溃疡性结肠炎并脑出血、脑梗塞、血小板减少症1例

溃疡性结肠炎(ulcerative colitis,UC)又称非特异性UC,是一种病因尚不十分清楚的结肠和直肠慢性非特异性炎症性疾病,病变局限于大肠黏膜及黏膜下层.通过本病例的学习希望临床医生对该病引起足够的重视.     

生物制剂治疗中重度溃疡性结肠炎的研究进展

溃疡性结肠炎(UC)是一种病因尚不明确、反复发作、迁延进展的肠道非特异性炎症性疾病.近年来生物制剂已用于治疗UC,其疗效优于传统的治疗药物,但也带来诸多不可避免的问题.本文就生物制剂在中重度UC中的应用、药物浓度监测以及用药过程中的特殊情况和处理作一综述.     

血小板功能和参数在溃疡性结肠炎中的变化及意义的研究进展

溃疡性结肠炎(UC)是一种慢性非特异性的炎性肠病,其发生部位主要位于肠道黏膜和黏膜下层,病情反复发作,病程迁延不愈.随着人们饮食结构的不断改变,生活节奏的不断加快,UC的发病率逐年升高.血小板的异常参与了UC的病理改变,对于判断UC的发病部位、疾病的严重程度及预后具有重要的意义.该文主要对UC患者血小板功能和参数的变化...     

螺杆菌在溃疡性结肠炎中的研究

溃疡性结肠炎(ulcerative colitis,UC)是一种活动期与缓解期交替出现、病因不明的慢性非特异性炎症性肠病(inflammatory bowel disease,IBD)。目前有证据表明,UC由肠道菌群和黏膜免疫系统之间的稳态失调,及遗传和环境因素的共同作用引起。国内外越来越多的报道表明,幽门螺杆菌(Helicobacter pylori,H.pylori)感染对UC的保护作用,肠肝螺杆菌(enterohepatic Helicobacter species,EHS)有可能是UC的主要病因或伴随因素。因此,了解螺杆菌感染在UC中的关键作用,可以为治疗UC提供新思路。     

溃疡性结肠炎患者食物不耐受及血清学标记物相关性分析

目的分析本组溃疡性结肠炎(UC)患者血清食物特异性IgG抗体与UC的相关性及与p-ANCA、GAB的可能相关性。方法按照《中国炎症性肠病诊断治疗规范的共识意见》,对59例UC患者及52例对照组患者进行血清p-ANCA、GAB及食物特异性IgG抗体检测。结果 59例UC患者中,出现食物特异性抗体IgG者51例,阳性率为86.44%。与对照组阳性率比较,差异有统计学意义(P<0.05)。不同病变范围的食物特异性抗体IgG阳性率差异无统计学意义(P>0.05)。p-ANCA阳性时出现食物不耐受的阳性率明显高于GAB阳性时,差异有统计学意义(P<0.05)。结论食物不耐受与UC发生发展存在一定的关联,但与病变部位不相关。p-ANCA阳性的患者多存在食物不耐受。     

NLR、MLR在溃疡性结肠炎中的临床意义

背景:外周血白细胞或白细胞分类作为临床检查的常规项目,被认为是炎症性疾病的简捷生物学标志物,中性粒细胞和外周血单核细胞与多种疾病的活动度和严重程度密切相关。目的:探讨外周血中性粒细胞/淋巴细胞比值(NLR)、单核细胞/淋巴细胞比值(MLR)在溃疡性结肠炎(UC)中的临床意义。方法:收集2017年10月—2019年7月郑州大学第二附属医院收治的62例UC患者,以42名健康体检者作为对照组。比较两组中性粒细胞计数、单核细胞计数、淋巴细胞计数、NLR、MLR,并分析其与C反应蛋白(CRP)、红细胞沉降率(ESR)、Mayo评分、UCEIS评分之间的相关性。ROC曲线分析各指标诊断UC的效能。结果:UC患者中性粒细胞计数、单核细胞计数、NLR以及MLR显著高于对照组(P 0. 05),淋巴细胞计数显著低于对照组(P 0. 05)。与轻度患者相比,中重度UC组中性粒细胞计数、单核细胞计数、NLR以及MLR显著升高(P 0. 05),淋巴细胞计数显著降低(P 0. 05)。中性粒细胞计数、单核细胞计数、NLR以及MLR与CRP、ESR、Mayo评分、UCEIS评分均存在正相关性,淋巴细胞计数与上述指标呈负相关性(P 0. 05)。Cut-off值为0. 470时,NLR诊断UC的敏感性为0. 613,特异性为0. 857,AUC为0. 731(95%CI:0. 636～0. 827); cut-off值为0. 439时,MLR诊断UC的敏感性为0. 629,特异性为0. 810,AUC为0. 726(95%CI:0. 630～0. 822)。结论:NLR和MLR在UC患者中升高,且可反映疾病活动状况,有望成为诊断和评估UC的血清学标志物。     

