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1.
J Pathol ; 2020 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-32207854

RESUMO

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 5 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 5-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. This article is protected by copyright. All rights reserved.

2.
Medicine (Baltimore) ; 99(5): e18927, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32000406

RESUMO

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.


Assuntos
Infecções por Citomegalovirus/diagnóstico , Infecções por Citomegalovirus/epidemiologia , Gastrite/diagnóstico , Gastrite/epidemiologia , Dor Abdominal/diagnóstico , Dor Abdominal/tratamento farmacológico , Dor Abdominal/epidemiologia , Dor Abdominal/etiologia , Adulto , Idoso , Biomarcadores/sangue , Biópsia , Infecções por Citomegalovirus/tratamento farmacológico , Infecções por Citomegalovirus/patologia , Feminino , Gastrite/tratamento farmacológico , Gastrite/patologia , Gastroscopia , Humanos , Masculino , Pessoa de Meia-Idade , Náusea/diagnóstico , Náusea/tratamento farmacológico , Náusea/epidemiologia , Náusea/etiologia , Prognóstico , Estudos Retrospectivos , Estômago/diagnóstico por imagem , Estômago/patologia , Centros de Atenção Terciária , Vômito/diagnóstico , Vômito/tratamento farmacológico , Vômito/epidemiologia , Vômito/etiologia
3.
Gut ; 69(2): 224-230, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31409606

RESUMO

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.


Assuntos
Esofagite Péptica/tratamento farmacológico , Lansoprazol/uso terapêutico , Inibidores da Bomba de Prótons/uso terapêutico , Pirróis/uso terapêutico , Sulfonamidas/uso terapêutico , Adulto , Idoso , Método Duplo-Cego , Esquema de Medicação , Feminino , Humanos , Lansoprazol/administração & dosagem , Lansoprazol/efeitos adversos , Masculino , Pessoa de Meia-Idade , Inibidores da Bomba de Prótons/administração & dosagem , Inibidores da Bomba de Prótons/efeitos adversos , Pirróis/administração & dosagem , Pirróis/efeitos adversos , Índice de Gravidade de Doença , Sulfonamidas/administração & dosagem , Sulfonamidas/efeitos adversos , Resultado do Tratamento , Cicatrização
4.
J Dig Dis ; 20(10): 523-531, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31291055

RESUMO

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.

5.
Neurogastroenterol Motil ; 30(12): e13457, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30230140

RESUMO

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.


Assuntos
Autoanticorpos/sangue , Síndrome do Intestino Irritável/sangue , Síndrome do Intestino Irritável/imunologia , Plexo Mientérico/imunologia , Neurônios/imunologia , Adulto , Animais , Apoptose/imunologia , Autoantígenos/imunologia , Feminino , Cobaias , Humanos , Masculino , Pessoa de Meia-Idade
6.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 40(4): 534-538, 2018 Aug 30.
Artigo em Chinês | MEDLINE | ID: mdl-30193608

RESUMO

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.


Assuntos
Ascite/microbiologia , Mycobacterium tuberculosis , Peritonite Tuberculosa/diagnóstico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Sensibilidade e Especificidade , Adulto Jovem
7.
J Gastroenterol Hepatol ; 33(10): 1722-1727, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29575167

RESUMO

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.


Assuntos
Esomeprazol/administração & dosagem , Esomeprazol/uso terapêutico , Refluxo Gastroesofágico/tratamento farmacológico , Pacientes Ambulatoriais , Inibidores da Bomba de Prótons/administração & dosagem , Inibidores da Bomba de Prótons/uso terapêutico , 2-Piridinilmetilsulfinilbenzimidazóis/administração & dosagem , 2-Piridinilmetilsulfinilbenzimidazóis/uso terapêutico , Adolescente , Adulto , Idoso , Grupo com Ancestrais do Continente Asiático , Feminino , Humanos , Lansoprazol/administração & dosagem , Lansoprazol/uso terapêutico , Masculino , Pessoa de Meia-Idade , Omeprazol/administração & dosagem , Omeprazol/uso terapêutico , Pantoprazol , Estudos Prospectivos , Rabeprazol/administração & dosagem , Rabeprazol/uso terapêutico , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
8.
World J Gastroenterol ; 23(42): 7635-7643, 2017 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-29204063

RESUMO

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.


