In the gut, where billions of non-self-antigens from the food and the microbiota are present, the immune response must be tightly regulated to ensure both host protection against pathogenic microorganisms and the abse...In the gut, where billions of non-self-antigens from the food and the microbiota are present, the immune response must be tightly regulated to ensure both host protection against pathogenic microorganisms and the absence of immune-related pathologies. It has been well documented that regulatory T cells(Tregs) play a pivotal role in this context. Indeed, Tregs are able to prevent excessive inflammation, which can lead to the rupture of intestinal homeostasis observed in inflammatory bowel diseases(IBDs). Both the worldwide incidence and prevalence of such diseases have increased throughout the latter part of the 20^(th) century. Therefore, it is crucial to understand how Tregs suppress the colitogenic immune cells to establish new treatments for patients suffering from IBDs. In this review, we will first summarize the results obtained in animal model studies that highlight the importance of Tregs in maintaining intestinal homeostasis and describe the specific suppressive mechanisms involved. Next, our current knowledge about Tregs contribution to human IBDs will be reviewed, as well as the current therapeutic perspective on using Tregs for clinical IBD treatment and the challenges that remain to be resolved to ensure both the safety and effectiveness of these therapies in targeting this critical immune-regulatory cell population.展开更多
Diagnostic imaging plays a key role in the diagnosis and management of inflammatory bowel disease(IBD). However due to the relapsing nature of IBD, there is growing concern that IBD patients may be exposed to potentia...Diagnostic imaging plays a key role in the diagnosis and management of inflammatory bowel disease(IBD). However due to the relapsing nature of IBD, there is growing concern that IBD patients may be exposed to potentially harmful cumulative levels of ionising radiation in their lifetime, increasing malignant potential in a population already at risk. In this review we explore the proportion of IBD patients exposed to high cumulative radiation doses, the risk factors associated with higher radiation exposures, and we compare conventional diagnostic imaging with newer radiation-free imaging techniques used in the evaluation of patients with IBD. While computed tomography(CT) performs well as an imaging modality for IBD, the effective radiation dose is considerably higher than other abdominal imaging modalities. It is increasingly recognised that CT imaging remains responsible for the majority of diagnostic medical radiation to which IBD patients are exposed. Magnetic resonance imaging(MRI) and small intestine contrast enhanced ultrasonography(SICUS) have now emerged as suitable radiation-free alternatives to CT imaging, with comparable diagnostic accuracy. The routine use of MRI and SICUS for the clinical evaluation of patients with known or suspected small bowel Crohn's disease is to be encouraged wherever possible. More provision is needed for out-of-hours radiation-free imaging modalities to reduce the need for CT.展开更多
AIM: To investigate the effect of chymase inhibitor TY-51469 in the therapy of inflammatory bowel disease and the underlying mechanism. METHODS: Seventy-five healthy Sprague-Dawley rats were randomly assigned to one o...AIM: To investigate the effect of chymase inhibitor TY-51469 in the therapy of inflammatory bowel disease and the underlying mechanism. METHODS: Seventy-five healthy Sprague-Dawley rats were randomly assigned to one of the three groups(control group, model group and TY-51469 experiment group) and each group had twenty-five rats. The rats of the model group and experiment group were subjected to treatment with 3.5% dextran sulfate