紫菀酮通过抑制肠上皮细胞凋亡改善TNBS诱导的克罗恩病样结肠炎

目的研究紫菀酮(SHI)对2,4,6-三硝基苯磺酸(TNBS)诱导的小鼠克罗恩病(CD)样结肠炎的作用及潜在机制。方法18只野生型小鼠随机分为3组:对照组(WT组)、模型组(TNBS组)和SHI干预组(SHI组),每组6只。TNBS组小鼠肛门推注5%TNBS诱导CD样结肠炎;SHI组在TNBS造模的同时给予SHI灌胃干预[40 mg/(kg·d)],WT组和TNBS组每日给予等量的生理盐水灌胃。1周后处死小鼠,采用疾病活动度(DAI)评分、体质量改变、结肠长度、组织学炎症评分和小鼠结肠黏膜肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)、白细胞介素-1β(IL-1β)水平评估肠炎程度。采用荧光素异硫氰酸酯-右旋糖酐(FITC)渗透性测定、肠型脂肪酸结合蛋白(I-FABP)测定、细菌移位率评估肠屏障功能。通过TUNEL染色检测小鼠肠上皮细胞凋亡情况;通过Western blot检测小鼠凋亡相关蛋白(Bcl-2和Bax)的表达量。采用网络药理学以及生信富集分析预测SHI干预对小鼠CD样结肠炎保护作用的可能途径。结果与WT组比较,TNBS组DAI评分、体质量降低幅度、组织学炎症评分和结肠黏膜TNF-α、IL-6、IL-1β水平显著升高(P<0.05);与TNBS组比较,SHI组DAI评分、体质量降低幅度、组织学炎症评分和结肠黏膜TNF-α、IL-6、IL-1β水平显著降低(P<0.05)。与WT组比较,TNBS组小鼠结肠长度缩短(P<0.05);与TNBS组比较,SHI组小鼠结肠长度增加(P<0.05)。网络药理学以及生信富集分析发现SHI可能通过拮抗肠上皮细胞凋亡治疗CD。与TNBS组比较,SHI组小鼠外周血FITC-dextran、I-FABP水平和肝脏、肠系膜淋巴结的细菌移位率较低(P<0.05)。TUNEL染色结果显示,与TNBS组比较,SHI组小鼠结肠组织中肠上皮细胞凋亡数量显著减少(P<0.05),Bax的表达下调,Bcl-2的表达上调(均P<0.05)。结论SHI可能通过抑制肠上皮细胞凋亡进而缓解TNBS诱导的小鼠CD样结肠炎。

MSCT对结肠Crohn病的诊断价值

目的:探讨MSCT对结肠Crohn病的诊断价值。方法:回顾性分析经内镜、手术及病理证实的39例结肠Crohn病患者的MSCT影像学表现。结果:39例中多节段病变30例(76.9%),单独大肠受累4例(10.3%)、大肠伴小肠受累35例(89.7%)。大肠病变累及盲肠31例(79.5%)、升结肠26例(66.7%)、横结肠17例(43.6%)、降结肠10例(25.6%)、乙状结肠16例(41.0%)、直肠6例(15.4%)。MSCT征象:肠壁增厚、强化增加、肠壁分层、肠腔狭窄、肠壁脓肿、肠系膜血管增多("梳征")、病变肠管周围纤维脂肪增多、蜂窝织炎、腹腔脓肿和炎性肿块、肛周病变、瘘管/窦道、系膜淋巴结肿等。肠管增厚、肠壁分层、强化增加、肠壁内脓肿、病变肠管周围蜂窝织炎、"梳征"等可提示病变处在活动期。结论:结肠Crohn病易累及盲、升结肠,MSCT表现有一定特征性,MSCT在显示肠壁病变及肠腔外并发症以及判断病变是否在活动期具有优势。

