血细胞分离术在炎症性肠病治疗中的研究进展

炎症性肠病(IBD)是一种慢性非特异性肠道炎性疾病,其病因和发病机制尚未完全明确。研究认为免疫因素在IBD的发病中发挥重要作用。血细胞分离术(CAP)作为一种新型血液净化方法,可选择性滤过或吸附循环中的炎性细胞和炎性因子,诸多研究证实其对IBD有一定治疗效果。本文就CAP在IBD治疗中的研究进展作一综述。     

白细胞介素23与炎症性肠病

炎症性肠病(IBD)是一类病因不明的胃肠道慢性非特异性炎症,包括克罗恩病(CD)和溃疡性结肠炎(UC).促炎因子和抗炎因子的失衡被视为一个重要的病因[1].白细胞介素23(IL-23)属于前炎性因子,在IBD的发生、发展中起重要作用.此文就近年来IL-23在IBD发生、发展和治疗中的作用作一综述.     

巨噬细胞在炎症性肠病中作用的研究进展

炎症性肠病(IBD)是一种病因不明的慢性非特异性肠道炎性疾病,由巨噬细胞介导的炎性反应在IBD的发展过程中起着关键作用。研究发现,在IBD患者的肠道炎性反应中,巨噬细胞的数量明显增加,并且可释放白细胞介素-1(IL-1)、IL-6、IL-18、转化生长因子-β(TGF-β)和肿瘤坏死因子-α(TNF-α)等多种生物活性物质,在IBD的发生发展中起重要作用。因此,了解巨噬细胞释放的细胞因子和化学介质在IBD中的关键作用,可以为治疗IBD开拓新的方法。     

靶向NF-κB治疗炎症性肠病的研究进展

炎症性肠病(IBD)是一组慢性肠道炎性疾病,主要包括溃疡性结肠炎(UC)和克罗恩病(CD).IBD的病因和发病机制尚不明确,目前认为其发病与遗传、环境、微生物感染、免疫等因素相互作用有关.近年来研究发现核因子-κB(NF-κB)在IBD的发病和进展中起着尤为重要的作用,此文就靶向NF-κB治疗IBD的研究进展作一综述.     

血管内皮生长因子与炎症性肠病发病机制的关系

血管内皮生长因子(VEGF)主要通过调控组织中血管与淋巴管生成来影响炎性反应、肿瘤等疾病的进展。目前越来越多的研究表明,炎症性肠病(IBD)中炎性肠组织的血管和淋巴管明显增多。同时,近年来大量研究表明VEGF家族在IBD的发病过程中可能起着重要的作用。因此,研究VEGF与IBD的关系,对探讨IBD的发病机制及寻找IBD新的治疗靶点有重要意义。     

炎症性肠病与血管生成

炎症性肠病(IBD)是一组慢性非特异性肠道炎性疾病,包括溃疡性结肠炎(UC)和克罗恩病(CD).IBD的病因和发病机制至今未完全明确,主要与遗传、免疫、感染、环境及精神等因素有关.近年来有关IBD患者和动物模型的研究对血管生成机制及其病理生理过程进行了探讨,对慢性炎症有了更深层次的理解.此文就IBD与血管生成的关系及其相关治疗作一综述.     

自体造血干细胞移植治疗难治性炎症性肠病10例回顾与随访

目的 回顾自体造血干细胞移植(HSCT)治疗10例炎症性肠病(IBD)患者的疗效及安全性.方法 2004年1月至2006年8月,采用HSCT治疗9例糖皮质激素及免疫抑制剂治疗无效的克罗恩病(CD)患者及1例Truelove临床重型溃疡性结肠炎(UC)患者.CD患者中2例CD活动指数(CDAD大于450(严重型),6例CDAI为150～450(活动型).1例UC患者为全结肠炎型.经环磷酰胺(CTX)及粒细胞刺激因子动员后,采集患者外周血于细胞,行CD34+细胞分选并置液氮保存,2周后行CTX及抗淋巴细胞球蛋白预处理,将解冻的干细胞回输.结果 HSCT后3和12个月时分别有5例和1例患者CDAI<150(完全缓解).2例术后CDAI分值下降但未达缓解标准;完全缓解者症状消失,血液检查指标正常,体重明显增加(5～20 kg).平均随访16.1个月,复发4例,除1例病情严重外,余均较术前病情减轻;5例患者获长期缓解.1例UC患者术后10个月无复发症状,血液检查指标均正常,但肠镜复查示无明显改善.与HSCT治疗相关的并发症有干细胞回输期间与白细胞减少相关的发热及感染、术后脱发,1例乙型肝炎病毒(HBV)携带者术后转氨酶水平及HBV-DNA滴度增高.结论 HSCT可改善其他方法治疗无效的难治性IBD,近期疗效满意,部分患者可获较长期的缓解,治疗期间无严重不良反应,但不能阻止病情复发,且不能改善患者肠道病理改变.     

