关键词： inflammatory bowel disease   inflammation   soy protein   lymphatics   bone   cytokines  

摘要： Inflammatory bowel disease is a condition that leads to gut pathologies such as abnormal lymphatic architecture, as well as to systemic comorbidities such as bone loss. Furthermore, current therapies are limited to low efficacy and incur side effects. Dietary interventions have been explored minimally, but may provide a treatment for improving gut outcomes and comorbidities. Indeed, plant-based soy protein has been shown to exert anti-inflammatory effects. Here, we tested the impact of a moderately elevated soy protein diet in a chronic, 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis model on gut and bone inflammatory-mediated pathophysiological adaptations. Colitis was induced by intrarectal administration of TNBS. Gut histopathology was scored, and lymphatic structural changes and the local inflammatory state were assessed via immunofluorescence. In addition, the effects of gut inflammation on bone turnover and osteocyte proteins were determined via histonior-phometry and immunohistochemistry, respectively. The moderately elevated soy protein diet produced improvements in both colonic and bone tissues. In TNBS animals given the soy protein intervention, colon histological scores were reduced and the abnormal lymphatic architecture resolved. There were also improvements in bone formation and reduced bone resorption. In addition, TNBS increased inflammatory cytokines such as tumor necrosis factor-a and receptor activator of nuclear factor kappa-B ligand in the gut and bone, but this was resolved in both tissues with the dietary soy protein intervention. The moderately elevated soy protein diet mitigated gut and bone inflammation in a chronic, TNBS-induced colitis model, demonstrating the potential for soy protein as a potential anti-inflammatory dietary intervention for inflammatory bowel disease.

关键词： Inflammatory bowel disease   TAK-828F   RORt inverse agonist   IL-23   Th17 pathway   Mouse colitis model  

摘要： Objective and designTo evaluate the potency of RORt blockade for treatment of Inflammatory Bowel Disease (IBD), the efficacy of TAK-828F, a novel RORt inverse agonist, in anti-TNF- mAb non-responsive mouse colitis model and effect of TAK-828F on IL-17 production in peripheral mononuclear blood cells (PBMCs) of anti-TNF- naive and treatment-failure patients of IBD was *** and resultsThe colitis model showed Th17-dependent pathogenicity and response to anti-IL-12/23p40 monoclonal antibody (mAb), but no response to anti-TNF- mAb. In the model, TAK-828F, at oral dosages of 1 and 3mg/kg, inhibited progression of colitis and reduced the immune reaction that characterize Th17 cells. Anti-IL-17A mAb showed neither efficacy nor change in the T cell population and colonic gene expression in the model. In the normal mouse, a 4-week treatment of TAK-828F at 30mg/kg did not severely reduce lymphocyte cell counts in peripheral and intestinal mucosa, which was observed in ROR-/- mice. TAK-828F strongly inhibited IL-17 gene expression with IC50 values from 21.4 to 34.4nmol/L in PBMCs from anti-TNF mAb naive and treatment-failure patients of *** results indicate that RORt blockade would provide an effective approach for treating refractory patients with IBD by blocking IL-23/Th17 pathway.

关键词： arthritis   Crohn   sacroiliitis  

摘要： A comparison of 23 children with inflammatory bowel disease presenting with musculoskeletal symptoms and 46 children with arthritis of other causes yielded significantly higher rates in the inflammatory bowel disease group of sacroiliitis, arthralgia, additive and recurrent arthritis, microcytic anemia, elevated inflammatory markers, and hypoalbuminemia. Clinical awareness of these findings could expedite diagnosis and treatment.

摘要： The authors reply to a comment on their study that investigated the emergence of severe spondyloarthopathy (SpA)-related entheseal pathology following vedolizumab (VDZ) treatment for inflammatory bowel disease (IBD). They claim that evidences of synovitis pointed by reviewers support an underlying mucosal-vascular addressin cell adhesion molecule independent process. They also support further investigation on the pathogenic link between IBD and SpA in the context of VDZ-treatment related SpA.