FT3、FT4、FT3/FT4、TSH与克罗恩病维得利珠单抗治疗后临床活动度变化关系的研究

目的:探究血清游离三碘甲状腺原氨酸(FT3)、游离四碘甲状腺原氨酸(FT4)、FT3/FT4、促甲状腺激素(TSH)对克罗恩病(CD)患者维得利珠单抗(VDZ)治疗后临床应答的预测价值。方法:纳入2020年5月至2022年5月我院接受VDZ治疗且疗程超过3个月的CD患者54例,对照组89例。收集对照组及CD患者使用VDZ治疗前、治疗3个月后FT3、FT4、FT3/FT4、TSH等甲状腺功能指标数据,用CD活动指数(CDAI)评估CD疾病活动度。比较CD患者与对照组甲状腺功能指标差异。根据VDZ治疗前后CDAI差值(ΔCDAI)是否≥100分分为应答组及无应答组,比较两组患者VDZ治疗前后甲状腺功能指标变化及其差值(ΔFT3、ΔFT4、ΔFT3/FT4、ΔTSH)与ΔCDAI相关性;用受试者工作特征(ROC)曲线分析上述差值对VDZ临床应答的预测价值。结果:CD患者治疗前FT3、FT3/FT4低于对照组(P<0.05);VDZ治疗3个月后FT3、FT3/FT4较前提高,FT4降低(P<0.05)。应答组FT3、FT4、FT3/FT4、CDAI在VDZ治疗前后自身比较,差异均有统计学意义(P<0.05)。VDZ治疗前后ΔFT3、ΔFT3/FT4与ΔCDAI间呈负相关(P<0.05),ΔFT4、ΔTSH与ΔCDAI无直线相关关系(P>0.05)。ΔFT3、ΔFT3/FT4预测VDZ治疗临床应答潜能的ROC曲线下面积(AUC)分别为0.837、0.827,灵敏度为82.9%、80.5%,特异度均为81.8%。结论:血清游离甲状腺功能指标变化尤其是FT3、FT3/FT4变化与CD患者VDZ治疗后临床活动指数变化呈负相关,并对其临床应答有一定预测价值。

Are we ready for telemonitoring inflammatory bowel disease?A review of advances,enablers,and barriers

This review summarizes the evidence about telemonitoring in patients with inflammatory bowel disease(IBD). To give an overview of the advances performed, as well as the enablers and barriers which favoured/hindered telemonitoring implementation. We performed a literature search in Pub Med, EMBASE, MEDLINE, Cochrane Database, Web of Science and Conference Proceedings. Titles and abstracts published up to September 2022 were screened for a set of inclusion criteria: telemonitoring intervention, IBD as the main disease, and a primary study performed. Ninety-seven reports were selected for full review. Finally, 20 were included for data extraction and critical appraisal. Most studies used telemonitoring combined with tele-education, and programs evolved from home telemanagement systems towards web portals through m Health applications. Web systems demonstrated patients’ acceptance, improvement in quality of life, disease activity and knowledge, with a good cost-effectiveness profile in the short-term. Initially, telemonitoring was almost restricted to ulcerative colitis, but new patient reported outcome measures, home-based tests and mobile devices favoured its expansion to different patients’ categories. However, technological and knowledge advances led to legal, ethical, economical and logistic issues. Standardization of remote healthcare is necessary, to improve the interoperability of systems as well as to address liability concerns and users’ preferences. Telemonitoring IBD is well accepted and improves clinical outcomes at a lower cost in the short-term. Funders, policymakers, providers, and patients need to align their interests to overcome the emerging barriers for its full implementation.

