正二十八烷醇抑制DSS诱导的小鼠结肠炎症及其分子机理

以3%葡聚糖硫酸钠(DSS)为诱导剂,建立ICR小鼠结肠炎症模型,评估二十八烷醇的抗炎功效与分子机理。结果发现:二十八烷醇能显著改善结肠炎症小鼠的健康状况,减少DAI评分,减轻病理组织的损伤,改善炎症相关生化指标。RT-qPCR分析发现,二十八烷醇可使结肠组织前体炎症因子TNF-α、IL-1β、IL-6和iNOS等基因mRNA表达水平降低,Westem blot分析进一步证实了二十八烷醇抑制炎症因子蛋白表达水平的功效。

伴有肛周疾病的炎症性肠病患者肛门功能及生活质量分析

目的分析肛周疾病对炎症性肠病(IBD)患者肛门直肠功能和生活质量的影响。方法回顾性分析2018年6月至2020年6月淮安市第二人民医院收治的伴有肛门不适的53例IBD患者(IBD组)。其中CD43例,UC10例。包括肛瘘35例,大便失禁15例,肛门纤维化8例。选择同期来淮安市第二人民医院体检的健康人20名作为健康对照组。通过肛门直肠测压对IBD患者和健康对照组受试者肛门功能进行评估并进行比较。采用炎症性肠病患者生活质量量表(IBDQ)评分对IBD患者生活质量进行评估。结果IBD患者与健康对照组最大肛门静息压、最大挤压压、直肠容量感觉阈值、最大耐受容量、肛管抑制反射阳性水平差异均无统计学意义(P均>0.05)。大便失禁的IBD患者最大肛门静息压、IBDQ评分均低于非大便失禁的IBD患者,且差异均有统计学意义(P<0.05)。CD与UC患者IBDQ评分差异无统计学意义(P>0.05);大便失禁IBD患者IBDQ评分低于非大便失禁IBD患者,且差异有统计学意义(P<0.05)。结论合并肛周疾病的IBD患者肛门直肠功能受损,大便失禁的患者生活质量差。

Positions of selective leukocytapheresis in the medical therapy of ulcerative colitis

Ulcerative colitis （UC） and Crohn＇s disease （CD） are the major forms of idiopathic inflammatory bowel disease （IBD）. Both UC and CD are debilitating chronic disorders that afflict millions of individuals throughout the world with symptoms which impair function and quality of life. The etiology of IBD is inadequately understood and therefore, drug therapy has been empirical instead of being based on sound understanding of IBD pathogenesis. This is a major factor for poor drug efficacy and drug related side effects that often add to the disease complexity. The development of biologicals notably infliximab to intercept tumor necrosis factor （TNF）-α reflects some progress, albeit major concern about their side effects and lack of long-term safety and efficacy profiles. However, IBD seems to be perpetuated by inflammatory cytokines like TNF-α, interleukin （IL）-Iβ, IL-6 and IL-8 for which activated peripheral granulocytes and monocytes/macrophages （GH） are major sources. Further, in IBD, peripheral GHs are elevated with activation behavior, increased survival time and are found in vast numbers within the inflamed intestinal mucosa; they are suspected to be major factors in the immunopathogenesis of IBD. Hence, peripheral blood GMs should be appropriate targets of therapy. The Adacolumn is a medical device developed for selective depletion of GH by receptor-mediated adsorption （GHA）. Clinical data show GMA, in patients with steroid dependent or steroid refractory UC, is associated with up to 85% efficacy and tapering or discontinuation of steroids, while in steroid nai＇ve patients （the best responders）, GHA spares patients from exposure to steroids. Likewise, GMA at appropriate intervals in patients at a high risk of clinical relapse suppresses relapse thus sparing the patients from the morbidity associated with IBD relapse. Further, GHA appears to reduce the number of patients being submitted to colectomy or exposure to unsafe immunosupressants. First UC episode, steroid naivety and short disease duration appear good predictors of response to GMA and based on the available data, GMA seems to have an excellent safety profile.

