胃肠道免疫与ITP发病的相关性研究进展

原发免疫性血小板减少症(ITP)是一种以免疫紊乱为主的出血性疾病。近年来大量的临床研究表明:发现在确定自身免疫抗体之前,多数患者可以检测到胃肠道感染征象,且经抗感染治疗后,患者外周血小板能够获得提高。本文旨通过文献综述来讨论胃肠道免疫与ITP发病的相关性,以期指导临床。

免疫检查点抑制剂所致胃肠道免疫相关不良反应的中医病因病机及治法探讨

该文结合免疫检查点抑制剂(ICIs)的中医属性、胃肠道免疫相关不良反应(irAEs)易感人群的特征及临床表现等,探讨胃肠道irAEs的中医病因病机及治法。胃肠道irAEs总属虚实夹杂之证,热毒损伤肠腑为发病的病机关键,先后天之本受损为发病基础,治疗应扶正与祛邪并用,扶正以健脾益气、补脾益肾为主,祛邪以清热燥湿、淡渗利湿为主。

免疫检查点抑制剂所致胃肠道不良反应机制及中西医结合治疗

免疫检查点抑制剂已成为恶性肿瘤免疫治疗的热点,而胃肠道免疫相关不良反应是临床较常见的不良反应,根据临床症状可归属为中医“泄泻”“肠澼”的范畴。从胃肠道免疫相关不良反应情况及西医机制、治疗,并根据脾胃虚弱、湿热伤中、寒湿内盛,脾肾阳虚等进行中医辨证论治,通过外治法艾灸、穴位贴敷、灌肠等进行探讨,取得明显疗效,提高患者生活质量,达到减毒增效的效果,可为肿瘤临床免疫制剂应用以及不良反应治疗提供新的解决思路。

胃肠道微生态研究和益生素应用

本文综述动物胃肠道微生态研究有关进展,主要是胃肠道微生物丛与宿主免疫互作的研究进展以及益生素对宿主的免疫调节应用,简要讨论益生素产品研制和应用中需要注意的有关问题。

鸡IFITM3基因的序列分析和组织表达特征

目的:探讨干扰素诱导跨膜蛋白3(IFITM3)基因在鸡体内的表达与功能,为IFITM3的深入研究和禽流感的防治提供有价值的参考。方法:本研究通过搜索鸡的基因组数据获得鸡的IFITM3,使用生物信息学分析方法、荧光定量RT-PCR技术对鸡IFITM3基因的遗传进化、蛋白特性和组织表达分布进行了研究。结果:鸡的IFITM3蛋白序列全长113个氨基酸,含有两个长度相似的跨膜区和一个CD225结构域,二级结构与人的IFITM3相似,但N末端差异较大。S-棕榈酰化修饰对于IFITM3的抗病毒活性起着决定性作用。分析显示,鸡的IFITM3共含有4个潜在的S-棕榈酰化位点,即Cys45/49/53/89,意味着鸡的IFITM3蛋白也具有抗病毒活性。荧光定量RT-PCR结果显示,IFITM3在鸡的各组织表达广泛。在检测的17种组织中,仅血液没有表达。另外,IFITM3在以肺、脾为代表的非消化道组织表达量低,在以十二指肠、盲肠为代表的消化道组织和肝脏组织表达量高。鸡的IFITM3与人的IFITM3组织表达特征相似。结论:鸡的IFITM3基因对胃肠道免疫和肝脏免疫有重要作用。

FoxO4 is the main forkhead transcriptional factor localized in the gastrointestinal tracts of pigs

Forkhead box （Fox） proteins play critical roles in the regulation of differentiation, proliferation, immunity and aging of cells. Most studies on Fox proteins are limited to cultured cells and rodent. The aim of the current study is to detect by immunohistrochemistry whether FoxO1, FoxO3a and FoxO4 proteins are localized in the stomach and intestine of the pig. The results showed that FoxO4 exists in the mucosa in all parts of the stomach and intestine; FoxO3a exists mainly in the lamina propria and muscularis of some parts. However, FoxOl is not detectable in all parts of the stomach and intestine. Collectively, the results of the present study indicate that there exists a distinct expression pattern of Fox proteins, and that FoxO4 is a primary forkhead transcriptional factor localized in the gastrointestinal tracts of the pig.