Assuntos
Síndrome do Intestino Irritável/terapia , Aceitação pelo Paciente de Cuidados de Saúde , Adulto , Grupo com Ancestrais do Continente Asiático , Colonoscopia/estatística & dados numéricos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
9.
PLoS One ; 12(4): e0175276, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28437458

RESUMO

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.


Assuntos
Trânsito Gastrointestinal/efeitos dos fármacos , Hiperalgesia/tratamento farmacológico , Íleo/efeitos dos fármacos , Mucosa Intestinal/efeitos dos fármacos , Prebióticos , Animais , Comportamento Animal/efeitos dos fármacos , Modelos Animais de Doenças , Hiperalgesia/microbiologia , Mucosa Intestinal/microbiologia , Masculino , Ratos , Ratos Wistar , Estresse Psicológico/microbiologia , Resultado do Tratamento
10.
Chin Med J (Engl) ; 129(11): 1330-3, 2016 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-27231171

RESUMO

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.


Assuntos
Tuberculose Gastrointestinal/diagnóstico , Adulto , Técnicas de Laboratório Clínico/métodos , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Peritonite Tuberculosa/diagnóstico , Estudos Retrospectivos , Tuberculose Pulmonar/diagnóstico , Adulto Jovem
11.
J Neurogastroenterol Motil ; 22(2): 310-20, 2016 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-26645247

RESUMO

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.

12.
Zhonghua Nei Ke Za Zhi ; 54(10): 865-9, 2015 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-26675026

RESUMO

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.


Assuntos
Monitoramento do pH Esofágico , Esôfago/anormalidades , Refluxo Gastroesofágico/fisiopatologia , Estudos de Casos e Controles , Transtornos da Motilidade Esofágica/fisiopatologia , Humanos , Manometria , Estudos Prospectivos
13.
World J Gastroenterol ; 21(30): 9156-62, 2015 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-26290643

RESUMO

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.


Assuntos
Detecção Precoce de Câncer/métodos , Gastroscopia , Aumento da Imagem , Imagem de Banda Estreita , Neoplasias Gástricas/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia , China , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Variações Dependentes do Observador , Valor Preditivo dos Testes , Prognóstico , Estudos Prospectivos , Reprodutibilidade dos Testes
14.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 37(1): 23-9, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25676266

RESUMO

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.


Assuntos
Regulação Neoplásica da Expressão Gênica , Genoma Humano , Gastropatias , Neoplasias Gástricas , Algoritmos , Regulação para Baixo , Humanos , Metabolismo dos Lipídeos , Software , Regulação para Cima
15.
World J Gastroenterol ; 20(47): 17883-93, 2014 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-25548486

RESUMO

AIM: To investigate the differentiated whole genome expression profiling of gastric high- and low-grade intraepithelial neoplasia and early-stage adenocarcinoma. METHODS: Gastric specimens from an upper magnifying chromoendoscopic targeted biopsy were collected from March 2010 to May 2013. Whole genome expression profiling was performed on 19 low-grade intraepithelial neoplasia (LGIN), 20 high-grade intraepithelial neoplasia (HGIN), 19 early-stage adenocarcinoma (EGC), and 19 chronic gastritis tissue 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. The differentially expressed gene was verified using a real-time TaqMan® PCR assay with independent tissue samples, including 26 LGIN, 15 HGIN, 14 EGC, and 20 chronic gastritis. The expression of G0S2 were further validated by immunohistochemical staining (IHC) in 24 LGIN, 40 HGIN, 30 EGC and 61 chronic gastritis specimens. RESULTS: The gene expression patterns of LGIN and HGIN tissues were distinct. There were 2521 significantly differentially expressed transcripts in HGIN, with 951 upregulated and 1570 downregulated. A GO enrichment analysis demonstrated that the most striking overexpressed transcripts in HGIN compared with LGIN were in the category of metabolism, defense response, and nuclear factor κB (NF-κB) cascade. While the vast majority of transcripts had barely altered expression in HGIN and EGC tissues, only 38 transcripts were upregulated in EGC. A GO enrichment analysis revealed that the alterations of the immune response were most prominent in the progression from HGIN to EGC. It is worth noting that, compared with LGIN, 289 transcripts were expressed at higher levels both in HGIN and EGC. A characteristic gene, G0/G1 switch 2 (G0S2) was one of the 289 transcripts and related to metabolism, the immune response, and the NF-κB cascade, and its expression was validated in independent samples through real-time TaqMan® PCR and immunohistochemical staining. In real-time PCR analysis, the expression of G0S2 was elevated both in HGIN and EGC compared with that in LGIN (P < 0.01 and P < 0.001, respectively). In IHC analysis, G0S2 immunoreactivity was detected in the cytoplasmic of neoplastic cells, but was undetectable in chronic gastritis cells. The G0S2 expression in HGIN was higher than that of LGIN (P = 0.012, χ (2) = 6.28) and EGC (P = 0.008, χ (2) = 6.94). CONCLUSION: A clear biological distinction between gastric high- and low-grade intraepithelial neoplasia was identified, and provides molecular evidence for clinical application.