Nutritional status and nutritional therapy in inflammatory bowel diseases

Underweight and specific nutrient deficiencies are frequent in adult patients with inflammatory bowel disease(IBD).In addition,a significant number of children with IBD,especially Crohn's disease(CD) have impaired linear growth.Nutrition has an important role in the management of IBD.In adults with CD,enteral nutrition(EN) is effective in inducing clinical remission of IBD,although it is less efficient than corticosteroids.Exclusive EN is an established primary therapy for pediatric CD.Limited data suggests that EN is as efficient as corticosteroids for induction of remission.Additional advantages of nutritional therapy are control of inflammation,mucosal healing,positive benefits to growth and overall nutritional status with minimal adverse effects.The available evidence suggests that supplementary EN may be effective also for maintenance of remission in CD.More studies are needed to confirm these findings.However,EN supplementation could be considered as an alternative or as an adjunct to maintenance drug therapy in CD.EN does not have a primary therapeutic role in ulcerative colitis.Specific compositions of enteral dietselemental diets or diets containing specific components-were not shown to have any advantage over standard polymeric diets and their place in the treatment of CD or UC need further evaluation.Recent theories suggest that diet may be implicated in the etiology of IBD,however there are no proven dietary approaches to reduce the risk of developing IBD.

Haemostatic system in inflammatory bowel diseases:New players in gut inflammation

Inflammation and coagulation constantly influence each other and are constantly in balance.Emerging evidence supports this statement in acute inflammatory diseases,such as sepsis,but it also seems to be very important in chronic inflammatory settings,such as inflammatory bowel disease(IBD).Patients with Crohn's disease and ulcerative colitis have an increased risk of thromboembolic events,and several abnormalities concerning coagulation components occur in the endothelial cells of intestinal vessels,where most severe inflammatory abnormalities occur.The aims of this review are to update and classify the type of coagulation system abnormalities in IBD,and analyze the strict and delicate balance between coagulation and inflammation at the mucosal level.Recent studies on possible therapeutic applications arising from investigations on coagulation abnormalities associated with IBD pathogenesis will also be briefly presented and critically reviewed.

Immunopathogenesis of inflammatory bowel disease

Crohn＇s disease and ulcerative colitis are chronic relapsing immune mediated disorders that results from an aberrant response to gut luminal antigen in genetically susceptible host. The adaptive immune response that is then triggered was widely considered to be a T-helper-1 mediated condition in Crohn＇s disease and T-helpero2 mediated condition in ulcerative colitis. Recent studies in animal models, genome wide association, and basic science has provided important insights in in the immunopathogenesis of inflammatory bowel disease, one of which was the characterization of the interleukin-23/Th-17 axis.

Recent trends in the surgical management of inflammatory bowel disease

Surgery is required in the vast majority of patients with Crohn’s disease (CD) and in approximately one-third of patients with ulcerative colitis (UC). Similar to medical treatments for IBD, significant advances have occurred in surgery. Advances in CD include an emphasis upon conservatism as exemplified by more limited resections, strictureplasties, and laparoscopic resections. The use of probiotics in selected patients has improved the outcome in patients with pouchitis following restorative proctocolectomy for UC. It is anticipated that ongoing discoveries in the molecular basis of IBD will in turn identify those patients who will best respond to surgery.

