoscopic diagnosis of each lesion was determined by consultation when a disagreement occurred. We used histopathological results as the gold standard for the diagnosis of EGC. RESULTS: Among the 3675 lesions found, 1508 were validated by pathological findings as chronic gastritis, 1279 as chronic gastritis with intestinal metaplasia, 631 as low-grade neoplasia, and 257 as EGC. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of HD-WLE for the diagnosis of EGC were 71.2%, 99.1%, 85.5%, 97.9% and 97.1%, respectively. The results of ME for diagnosing EGC were 81.3%, 98.8%, 83.3%, 98.6% and 97.6%, respectively. The results of ME-NBI for the diagnosis of EGC were 87.2%, 98.6%, 82.1%, 99.0% and 97.8%, respectively. The diagnostic sensitivity and accuracy of paired ME and ME-NBI were significantly better than those of HD-WLE (P < 0.05). CONCLUSION: HD-WLE has a relatively high accuracy for diagnosing EGC and is an effective screening tool. Further investigations of ME and ME-NBI are required to achieve superior accuracy.

Whole genome expression profiling of gastric high-grade intraepithelial neoplasia with or without cancer.

OBJECTIVE: To investigate the whole genome expression profiles between gastric high-grade intraepithelial neoplasia (HGIN) tissues with cancer and HGIN tissues without cancer. METHODS: Gastric specimens from an upper magnifying chromoendoscopic targeted biopsy were collected at Peking Union Medical College Hospital from March 2010 to May 2013. Each of the forceps biopsies from the 21 patients was HGIN,but there were 10 HGIN and 11 HGIN with cancer after the endoscopic submucosal dissection. The whole genome expression profiling was performed on 10 HGIN samples and 11 HGIN with cancer samples using Agilent 4 × 44K Whole Human Genome microarrays. Differentially expressed genes between different types of lesions were identified using an unpaired t-test and corrected with the Benjamini and Hochberg false discovery rate algorithm. A gene ontology(GO)enrichment analysis was performed using the GeneSpring software GX 12.6. RESULTS: The gene expression patterns were different between HGIN tissues with cancer and HGIN tissues without cancer. There were 470 significantly differentially expressed transcripts between them (P<0.05,Fold Change>2), with 180 up-regulated genes and 290 down-regulated genes in HGIN tissues with cancer. A GO enrichment analysis demonstrated that the most striking over-expressed transcripts in HGIN with cancer were in the category of triglyceride biosynthetic process,acylglycerol biosynthetic process,neutral lipid biosynthetic process,glycerol ether metabolic process,organic ether metabolic process,and glycerolipid metabolic process. CONCLUSION: The change of lipid metabolism may contribute to the pathogenesis of gastric cancer at an early stage.