Assuntos
Adenocarcinoma/patologia , Biomarcadores Tumorais/genética , Carcinoma in Situ/genética , Perfilação da Expressão Gênica , Neoplasias Gástricas/genética , Adenocarcinoma/química , Adenocarcinoma/metabolismo , Adulto , Idoso , Biomarcadores Tumorais/análise , Biópsia , Carcinoma in Situ/química , Carcinoma in Situ/patologia , Proteínas de Ciclo Celular/análise , Proteínas de Ciclo Celular/genética , Biologia Computacional , Bases de Dados Genéticas , Diagnóstico Diferencial , Feminino , Perfilação da Expressão Gênica/métodos , Regulação Neoplásica da Expressão Gênica , Predisposição Genética para Doença , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Análise de Sequência com Séries de Oligonucleotídeos , Fenótipo , Valor Preditivo dos Testes , Reação em Cadeia da Polimerase em Tempo Real , Reprodutibilidade dos Testes , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Neoplasias Gástricas/química , Neoplasias Gástricas/patologia , Transcrição Genética
16.
Am J Physiol Gastrointest Liver Physiol ; 304(10): G855-63, 2013 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-23518679

RESUMO

Serotonin [5-hydroxytryptamine (5-HT)] is released from enterochromaffin cells in the mucosa of the small intestine. We tested a hypothesis that elevation of 5-HT in the environment of enteric mast cells might degranulate the mast cells and release mediators that become paracrine signals to the enteric nervous system, spinal afferents, and secretory glands. Western blotting, immunofluorescence, ELISA, and pharmacological analysis were used to study expression of 5-HT receptors by mast cells in the small intestine and action of 5-HT to degranulate the mast cells and release histamine in guinea pig small intestine and segments of human jejunum discarded during Roux-en-Y gastric bypass surgeries. Mast cells in human and guinea pig preparations expressed the 5-HT1A receptor. ELISA detected spontaneous release of histamine in guinea pig and human preparations. The selective 5-HT1A receptor agonist 8-hydroxy-PIPAT evoked release of histamine. A selective 5-HT1A receptor antagonist, WAY-100135, suppressed stimulation of histamine release by 5-HT or 8-hydroxy-PIPAT. Mast cell-stabilizing drugs, doxantrazole and cromolyn sodium, suppressed the release of histamine evoked by 5-HT or 8-hydroxy-PIPAT in guinea pig and human preparations. Our results support the hypothesis that serotonergic degranulation of enteric mast cells and release of preformed mediators, including histamine, are mediated by the 5-HT1A serotonergic receptor. Association of 5-HT with the pathophysiology of functional gastrointestinal disorders (e.g., irritable bowel syndrome) underlies a question of whether selective 5-HT1A receptor antagonists might have therapeutic application in disorders of this nature.


Assuntos
Mucosa Intestinal/metabolismo , Mastócitos/metabolismo , Receptor 5-HT1A de Serotonina/biossíntese , Animais , Western Blotting , Cromolina Sódica/farmacologia , Sistema Nervoso Entérico/metabolismo , Ensaio de Imunoadsorção Enzimática , Cobaias , Antagonistas dos Receptores Histamínicos H1/farmacologia , Humanos , Imuno-Histoquímica , Indicadores e Reagentes , Intestinos/citologia , Intestinos/efeitos dos fármacos , Cetotifeno/farmacologia , Masculino , Mastócitos/efeitos dos fármacos , Neuroglia/fisiologia , Neurônios/fisiologia , Inibidores de Fosfodiesterase/farmacologia , Piperazinas/farmacologia , Antagonistas da Serotonina/farmacologia , Tetrodotoxina/farmacologia , Tioxantenos/farmacologia , Xantonas/farmacologia , p-Metoxi-N-metilfenetilamina/farmacologia
17.
Zhonghua Nei Ke Za Zhi ; 52(12): 1045-7, 2013 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-24503404