Diagnostics in inflammatory bowel disease: Ultrasound

Diagnosis of chronic inflammatory bowel diseases (IBD) is based on a combination of clinical symptoms, laboratory tests and imaging data. Imaging of the morphological characteristics of IBD includes the assessment of mucosal alterations, transmural involvement and extraintestinal manifestations. No single imaging technique serves as a diagnostic gold standard to encompass all disease manifestations. Ultrasound, computed tomography (CT) or magnetic resonance imaging (MRI) allow cross-sectional imaging of the transmural alterations and extraintestinal manifestations. While in the USA the technique of choice is CT, in Europe the focus is more on MRI and ultrasound (US). Most patients with chronic IBD are diagnosed at a young age. After baseline diagnosis many of these young patients have to undergo repetitive imaging procedures during the variable clinical course of the disease, characterized by alternate periods of remission and active disease, and in monitoring the response to treatment. US has the advantage of being noninvasive, less costly, and easily repeatable, and thus can be very useful in following up patients with IBD. In addition, rising concern about radiation exposure in young adults indicates the demand for radiation-sparing techniques like US and MRI. This article focuses on the current clinical practice of US in IBD, describing the current technologies used in transabdominal intestinal US and the characteristic sonographic findings in Crohn′s disease and ulcerative colitis.

Ileal pouch surgery for ulcerative colitis

Ulcerative colitis (UC) is a relapsing and remitting disease characterised by chronic mucosal and submucosal inflammation of the colon and rectum. Treatment may vary depending upon the extent and severity of inflammation. Broadly speaking medical treatments aim to induce and then maintain remission. Surgery is indicated for inflammatory disease that is refractory to medical treatment or in cases of neoplastic transformation. Approximately 25% of patients with UC ultimately require colectomy. Ileal pouch-anal anastomosis (IPAA) has become the standard of care for patients with ulcerative colitis who ultimately require colectomy. This review will examine indications for IPAA, patient selection, technical aspects of surgery, management of complications and long term outcome following this procedure.

Cancer risk in IBD: How to diagnose and how to manage DALM and ALM

The risk of developing neoplasia leading to colorectal cancer is significantly increased in ulcerative colitis (UC) and most likely in Crohn's disease. Several endoscopic surveillance strategies have been implemented to identify these lesions. The main issue is that colitisassociated neoplasms often occurs in flat mucosa, often being detected on taking random biopsies rather than by identification of these lesions via endoscopic imaging. The standard diagnostic procedure in long lasting UC is to take four biopsies every 10 cm. Image enhancement methods, such as chromoendoscopy and virtual histology using endomicroscopy, have greatly im- proved neoplasia detection rates and may contribute toreduced random biopsies by taking targeted "smart" biopsies. Chromoendoscopy may effectively be performed by experienced endoscopists for routine screening of UC patients. By contrast, endomicroscopy is often only available in selected specialized endoscopic centers. Importantly, advanced endoscopic imaging has the poten- tial to increase the detection rate of neoplasia whereas the interplay between endoscopic experience and interpretation of histological biopsy evaluation allows the physician to make a proper diagnosis and to find the appropriate therapeutic approach. Colitis-associated intraepithelial neoplasms may occur in flat mucosa of endoscopically normal appearance or may arise as dysplasia-associated lesion or mass (DALM), which may be indistinguishable from sporadic adenomas in healthy or non-colitis mucosa [adenoma-like mass (ALM)]. The aim of this review was to summarize endoscopic and histological characteristics of DALM and ALM in the context of therapeutic procedures.

Old-age inflammatory bowel disease onset:A different problem?

Inflammatory bowel disease （IBD） in patients aged 60 accounts for 10%-15% of cases of the disease. Diganostic methods are the same as for other age groups. Care has to be taken to distinguish an IBD colitis from other forms of colitis that can mimick clinically, endoscopically and even histologically the IBD entity. The clinical pattern in ulcerative colitis （UC） is proctitis and left-sided UC, while granulomatous colitis with an inflammatory pattern is more common in Crohn’s disease （CD）. The treatment options are those used in younger patients, but a series of considerations related to potential pharmacological interactions and side effects of the drugs must be taken into account. The safety profile of conventional immunomodulators and biological therapy is acceptable but more data are required on the safety of use of these drugs in the elderly population. Biological therapy has risen question on the possibility of increased side effects, however this needs to be confirmed. Adherence to performing all the test prior to biologic treatment administration is very important. The overall response to treatment is similar in the different patient age groups but elderly patients have fewer recurrences. The number of hospitalizations in patients 65 years is greater than in younger group, accounting for 25% of all admissions for IBD. Mortality is similar in UC and slightly higher in CD, but significantly increased in hospitalized patients. Failure of medicaltreatment continues to be the most common indication for surgery in patients aged 60 years. Age is not considered a contraindication for performing restorative proctocolectomy with an ileal pouch-anal anastomosis. However, incontinence evaluation should be taken into account an individualized options should be considered