非侵入性分子标志物对溃疡性结肠炎内镜活动度的判断价值

背景:溃疡性结肠炎(UC)是复发与缓解交替的肠道慢性炎症性疾病,及时判断疾病活动度对指导临床医师制定合理的治疗方案以及预测患者预后具有重要意义。目的:评估非侵入性分子标志物对UC患者内镜活动度的判断价值。方法:选取2016年8月—2018年3月襄阳市中心医院收治的56例UC患者,以25例肠易激综合征(IBS)患者作为对照。采用ELISA法测定粪钙卫蛋白(FC)浓度,评估临床活动指数(CAI)评分,检测C反应蛋白(CRP)、红细胞沉降率(ESR),以Mayo评分评估内镜活动度。分析非侵入性标志物对UC内镜活动度的判断价值。结果:UC患者FC浓度明显高于IBS患者(P 0. 001)。活动期UC患者FC、CAI、CRP、ESR均显著高于缓解期UC患者(P 0. 001)。UC患者FC、CAI、CRP、ESR与Mayo评分均相关(r分别为0. 814、0. 724、0. 610、0. 657,P均0. 001)。FC临界值为200μg/g时,预测UC内镜活动度的敏感性和特异性分别为92. 3%和94. 1%。结论:与CAI、CRP、ESR相比,FC能更有效地发现UC患者的内镜下活动性炎症。     

抗中性粒细胞胞浆抗体对维吾尔族及汉族溃疡性结肠炎的诊断意义

目的了解抗中性粒细胞胞浆抗体(ANCA)在新疆地区维吾尔族(维族)及汉族溃疡性结肠炎(UC)患者中的阳性率,确定其对维族及汉族UC的诊断及鉴别诊断意义,同时通过比较维族及汉族UC患者中ANCA的阳性率,了解是否存在同一地区不同种族UC的ANCA阳性率的差异,评价ANCA是UC遗传易感性标志的可能性.方法用间接免疫荧光法检测UC患者(维族39例,汉族31例)、腹泻患者(维族30例,汉族30例)及健康对照者(维族30例,汉族30例)的血清ANCA,比较不同组间及不同种族间ANCA的阳性率.结果UC组中维族及汉族的ANCA阳性率与对照组相比,差异均有显著性(P＜0.05);UC组中维族与汉族间的ANCA表达,差异亦有显著性(P＜0.05),ANCA在维族与汉族UC中的阳性率与病变范围及病情程度无关(P＞0.05).结论ANCA对UC具有较高的敏感性及特异性,是UC诊断的一个辅助手段,并具有鉴别诊断意义.同时提示,ANCA可能为UC遗传易感性的标志.     

新疆维吾尔族和汉族溃疡性结肠炎与人类白细胞抗原-DRB1基因多态性的关联研究

溃疡性结肠炎(ulcerative colitis,UC)是一种病因不明的慢性非特异性结肠炎性反应.HLA是调控人类免疫应答的一个关键因素,其中HLAⅡ类抗原在抗原识别和免疫反应中起重要作用.研究表明,新疆维吾尔族及汉族的结肠镜UC检出率均高于国内外水平,且维吾尔族中、重型UC患者多于汉族[1].分析维吾尔族及汉族UC患者HLA-DRB1基因多态性的差异,探讨新疆汉族及维吾尔族UC患者中遗传因素与UC的相关性及易感基因,为UC的诊断、个体化治疗和确定预防策略奠定基础.     