sodium(DSS) 10 mg/kg to induce colitis. The control group and model group were subjected to intraperitoneal injection of saline, while the experiment group was subjected to intraperitoneal injection of 10 mg/kg TY-51469 each day. Five rats of each group were sacrificed on 0, 7, 14, 21 and 28 d, respectively. The degree of inflammation was assessed by histopathological scoring; flow cytometry was performed to detect the proportion of CD4+CD25+ Tregs in peripheral blood; colon tissues of rats were collected to measure m RNA and protein expression by PCR, Western blot and immunohistochemistry; serum levels of interleukin(IL)-10, transforming growth factor(TGF)-β1 and IL-17A were detected by ELISA. RESULTS: The rats in the experiment group and model group had significantly more severe colitis than the ones in the control group(P < 0.05) before treatment on day 0; no significant difference was observed between the experiment group and model group(P > 0.05). After treatment with TY-51469, the rats in the experiment group had significantly less severe colitis compared with the model group on 7, 14, 21 and 28 d(P < 0.05). The proportion of CD4+CD25+ Tregs was lower in the model group and experiment group than in the control group; the experiment group had a significantly higher proportion of CD4+CD25+ Tregs than that in the model group(P < 0.05). The model group and experiment group demonstrated lower expression of Foxp3 than the control group; the experiment group had higher Foxp3 expression than the model group(P < 0.05). Cytokines IL-10, TGF-β1 and IL-17 A were lower in the model group and experiment group than in the control group; the experiment group had higher expression than the model group(P < 0.05). CONCLUSION: After treatment with chymase inhibitor TY-51469, the experiment group demonstrated more significantly reduced intestinal inflammation and higher expression of immune tolerance related cytokines(IL-10, TGF-β1, IL-17A) and Foxp3 which is specifically expressed in Tregs compared with the model group. Therefore, chymase inhibitor TY-51469 might ameliorate the progression of DSS-induced colitis possibly by increasing the expression of Tregs and cytokines.展开更多
目的:评估炎症性肠病(inflammatory bowel disease,IBD)患者腹部双能量CT(dual-energy CT,DECT)扫描不同能级噪声优化的虚拟单能量图像(noise-optimized virtual monoenergetic imaging,VMI+)的主观和客观图像质量,得出最佳重建参数,提...目的:评估炎症性肠病(inflammatory bowel disease,IBD)患者腹部双能量CT(dual-energy CT,DECT)扫描不同能级噪声优化的虚拟单能量图像(noise-optimized virtual monoenergetic imaging,VMI+)的主观和客观图像质量,得出最佳重建参数,提高IBD诊断准确率。方法:选取2016年4月到2017年6月确诊为IBD的32名患者腹部DECT扫描图像进行线性融合(M_0.6)、VMI+、传统虚拟单能量图像(virtual monoenergetic imaging,VMI)重建,虚拟能级为40~100 ke V,间隔为10 ke V。以病变肠段部位的图像信噪比(signal-to-noise ratio,SNR)和对比噪声比(contrast-to-noise ratio,CNR)作为客观图像质量评价标准,主观图像质量评价由3名放射科医生对总体图像质量、锐利度、病变轮廓、噪声4个方面进行双盲评估。结果:客观图像质量评价最佳重建参数为40 ke V VMI+(SNR 8.28±2.34;CNR 5.10±2.10),优于线性融合图像(SNR 5.82±1.44;CNR 1.53±0.86)和传统VMI(P<0.01)。主观图像质量评价中,50 ke V VMI+总体图像质量(均值4.80)高于其他图像(P<0.01),40和50 ke V VMI+锐利度最高(均值分别为4.14和4.25,P=0.415),40 ke V VMI+显示病变轮廓能力评分高于其他图像(均值4.52,P<0.01)。100 ke V VMI+和100 ke V VMI噪声最低(均值分别为4.58和4.40,P≥0.11)。结论:相比于线性融合和传统VMI重建,低能级VMI+可显著提高IBD病变部位的腹部DECT扫描图像的主观和客观图像质量。展开更多
自滤泡辅助性T细胞(follicular helper T cells,Tfh细胞)发现以来,大量证据表明与炎症性肠病的发病有关.Tfh细胞及其亚群分泌不同细胞因子皆可在炎症性肠病的发病过程中扮演重要角色,为靶向治疗炎症性肠病提供重要思路.BCL-6信号作为Tf...自滤泡辅助性T细胞(follicular helper T cells,Tfh细胞)发现以来,大量证据表明与炎症性肠病的发病有关.Tfh细胞及其亚群分泌不同细胞因子皆可在炎症性肠病的发病过程中扮演重要角色,为靶向治疗炎症性肠病提供重要思路.BCL-6信号作为Tfh细胞分化途径上的关键性转录因子,可调控Tfh细胞的增殖、分化.在BCL-6信号缺乏时无法产生Tfh细胞,且BCL-6信号也可通过正性调控、负性调控以及表观遗传学等多种途径有效调控Tfh细胞的分化.在BCL-6信号调控异常时可导致Tfh的分化异常导致炎症性肠病的发生.因此可以通过干预BCL-6信号来调控Tfh细胞分化来作为治疗炎症性肠病新的有效靶点.展开更多