MAPK信号通路在炎症性肠病中的研究进展

促分裂原活化蛋白激酶(mitogen-activated protein kinase,MAPK)是细胞浆内一类高度保守的丝氨酸蛋白激酶,其介导的信号转导通路在机体的炎性反应中发挥重大作用.他与炎症性肠病(inflammatory bowel diseases,IBD关系密切,不仅参与IBD炎性介质的调节,还参与调控IBD发病发展相关基因.本文综述了MAPK信号通路在IBD发病机制中的作用,旨在为IBD的诊治研究提供新的思路.     

缓解期炎症性肠病患者的肠易激综合征样症状研究进展

炎症性肠病(IBD)和肠易激综合征(IBS)是两种疾病,近年来研究表明,缓解期IBD患者的IBS样症状发生率高于普通人群,这对缓解期IBD的后续治疗造成了不小的困扰,因为出现IBS样症状时难以判断是IBD的炎性反应持续存在还是合并了IBS。该文就缓解期IBD患者的IBS样症状的研究进展作一综述。     

蠕虫治疗炎症性肠病的研究进展

炎症性肠病(IBD)是一类病因不明的肠道慢性非特异性炎性疾病,包括溃疡性结肠炎(UC)和克罗恩病(CD)。已知与IBD发病相关的危险因素包括环境、遗传和免疫因素等。近年有关蠕虫治疗IBD的基础和临床研究逐渐增多,认为蠕虫对IBD有积极的治疗作用且安全性较高。本文就蠕虫治疗IBD的研究进展作一综述。     

Therapy with stem cells in inflammatory bowel disease

Inflammatory bowel disease(IBD) affects a part of the young population and has a strong impact upon quality of life. The underlying etiology is not known, and the existing treatments are not curative. Furthermore, a significant percentage of patients are refractory to therapy. In recent years there have been great advances in our knowledge of stem cells and their therapeutic applications. In this context, autologous hematopoietic stem cell transplantation(HSCT) has been used in application to severe refractory Crohn’s disease(CD), with encouraging results. Allogenic HSCT would correct the genetic defects of the immune system, but is currently not accepted for the treatment of IBD because of its considerable risks. Mesenchymal stem cells(MSCs) have immune regulatory and regenerative properties, and low immunogenicity(both autologous and allogenic MSCs). Based on these properties, MSCs have been used via the systemic route in IBD with promising results, though it is still too soon to draw firm conclusions. Their local administration in perianal CD is the field where most progress has been made in recent years, with encouraging results. The next few years will be decisive for defining the role of such therapy in the management of IBD.     

肠道蠕虫与炎症性肠病的治疗

炎症性肠病(IBD)是一种病因不明,反复发作性的肠道特异性疾病。随着遗传因素、环境因素与免疫反应异常等发病机制方面研究的不断进展,IBD的治疗发生了重大的变化,其中直接改善肠道微环境逐渐受到重视。在动物模型和人体寄生虫感染研究中,有丰富的资料支持寄生虫感染有免疫调节作用,近来这个概念已经用来治疗IBD,不断有肠道蠕虫治疗IBD的报道。现就肠道蠕虫治疗IBD的研究作一综述。     

环孢素A治疗炎症性肠病进展

炎症性肠病(IBD)是一组反复发作的肠道慢性炎症性疾病,包括溃疡性结肠炎和克罗恩病。其病因不明,可能与遗传、环境、免疫等因素有关。目前尚无针对病因的治疗方法,主要是根据其发病机制及病理生理进行治疗。目前临床治疗药物较多,此文介绍环孢素A治疗IBD的进展。     

Selective granulocyte and monocyte apheresis in inflammatory bowel disease: Its past,present and future

The etiology and pathogenesis of inflammatory bowel disease(IBD), including ulcerative colitis and Crohn's disease, are not fully understood so far. Therefore,IBD still remains incurable despite the fact that significant progress has been achieved in recent years in its treatment with innovative medicine. About 20 years ago, selective granulocyte and monocyte apheresis(GMA) was invented in Japan and later approved by the Japanese health authority for IBD treatment.From then on this technique was extensively used for IBD patients in Japan and later in Europe. Clinical trials from Japan and European countries have verified the effectiveness and safety of GMA therapy in patients with IBD. In 2013, GMA therapy was approved by China State Food and Drug Administration for therapeutic use for the Chinese IBD patients. However, GMA therapy has not been extensively used in China, although a few clinical studies also showed that it was effective in clinical and endoscopic induction of remission in Chinese IBD patients with a high safety profile. This article reviews past history, present clinical application as well as the future prospective of GMA therapy for patients with IBD.     