抗酿酒酵母抗体和抗中性粒细胞胞质抗体对炎症性肠病的诊断价值

目的 了解抗酿酒酵母抗体(ASCA)和核周型抗中性粒细胞胞质抗体(pANCA)的分布,观察其在炎症性肠病(IBD)诊断及鉴别诊断中的意义.方法 选择2002年9月至2007年7月在北京协和医院就诊并行ASCA、pANCA检查的IBD患者175例,其中克罗恩病(CD)62例、溃疡性结肠炎(UC)97例、未定型16例.另取对照者167例.采用酶联免疫吸附法测定血清ASCA水平,间接免疫荧光法测定血清pANCA水平.结果 在CD、UC、未定型者、对照者中,ASCA的阳性率分别为45.2%、14.4%、11/16、29.3%,pANCA的阳性率分别为4.8%、56.7 0A、1/16、4.8%.对照者中,ASCA在恶性肿瘤、嗜酸性粒细胞增多症、自身免疫性肝病、弥漫性结缔组织病及肠结核中的阳性率较高(分别为42.1%、2/5、4/10、4/19、4/14).ASCA诊断CD的敏感性、特异性及阳性预测值分别为45.2%、85.6%、66.7%.pANCA诊断UC的敏感性、特异性及阳性预测值分别为56.7%、95.2%、94.8%.联合检测ASCA+/pANCA-诊断CD的敏感性、特异性及阳性预测值分别为41.9%、93.8%,81.3%.联合检测ASCA-/pANCA+诊断UC的敏感性、特异性和阳性预测值分别为48.5%、98.4%、97.9%.结论 ASCA和pANCA不适于作为IBD筛查指标,联合检测有利于UC与CD的鉴别诊断.     

Steroid-sparing strategies in the management of ulcerative colitis: Efficacy of leukocytapheresis

Active ulcerative colitis (UC) is frequently associated with infiltration of a large number of leukocytes into the bowel mucosa. Leukocytapheresis is a novel nonpharmacologic approach for active UC, in which leukocytes are mechanically removed from the circulatory system. Current data indicate that leukocytapheresis is efficacious in improving response and remission rates with excellent tolerability and safety in patients with UC. Corticosteroid therapy remains a mainstay in the treatment of active UC; however, long-term, high doses of corticosteroids usually produce predictable and potentially serious side effects. If leukocytapheresis can spare patients from exposure to corticosteroids, the risk of steroid-induced adverse events should be minimized. This may be of great benefit to patients because severe side effects of steroids seriously impair health-related quality of life. In this article, we reviewed current evidence on whether leukocytapheresis can avoid or reduce the use of corticosteroids in the management of patients with UC. Several studies have shown that leukocytapheresis was effective for steroid-naïve patients with active UC. Furthermore, both short-term and long-term studies have demonstrated the steroid-sparing effects of leukocytapheresis therapy in patients with UC. Although the evidence level is not striking, the available data suggest that leukocytapheresis can avoid or reduce the use of corticosteroids in the management of UC. Large, well-designed clinical trials are necessary to more accurately evaluate the steroid-sparing effects of leukocytapheresis in the management of UC.     