Quality of care for patients with inflammatory bowel disease in East China

AIM： To investigate the quality of care for a hospital based-cohort of patients with inflammatory bowel disease （IBD） from East China according to the current practice guidelines, METHODS： A retrospective review was conducted, involving 177 patients with IBD admitted to Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University between June 2000 and June 2006. Data regarding demographic and clinical characteristics as well as medical therapy including use of oral aminosalisylates, topical therapy, corticosteroid agents, immunomodulatory agents （such as azathioprine） at admission and outpatient clinic visit were analyzed. RESULTS： A total of 177 eligible patients were evaluated in this study, including 71 patients with Crohn＇s disease （CD） and 106 with ulcerative colitis （UC）. All were the Han nationality Chinese with active disease at baseline. All the 106 patients with ulcerative colitis received optimal doses of aminosalisylate while 27 of 68 （39.7%） patients with ileal or colonic CD received the suboptimal doses of aminosalisylate. The incidence of suboptimal dose of aminosalisylate was significantly higher in CD patients with small intestine involvement only （52.8% vs 25.0%, P = 0.019）. Thirty-one （54.4%） patients with active distal or left-sided ulcerative colitis received topical therapy, and 27.8% of patients suffering from severe inflammatory bowel disease did not receive oral or intravenous steroid therapy. Among the 51 patients for whom thiopurine was indicated, only 10 （19.6%） received immunomodulatory agents, and more thanhalf of the 8 patients received a suboptimal dose of azathiopurine with no attempt to increase its dosage. CONCLUSION： The quality of care for IBD patients can be further improved. A suboptimal dose of aminosalicylate is used in treatment of patients with CD, especially in those with small intestine involved only. Topical mesalazine is inadequately used in patients with distal or left-sided colitis. Oral or intravenous steroid therapy is not used in some patients with severe IBD. Use of immunomodulatory medication is limited. Larger prospective studies are needed to investigate the quality of care for patients with IBD to establish our own evidence-based guidelines.

Inflammatory bowel disease:Genetic and epidemiologic considerations

Genome-wide association studies have firmly established that many genomic loci contribute to inflammatory bowel disease, especially in Crohn’s disease. These studies have newly-established the importance of the interleukin 23 and autophagy pathways in disease pathogenesis. Future challenges include: (1) the establishment of precisely causal alleles, (2) definition of altered functional outcomes of associated and causal alleles and (3) integration of genetic findings with environmental factors.

Rifaximin in the treatment of inflammatory bowel disease

The gut microbiota plays a role in promoting and maintaining inflammation in inflammatory bowel diseases （IBD）, hence the rationale for the use of antibiotics in the treatment of those disorders. Antibiotics, however, may induce untoward effects, especially during longterm therapy. Rifaximin α polymer is an antibacterial agent that is virtually unabsorbed after oral administration and is devoid of systemic side effects. Rifaximin has provided promising results in inducing remission of Crohn＇s disease （up to 69% in open studies and significantly higher rates than placebo in double blind trials） and ulcerative colitis （76% in open studies and significantly higher rates than placebo in controlled studies） and might also have a role in maintaining remission of ulcerative colitis and pouchitis. The potential therapeutic activity of rifaximin in IBD deserves to be further investigated and confirmed in larger, controlled studies. The optimal dosage still needs to be better defined.