Hepatitis C Virus and Inflammatory Bowel Disease

Gastroenterologists frequently treat patients with complex illnesses such as chronic hepatitis C infections and inflammatory bowel disease (IBD). Occasionally, a patient will present with these two diseases which behave very differently and the treatment for one may potentially exacerbate the other. The purpose of this article is to review the current literature regarding hepatitis C virus therapy in the setting of IBD as well as the effects of common IBD therapies on the hepatitis C virus. Based on limited data, anti-viral therapy is probably safe in patients with well-controlled IBD, but there might be a risk of causing new onset of IBD. Also, it does not appear that the commonly used medications for IBD have much of an effect on the hepatitis C virus (HCV) or its course.     

Therapeutic drug monitoring in inflammatory bowel disease: At the right time in the right place

Therapeutic drug monitoring (TDM) was one of most sought-after objective tools to determine therapeutic efficiency of different biologics and its role in the management of patients with inflammatory bowel disease (IBD) was regarded with great anticipation. But implementation of the TDM in clinical practice was challenged by several factors including uncertainty of the optimal cut-off values, assay variable sensitivity in detecting drug levels and antibodies and, most importantly, individual pharmacokinetics. While reactive TDM was embraced in clinical practice as a useful tool in assessing lack of response to therapy, the utility of proactive TDM in managing IBD therapy is still challenged by the lack of consistency between evidence. Described here, there are four groups of IBD patients for whom proactive TDM has the potential to greatly impact their therapeutic outcomes: Patients with perianal Crohn’s disease, patients with severe ulcerative colitis, pregnant women with IBD and children. As the future of IBD management moves towards personalizing treatment, TDM will be an important decision node in a machine learning based algorithm predicting the best strategy to maximize treatment results while minimizing the loss of response to therapy.     

Nephrolithiasis as an extra-intestinal presentation of pediatric inflammatory bowel disease unclassified

Urolithiasis is quite rare in pediatric inflammatory bowel disease (IBD) compared with the incidence at 9–18% in adult cases. The diagnosis and treatment of pediatric IBD is challenging. Indeterminate colitis (IC), originally proposed as a subgroup of fulminant IBD, has also been used for patients when the diagnosis of either UC or CD cannot be made with certainty. Such patients should be diagnosed as having “IBD unclassified” based on evidence including mucosal biopsy samples. We report herewith a 9-year-old boy with isolated colitis that reached a diagnosis of IBD unclassified. Infliximab therapy led to a successful remission after the refractory course. However, urolithiases were impacted in the urethral valves and vesico-ureteral junction. Microhematuria was noticed from the onset of colitis. Renal calculi were detected on the X-ray films during the first line treatment. Transurethrally crushed stones consisted of calcium oxalate. Renal calculi are more closely associated with CD than ulcerative colitis in adult patients for the ileal involvement. The oxalate stones and treatment response indicated a CD-like pathophysiology. Nephrolithiasis might be a rare but noticeable extra-intestinal presentation of pediatric IBD. Infliximab therapy could be an option in pediatric refractory colitis to change the critical steroid dependency.     

Role of the combination of biologics and/or small molecules in the treatment of patients with inflammatory bowel disease

Inflammatory bowel disease (IBD) is a group of chronic diseases that includes ulcerative colitis, Crohn’s disease, and indeterminate colitis. Patients with IBD require prolonged treatment and high utilization of healthcare resources for proper management. The treatment of patients with IBD is focused on achieving therapeutic goals including clinical, biochemical, and endoscopic variables that result in improvement of the quality of life and prevention of disability. Advanced IBD treatment includes tumor necrosis factor inhibitors, integrin antagonist, antagonist of the p40 subunit of interleukin 12/23, and small molecule drugs. However, despite the multiple treatments available, about 40% of patients are refractory to therapy and present with persistent symptoms that have a great impact on their quality of life, with hospitalization and surgery being necessary in many cases. Dual therapy, a strategy sometimes applicable to refractory IBD patients, includes the combination of two biologics or a biologic in combination with a small molecule drug. There are two distinct scenarios in IBD patients in which this approach can be used: (1) Refractory active luminal disease without extraintestinal manifestations; and (2) patients with IBD in remission, but with active extraintestinal manifestations or immune-mediated inflammatory diseases. This review provides a summary of the results (clinical response and remission) of different combinations of advanced drugs in patients with IBD, both in adults and in the pediatric population. In addition, the safety profile of different combinations of dual therapy is analyzed. The use of newer combinations, including recently approved treatments, the application of new biomarkers and artificial intelligence, and clinical trials to establish effectiveness during long-term follow-up, are needed to establish new strategies for the use of advanced treatments in patients with refractory IBD.