Crohn’s病的肠外表现特征及其临床意义

目的探讨Crohn’s病(CD)患者肠外表现的特点和临床意义。方法回顾性收集有肠外并发症表现的51例CD患者的临床资料,分析患者出现肠外并发症的特征表现,结合文献报道对比复习这些肠外并发症在Crohn’s的诊断和治疗中的意义。结果51例患者肠外表现依次为骨关节病变、口腔溃疡、肝胆病变、皮肤病变、眼部、代谢性骨病、血管闭塞等。出现一种肠外病变的29例,两种肠外病变的为13例,三种或以上病变的为9例。原发CD病灶的受累范围越广,其肠外表现的种类越多。结论肠外表现与Crohn’s病的累及部位与严重度有一定关系,肠外并发症对其原发Crohn’s病诊断和治疗均有一定的影响。

Natural history and long-term clinical course of Crohn's disease

Crohn’s disease is a chronic inflammatory disease process involving different sites in the gastrointestinal tract.Occasionally,so-called metastatic disease occurs in extra-intestinal sites.Granulomatous inflammation may be detected in endoscopic biopsies or resected tissues.Genetic,epigenetic and environmental factors appear to play a role.Multiple susceptibility genes have been described in both familial and non-familial forms while the disease is phenotypically heterogeneous with a female predominance.The disorder occurs over a broad age spectrum,from early childhood to late adulthood.More than 80%are diagnosed before age 40 years usually with terminal ileal and colonic involvement.Pediatric-onset disease is more severe and more extensive,usually with a higher chance of upper gastrointestinal tract disease,compared to adult-onset disease.Long-term studies have shown that the disorder may evolve with time into more complex disease with stricture formation and penetrating disease complications(i.e.,fistula,abscess).Although prolonged remission may occur,discrete periods of symptomatic disease may re-appear over many decades suggesting recurrence or re-activation of this inflammatory process.Eventual development of a cure will likely depend on identification of an etiologic cause and a fundamental understanding of its pathogenesis.Until now,treatment has focused on removing risk factors,particularly cigarette smoking,and improving symptoms.In clinical trials,clinical remission is largely defined as improved numerical and endoscopic indices for"mucosal healing"."Deep remission"is a conceptual,more"extended"goal that may or may not alter the long-term natural history of the disease in selected patients,albeit at a significant risk for treatment complications,including serious and unusual opportunistic infections.

Association between NOD2/CARD15 gene polymorphisms and Crohn's disease in Chinese Zhuang patients

AIM:To assess the relationship between the P268S,JW1 and N852S polymorphisms and Crohn’s disease(CD)susceptibility in Zhuang patients in Guangxi,China.METHODS:Intestinal tissues from 102 Zhuang[48CD and 54 ulcerative colitis(UC)]and 100 Han(50 CD and 50 UC)unrelated patients with inflammatory bowel disease and 72 Zhuang and 78 Han unrelated healthy individuals were collected in the Guangxi Zhuang Autonomous Region from January 2009 to March 2013.Genomic DNA was extracted using the phenol chloroform method.The P268S,JW1 and N852S polymorphisms were amplified using polymerase chain reaction(PCR),detected by restriction fragment length polymorphism(RFLP),and verified by gene sequencing.RESULTS:Heterozygous mutation of P268S in the NOD2/CARD15 gene was detected in 10 CD cases(six Zhuang and four Han),two Han UC cases,and one Zhuang healthy control,and P268S was strongly associated with the Chinese Zhuang and Han CD populations(P=0.016 and 0.022,respectively).No homozygous mutant P268S was detected in any of the groups.No significant difference was found in P268S genotype and allele frequencies between UC and control groups(P>0.05).Patients with CD who carried P268S were likely to be≤40 years of age(P=0.040),but were not significantly different with regard to race,lesion site,complications,and other clinical features(P>0.05).Neither JW1 nor N852S polymorphisms of the NOD2/CARD15gene were found in any of the subjects(P>0.05).CONCLUSION:P268S polymorphism may be associated with CD susceptibility in the Zhuang population in the Guangxi Zhuang Autonomous Region,China.In contrast,JW1 and N852S polymorphisms may not be related to CD susceptibility in these patients.

