炎症性肠病治疗中的新概念

炎症性肠病（IBD）主要包括溃疡性结肠炎（UC）和克罗恩病（CD）,其治疗疗程长、效果不佳、容易反复,主要原因为目前对该病的发病机制仍不甚了解以及缺乏特异性治疗药物。随着对IBD发病机制认识的不断深入,其发病过程中的炎症和免疫途径不断被揭示,这些新理念的发展直接导致了新的治疗药物和治疗方法的出现。本文主要结合目前IBD发病机制的研究进展,对其治疗中的一些新概念作一论述。     

炎症性肠病动物模型研究进展

炎症性肠病（IBD）包括溃疡性结肠炎（UC）和克罗恩病（CD）。目前IBD的确切病因和发病机制尚不清楚。相当一部分IBD的研究成果源于动物模型的研究,因此建立合适的动物模型至关重要。本文就几种常用的IBD实验动物模型作一综述。     

中国炎症性肠病研究40年(1980-2020)

中国炎症性肠病(IBD)的临床诊疗与研究工作起步晚于西方国家。近年来,我国IBD发病率和患病率逐渐上升。与此同时,IBD的研究方法和诊疗手段也日新月异。在各位同道的努力下,我国IBD的诊疗能力和研究水平显著提高,成就有目共睹。基于《中华消化杂志》创刊40年来刊登的文献,本文简要回顾了我国IBD领域在过去40年内的发展和...     

原发性硬化性胆管炎合并炎症性肠病患者的临床特征分析

目的通过比较原发性硬化性胆管炎(PSC)合并炎症性肠病(IBD)患者和PSC未合并IBD患者临床特征的差异, 进一步探讨PSC合并IBD的疾病特点。方法横断面研究。纳入2000年1月至2021年1月北京协和医院收治的PSC患者42例, 其中合并IBD患者14例;对其人口学特征、临床表现、伴随疾病、辅助检查及治疗情况进行回顾性分析。结果 42例PSC患者的确诊年龄为11～74(43±18)岁, 其中14例合并IBD, 共患率33.3%, 确诊年龄为12～63(42±17)岁。PSC合并IBD患者与PSC未合并IBD患者相比较, 腹泻发生率更高, 黄疸、乏力发生率更低(均P<0.05)。PSC未合并IBD患者丙氨酸转氨酶、总胆红素、直接胆红素、总胆汁酸、糖类抗原19-9水平更高(均P<0.05), 而PSC合并IBD患者抗核抗体及粪便潜血的阳性率更高(均P<0.05)。PSC合并溃疡性结肠炎患者肠镜表现以广泛结肠受累为主。PSC合并IBD患者5-氨基水杨酸、糖皮质激素应用比例更高(P=0.025)。结论北京协和医院单中心PSC合并IBD的共患率低于西方国家。对于腹泻及粪便...     

肠外营养在炎症性肠病中的应用

目的分析和探讨肠外营养在炎症性肠病中的应用。方法 参照１９９３年全国慢性非感染肠道疾病学术研讨会制定的炎症性肠病的诊断标准对武汉同济医院消化内科１９８６年１月至１９９６年１２月的炎症性肠病住院病人进行了分析，着重探讨了以炎症性肠病的内科治疗，尤其是肠外营养的应用。结果 １１年间炎症性脾性病的年平均住院人数有所上升；其内科治疗除以柳氮磺胺吡啶５－氨基水杨酸为主要药物外，合理的肠外营养，明显改善了炎症     

炎症性肠病的病因与发病机制

炎症性肠病(inflammatory bowel disease,IBD)是一组病因未明的慢性肠道炎症性疾病,指慢性非特异性溃疡性结肠炎(ulcerative colitis,UC)和克罗恩病(Crohns disease,CD)。大约10％的结肠炎症尚不能区别是CD抑或UC,在西方国家称为不明确的结肠炎(indeterminate colitis)。随访研究可发现这些患者大多数发展成为UC。迄今,IBD的病因不明,目前认为是由多因素相互作用所致,主要包括环境、免疫以及遗传等因素。发病机制的假设是感染、饮食等环境因素作用于遗传易感的人群,使之肠免疫反应过度亢进导致肠粘膜损伤,但目前还不清楚这种过度亢进的免疫反应是特异的抗原     

