关键词： effector protein   nanoparticles   colitis   intracellular delivery   anti-inflammatory  

摘要： Bacterial enteric pathogens have evolved efficient mechanisms to suppress mammalian inflammatory and immunoregulatory pathways. By exploiting the evolutionary relationship between the gut and pathogenic bacteria, we have developed a potential mucosal therapeutic. Our findings suggest that engineered preparations of the Salmonella acetyltransferase, AvrA, suppress acute inflammatory responses such as those observed in inflammatory bowel disease (IBD). We created 125 nm diameter cross-linked protein nanoparticles directly from AvrA and carrier protein to deliver AvrA in the absence of Salmonella. AvrA nanoparticles are internalized in vitro and in vivo into barrier epithelial and lamina propria monocytic cells. AvrA nanoparticles inhibit inflammatory signaling and confer cytoprotection in vitro, and in murine colitis models, we observe decreased clinical and histological indices of inflammation. Thus, we have combined naturally evolved immunomodulatory proteins with modern bioengineering to produce AvrA nanoparticles, a potential treatment for IBD.

关键词： 肛肠疾病   术后尿潴留   治疗方式   护理方式  

摘要： 尿潴留是指膀胱内充满尿液而不能自行排出,常常由排尿困难发展到一定程度引起。属于肛肠疾病术后常见的并发症之一,导致患者出现尿潴留现象的因素较多,为此,主治医师和护理人员需要结合不同因素选择不同的治疗和护理方式。本文则以论述肛肠疾病术后尿潴留现象产生的原因出发,并在基础上分析和总结了不同的尿潴留治疗和护理方式,旨在为肛肠疾病术后尿潴留的治疗提供参考意见。

关键词： Inflammatory bowel disease   2-Benzylidene-2,3-dihydro-1H-inden-1-one   Benzofuran-3(2H)-one   TNF-alpha   Structure-activity relationship  

摘要： To develop effective therapeutics for inflammatory bowel disease (IBD), 2-benzylidene-2,3-dihydro-1-Hinden-1-one and benzofuran-3(2H)-one derivatives, were designed and synthesized and their structure activity relationships (SAR) were investigated. Compounds 7, 25, 26, 32, 39, 41, 52, 54, and 55 showed potent inhibitory effect (>70%) on the TNF-alpha-induced adhesion of monocytes to colon epithelial cells, which is one of the hallmark events leading to IBD. Such inhibitory activity of the compounds correlated with their suppressive activities against the TNF-alpha-induced production of ROS;ICAM-1 and MCP-1 expression, critical molecules involved in monocyte-epithelial adhesion;and NF-kappa B transcriptional activity. In addition, compounds 41 and 55 significantly suppressed the lipopolysaccharide (LPS)-induced expression of the TNF-alpha gene, with compound 55 showing better efficacy. This inhibition of TNF-alpha expression by compounds 41 and 55 corresponded to their additional inhibitory activity against AP-1 transcriptional activity, which is another transcription factor required for high level TNF-alpha expression. The strong inhibitory activity of compound 55 against an in vivo colitis model was confirmed by its dose dependent inhibitory activity in a rat model of 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced colitis, demonstrating compound 55 as a new potential candidate for the development of therapeutics against IBD. (C) 2017 Elsevier Masson SAS. All rights reserved.

摘要： Background Tight and personalised control of inflammatory bowel disease in a traditional setting is challenging because of the disease complexity, high pressure on outpatient clinics, and rising incidence. We compared the effects of self-management with a telemedicine system, which was developed for all subtypes of inflammatory bowel disease, on health-care utilisation and patient-reported quality of care versus standard care. Methods We did this pragmatic, randomised trial in two academic and two non-academic hospitals in the Netherlands. Outpatients aged 18-75 years with inflammatory bowel disease and without an ileoanal or ileorectal pouch anastomosis, who had internet access and Dutch proficiency, were randomly assigned (1: 1) to care via a telemedicine system (myIBDcoach) that monitors and registers disease activity or standard care and followed up for 12 months. Randomisation was done with a computer-generated sequence and used the minimisation method. Participants, health-care providers, and staff who assessed outcome measures were not masked to treatment allocation. Primary outcomes were the number of outpatient visits and patient-reported quality of care (assessed by visual analogue scale score 0-10). Safety endpoints were the numbers of flares, corticosteroid courses, hospital admissions, emergency visits, and surgeries. Analyses were by intention to treat. This trial is registered with ClinicalTrials. gov, number NCT02173002. Findings Between Sept 9, 2014, and May 18, 2015, 909 patients were randomly assigned to telemedicine (n=465) or standard care (n=444). At 12 months, the mean number of outpatient visits to the gastroenterologist or nurse was significantly lower in the telemedicine group (1.55 [SD1.50]) than in the standard care group (2.34 [1.64];difference -0.79 [95%CI -0.98 to -0.59];p < 0.0001), as was the mean number of hospital admissions (0.05 [0.28] vs 0.10 [0.43];difference -0.05 [-0.10 to 0.00];p=0.046). At 12 months, both groups reported hi