Identification of pathologic features associated with “ulcerative colitis-like” Crohn's disease

AIM: To identify pathologic features associated with this "ulcerative colitis(UC)-like" subgroup of Crohn's disease(CD).METHODS: Seventeen subjects diagnosed as having UC who underwent proctocolectomy(RPC) from 2003-2007 and subsequently developed CD of the ileal pouch were identified. UC was diagnosed based on preoperative clinical, endoscopic, and pathologic studies. Eighteen patients who underwent RPC for UC within the same time period without subsequently developing CD were randomly selected and used as controls. Pathology reports and histological slides were reviewed for a wide range of gross and microscopic pathological features, as well as extent of disease. The demographics, gross description and histopathology of the resection specimens were reviewed and compared between the two groups. RESULTS: Patients with "UC-like" CD were on average 13 years younger than those with "true" UC(P < 0.01). More severe disease in the proximal involved region and active ileitis with/without architectural distortion were observed in 6 of 17(35%) and 7 of 17(41%) "UC-like" CD cases, respectively, but in none of the "true" UC cases(P < 0.05). Active appendicitis occurred in 8 of 16(50%) "UC-like" CD cases but in only two(11%) "true" UC cases(P < 0.05). Conspicuous lamina propria neutrophils were more specific for "UClike" CD(76% vs 22%, P < 0.05). In addition, prominent lymphoid aggregates tended to be more common in "UC-like" CD(P = 0.07). The "true" UC group contained a greater number of cases with severe activity(78% vs 47%). Therefore, the features more commonly seen in "UC-like" CD were not due to a more severe disease process. Crohn's granulomas and transmural inflammation in non-ulcerated areas were absent in both groups.CONCLUSION: More severe disease in the proximal involved region, terminal ileum involvement, active appendicitis, and prominent lamina propria neutrophils may be morphological factors associated with "UC-like" CD.

Surgery for luminal Crohn's disease

Many patients with Crohn’s disease(CD)require surgery.Indications for surgery include failure of medical treatment,bowel obstruction,fistula or abscess formation.The most common surgical procedure is resection.In jejunoileal CD,strictureplasty is an accepted surgical technique that relieves the obstructive symptoms,while preserving intestinal length and avoiding the development of short bowel syndrome.However,the role of strictureplasty in duodenal and colonic diseases remains controversial.In extensive colitis,after total colectomy with ileorectal anastomosis(IRA),the recurrence rates and functional outcomes are reasonable.For patients with extensive colitis and rectal involvement,total colectomy and end-ileostomy is safe and effective;however,a few patients can have subsequent IRA,and half of the patients will require proctectomy later.Proctocolectomy is associated with a high incidence of delayed perineal wound healing,but it carries a low recurrence rate.Patients undergoing proctocolectomy with ileal pouch-anal anastomosis had poor functional outcomes and high failure rates.Laparoscopic surgery has been introduced as a minimal invasive procedure.Patients who undergo laparoscopic surgery have a more rapid recovery of bowel function and a shorter hospital stay.The morbidity also is lower,and the rate of disease recurrence is similar compared with open procedures.

Plasma long noncoding RNA expression profile identified by microarray in patients with Crohn's disease

AIM: To investigate the expression pattern of plasma long noncoding RNAs(lnc RNAs) in Chrohn's disease(CD) patients.METHODS: Microarray screening and q RT-PCR verification of lnc RNAs and m RNAs were performed in CD and control subjects, followed by hierarchy c l u s t e r i n g, G O a n d K E G G p a t h w a y a n a l y s e s. Significantly dysregulated lnc RNAs were categorized into subgroups of antisense lnc RNAs, enhancer lnc RNAs and linc RNAs. To predict the regulatory effect of lnc RNAs on m RNAs, a CNC network analysis was performed and cross linked with significantly changed lnc RNAs. The overlapping lnc RNAs were randomly selected and verified by q RT-PCR in a larger cohort. RESULTS: Initially, there were 1211 up-regulated and 777 down-regulated lnc RNAs as well as 1020 up-regulated and 953 down-regulated m RNAs after microarray analysis; a heat map based on these results showed good categorization into the CD and control groups. GUSBP2 and AF113016 had the highest fold change of the up- and down-regulated lnc RNAs, whereas TBC1D17 and CCL3L3 had the highest foldchange of the up- and down-regulated m RNAs. Six(SNX1, CYFIP2, CD6, CMTM8, STAT4 and IGFBP7) of 10 m RNAs and 8(NR_033913, NR_038218, NR_036512, NR_049759, NR_033951, NR_045408, NR_038377 and NR_039976) of 14 lnc RNAs showed the same change trends on the microarray and q RT-PCR results with statistical significance. Based on the q RT-PCR verified m RNAs, 1358 potential lnc RNAs with 2697 positive correlations and 2287 negative correlations were predicted by the CNC network. CONCLUSION: The plasma lnc RNAs profiles provide preliminary data for the non-invasive diagnosis of CD and a resource for further specific lnc RNA-m RNA pathway exploration.