炎症性肠病动物模型研究进展

炎症性肠病是消化系疾病研究的难点之一，选择合适的动物模型对于研究发病机制及寻求有效治疗手段十分重要。随着对该病研究的深入和新兴生物学技术的大规模应用，产生了很多新的模型制备方法，其动物模型日趋多样。     

肠道微生态改变在炎症性肠病中的作用

炎症性肠病（IBD）主要包括溃疡性结肠炎（UC）和克罗恩病（CD），其病因和发病机制尚未明确。目前认为IBD的病因为肠道微环境（肠道菌群）、宿主遗传易感性和黏膜免疫因素三者间的相互作用。近年来．随着微生态学的发展，肠道菌群与IBD发病的关系日益受到关注。本文就IBD时肠道菌群的变化、肠道微生态改变对IBD的影响以及微生态制剂对IBD的治疗作用作一综述。     

炎症性肠病并发低骨量/骨质疏松的危险因素分析

目的 对炎症性肠病(IBD)患者的骨密度状况进行评估,探讨其下降的危险因素.方法 通过对IBD患者血液学指标、身高、体重及腰椎骨密度进行测量,并与健康志愿者比较,分析IBD患者骨质疏松的危险因素.结果 共收集克罗恩病(CD)77例,溃疡性结肠炎(UC)43例,37例健康志愿者作为对照组.CD组、UC组及对照组的腰椎骨质的T值分别为-1.72±1.20、-1.26±1.12和-0.62±0.87,CD组的T值低于UC组(P=0.045)和对照组(P=0.000),UC组T值低于对照组(P=0.014).CD组、UC组及对照组的腰椎骨质疏松的发生率分别为23.3%、14.0%和0;CD组的腰椎骨质疏松发生率高于对照组,差异有统计学意义(P=0.003);UC组的腰椎骨质疏松发生率有高于对照组的趋势,但差异无统计学意义(P=0.053).多元回归分析显示,低体重(BMI≤18.4kg/m~2)是CD(OR=11.25,95%CI 3.198～39.580,P=0.000)和UC(OR=14.50,95%CI 1.058～88.200,P=0.045)患者骨质疏松的危险因素.年龄、病程、病变部位、CD活动指数(CDAI)、服用糖皮质激素、服用免疫抑制剂、血清25-羟基维生素D浓度等因素与骨质疏松的发生无相关性.结论 骨密度下降的发生在IBD患者中较为普遍,低体重是IBD患者骨质丢失的危险因素.     

干细胞治疗在炎症性肠病中的研究进展

我国炎症性肠病(IBD)发病率近年来呈明显上升趋势,危重病例也逐渐增多。现有的IBD治疗主要着眼于控制活动性炎症和调节免疫紊乱,常用药物有5-氨基水杨酸类制剂、糖皮质激素、免疫抑制剂等,对危重及难治性病例疗效有限,且存在许多不良反应。干细胞移植治疗是一种新兴的治疗方法,也是近年来IBD治疗领域的研究热点之一。本文对既往干细胞移植治疗IBD的临床和基础研究进行回顾,着重介绍近年来该领域的新进展。     

Increased Serum Levels of Eotaxin in Patients with Inflammatory Bowel Disease

Background: The CC-chemokines eotaxin and eotaxin-2, produced by epithelial and phagocytic cells, are potent and selective chemoattractants for eosinophils and basophils. The eosinophil is a potent inflammatory cell thought to play an important role in the pathogenesis of inflammatory bowel disease (IBD). In this study we investigated the serum concentrations of eotaxin and eotaxin-2 in patients with Crohn disease and ulcerative colitis. Methods: Thirty-one patients with Crohn disease, 35 patients with ulcerative colitis and 41 control patients were studied. Eotaxin and eotaxin-2 serum levels were measured with solid phase sandwich enzyme-linked immunosorbent assays. Results:     