关键词： ATRIAL fibrillation   PATIENTS   INTESTINAL ischemia  

关键词： 肠疾病   Hirschsprung病   免疫组织化学   钙视网膜蛋白  

摘要： 目的 研究钙视网膜蛋白（calretinin,CR）在全结肠无神经节细胞症（total colonic aganglionosis, TCA）不同肠段的表达,探讨其临床意义.方法 收集华中科技大学同济医学院附属武汉儿童医院2010至2016年TCA行回肠结肠根治手术病例9例,另选取9例因其他疾病切除肠管的正常手术切断缘作为对照.对其进行常规HE及免疫组织化学EnVision法染色,观察CR在结肠、回肠及TCA不同肠段中的表达模式,并对黏膜固有层及黏膜肌层内CR阳性纤维进行计数,同时应用图像分析软件（Image-Pro-Plus）判定CR阳性染色在黏膜固有膜内的平均吸光度,分析其在不同肠段中的表达差异.结果 CR在回肠和结肠中的染色模式相似,含神经节细胞的回肠和结肠黏膜固有膜和黏膜肌层均可见CR染色阳性纤维,其数量差异无统计学意义（P〉0.05）;无节细胞的回肠和结肠CR阳性纤维数量显著少于对照组和切断缘（P〈0.01）;回肠移行段黏膜CR阳性神经纤维数量明显少于回肠切断缘（P〈0.01）,其黏膜下及肌间可见小的神经丛,CR神经纤维呈不连续的束状染色.结论CR在TCA含节细胞肠段和无节细胞肠段的表达存在显著差异,具备辅助诊断TCA的潜在价值,有望成为诊断TCA的重要方法.

关键词： 超声检查   造影剂   胃十二指肠疾病   筛查  

摘要： 目的探讨口服超声造影(OCUS)筛查农村无症状人群胃十二指肠病变的临床价值。方法选取上海市崇明县农村地区5个自然村无症状人群计3240例,开展OCUS筛查胃十二指肠疾病。让受检者口服超声造影剂,实时测量贲门内径、胃体部胃壁厚度、幽门管内径等,观察各部位形态、层次结构及其动态改变。凡检出声像图异常改变者行胃镜检查。采用Kappa检验分析OCUS筛查结果与病理结果的一致性。结果 OCUS筛查检出各类胃十二指肠病变共51例,检出率为1.57%(51/3240),筛查结果与胃镜和(或)手术病理检查符合率为93.75%(45/48),一致性好(Kappa=0.905)。共检出胃癌5例,检出率为0.15%(5/3240)。结论 OCUS可用于农村地区胃十二指肠疾病筛查,值得进一步研究评估。

关键词： Inflammatory bowel diseases   Ulcerative colitis   Crohn's disease   Glucocorticoid dependence   Glucocorticoid resistance  

摘要： Inflammatory bowel diseases(IBDs),such as ulcerative colitis and Crohn's disease,are chronic pathologies associated with a deregulated immune response in the intestinal mucosa,and they are triggered by environmental factors in genetically susceptible *** glucocorticoids(GCs)are widely used as anti-inflammatory therapy in *** the past,patients with moderate or severe states of inflammation received GCs as a first line therapy with an important effectiveness in terms of reduction of the disease activity and the induction of ***,this treatment often results in detrimental side *** downside drove the development of second generation GCs and more precise(non-systemic)drugdelivery *** clinical trials show that most of these new treatments have similar effectiveness to first generation GCs with fewer adverse *** remaining challenge in successful treatment of IBDs concerns the refractoriness and dependency that some patients encounter during GCs treatment.A deeper understanding of the molecular mechanisms underlying GC response is key to personalizing drug choice for IBDs patients to optimize their response to *** this review,we examine the clinical characteristics of treatment with GCs,followed by an in depth analysis of the proposed molecular mechanisms involved in its resistance and dependence associated with *** thorough analysis of current clinical and biomedical literature may help guide physicians in determining a course of treatment for IBDs patients and identifies important areas needing further study.