Intestinal dendritic cells in the pathogenesis of inflammatory bowel disease

The gastrointestinal tract harbors a large number and diverse array of commensal bacteria and is an important entry site for pathogens.For these reasons,the intestinal immune system is uniquely dedicated to protect against infections,while avoiding the development of destructive inflammatory responses to the microbiota.Several models have been proposed to explain how the immune system discriminates between,and appropriately responds to,commensal and pathogenic microorganisms.Dendritic cells(DCs)and regulatory T cells(Treg)are instrumental in maintaining immune homeostasis and tolerance in the gut.DCs are virtually omnipresent and are remarkably plastic,having the ability to adapt to the influences of the microenvironment.Different DC populations with partially overlapping phenotypic and functional properties have been described in different anatomical locations.DCs in the draining mesenteric lymph nodes,in the intestinal lamina propria and in Peyer's patches partake both in the control of intestinal inflammation and in the maintenance of gut tolerance.In this respect,gutresident DCs and macrophages exert tolerogenic functions as they regularly encounter and sense commensal bacteria.In contrast,migrating DC subsets that are recruited to the gut as a result of pathogenic insults initiate immune responses.Importantly,tolerogenic DCs act by promoting the differentiation and expansion of Treg cells that efficiently modulate gut inflammation,as shown both in preclinical models of colitis and in patients with inflammatory bowel disease(IBD).This article reviews the phenotypic and functional features of gut DC subsets and discusses the current evidence underpinning the DC contribution to the pathogenesis of the major clinical subtypes of human IBD.It also addresses the potential clinical benefit derived from DC targeting either in vivo or in vitro.

Mucosal Schwann cell “Hamartoma”:A new entity?

Schwannoma is a well-described,benign nerve sheath tumor of the soft tissue,but is rare in the gastrointestinal tract.Gastrointestinal schwannomas are often incidentally discovered as small polypoid intraluminal lesions.In this report,we describe the clinicopathologic and immunohistochemical features of a distinctive neural mucosal polyp composed of a diffuse cellular proliferation of uniform bland spindled cells in the lamina propria that entraps the colonic crypts.Immunohistochemical analysis revealed strong and diffuse positivity for the S-100 protein.To avoid confusion of these solitary colorectal polyps containing pure spindled Schwann cell proliferation in the lamina propria with neural lesions that have significant association with inherited syndromes,it is better to use the designation "mucosal Schwann hamartoma".

Evaluation of malignancy using Ki-67,p53,EGFR and COX-2 expressions in gastrointestinal stromal tumors

AIM:To investigate the role of expressions of Ki-67, p53,epidermal growth factor receptor(EGFR)and cyclooxygenase-2(COX-2)in gastrointestinal stromal tumor(GIST)grading and prognosis. METHODS:Tumor tissue was collected retrospectively from 96 patients with GIST.Antibodies against Ki-67, p53,EGFR and COX-2 were used for immunohistochemical staining.Tumor grading was designated according to a consensus system and the staining was quantified in 3 categories for each antibody in the statistical analysis. RESULTS:The Ki-67 expression in GISTs was significantly associated with the size of the tumors,mitotic rate and the risk of malignancy(x2=15.51,P=0.02; x2=22.27,P<0.001;x2=20.05;P<0.001).The p53 expression was also significantly correlated with mitotic rate and the risk of malignancy(x2=9.92,P= 0.04;x2=9.97;P=0.04).Over-expression of Ki-67 was strongly correlated with poor survival(x2=10.44, P=0.006),but no correlation was found between the expression of p53,EGFR or COX-2 and survival. Multivariate analysis further demonstrated that Ki-67 expression(relative risk=15.78,95%CI:4.25-59.37) could be used as an independent prognostic value for GIST patients.Adjuvant imatinib therapy could improve clinical outcomes in the patients with high risk and intermediate risk of recurrence after complete tumor resections(median survival time:52 mo vs 37 mo, x2=7.618,P=0.006). CONCLUSION:Our results indicated that the expression of Ki-67 could be used as an independent prognostic factor for GIST patients.