Drug therapy for ulcerative colitis

Ulcerative colitis (UC) is an inflammatory destructive disease of the large intestine occurred usually in the rectum and lower part of the colon as well as the entire colon. Drug therapy is not the only choice for UC treatment and medical management should be as a comprehensive whole.Azulfidine, Asacol, Pentasa, Dipentum, and Rowasa all contain 5-aminosalicylic acid (5-ASA), which is the topical anti-inflammatory ingredient. Pentasa is more commonly used in treating Crohn‘s ileitis because Pentasa capsules release more 5-ASA into the small intestine than Asacol tablets. Pentasa can also be used for treating mild to moderate UC. Rowasa enemas are safe and effective in treating ulcerative proctitis and proctosigmoiditis. The sulfafree 5-ASA agents (Asacol, Pentasa, Dipentum and Rowasa) have fewer side effects than sulfa-containing Azulfidine. In UC patients with moderate to severe disease and in patients who failed to respond to 5-ASA compounds,systemic (oral) corticosteroids should be used. Systemic corticosteroids (prednisone, prednisolone, cortisone, etc.)are potent and fast-acting drugs for treating UC, Crohn‘s ileitis and ileocolitis. Systemic corticosteroids are not effective in maintaining remission in patients with UC.Serious side effects can result from prolonged corticosteroid treatment. To minimize side effects, corticosteroids should be gradually reduced as soon as the disease remission is achieved. In patients with corticosteroid-dependent or unresponsive to corticosteroid treatment, surgery or immunomodulator is considered. Immunomodulators used for treating severe UC include azathioprine/6-MP,methotrexate, and cyclosporine. Integrated traditional Chinese and Western medicine is safe and effective in maintaining remission in patients with UC.     

Use of infliximab in ulcerative colitis

Infliximab, a chimeric monoclonal anti-tumour necrosis factor alpha (TNF) antibody has dramatically changed the management of various chronic inflammatory disorders such as Crohn's disease (CD), rheumatoid arthritis, ankylosing spondylitis or psoriasis. This drug is well established for the treatment of CD in case of steroid-refractoriness, failure to respond to an immunosuppressant agent or fistulizing disease. The immunological concept that ulcerative colitis (UC) reflects primarily a T-helper cell type-2 mediated disease prevented the earlier use of anti-TNF agents in this disease. Promising initial pilot studies in steroid-refractory UC patients led to two large placebo-controlled trials in patients with moderate to severe UC. These studies clearly showed a benefit for infliximab treatment in UC with mucosal healing and improved life quality. Infliximab therefore can be used in patients not responding adequately to steroids and/or immunosuppressants. Furthermore, one study showed evidence that infliximab might also be effective in severe, intravenous steroid-refractory UC. Therefore, infliximab might be used alternatively to cyclosporine A or tacrolimus in this patient group. Infliximab has now been established as an additional treatment option in patients with chronic-active UC not responding to an immunosuppressive agent and/or in case of severe acute UC. Experienced gastroenterologists should be involved in the decision making for such a therapy to balance thoroughly the benefit/risk ratio for our patients.     

Genetic update on inflammatory factors in ulcerative colitis: Review of the current literature

Ulcerative colitis(UC) is one of the main types of inflammatory bowel disease, which is caused by dysregulated immune responses in genetically predisposed individuals. Several genetic factors, including interleukin and interleukin receptor gene polymorphisms and other inflammation-related genes play central role in mediating and modulating the inflammation in the human body, thereby these can be the main cause of development of the disease. It is clear these data are very important for understanding the base of the disease, especially in terms of clinical utility and validity, but summarized literature is exiguous for challenge health specialist that can used in the clinical practice nowadays. This review summarizes the current literature on inflammationrelated genetic polymorphisms which are associated with UC. We performed an electronic search of Pubmed Database among publications of the last 10 years, using the following medical subject heading terms: UC, ulcerative colitis, inflammation, genes, polymorphisms, and susceptibility.     

Theoretical Mechanism on the Cellulose Regeneration from a Cellulose/EmimOAc Mixture in Anti-Solvents

The experiments on cellulose dissolution/regeneration have made some achievements to some extent, but the mechanism of cellulose regeneration in ionic liquids (ILs) and anti-solvent mixtures remains elusive. In this work, the cellulose regeneration mechanism in different anti-solvents, and at different temperatures and concentrations, has been studied with molecular dynamics (MD) simulations. The IL considered is 1-ethyl-3-methylimidazolium acetate (EmimOAc). In addition, to investigate the microcosmic effects of ILs and anti-solvents, EmimOAc-nH₂O (n = 0–6) clusters have been optimized by Density Functional Theory (DFT) calculations. It can be found that water is beneficial to the regeneration of cellulose due to its strong polarity. The interactions between ILs and cellulose will become strong with the increase in temperature. The H-bonds of cellulose chains would increase with the rising concentrations of anti-solvents. The interaction energies between cellulose and the anions of ILs are stronger than that of cations. Furthermore, the anti-solvents possess a strong affinity for ILs, cation–anion pairs are dissociated to form H-bonds with anti-solvents, and the H-bonds between cellulose and ILs are destroyed to promote cellulose regeneration.     