RESUMO

OBJECTIVE: To summarize the clinical features of the third portion of duodenum (PATD) for improving the understanding of PATD. METHODS: Sixteen cases with PATD in Peking Union Medical College Hospital(PUMCH) were retrospectively analyzed. RESULTS: The most common symptoms of PATD were upper abdominal pain (12/16) , vomiting (9/16) and distention (7/16).On average, the disease had progressed 5.5 months (including 2.5 months of diagnostic workup) before the diagnosis was established. Patients with pathologically poorly differentiated PATD had shorter course of disease (6.5 vs 16.6 months, P = 0.56) and lower chance of cancer-directed surgery (1/8 vs 6/8, P = 0.04) than those with well differentiated PATD. The diagnostic rate was 11/14 by CT scan while only 2/7 by upper gastrointestinal radiography. Three cases were misdiagnosed as superior mesenteric artery syndrome by barium examination. CONCLUSIONS: PATD should be considered in patients presenting upper abdominal symptoms with negative gastro endoscopy and barium examination.Overall, CT scan plays a pivotal role in diagnosing PATD. Making a correct diagnosis timely can improve the outcome of PATD patients, particularly, in those with poorly differentiated pathology.


Assuntos
Neoplasias Duodenais , Adulto , Idoso , Neoplasias Duodenais/diagnóstico , Neoplasias Duodenais/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
18.
Zhonghua Nei Ke Za Zhi ; 50(3): 209-11, 2011 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-21600083

RESUMO

OBJECTIVE: To increase the understanding in protein-losing enteropathy (PLE). METHODS: Sixty-one PLE patients were enrolled in the study and the clinical characteristics, complicated disease, diagnosis and treatment were analyzed. RESULTS: The age of the patients was 16 - 77 (40 ± 15) years, and the gender ratio was 35:26 (female:male). The main clinical manifestations were bilateral lower limb edema in 51 cases, ascites in 41 cases, bilateral pleural effusion in 23 cases, pericardial effusion in 13 cases, abdominal pain in 16 cases and diarrhea in 33 cases. The prominent abnormality in laboratory examinations was hypoalbuminemia. The underlying diseases include systemic lupus erythematosus (SLE) in 28 cases, intestinal lymphangiectasia in 12 cases, hepatic cirrhosis in 5 cases, heart diseases in 5 cases, Crohn's disease in 3 cases, membranous nephropathy in 2 cases, Budd-Chiari syndrome in 1 case. Four cases happened after abdominal operation and 1 case after radiation therapy of gastric cardia cancer. Thirty-seven cases were diagnosed by (99)Tc(m)-labelled human serum albumin scintigraphy and 24 cases were diagnosed clinically. Treatment was focused on underlying diseases. The clinical manifestations in 21 cases of SLE improved after SLE was controlled. In 2 cases of intestinal lymphangiectasia and one with Crohn's disease, the clinical manifestations improved after surgery. The other patients had no improvement. CONCLUSIONS: PLE was not uncommon in clinical practice. Its predominant characteristics were severe hypoalbuminemia, edema and dropsy of serous cavity. PLE can complicate other diseases such as SLE, intestinal lymphangiectasia. Treatment should be focused on primary disease.


Assuntos
Enteropatias Perdedoras de Proteínas , Adolescente , Adulto , Idoso , Feminino , Humanos , Lúpus Eritematoso Sistêmico/complicações , Linfangiectasia Intestinal/complicações , Masculino , Pessoa de Meia-Idade , Enteropatias Perdedoras de Proteínas/complicações , Enteropatias Perdedoras de Proteínas/diagnóstico , Enteropatias Perdedoras de Proteínas/terapia , Agregado de Albumina Marcado com Tecnécio Tc 99m , Adulto Jovem
19.
J Pharmacol Exp Ther ; 334(1): 333-40, 2010 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-20406855