Crohn's disease presenting as acute gastrointestinal hemorrhage

Severe gastrointestinal(GI) hemorrhage is a rare complication of Crohn's disease(CD). Although several surgical and non-surgical approaches have been described over the last 2 decades this complication still poses significant diagnostic and therapeutic challenges. Given the relative infrequency of severe bleeding in CD, available medical literature on this topic is mostly in the form of retrospective case series and reports. In this article we review the risk factors, diagnostic modalities and treatment options for the management of CD presenting as GI hemorrhage.

RAGE gene three polymorphisms with Crohn's disease susceptibility in Chinese Han population

AIM:To investigate the association of three polymorphisms in the receptor for advanced glycation end product(RAGE)gene with Crohn’s disease(CD)risk in a Chinese population.METHODS:A hospital-based case-control association study involving 312 CD patients and 479 healthy controls was conducted.Peripheral blood samples were collected from 791 study subjects,and genomic DNA was extracted.Genotyping was performed using polymerase chain reaction-ligase detection reaction method.The association between polymorphic genotype and CD predisposition was determined using odds ratio and95%confidence interval(CI).Data were analyzed using Haplo.stats program.RESULTS:Significant differences were observed between patients and controls in allele/genotype distributions of rs1800624(P allele=0.012;P genotype=0.005)and in allele distributions of rs2070600(P=0.02).The risk for CD associated with the rs1800624-A mutant allele decreased by 36%(95%CI:0.47-0.88,P=0.005)under the additive model and by 35%(95%CI:0.46-0.91,P=0.013)under the dominant model.Carriers of rs2070600-A mutant allele showed a 37%(95%CI:1.02-1.83,P=0.036)increased risk of developing CD relative to the GG genotype carriers.In haplotype analysis,haplotype T-A-G(in the order rs1800625,rs1800624,and rs2070600)decreased the odds of CD by 33%(95%CI:0.49-0.94,P=0.018).CONCLUSION:CD is an immune-related disease with genetic predisposition.Genetic defects in the RAGE gene are strongly associated with CD in Chinese population.

Endoscopy-based management decreases the risk of postoperative recurrences in Crohn's disease

AIM: To investigate whether an endoscopy-based management could prevent the long-term risk of postoperative recurrence.METHODS: From the pathology department database, we retrospectively retrieved the data of all the patients operated on for Crohn's disease(CD) in our center(1986-2015). Endoscopy-based management was defined as systematic postoperative colonoscopy(median time after surgery = 9.5 mo) in patients with no clinical postoperative recurrence at the time of endoscopy. RESULTS: From 205 patients who underwent surgery, 161 patients(follow-up > 6 mo) were included. Endoscopic postoperative recurrence occurred in 67.6%, 79.7%, and 95.5% of the patients, respectively 5, 10 and 20 years after surgery. The rate of clinical postoperative recurrence was 61.4%, 75.9%, and 92.5% at 5, 10 and 20 years, respectively. The rate of surgical postoperative recurrence was 19.0%, 38.9% and 64.7%, respectively, 5, 10 and 20 years after surgery. In multivariate analysis, previous intestinal resection, prior exposure to anti-TNF therapy before surgery, and fistulizing phenotype(B3) were postoperative risk factors. Previous perianal abscess/fistula(other perianal lesions excluded), were predictive of only symptomatic recurrence. In multivariate analysis, an endoscopy-based management(n = 49/161) prevented clinical(HR = 0.4, 95%CI: 0.25-0.66, P < 0.001) and surgical postoperative recurrence(HR = 0.30, 95%CI: 0.13-0.70, P = 0.006).CONCLUSION: Endoscopy-based management should be recommended in all CD patients within the first year after surgery as it highly decreases the long-term risk of clinical recurrence and reoperation.