Guidelines for the management of ulcerative colitis

Ulcerative colitis (UC) is a chronic inflammatory bowel disorder characterized by a relapsing and remitting course. The quality of life can decreases significantly during exacerbations of the disease. The incidence and prevalence of UC in Korea are still lower than those of Western countries, but have been rapidly increasing during the past decades. Various medical and surgical therapies are currently used for the management of UC. However, many challenging issues exist and sometimes these lead to differences in practice between clinicians. Therefore, Inflammatory Bowel Diseases (IBD) Study Group of Korean Association for the Study of Intestinal Diseases (KASID) set out the Korean guidelines for the management of UC. These guidelines are made by the adaptation using several foreign guidelines and encompass treatment of active colitis, maintenance of remission and indication for surgery in UC. The specific recommendations are presented with the quality of evidence. These are the first Korean treatment guidelines for UC and will be revised with new evidences on treatment of UC.     

Clinical value of fecal calprotectin in determining disease activity of ulcerative colitis

AIM： To investigate possibility and clinical application of fecal calprotectin in determining disease activity of ulcerative colitis （UC）. METHODS： The enzyme-linked immunosorbent assay （ELISA） was used to measure the concentrations of calprotectin in feces obtained from 66 patients with UC and 20 controls. C-reactive protein （CRP）, erythrocyte sedimentation rate （ESR）, acid glycoprotein （AGP） were also measured and were compared with calprotectin in determining disease activity of UC. The disease activity of UC was also determined by the Sutherland criteria. RESULTS： The fecal calprotectin concentration in the patients with active UC was significantly higher than that in the inactive UC and in the controls （402.16 ± 48.0 μg/g vs 35.93 ± 3.39 μg/g, 11.5 ± 3.42 μg/g, P 〈 0.01）. The fecal calprotectin concentration in the inactive UC group was significantly higher than that in the control group （P 〈 0.05）. A significant difference was also found in the patients with active UC of mild, moderate and severe degrees. The area under the curve of the receiver operating characteristics （AUCR~c） was 0.975, 0.740, 0.692 and 0.737 for fecal calprotectin, CRP, ESR and AGP, respectively. There was a strong correlation between the fecal calprotectin concentration and the endoscopic gradings for UC （r = 0.866, P 〈 0.001）. CONCLUSION： Calprotectin in the patient＇s feces can reflect the disease activity of UC and can be used as a rational fecal marker for intestinal inflammation in clinical practice. This kind of marker is relatively precise, simple and noninvasive when compared with other commonlyused markers such as CRP, ESR and AGP.     

Heat shock protein gene 70-2 polymorphism is differentially associated with the clinical phenotypes of ulcerative colitis and Crohn's disease

BACKGROUND AND AIM: A single nucleotide polymorphism in heat shock protein 70-2 (HSP70-2) has been shown to be associated with a severe clinical course in Crohn's disease (CD), but it is not known if such a relationship exists in ulcerative colitis (UC). The aim of the present study was to identify associations between the HSP70-2 polymorphism and the clinical courses of CD and UC in Koreans. METHODS: Restriction fragment length polymorphism analysis was performed for HSP70-2 polymorphisms using the PstI-cleavage site present in the B allele but not in the A allele of the DNA obtained from 101 patients with CD, 144 patients with UC, and 245 age- and sex-matched healthy controls. Study subjects were classified by disease behavior, severity and extent of disease. RESULTS: In CD, multivariate analysis showed that the AA genotype of HSP70-2 polymorphisms was associated with non-perforating disease (OR 10.10, 95% CI 1.66-15.38) and male sex (OR 3.56, 95% CI 1.04-12.23), and that the BB genotype was associated with severe CD (OR 12.03, 95% CI 1.60-101.56). In contrast, multivariate analysis for UC showed that the AA genotype was associated with severe UC (OR 2.02, 95% CI 1.34-3.03). CONCLUSIONS: CD patients with BB genotype of HSP70-2 polymorphism tend to experience a more severe clinical course and allele A is associated with more severe UC. HSP70-2 polymorphism may be used to predict CD and UC phenotypes, which can illuminate immunological differences in CD and UC.     