Recent results of laparoscopic surgery in inflammatory bowel disease

Inflammatory bowel diseases are an ideal indication for the laparoscopic surgical approach as they are basically benign diseases not requiring lymphadenectomy and extended mesenteric excision;well-established surgical procedures are available for the conventional approach.Inflammatory alterations and fragility of the bowel and mesentery,however,may demand a high level of laparoscopic experience.A broad spectrum of operations from the rather easy enterostomy formation for anal Crohn’s disease(CD)to restorative proctocolectomies for ulcerative colitis(UC)may be managed laparoscopically.The current evidence base for the use of laparoscopic techniques in the surgical therapy of inflammatory bowel diseases is presented.CD limited to the terminal ileum has become a common indication for laparoscopic surgical therapy.In severe anal CD, laparoscopic stoma formation is a standard procedure with low morbidity and short operative time.Studies comparing conventional and laparoscopic bowel resections,have found shorter times to first postoperative bowel movements and shorter hospital stays as well as lower complication rates in favour of the laparoscopic approach.Even complicated cases with previous surgery,abscess formation and enteric fistulas may be op-erated on laparoscopically with a low morbidity.In UC, restorative proctocolectomy is the standard procedure in elective surgery.The demanding laparoscopic approach is increasingly used,however,mainly in major centers; its feasibility has been proven in various studies.An increased body mass index and acute inflammation of the bowel may be relative contraindications.Short and longterm outcomes like quality of life seem to be equivalent for open and laparoscopic surgery.Multiple studies have proven that the laparoscopic approach to CD and UC is a safe and successful alternative for selected patients. The appropriate selection criteria are still under investigation.Technical considerations are playing an important role for the complexity of both diseases.

Role of ATG16L,NOD2 and IL23R in Crohn's disease pathogenesis

Inflammatory bowel disease is a group of diseases that includes Crohn＇s disease （CD） and ulcerative colitis. CD is characterized as a chronic inflammatory disease of the gastrointestinal tract, ranging from the mouth to the anus. Although there are gross pathological and histological similarities between CD and Johne＇s dis- ease of cattle, the cause of CD remains controversial. It is vital to understand fully the cause of this disease because it affects approximately 500 000 people in North America and Europe. It ranges from 27 to 48 cases per 100 000 people. There are many theories on the cause of CD ranging from possible association with environmental factors including microorganisms to imbalance in the intestinal normal flora of the pa- tients. Regardless of the environmental trigger, there is strong evidence that a genetic disposition is a major key in acquiring CD. Many studies have proven the link between mutations in the ATG16L, NOD2/CARD15, IBDS, CTLA4, TNFSF15 and IL23R genes, and CD. The purpose of this review is to examine all genetic aspects and theories of CD, including up to date multiple popu- lation studies performed worldwide.

Autofluorescence imaging endoscopy for identifi cation and assessment of inflammatory ulcerative colitis

AIM:To validate the clinical relevance of autofluores-cence imaging(AFI)endoscopy for the assessment of inflammatory ulcerative colitis(UC).METHODS:A total of 572 endoscopic images were se-lected from 42 UC patients:286 taken with white light imaging(WLI)and 286 with AFI from the same sites.WLI images were assessed for overall mucosal inflammation according to Mayo endoscopic subscore(MES),and for seven characteristic endoscopic features.Likewise,AFI photographs were scored according to relative abundance of red,green and blue color com-ponents within each image based on an RGB additive color model.WLI and AFI endoscopic scores from the same sites were compared.Histological evaluation of biopsies was according to the Riley Index.RESULTS:Relative to red(r=0.52,P<0.01)or blue(r=0.56,P<0.01)color component,the green color component of AFI(r=-0.62,P<0.01)corresponded more closely with mucosal inflammation sites.There were signif icant differences in green color components between MES-0(0.396±0.043)and MES-1(0.340± 0.035)(P<0.01),and between MES-1 and ≥ MES-2(0.318±0.037)(P<0.01).The WLI scores for "vascu-lar patterns"(r=-0.65,P<0.01),"edema"(r=-0.62,P<0.01),histology scores for "polymorphonuclear cells in the lamina propria"(r=-0.51,P<0.01)and "crypt architectural irregularities"(r=-0.51,P<0.01)showed correlation with the green color component of AFI.There were significant differences in green color components between limited(0.399± 0.042)and extensive(0.375±0.044)(P=0.014)polymorpho-nuclear cell inf iltration within MES-0.As the severity of the mucosal inflammation increased,the green color component of AFI decreased.The AFI green color com-ponent was well correlated with the characteristic en-doscopic and histological inflammatory features of UC.CONCLUSION:AFI has application in detecting inflammatory lesions,including microscopic activity in the co-lonic mucosa of UC patients,based on the green color component of images.