Spontaneous rupture of the giant gastric stromal tumor(> 35 cm) as a rare cause of acute abdomen: a case report

A case of spontaneous rupture of giant gastrointestinal stromal tumor(GIST) of stomach causing acute abdomen is described below. A male patient with abdominal mass presented with symptoms and signs of acute abdomen after admitting for 1 day. After preoperative management and evaluation, an exploratory laparotomy was performed, where rupture of a huge tumor in the stomach was found. A subtotal gastrectomy including the mass was performed and the final immunohistochemical examination verified that the neoplasm was a high risk GIST. The postoperative period was uneventful and the patient received treatment with imatinib mesylate, and regular follow-up without recurrence.

A clinicopathologic and immunohistochemical study of gastrointestinal stromal tumors based on 122 cases

Objective:The aim of the study was to review the clinical records of 122 patients with gastrointestinal stromal tumors(GISTs) and analyze their clinicopathologic and immunohistochemical characteristics.Methods:The medic records of 122 patients with GISTs during the periods from January 2002 to May 2010 were reviewed.All tumors were confirmed by histological and immunohistochemical analyses.Results:The tumors occurred in 59 males and 63 females,ranging from 25 to 77 years.Of all cases,46 cases originated from stomach,42 from small intestine,17 from colon and rectum and 9 from retroperitoneal cavity and 4 cases from extra-gastrointestinal site.Liver was the most common organ that tumors metastases involved.Immunohistochemically,there were 114 tumors being positive for CD117 while 8 tumors negative for it.The frequencies of CD34 positive were higher in the stomach and rectum(89.1% and 86.7% respectively) than in the small intestine(64.3%,P < 0.05).Higher expression of SMA was in the tumors located in small intestine(54.8%) while the expressions of SMA in the gastric and rectal tumors were relatively low(21.7% and 20.0% respectively,P < 0.05).Conclusion:Gastrointestinal stromal tumors can occur in the gastrointestinal tract as well as in the extra-gastrointestinal sites.The frequencies of CD34 and SMA expression vary significantly with different locations.

Role of the endothelium in inflammatory bowel diseases

Inflammatory bowel diseases(IBD) are a complex group of diseases involving alterations in mucosal immunity and gastrointestinal physiology during both initiation and progressive phases of the disease.At the core of these alterations are endothelial cells,whose continual adjustments in structure and function coordinate vascular supply,immune cell emigration,and regulation of the tissue environment.Expansion of the endothelium in IBD(angiogenesis),mediated by inflammatory growth factors,cytokines and chemokines,is a hallmark of active gut disease and is closely related to disease severity.The endothelium in newly formed or inflamed vessels differs from that in normal vessels in the production of and response to inflammatory cytokines,growth factors,and adhesion molecules,altering coagulant capacity,barrier function and blood cell recruitment in injury.This review examines the roles of the endothelium in the initiation and propagation of IBD pathology and distinctive features of the intestinal endothelium contributing to these conditions.

Identification of TRPM7 channels in human intestinal interstitial cells of Cajal

AIM： To investigate the characteristics of slow electrical waves and the presence of transient receptor potential melastatin-type 7 （TRPM7） in the human gastrointestinal （GI） tract. METHODS： Conventional microelectrode techniques were used to record intracellular electrical responses from human GI smooth muscle tissue. Immunohistochemistry was used to identify TRPM7 channels in interstitial cells of Cajat （ICCs）. RESULTS： The human GI tract generated slow electrical waves and had ICCs which functioned as pacemak er cells. Flufenamic acid, a nonselective cation channel blocker, and 2-APB （2-aminoethoxydiphenyl borate） and La3＋, TRPM7 channel blockers, inhibited the slowwaves. Also, TRPM7 channels were expressed in ICCs in human tissue. CONCLUSION： These results suggest that the human GI tract generates slow waves and that TRPM7 channels expressed in the ICCs may be involved in the gen- eration of the slow waves.