关键词： inflammatory bowel disease unclassified   prognosis   treatment  

摘要： Background and Aim A definitive diagnosis of Crohn's disease (CD) or ulcerative colitis (UC) is not always possible, and a proportion of patients will be diagnosed as inflammatory bowel disease unclassified (IBDU). The aim of the study was to investigate the prognosis of patients initially diagnosed with IBDU and the disease course during the following 5 years. Methods The Epi-IBD study is a prospective population-based cohort of 1289 IBD patients diagnosed in centers across Europe. Clinical data were captured prospectively throughout the follow-up period. Results Overall, 476 (37%) patients were initially diagnosed with CD, 701 (54%) with UC, and 112 (9%) with IBDU. During follow-up, 28 (25%) IBDU patients were changed diagnoses to either UC (n = 20, 71%) or CD (n = 8, 29%) after a median of 6 months (interquartile range: 4-12), while 84 (7% of the total cohort) remained IBDU. A total of 17 (15%) IBDU patients were hospitalized for their IBD during follow-up, while 8 (7%) patients underwent surgery. Most surgeries (n = 6, 75%) were performed on patients whose diagnosis was later changed to UC;three of these colectomies led to a definitive diagnosis of UC. Most patients (n = 107, 96%) received 5-aminosalicylic acid, while 11 (10%) patients received biologicals, of whom five remained classified as IBDU. Conclusions In a population-based inception cohort, 7% of IBD patients were not given a definitive diagnosis of IBD after 5 years of follow-up. One in four patients with IBDU eventually was classified as CD or UC. Overall, the disease course and medication burden in IBDU patients were mild.

关键词： Crohn's diseaseMicrobiomeSystems analysisUlcerative colitis  

摘要： Inflammatory bowel diseases, which include Crohn's disease and ulcerative colitis, affect several million individuals worldwide. Crohn's disease and ulcerative colitis are complex diseases that are heterogeneous at the clinical, immunological, molecular, genetic, and microbial levels. Individual contributing factors have been the focus of extensive research. As part of the Integrative Human Microbiome Project (HMP2 or iHMP), we followed 132 subjects for one year each to generate integrated longitudinal molecular profiles of host and microbial activity during disease (up to 24 time points each;in total 2,965 stool, biopsy, and blood specimens). Here we present the results, which provide a comprehensive view of functional dysbiosis in the gut microbiome during inflammatory bowel disease activity. We demonstrate a characteristic increase in facultative anaerobes at the expense of obligate anaerobes, as well as molecular disruptions in microbial transcription (for example, among clostridia), metabolite pools (acylcarnitines, bile acids, and short-chain fatty acids), and levels of antibodies in host serum. Periods of disease activity were also marked by increases in temporal variability, with characteristic taxonomic, functional, and biochemical shifts. Finally, integrative analysis identified microbial, biochemical, and host factors central to this dysregulation. The study's infrastructure resources, results, and data, which are available through the Inflammatory Bowel Disease Multi'omics Database (http://***), provide the most comprehensive description to date of host and microbial activities in inflammatory bowel diseases.

关键词： Bacterial beta-glucuronidase   Colitis   Inflammatory bowel disease   Digestive proteases  