Clinical features and epidemiology of spondyloarthritides associated with inflammatory bowel disease

Inflammation of axial and/or peripheral joints is one of the most frequent extra-intestinal manifestations complicating the clinical course and therapeutic approach in inflammatory bowel diseases(IBD).The frequency of these complications seems to be similar for both diseases, Crohn's disease and ulcerative colitis.Arthritis associated with IBD belongs to the category of spondyloarthropathies.Axial involvement ranges from isolated inflammatory back pain to ankylosing spondylitis, whereas peripheral arthritis is noted in pauciarticular and in polyarticular disease.Asymptomatic radiological involvement of the sacroiliac joints is reported to occur in up to 50% of patients.Other musculoskeletal manifestations such as buttock pain, dactylitis, calcaneal enthesitis, and thoracic pain are frequently underdiagnosed and, consequently, are not treated appropriately.Several diagnostic approaches and criteria have been proposed over the past 40 years in an attempt to correctly classify and diagnose such manifestations.The correct recognition of spondylarthropathies needs an integrated multidisciplinary approach in order to identify common therapeutic strategies, especially in the era of the new biologic therapies.

Clinical,serological and genetic predictors of inflammatory bowel disease course

Patients with extensive or complicated Crohn's disease(CD) at diagnosis should be treated straightaway with immunosuppressive therapy according to the most recent guidelines.In patients with localized and uncomplicated CD at diagnosis,early use of immunosuppressive therapy is debated for preventing disease progression and limiting the disabling clinical impact.In this context,there is a need for predictors of benign or unfavourable subsequent clinical course,in order to avoid over-treating with risky drugs those patients who would have experienced spontaneous mid-term asymptomatic disease without progression towards irreversible intestinal lesions.At diagnosis,an age below 40 years,the presence of perianal lesions and the need for treating the first flare with steroids have been consistently associated with an unfavourable subsequent 5-year or 10-year clinical course.The positive predictive value of unfavourable course in patients with 2 or 3 predictors ranges between 0.75 and 0.95 in population-based and referral centre cohorts.Consequently,the use of these predictors can be integrated into the elements that influence individual decisions.In the CD postoperative context,keeping smoking and history of prior resection are the stron-gest predictors of disease symptomatic recurrence.However,these clinical predictors alone are not as reliable as severity of early postoperative endoscopic recurrence in clinical practice.In ulcerative colitis(UC),extensive colitis at diagnosis is associated with unfavourable clinical course in the first 5 to 10 years of the disease,and also with long-term colectomy and colorectal inflammation-associated colorectal cancer.In patients with extensive UC at diagnosis,a rapid step-up strategy aiming to achieve sustained deep remission should therefore be considered.At the moment,no reliable serological or genetic predictor of inflammatory bowel disease clinical course has been identified.

What's hot in inflammatory bowel disease in 2011?

Ulcerative colitis and Crohn's disease(CD) are the two major forms of inflammatory bowel disease(IBD).In this highlight topic series of articles,the most recent advances in the IBD field are reviewed,especially the newly described cytokines,including the therapeutic implications for their manipulation.In addition,the interplay between the intestinal microbiota and the host is reviewed,including the role of defensins and dysbiosis in CD pathogenesis.Finally,the importance of the non immune systems such as endothelial cells and the hemostatic system are highlighted as new players in IBD pathogenesis.