Immunohistochemical Study of Hexose Transporters GLUT-2 and GLUT-5 in Birds Gastrointestinal Tract

The hexoses glucose, galactose and fructose serve as important dietary energy sources in animals and glucose plays a central role in energy homeostasis within eucaryotic cells. As relatively little is known about patterns of hexose transporters expression in birds gastrointestinal tract, the aim of the study was to examine glucose transporters 2 （GLUT-2） and glucose transporters 5 （GLUT-5） expression in stomach and duodenal epithelium of two different species--broilers （Gallus gallus domesticus） and ostriches （Struthio camelus var. domesticus） chicken. Materials from the two parts of gastrointestinal tract were collected from six 7-day-old female broilers and six 7-day-old female ostriches. Specimens were fixed with 10% formalin, embedded into paraffin, cut into 7 lain thick slices, followed by immunohistochemical staining with polyclonal primary antibodies rabbit anti-GLUT-2 and rabbit anti-GLUT-5; the staining was carried out according to the manufacturers guidelines （IHC kit, Abcam, UK）. The investigation showed that the staining for both antibodies was more intensive in the epithelial cells of stomach and duodenum of the 7-day-old broilers. In duodenal epithelium, goblet cells and brush border membranes were stained in both species, however the signal was stronger for GLUT-5 than GLUT-2. Staining for GLUT-2 and GLUT-5 occurred in different parts of gastrointestinal tract of 7-day-old ostriches, but was weaker compared to 7-day-old broilers, which showed that the gastrointestinal tract of 7-day-old female broilers was more developed for transportation ofhexoses than 7-day-old female ostriches.

Celiac disease and microscopic colitis:A report of 4 cases

Celiac disease (CD) is an autoimmune disorder of the small intestine that occurs in genetically predisposed people at all ages.However,it can be associated also to other immunopathological disorders,and may be associated with abnormal histology in segments of the gut other than the small bowel including colonic inflammation.While guidelines for endoscopic investigation of the jejunum are well defined,no indication is defined for colonic investigation.We describe four cases of concurrent CD and microscopic colitis (MC) diagnosed at our department over a 10-year period and analyzed the main features and outcomes of CD in this setting.The symptoms of these patients were improved initially by a gluten-free diet before the onset of MC symptoms.Two of the patients were siblings and had an atypical form of CD.The other two patients with CD and MC also presented with fibrosing alveolitis and were anti-Saccharomyces cerevisiae antibody positive.The co-existence of immune-mediated small bowel and colonic inflammatory and pulmonary diseases are not well-known,and no systematic approach has been used to identify the lifelong patterns of these immune-based diseases.Patients can develop,or present with CD at any stage in life,which can co-exist with other gastrointestinal diseases of (auto-) immune origin.In addition,the fa-milial co-existence and prevalence of MC in patients with a prior diagnosis of CD are unclear.Clinicians managing celiac disease should be aware of these associations and understand when to consider colon investigation.

To resolve recent natural immune defense effects of antimicrobial peptides in the gastrointestinal tract

The human gut is the normal habitat of a lot of microorganisms; in the long process of evolution they have developed a symbiotic relationship with the host. Under normal circumstances they do not damage the health, which totally owes to the barrier functions of the integral intestinal mucosa. Intestinal lnucosal barriers are mainly composed of four parts： mechanical barrier, immune barrier, chemical and biological barrier. Each of these functions has corresponding structural basis, an important barrier to prevent harmful substances and pathogens in the gut into the inner environment of the body, and to maintain a stable internal environment.