AIM: to evaluate the effectiveness of probiotic therapy for suppressing relapse in patients with inactive ulcerative colitis(UC).METHODS: Bio-Three tablets, each containing 2 mg of lactomin(Streptococcus faecalis T-11...AIM: to evaluate the effectiveness of probiotic therapy for suppressing relapse in patients with inactive ulcerative colitis(UC).METHODS: Bio-Three tablets, each containing 2 mg of lactomin(Streptococcus faecalis T-110), 10 mg of Clostridium butyricum TO-A, and 10 mg of Bacillus mesentericus TO-A, were used as probiotic therapy.Sixty outpatients with UC in remission were randomly assigned to receive 9 Bio-Three tablets/day(BioThree group) or 9 placebo tablets/day(placebo group)for 12 mo in addition to their ongoing medications.Clinical symptoms were evaluated monthly or on the exacerbation of symptoms or need for additional medication. Fecal samples were collected to analyze bacterial DNA at baseline and 3-mo intervals. Terminal restriction fragment length polymorphism and cluster analyses were done to examine bacterial components of the fecal microflora.RESULTS: Forty-six patients, 23 in each group,completed the study, and 14 were excluded. The relapse rates in the Bio-Three and placebo groups were respectively 0.0% vs 17.4% at 3 mo(P = 0.036), 8.7%vs 26.1% at 6 mo(P = 0.119), and 21.7% vs 34.8%(P = 0.326) at 9 mo. At 12 mo, the remission rate was 69.5% in the Bio-Three group and 56.6% in the placebo group(P = 0.248). On cluster analysis of fecal flora, 7 patients belonged to cluster Ⅰ, 32 to cluster Ⅱ,and 7 to cluster Ⅲ.CONCLUSION: Probiotics may be effective formaintaining clinical remission in patients with quiescent UC, especially those who belong to cluster Ⅰ on fecal bacterial analysis.展开更多
Inflammatory bowel diseases(IBD), including ulcerative colitis and Crohn's disease are chronic, life-long, and relapsing diseases of the gastrointestinal tract. Currently, there are no complete cure possibilities,...Inflammatory bowel diseases(IBD), including ulcerative colitis and Crohn's disease are chronic, life-long, and relapsing diseases of the gastrointestinal tract. Currently, there are no complete cure possibilities, but combined pharmacological and nutritional therapy may induce remission of the disease. Malnutrition and specific nutritional deficiencies are frequent among IBD patients, so the majority of them need nutritional treatment, which not only improves the state of nutrition of the patients but has strong anti-inflammatory activity as well. Moreover, some nutrients, from early stages of life are suspected as triggering factors in the etiopathogenesis of IBD. Both parenteral and enteral nutrition is used in IBD therapy, but their practical utility in different populations and in different countries is not clearly established, and there are sometimes conflicting theories concerning the role of nutrition in IBD. This review presents the actual data from research studies on the influence of nutrition on the etiopathogenesis of IBD and the latest findings regarding its mechanisms of action. The use of both parenteral and enteral nutrition as therapeutic methods in induction and maintenance therapy in IBD treatment is also extensively discussed. Comparison of the latest research data, scientific theories concerning the role of nutrition in IBD, and different opinions about them are also presented and discussed. Additionally, some potential future perspectives for nutritional therapy are highlighted.展开更多
The purpose of this work was to assess the evidence for effectiveness of acupuncture （AC） treatment in gastrointestinal diseases. A systematic review of the Medline-cited literature for clinical trials was performed...The purpose of this work was to assess the evidence for effectiveness of acupuncture （AC） treatment in gastrointestinal diseases. A systematic review of the Medline-cited literature for clinical trials was performed up to May 2006. Controlled trials assessing acupuncture point stimulation for patients with gastrointestinal diseases were considered for inclusion. The search identified 18 relevant trials meeting the inclusion criteria. Two irritable bowel