Staphylococcus aureus in Inflammatory Bowel Disease

Background: The potential role of superantigens in inflammatory bowel disease (IBD), particularly Crohn disease, has been broached in studies of the functions of T cell receptors. Staphylococcal cells have been found in intestinal lymph follicles of IBDs. To clarify a role of staphylococcal superantigens in IBD, we attempted to determine whether Staphylococcus aureus could be detected in intestinal mucosa, including surgical specimens and lymph follicles of initial cases. Methods: One-hundred-and-six colonic and ileal specimens were obtained from 38 Crohn disease, 25 ulcerative colitis and 36 non-IBD patients through therapeutic surgery or endoscopic biopsy. In Crohn disease, 23 surgical specimens and 11 biopsy specimens from initial cases were included. DNA was extracted with phenol-chloroform after homogenization and proteinase K treatment in 73 mucosal specimens. Using an inverted microscope, lymph follicle tissue was microdissected from the remaining 33, mostly biopsy, specimens. DNA was then extracted by freeze-thawing. A coagulase gene characteristic of S. aureus was sought. A nested polymerase chain reaction was performed utilizing primers that amplify a region of the coagulase gene. Polymerase chain reaction products were analyzed with polyacrylamide gel electrophoresis. Results: Only one surgically resected colonic specimen, from a 42-year-old male ulcerative colitis patient, registered positive staphylocoagulase amplification. Conclusions: Staphylococcal superantigens are not involved in either the early lesions or the established lesions of Crohn disease. However, S. aureus infection occasionally may occur during the course of IBD.     

Musculoskeletal Manifestations in a Population-based Cohort of Inflammatory Bowel Disease Patients

Background: Musculoskeletal disorders are the most common extra-intestinal manifestation of inflammatory bowel disease (IBD). Wide ranges of prevalence have been reported depending on the criteria used to define spondylarthropathy and on the selection of patients. We aimed to evaluate the prevalence and clinical spectrum of musculoskeletal manifestations in an inception cohort of European IBD patients. Methods: From 1 October 1991 to 30 September 1993, 202 IBD patients were diagnosed in three centres of two countries (Italy and The Netherlands) by means of a population-based inception cohort study. Of this group of patients, 160 (79%) were interviewed and examined by a rheumatologist and a gastroenterologist in the period June-September 1996. A total of 139/160 patients had an anteroposterior radiograph of the pelvis, and in 140/160 HLA-B27 was determined. Results: 53 (33.1%) of the 160 patients had experienced at least one musculoskeletal manifestation, 29 (18.1%) satisfied the European Spondylarthropathy Study Group (ESSG) criteria for spondylarthropathy and 5 (3.1%) satisfied the modified New York criteria for ankylosing spondylitis. However, 23 (14.4%) patients developed one or more spondylarthropathy-related manifestations without fulfilling any of the classification criteria. In patients satisfying ESSG criteria a significantly higher frequency of women ( P = 0.03), of ocular and liver involvement ( P = 0.01 and P = 0.03, respectively), and use of immunosuppressive drugs ( P = 0.02) was observed. Conclusion: Our study shows a high prevalence of musculoskeletal manifestations in an inception cohort of IBD patients. The clinical spectrum is broader than that defined by spondylarthropathy criteria.     

Disease Outcome in Inflammatory Bowel Disease: Mortality,Morbidity and Therapeutic Management of a 796-Person Inception Cohort in the European Collaborative Study on Inflammatory Bowel Disease (EC-IBD)

Background: The course of inflammatory bowel diseases (IBD) has mainly been studied using different methods in single patient cohorts. The aim of the present study was to assess clinical aspects of disease outcome in a population-based cohort of IBD patients over a 4-year period in multiple centres across Europe. Methods: A total of 796 patients with IBD diagnosed in 10 centres between October 1991 and October 1993, registered at the EC IBD study centre (98% of the original cohort), participated in the study. Investigators filled out a standard follow-up form containing questions on the method of follow-up, vital status of the patient, change in diagnosis, extraintestinal manifestations, medical and surgical treatment, and physician's global assessment of disease activity. Results: Complete relief of the complaints was reported in 255 (48%) patients with ulcerative colitis (UC), 9 (50%) with indeterminate colitis (IC), but only in 87 (35%) of patients with Crohn disease (CD). Improvement was reported in 195 (37%) patients with UC, 113 (45%) with CD and 6 (33%) with IC. During the 4-year follow-up period, 23 patients died (14 UC, 8 CD, and 1 IC). The mean age at death was 69.3 years (s, 14.9 years). The deaths of three patients were recorded as directly due to IBD. Conclusions: With the present approach to therapeutic management the short-term outcome of patients with IBD seems to be favourable in 10 medical centres in the north and south of Europe. However, more detailed studies including both objective and subjective measures are necessary.     