Small intestinal bacterial overgrowth in inactive Crohn's disease:Influence of thiopurine and biological treatment

AIM:To investigate the influence of thiopurines and biological drugs on the presence of small intestinal bacterial overgrowth(SIBO) in patients with inactive Crohn's disease(CD).METHODS:This was a prospective study in patients with CD in remission and without corticosteroid treatment,included consecutively from 2004 to 2010.SIBO was investigated using the hydrogen glucose breath test.RESULTS:One hundred and seven patients with CD in remission were included.Almost 58%of patients used maintenance immunosuppressant therapy and 19.6%used biological therapy.The prevalence of SIBO was16.8%.No association was observed between SIBO and the use of thiopurine Immunosuppressant(12/62patients),administration of biological drugs(2/21 patients),or with double treatment with an anti-tumor necrosis factor drugs plus thiopurine(1/13 patients).Half of the patients had symptoms that were suggestive of SIBO,though meteorism was the only symptom that was significantly associated with the presence of SIBO on univariate analysis(P<0.05).Multivariate analysis revealed that the presence of meteorism and a fistulizing pattern were associated with the presence of SIBO(P<0.05).CONCLUSION:Immunosuppressants and/or biological drugs do not induce SIBO in inactive CD.Fistulizing disease pattern and meteorism are associated with SIBO.

Trefoil factor-3 is not a useful marker of mucosal healing in Crohn's disease treated with anti-TNF-α antibodies

AIM To evaluate whether repeated serum measurements of trefoil factor-3(TFF-3)can reliably reflect mucosal healing(MH)in Crohn’s disease(CD)patients treated with anti-tumor necrosis factor-α(anti-TNF-α)antibodies.METHODS Serum TFF-3 was measured before and after antiTNF-αinduction therapy in 30 CD patients.The results were related to clinical,biochemical and endoscopic parameters.MH was defined as a≥50%decrease in Simple Endoscopic Score for Crohn’s disease(SES-CD).RESULTS SES-CD correlated significantly with CD clinical activity and several standard biochemical parameters(albumin,leukocyte and platelet counts,C-reactive protein,erythrocyte sedimentation rate,fibrinogen).In contrast,SES-CD did not correlate with TFF-3(P=0.54).Moreover,TFF-3 levels did not change significantly after therapy irrespectively of whether the patients achieved MH or not.Likewise,TFF-3 did not correlate with changes in fecal calprotectin,which has been proposed as another biochemical marker of mucosal damage in CD.CONCLUSION Serum TFF-3 is not a convenient and reliable surrogate marker of MH during therapy with TNF-αantagonists in CD.

Pulmonary manifestations of Crohn's disease

Crohn’s disease(CD)is a systemic illness with a constellation of extraintestinal manifestations affecting various organs.Of these extraintestinal manifestations of CD,those involving the lung are relatively rare.However,there is a wide array of lung manifestations,ranging from subclinical alterations,airway diseases and lung parenchymal diseases to pleural diseases and drug-related diseases.The most frequent manifestation is bronchial inflammation and suppuration with or without bronchiectasis.Bronchoalveolar lavage findings show an increased percentage of neutrophils.Drug-related pulmonary abnormalities include disorders which are directly induced by sulfasalazine,mesalamine and methotrexate,and opportunistic lung infections due to immunosuppressive treatment.In most patients,the development of pulmonary disease parallels that of intestinal disease activity.Although infrequent,clinicians dealing with CD must be aware of these,sometimes life-threatening,conditions to avoid further impairment of health status and to alleviate patient symptoms by prompt recognition and treatment.The treatment of CD-related respiratory disorders depends on the specific pattern of involvement,and in most patients,steroids are required in the initial management.