Up-regulation of mitochondrial chaperone TRAP1 in ulcerative colitis associated colorectal cancer

AIM:To characterize tumor necrosis factor receptorassociated protein 1(TRAP1)expression in the progression of ulcerative colitis(UC)-associated colorectal cancer.METHODS:Chronic UC is an inflammatory bowel disease that predisposes to colorectal cancer.Immunohistochemical analysis was used to evaluate TRAP1expression on tissue microarrays containing colonic tissues from 42 UC progressors(patients with cancer or dysplasia)and 38 non-progressors(dysplasia/cancer free patients).Statistical analyses of the TRAP1immunohistochemistry staining were performed using Graph Pad Prism.Differences in the TRAP1 level between non-progressors and progressors were tested for statistical significance using the Mann-Whitney test.Receiver operating characteristic curve method was used to quantify marker performance in distinguishing diseased cases from controls.RESULTS:TRAP1 was up-regulated in the colon tissues from UC progressors,but not in the colon tissues from UC non-progressors.Moreover,up-regulation of TRAP1 preceded the neoplastic changes:it was present in both the dysplastic and non-dysplastic tissues of UC progressors.When TRAP1 staining in rectal tissue was used as a diagnostic marker,it could distinguish progressors from non-progressors with 59%sensitivity and 80%specificity.Our study further showed that the increase of TRAP1 expression positively correlated with the degree of inflammation in the colorectal cancer tissues,which could be related to the increased oxidation present in the colonic mucosa from UC progressors.We then investigated the cellular proteome changes underlying oxidative stress,and found that oxidative stress could induce up-regulation of TRAP1 along with several other negative modulators of apoptosis.CONCLUSION:These results suggest that oxidative stress in long standing UC could lead to the increase of cytoprotective protein TRAP1,which in turn could promote cancer progression by preventing or protecting the oxidative damaged epithelial cells from undergoing apoptosis.TRAP1 could be a potential diagnostic marker for UC associated colorectal cancer.     

Advances Brought by Hydrophilic Ionic Liquids in Fields Involving Pharmaceuticals

The negligible volatility and high tunable nature of ionic liquids (ILs) have been the main drivers of their investigation in a wide diversity of fields, among which is their application in areas involving pharmaceuticals. Although most literature dealing with ILs is still majorly devoted to hydrophobic ILs, evidence on the potential of hydrophilic ILs have been increasingly provided in the past decade, viz., ILs with improved therapeutic efficiency and bioavailability, ILs with the ability to increase drugs’ aqueous solubility, ILs with enhanced extraction performance for pharmaceuticals when employed in biphasic systems and other techniques, and ILs displaying low eco/cyto/toxicity and beneficial biological activities. Given their relevance, it is here overviewed the applications of hydrophilic ILs in fields involving pharmaceuticals, particularly focusing on achievements and advances witnessed during the last decade. The application of hydrophilic ILs within fields involving pharmaceuticals is here critically discussed according to four categories: (i) to improve pharmaceuticals solubility, envisioning improved bioavailability; (ii) as IL-based drug delivery systems; (iii) as pretreatment techniques to improve analytical methods performance dealing with pharmaceuticals, and (iv) in the recovery and purification of pharmaceuticals using IL-based systems. Key factors in the selection of appropriate ILs are identified. Insights and perspectives to bring renewed and effective solutions involving ILs able to compete with current commercial technologies are finally provided.