CTLA4 Gene Polymorphisms in Dutch and Chinese Patients with Inflammatory Bowel Disease

Background: Inflammatory bowel diseases (IBDs) are characterized by chronic intestinal inflammation as a result of an exaggerated T-cell response. CTLA4, a receptor of activated T cells, has an inhibitory function in regulating T-cell activation. Since CTLA4 gene polymorphisms have been associated with several autoimmune diseases, the aim was to study these gene polymorphisms in patients with IBD in two different populations. Methods: The C-318T polymorphism in the promoter region and A+49G polymorphism in exon 1 of the CTLA4 gene were investigated by a PCR-SSP method. We studied 139 unrelated patients with ulcerative colitis (UC), 163 patients with Crohn disease (CD) and 174 healthy controls of Dutch Caucasian origin as well as 35 patients with UC and 62 healthy controls from the Chinese Han population. Results: No significant differences in the distribution of allele, genotype and haplotype frequencies were observed between C-318T and A+49G gene polymorphisms and IBD in Dutch Caucasians and UC in the Chinese Han population. Although the haplotypes of the C-318T and A+49G polymorphisms were distributed differently between Dutch Caucasian and Chinese Han populations, there were no differences in the subgroups of patients with CD classified according to age, localization and behaviour in the Vienna classification and in those with UC classified according to age at onset, disease extension and presence of colectomy in the Dutch patients. However, the CTLA4-318 genotype CC was more frequent in patients with CD over 40 years (93%) than in younger patients (74%) ( P = 0.045). Conclusion: C-318T and A+49G CTLA4 gene polymorphisms and their haplotypes are not associated in Dutch Caucasian patients with IBD and in Chinese patients with UC.     

炎症性肠病流行病学研究进展

炎症性肠病(IBD)在不同地区、种族人群中的发病率有显著差异。近年来,IBD在既往高发病率的西方国家趋于稳定,而在亚洲国家呈逐渐增加趋势。IBD发病率在发展中国家逐年增高,可能与发展中国家经济高速发展、工业化进程加速有关,提示环境因素在IBD病因中扮演重要角色。目前国内关于IBD流行病学的研究处于起步阶段,有待联合更多医学中心进行以人群为基础的IBD流行病学研究。     

炎症性肠病患者外周血淋巴细胞功能相关抗原-1的表达与临床特征的关系

背景：淋巴细胞功能相关抗原-1（LFA-1）是B2整合素家族成员,广泛表达于几乎所有白细胞中。LFA-1／ICAM-1共刺激分子在炎症性肠病（IBD）的发生中发挥重要作用。目的：研究IBD患者外周血LFA-1的表达变化,分析其与患者临床特征的相关性。方法：纳入20名健康体检者和93例IBD患者（其中CD66例,UC27例）,流式细胞术检测外周血CD4＋细胞和外周血单个核细胞（PBMC）中LFA-1的平均荧光强度（MF1）,并分析其与疾病活动度、疾病部位、疾病行为和临床指标的相关性。结果：CD和UC患者PBMC中LFA-1的MFI均显著低于健康对照组（P〈0．05）。CD和UC患者缓解期外周血CD4＋细胞和PBMC中LFA-1的MFI与活动期无明显差异。空回肠型CD患者外周血CIM’细胞和PBMC中LFA-1的MFI较回肠型、结肠型、上消化道型CD患者明显升高（P〈0．05）;狭窄型CD患者外周血CD4＋细胞中LFA-1的MFI显著高于非狭窄非穿透型CD患者（P〈0．05）;有2种肛周病变的CD患者外周血CD4＋细胞和PBMC中LFA-1的MFI显著高于有1种肛周病变者（P〈0．05）。ESR、血清CRP与CDAI评分、Mayo评分呈正相关（P〈0．05）;HCT、Hb、血清ALB与CDAI评分、Mayo评分呈负相关（P〈0．05）。结论：LFA．1参与IBD的发病过程,与CD疾病行为的关系尤为密切,但用于判断疾病活动度尚需进一步研究。     

炎症性肠病的鉴别诊断

近年来我国炎症性肠病的发病率和患病率均呈上升趋势．作为临床难点的鉴别诊断问题日益引起临床医师的高度重视。本文对炎症性肠病与感染性结肠炎和非感染性结肠炎的鉴别诊断进行阐述．强调应对慢性腹泻、腹痛患者进行及时准确的诊断和鉴别诊断,以最大程度地降低临床漏诊率和误诊率。