Structural and molecular features of intestinal strictures in rats with Crohn's-like disease

AIM: To develop a new rat model we wanted to gain a better understanding of stricture formation in Crohn's disease(CD).METHODS: Chronic colitis was induced locally by the administration of 2,4,6-trinitrobenzenesulfonic acid(TNBS). The relapsing inflammation characteristic to CD was mimicked by repeated TNBS treatments. Animals were randomly divided into control, once, twice and three times TNBS-treated groups. Control animals received an enema of saline. Tissue samples were taken from the strictured colonic segments and also adjacent proximally and distally to its 60, 90 or 120 d after the last TNBS or saline administrations. The frequency and macroscopic extent of the strictures were measured on digital photographs. The structural features of strictured gut wall were studied by light- and electron microscopy. Inflammation related alterations in TGF-beta 2 and 3, matrix metalloproteinases 9(MMP9) and TIMP1 m RNA and protein expression were determined by quantitative real-time PCR and western blot analysis. The quantitative distribution of caspase 9 was determined by post-embedding immunohistochemistry.RESULTS: Intestinal strictures first appeared 60 d after TNBS treatments and the frequency of them increased up to day 120. From day 90 an intact lamina epithelialis, reversible thickening of lamina muscularis mucosae and irreversible thickening of the muscularis externa were demonstrated in the strictured colonic segments. Nevertheless the morphological signs of apoptosis were frequently seen and excess extracellular matrix deposition was recorded between smooth muscle cells(SMCs). Enhanced caspase 9 expression on day 90 in the SMCs and on day 120 also in myenteric neurons indicated the induction of apoptosis. The m RNA expression profile of TGF-betas after repeated TNBS doses was characteristic to CD, TGF-beta 2, but not TGF-beta 3 was up-regulated. Overexpression of MMP9 and down-regulation of TIMP1 were demonstrated. The progressive increase in the amount of MMP9 protein in the strictures was also obvious between days 90 and 120 but TIMP1 protein was practically undetectable at this time.CONCLUSION: These findings indicate that aligned structural and molecular changes in the gut wall rather than neuronal cell death play the primary role in stricture formation.

Optimal b value of diffusion-weighted imaging on a 3.0T magnetic resonance scanner in Crohn's disease

AIM:To determine the optimal b value of diffusionweighted imaging for detecting active inflammation in Crohn's disease.METHODS:Thirty-one patients clinically diagnosed with active Crohn’s disease were referred for magnetic resonance examination.All patients were scanned on a3.0T magnetic resonance scanner using the same protocol involving four different b values(800,1500,2000and 2500 s/mm2).The diagnostic effect of diffusionweighted imaging was evaluated and compared with endoscopic findings.The diffusion-weighted image quality of four b value groups was evaluated and apparent diffusion coefficient was measured for both nor-mal and inflammatory intestinal segments.RESULTS:The contrast-to-noise ratio and signal-tonoise ratio were not satisfied when b value 2000 or2500 s/mm2 was adopted(36.52±14.95 vs 34.78±24.83,P>0.05;53.58±23.45 vs 47.58±29.67,P>0.05).The qualitative image quality was not enough to meet diagnostic requirement.No matter which b value was chosen,the apparent diffusion coefficient of inflammatory intestinal segments was significantly lower than that of normal intestinal segments(1.38±0.28 vs 2.00±0.38,P<0.01;1.09±0.20 vs 1.50±0.28,P<0.01;0.95±0.19 vs 1.34±0.28,P<0.01;0.88±0.14 vs 1.20±0.21,P<0.01).The lesion detection rate(90.32%),diagnostic sensitivity(81.18%)and specificity(95.10%)would be appropriate when b value 1500 s/mm2 was adopted.CONCLUSION:High b value is suitable for intestinal DW examination on a high field MR scanner.

