关键词： Inflammatory bowel disease   Colitis   TNBS-induced   [F-18]FDG PET   Rat model  

摘要： Inflammatory bowel disease (IBD) is a group of chronic disorders of the gastrointestinal tract, which two main types are Crohn's disease and ulcerative colitis. It has multifactorial etiologies, being essential the use of animal models and disease activity measures to develop new therapies. With this aim, the use of animal models in combination with non-invasive molecular imaging can play an important role in the development of new treatments. In this study, IBD was induced in rats using 2,4,6-trinitrobenzenesulfonic acid (TNBS) and longitudinal [F-18]FDG PET/CT scans were conducted to assess disease progression post-TNBS administration. Afterwards, [F-18]FDG PET/CT scans were carried out after treatment with methylprednisolone to validate the model. In non-treated rats, SUVmax (Standardized Uptake Value) rapidly increased after IBD induction, being particularly significant (p < 0.01) on days 7-13 after induction. There were no significant differences between non-treated and treated IBD rats from days 0-3. Nevertheless, treated IBD rats showed a significant decrease in SUVmax between days 7-13 (p < 0.01). Histological examination showed descending and transverse colon as the most affected regions. There was a moderate (R-2 = 0.61) and strong (R-2 = 0.82) correlation of SUV(max )with Nancy grade (parameter for histological assessment of disease activity) and weight changes, respectively. In this study, we have performed the first longitudinal [F-18]FDG PET/CT assessment of TNBS-induced IBD in rats, demonstrating the potential role of preclinical molecular imaging for the evaluation of new therapies in combination with IBD rat models.

关键词： inflammatory bowel disease   mesenchyme   stromal cell   crypt niche   Wnts   TNFSF14   SOX6   stratification   target discovery   single-cell RNA-seq   CyTOF  

摘要： Intestinal mesenchymal cells play essential roles in epithelial homeostasis, matrix remodeling, immunity, and inflammation. But the extent of heterogeneity within the colonic mesenchyme in these processes remains unknown. Using unbiased single-cell profiling of over 16,500 colonic mesenchymal cells, we reveal four subsets of fibroblasts expressing divergent transcriptional regulators and functional pathways, in addition to pericytes and myofibroblasts. We identified a niche population located in proximity to epithelial crypts expressing SOX6, F3 (CD142), and WNT genes essential for colonic epithelial stem cell function. In colitis, we observed dysregulation of this niche and emergence of an activated mesenchymal population. This subset expressed TNF superfamily member 14 (TNFSF14), fibroblastic reticular cell-associated genes, IL-33, and Lysyl oxidases. Further, it induced factors that impaired epithelial proliferation and maturation and contributed to oxidative stress and disease severity in vivo. Our work defines how the colonic mesenchyme remodels to fuel inflammation and barrier dysfunction in IBD.

关键词： 炎性肠疾病/病理生理学   白细胞介素类/代谢   免疫组织化学   印迹法,蛋白质   随机对照试验   疾病模型,动物  

摘要： 目的:研究IL-35在炎性肠疾病中的抗炎作用及相关机制。方法:BALB/c雌性小鼠共30只,随机分为对照组、模型组(口服4%葡聚糖硫酸钠7 d)、IL-35组(口服4%葡聚糖硫酸钠7 d,第2～5天腹腔注射IL-35 2μg/d),每组10只。每天对小鼠进行疾病活动指数(DAI)评分; 7 d后处死小鼠,留取血清和肠道组织,观察结肠大体形态; HE染色观察各组结肠组织病理形态变化;流式细胞术检测各组结肠组织中巨噬细胞极化情况;实时定量RT-PCR检测各组结肠组织中细胞因子IL-6、TNF-α、γ干扰素(IFN-γ)、IL-10和Src同源系列2结构域的肌醇5-磷酸酶1(SHIP1)的mRNA表达量;免疫组织化学法检测各组结肠组织中SHIP1的表达及分布情况;蛋白质印迹法检测各组结肠组织中SHIP1蛋白的表达。结果:模型组在实验过程中DAI评分较对照组增加,而IL-35组自第4天起DAI评分较模型组减少(均P<0.01);与对照组比较,模型组结肠明显缩短(P<0.05),而IL-35组的结肠长度长于模型组,但差异无统计学意义(P>0.05);与模型组比较,IL-35组炎症细胞浸润减少、黏膜组织炎症评分和腺窝破坏组织评分较模型组减少(均P<0.05); IL-35组结肠组织中促炎因子IL-6、TNF-α和IFN-γ的mRNA相对表达量较模型组减少,而抑炎因子IL-10的mRNA相对表达量较模型组增加(均P<0.05);与对照组比较,模型组M1型巨噬细胞比例增加(P<0.05),而IL-35组M1型巨噬细胞的比例较模型组减少(P<0.05); IL-35组小鼠结肠组织中SHIP1mRNA和蛋白相对表达量均较模型组增加(均P<0.05)。结论:在炎性肠疾病中,IL-35可以通过调控SHIP1表达抑制M1型巨噬细胞极化,以及调节炎症因子的表达发挥抗炎作用。

关键词： 肠疾病   胶囊内窥镜检查   老年人   诊断  

摘要： 目的探讨胶囊内镜(CE)在老年小肠疾病诊断中的应用价值及安全性。方法选取2015年2月—2017年2月因不明原因消化道出血(OGIB)、慢性腹痛、慢性腹泻、腹胀不适、消瘦等症状在河南科技大学第一附属医院门诊或住院接受CE检查的患者137例。按照年龄分为老年组(≥60岁,75例)和对照组(<60岁,62例)。回顾性分析两组患者的CE检查情况,包括CE在胃及小肠运行时间、胶囊排出时间、全小肠检查完成率(即胶囊在电池耗尽后通过回盲瓣进入大肠的患者比例)及胶囊滞留率(指胶囊2周或超过2周时间仍不能从消化道排出的患者比例),CE的图像质量、对小肠疾病检出率及所见病变的类型。结果老年组CE在胃及小肠运行时间、胶囊排出时间均长于对照组(P<0.05);老年组全小肠检查完成率低于对照组(P<0.05);两组胶囊滞留率比较,差异无统计学意义(P>0.05)。老年组小肠疾病检出率(61.3%)高于对照组(43.5%)(P<0.05);老年组检出的小肠疾病以血管性病变和非甾体类抗炎药(NSAIDs)相关性黏膜损害为主,而对照组以小肠溃疡为主。老年组OGIB的CE小肠疾病检出率高于慢性腹痛、慢性腹泻、其他症状(P<0.05)。结论 CE在老年患者消化道运行时间较长,但胶囊滞留率与中青年患者无差异,是一项安全的检查方法,并且对老年小肠疾病检出率较高,尤其对OGIB具有较好的诊断价值。

关键词： Heart Failure   Inflammatory Bowel Diseases   Acute Myocardial Infarction   Intestinal Diseases   Patients  

关键词： Intestinal Diseases   Affection   Surgery   Resorts   driver circuits   decision making   Inflammatory Bowel Diseases  

关键词： INFLAMMATORY bowel diseases   ADRENAL insufficiency  

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