RESUMO

Lubiprostone activates ClC-2 chloride channels in epithelia. It is approved for treatment of chronic idiopathic constipation in adults and constipation-predominate irritable bowel syndrome in women. We tested a hypothesis that lubiprostone can reverse the constipating action of morphine and investigated the mechanism of action. Short-circuit current (Isc) was recorded in Ussing chambers as a marker for chloride secretion during pharmacological interactions between morphine and lubiprostone. Measurements of fecal wet weight were used to obtain information on morphine-lubiprostone interactions in conscious mice. Morphine decreased basal Isc, with an IC(50) of 96.1 nM. The action of dimethylphenylpiperazinium (DMPP), a nicotinic receptor agonist that stimulates neurogenic Isc, was suppressed by morphine. Lubiprostone applied after pretreatment with morphine reversed morphine suppression of both basal Isc and DMPP-evoked chloride secretion. Electrical field stimulation (EFS) of submucosal neurons evoked biphasic increases in Isc. Morphine abolished the first phase and marginally suppressed the second phase. Lubiprostone reversed, in concentration-dependent manner, the action of morphine on the first and second phases of the EFS-evoked responses. Subcutaneous lubiprostone increased fecal wet weight and numbers of pellets expelled. Morphine significantly reduced fecal wet weight and number of pellets. Injection of lubiprostone, 30-min after morphine, reversed morphine-induced suppression of fecal wet weight. We conclude that inhibitory action of morphine on chloride secretion reflects suppression of excitability of cholinergic secretomotor neurons in the enteric nervous system. Lubiprostone, which does not directly affect enteric neurons, bypasses the neurogenic constipating effects of morphine by directly opening chloride channels in the mucosal epithelium.


Assuntos
Alprostadil/análogos & derivados , Canais de Cloreto/metabolismo , Constipação Intestinal/prevenção & controle , Mucosa Intestinal/metabolismo , Morfina/efeitos adversos , Alprostadil/administração & dosagem , Alprostadil/farmacologia , Alprostadil/uso terapêutico , Animais , Canais de Cloreto/antagonistas & inibidores , Cloro/metabolismo , Constipação Intestinal/induzido quimicamente , Relação Dose-Resposta a Droga , Fezes/química , Cobaias , Técnicas In Vitro , Mucosa Intestinal/efeitos dos fármacos , Intestinos/efeitos dos fármacos , Ativação do Canal Iônico/efeitos dos fármacos , Lubiprostona , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Morfina/administração & dosagem , Neurônios/metabolismo , Neurônios/fisiologia , Prostaglandinas/metabolismo
20.
Am J Physiol Gastrointest Liver Physiol ; 296(4): G823-32, 2009 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-19179625

RESUMO

Actions of lubiprostone, a selective type-2 chloride channel activator, on mucosal secretion were investigated in guinea pig small intestine and colon. Flat-sheet preparations were mounted in Ussing flux chambers for recording short-circuit current (Isc) as a marker for electrogenic chloride secretion. Lubiprostone, applied to the small intestinal mucosa in eight concentrations ranging from 1-3000 nM, evoked increases in Isc in a concentration-dependent manner with an EC50 of 42.5 nM. Lubiprostone applied to the mucosa of the colon in eight concentrations ranging from 1-3000 nM evoked increases in Isc in a concentration-dependent manner with an EC50 of 31.7 nM. Blockade of enteric nerves by tetrodotoxin did not influence stimulation of Isc by lubiprostone. Antagonists acting at prostaglandin (PG)E2, EP1-3, or EP4 receptors did not suppress stimulation of Isc by lubiprostone but suppressed or abolished PGE2-evoked responses. Substitution of gluconate for chloride abolished all responses to lubiprostone. The selective CFTR channel blocker, CFTR(inh)-172, did not suppress lubiprostone-evoked Isc. The broadly acting blocker, glibenclamide, suppressed (P<0.001) lubiprostone-evoked Isc. Lubiprostone, in the presence of tetrodotoxin, enhanced carbachol-evoked Isc. The cholinergic component, but not the putative vasoactive intestinal peptide component, of neural responses to electrical field stimulation was enhanced by lubiprostone. Application of any of the prostaglandins, E2, F2, or I2, evoked depolarization of the resting membrane potential in enteric neurons. Unlike the prostaglandins, lubiprostone did not alter the electrical behavior of enteric neurons. Exposure to the histamine H2 receptor agonists increased basal Isc followed by persistent cyclical increases in Isc. Lubiprostone increased the peak amplitude of the dimaprit-evoked cycles.


Assuntos
Alprostadil/análogos & derivados , Colo/efeitos dos fármacos , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/metabolismo , Intestino Delgado/efeitos dos fármacos , Alprostadil/administração & dosagem , Alprostadil/farmacologia , Animais , Transporte Biológico/efeitos dos fármacos , Catárticos/farmacologia , Cloretos/metabolismo , Colo/metabolismo , Relação Dose-Resposta a Droga , Cobaias , Histamina/metabolismo , Intestino Delgado/metabolismo , Lubiprostona , Neurônios/fisiologia , Prostaglandinas/metabolismo
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