Polymorphisms in interleukin-10 gene according to mutations of NOD2/CARD15 gene and relation to phenotype in Spanish patients with Crohn's disease

瞄准：检验 interleukin-10 (IL-10 ) 的贡献基因多型性到 Crohnos 疾病(CD ) 显型，和在 IL-10 基因多型性和 CARD15/NOD2 基因变化之间的可能的基因排泄制止。方法：有 Crohn 从一个单个中心招募的疾病的 205 个西班牙的无关的病人的一个队被学习。所有病人是严厉地 phenotyped 并且为至少 3 年跟随起来(吝啬的时间， 12.5 年) 。临床的显型在 genotyping 以前被建立。结果：遗传型的关联 -- 维也纳分类组证明回肠结肠地点显著地在 NOD2/CARD15 变化积极的病人与 -1082G 等位基因被联系(RR=1.52， 95%CI， 1.21 ～ 1.91， P=0.008 ) 。多，变量分析证明在 NOD2/CARD15 变化的 IL-10 G14 微卫星等位基因积极病人与二个风险因素被联系，阑尾切除术的历史(RR=2.15， 95%CI=1.1-4.30， P=0.001 ) 并且在诊断的吸烟习惯(RR=1.29， 95%CI=1.04-4.3， P=0.04 ) 。结论：在从马德里的西班牙的人口，在带至少一个 NOD2/CARD15 变化的 CD 病人， -1082G 等位基因与回肠结肠疾病被联系， IL-10G14 微卫星等位基因在诊断与阑尾切除术和吸烟习惯的以前的历史被联系。这些数据为 CD 的临床的异质的一个基因基础提供进一步分子的证据。

Evaluation of “top-down” treatment of early Crohn's disease by double balloon enteroscopy

AIM: To assess "top-down" treatment for deep remission of early moderate to severe Crohn's disease(CD) by double balloon enteroscopy.METHODS: Patients with early active moderate to severe ileocolonic CD received either infusion of infliximab 5 mg/kg at weeks 0, 2, 6, 14, 22 and 30 with azathioprine from week 6 onwards(Group?Ⅰ), or prednisone from week 0 as induction therapy with azathioprine from week 6 onwards(Group Ⅱ). Endoscopic evaluation was performed at weeks 0, 30, 54 and 102 by double balloon enteroscopy. The primary endpoints were deep remission rates at weeks 30, 54 and 102. Secondary endpoints included the time to achieve clinical remission, clinical remission rates at weeks 2, 6, 14, 22, 30, 54 and 102, and improvement of Crohn's Disease Endoscopic Index of Severity scores at weeks 30 and 54 relative to baseline. Intention-to-treat analyses of the endpoints were performed.RESULTS: Seventy-seven patients were enrolled, with 38 in GroupⅠand 39 in Group Ⅱ. By week 30, deep remission rates were 44.7% and 17.9% in GroupsⅠand Ⅱ, respectively(P = 0.011). The median time to clinical remission was longer for patients in Group Ⅱ(14.2 wk) than for patients in GroupⅠ6.8 wk, P = 0.009). More patients in GroupⅠwere in clinical remission than in Group Ⅱ at weeks 2, 6, 22 and 30(2 wk: 26.3% vs 2.6%; 6 wk: 65.8% vs 28.2%; 22 wk: 71.1% vs 46.2%; 30 wk: 68.4% vs 43.6%, P < 0.05). The rates of clinical remission and deep remission were greater at weeks 54 and 102 in GroupⅠ, but the differences were insignificant.CONCLUSION: Top-down treatment with infliximab and azathioprine, as compared with corticosteroid and azathioprine, results in higher rates of earlier deep remission in early CD.