摘要： Objective: Inflammatory bowel diseases (IBD) including ulcerative colitis and Crohn's disease are devastating diseases of the gut. At present, all the treatments are mainly targeting symptoms like inflammation. The disease remains regarded as incurable, largely due to lacking of knowledge on its etiology. Our previous studies suggested that impaired inactivation of digestive proteases by deconjugated bilirubin in experimental colitis, thus bacterial beta-glucuronidase for catalyzing the reaction, may have played critical role in the pathogenesis of IBD. Methods: We first analyzed beta-glucuronidase activity in gut tissue and feces of mice by a colitis model. Then the effect of beta-glucuronidase on experimental colitis was investigated in detail by administration of beta-glucuronidase (from E. coli) and fecal material transplantation to mice with 3% DSS in drinking water for 7 days. Results: Mice with colitis showed unchanged activity of beta-glucuronidase in colon tissue but decreased activity in feces. Treatment with bacterial beta-glucuronidase at 100 U or above alleviated DSS-induced colitis as demonstrated by the less body weight loss, less disease activity score, increased expression of tight junction proteins and decreased gut permeability, decreases in MPO, TNF-alpha, IL-10, TLR-4 and MyD88, and increase in IL-10 and I kappa B3 alpha in gut, restored fecal beta-glucuronidase and gut microbiota along with decreases in fecal digestive proteases. Transplantation of fecal material from control to colitis mice showed similar effects as treatment with beta-glucuronidase. Conclusions: Bacterial beta-glucuronidase showed strong inhibition on colitis along with the reduction in fecal digestive proteases, which may be a crucial diagnostic and therapeutic target for IBD. (C) 2019 Published by Elsevier Inc.

关键词： Biopsy   Case series   Clinical medicine   Clinical research design   Clinical trials   Database and informatics methods   Database searching   Drug research and development   Gastroenterology and hepatology   Inflammatory bowel disease   Medicine and health sciences   Observational studies   Pharmacology   Randomized controlled trials   Research and analysis methods   Research Article   Research assessment   Research design   Routes of administration   Surgical and invasive medical procedures   Systematic reviews  

摘要： Background The recently established association between higher levels of DNA-incorporated thioguanine nucleotides and lower relapse risk in childhood acute lymphoblastic leukaemia (ALL) calls for reassessment of prolonged 6-thioguanine (6TG) treatment, while avoiding the risk of hepatotoxicity. Objectives To assess the incidence of hepatotoxicity in patients treated with 6TG, and to explore if a safe dose of continuous 6TG can be established. Data sources Databases, conference proceedings, and reference lists of included studies were systematically searched for 6TG and synonyms from 1998-2018. Methods We included studies of patients with ALL or inflammatory bowel disorder (IBD) treated with 6TG, excluding studies with 6TG as part of an intensive chemotherapy regimen. We uploaded a protocol to PROSPERO (registration number CRD42018089424). Database and manual searches yielded 1823 unique records. Of these, 395 full-texts were screened for eligibility. Finally, 134 reports representing 42 studies were included. Results and conclusions We included data from 42 studies of ALL and IBD patients;four randomised controlled trials (RCTs) including 3,993 patients, 20 observational studies including 796 patients, and 18 case reports including 60 patients. Hepatotoxicity in the form of sinusoidal obstruction syndrome (SOS) occurred in 9-25% of the ALL patients in two of the four included RCTs using 6TG doses of 40-60 mg/m(2)/day, and long-term hepatotoxicity in the form of nodular regenerative hyperplasia (NRH) was reported in 2.5%. In IBD patients treated with 6TG doses of approximately 23 mg/m(2)/day, NRH occurred in 14% of patients. At a 6TG dose of approximately 12 mg/m(2)/day, NRH was reported in 6% of IBD patients, which is similar to the background incidence. According to this review, doses at or below 12 mg/m(2)/day are rarely associated with notable hepatotoxicity and can probably be considered safe.

关键词： 中医护理适宜技术   肛肠疾病   术后尿潴留  

摘要： 研究肛肠疾病术后尿潴留患者实施中医护理适宜技术的价值。方法:纳入本院(2016年08月-2018年10月)接收肛肠疾病手术患者(n=106)作为研究对象;以随机表为基准;分为实验组(n=53;实施中医护理适宜技术)、对照组(n=53;实施常规护理);对106例患者尿潴留发生率、康复指标评估。结果:尿潴留发生率:实验组低于对照组;P<0.05。康复指标:实验组优于对照组;P<0.05。结论:肛肠疾病术后尿潴留患者实施中医护理适宜技术的价值显著;既可降低尿潴留发生率;又可提高排尿量;值得借鉴。