syndrome （IBS） trials, 1 Crohn＇s disease and 1 colitis ulcerosa trial had a robust random controlled trial （RCT） design. In regard to other gastrointestinal disorders, study quality was poor. In all trials, quality of life （QoL） improved significantly independently from the kind of acupuncture, real or sham. Real AC was significantly superior to sham acupuncture with regard to disease activity scores in the Crohn and Colitis trials. Efficacy of acupuncture related to QoL in IBS may be explained by unspecific effects. This is the same for QoL in inflammatory bowel diseases （IBD）, whereas specific acupuncture effects may be found in clinical scores. Further trials for IBDs and in particular for all other gastrointestinal disorders would be necessary to evaluate the efficacy of acupuncture treatment. However, it must be discussed on what terms patients benefit when this harmless and obviously powerful therapy with regard to QoL is demystified by further placebo controlled trials.展开更多
Utilization of mesenchymal stromal cells(MSCs) for the treatment of Crohn's disease and ulcerative colitis is of translational interest.Safety of MSC therapy has been well demonstrated in early phase clinical tria...Utilization of mesenchymal stromal cells(MSCs) for the treatment of Crohn's disease and ulcerative colitis is of translational interest.Safety of MSC therapy has been well demonstrated in early phase clinical trials but efficacy in randomized clinical trials needs to be demonstrated.Understanding MSC mechanisms of action to reduce gut injury and inflammation is necessary to improve current ongoing and future clinical trials.However, two major hurdles impede the direct translation of data derived from animal experiments to the clinical situation:(1) limitations of the currently available animal models of colitis that reflect human inflammatory bowel diseases(IBD).The etiology and progression of human IBD are multifactorial and hence a challenge to mimic in animal models; and(2) Species specific differences in the functionality of MSCs derived from mice versus humans.MSCs derived from mice and humans are not identical in their mechanisms of action in suppressing inflammation.Thus, preclinical animal studies with murine derived MSCs cannot be considered as an exact replica of human MSC based clinical trials.In the present review, we discuss the therapeutic properties of MSCs in preclinical and clinical studies of IBD.We also discuss the challenges and approaches of using appropriate animal models of colitis, not only to study putative MSC therapeutic efficacy and their mechanisms of action, but also the suitability of translating findings derived from such studies to the clinic.展开更多
AIM： To investigate the influence of infliximab （Remicade） on experimental colitis produced by 2,4,6,trinitrobenzene sulfonic add （TNBS） in rats. METHODS： Thirty-six Wistar rats were allocated into four groups ...AIM： To investigate the influence of infliximab （Remicade） on experimental colitis produced by 2,4,6,trinitrobenzene sulfonic add （TNBS） in rats. METHODS： Thirty-six Wistar rats were allocated into four groups （three groups of six animals each and a fourth of 12 animals）. Six more healthy animals served as normal controls （Group 5）. Group 1： colitis was induced by intracolonic installation of 25 mg of TNBS dissolved in 0.25 mL of 50% ethanol and infliximab was subcutaneously administered at a dose of 5 mg/kg BW; Group 2： colitis was induced and infliximab was subcutaneously administered at a dose of 10 mg/kg BW; Group 3： colitis was induced and infliximab was subcutaneously administered at a dose of 15 mg/kg BW; Group 4： colitis was induced without treatment with infliximab. Infliximab was administered on d 2-6. On the 7^th d, all animals were killed. The colon was fixed in 10% buffered formalin and examined by light microscopy for the presence and activity of colitis and the extent of tissue damage. Tumor necrosis factor-alpha （TNF-α） and malondialdehyde （MDA） were also measured. RESULTS： Significant differences concerning the presence of reparable lesions and the extent of bowel mucosa without active inflammation in all groups of animals treated with infliximab compared with controls were found. Significant reduction of the tissue levels of TNF-α in all groups of treated animals as compared with the untreated ones was found （0.47＋0.44, 1.09＋0.86, 0.43＋0.31 vs 18.73＋10.53 respectively）. Significant reduction in the tissue levels of MDA was noticed in group 1 as compared to group 4, as well as between groups 2 and 4. CONCLUSION： Subcutaneous administration of infliximab reduces the inflammatory activity as well as tissue TNF-α and MDA levels in chemical colitis in rats. Infliximab at a dose of 5 mg/kg BW achieves better histological results and produces higher reduction of the levels of TNF-α than at a dose of 10 mg/kg BW. Infliximab at a dose of 5 mg/kg BW produces higher reduction of tissue MDA levels than at a dose of 15 mg/ kg BW.展开更多
AIM:To investigate the effects of restraint stress on chronic colitis in interleukin(IL)-10 deficient(IL-10^(-/-))mice.METHODS:The first experiment compared the effect of restraint stress on the development of intesti...AIM:To investigate the effects of restraint stress on chronic colitis in interleukin(IL)-10 deficient(IL-10^(-/-))mice.METHODS:The first experiment compared the effect of restraint stress on the development of intestinal inflammation in wild-type and IL-10^(-/-) mice.Both wildtype and IL-10^(-/-) mice were physically restrained in a well-ventilated,50 cm3 conical polypropylene tube for2 h per day for three consecutive days.The second experiment was performed to assess the effect of restraint stress on exacerbation of colitis induced by piroxicam in IL-10^(-/-) mice.The IL-10^(-/-) mice were exposed to restraint stress for 2 h per day for 3consecutive days,and then treated with piroxicam for4 d at a dose of 200 ppm administered in the rodent chow.RESULTS:In the first experiment,none of the wildtype mice with or without restraint stress showed clinical and histopathological abnormality in the gut.However,IL-10^(-/-) mice exposed to restraint stress exhibited histologically significant intestinal inflammation as compared to those without restraint stress.In the second experiment,restraint stress significantly reduced body weight and increased the severity of intestinal inflammation assessed by histopathologic grading in IL-10^(-/-) mice.Colonic IL12p40 mRNA expression was strongly increased in mice exposed to restraint stress.CONCLUSION:This novel animal model could be useful in future study of psychological stress in the pathogenesis of inflammatory bowel disease.展开更多
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, howeve...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.展开更多
AIM: To investigate gene variants in a large Italian inflammatory bowel disease (IBD) cohort, and to analyze the correlation of sub-phenotypes (including age at diagnosis) and epistatic interaction with other IBD gene...AIM: To investigate gene variants in a large Italian inflammatory bowel disease (IBD) cohort, and to analyze the correlation of sub-phenotypes (including age at diagnosis) and epistatic interaction with other IBD genes. METHODS: Total of 763 patients with Crohn's disease (CD, 189 diagnosed at age < 19 years), 843 with ulcerative colitis (UC, 179 diagnosed <19 years), 749 healthy controls, and 546 healthy parents (273 trios) were included in the study. The rs2241880 [autophagy-related 16-like 1 (ATG16L1)], rs11209026 and rs7517847 [interleukin 23 receptor (IL23R)], rs2066844, rs2066845, rs2066847 (CARD15), rs1050152 (OCTN1), and rs2631367 (OCTN2) gene variants were genotyped. RESULTS: The frequency of G allele of ATG16L1 SNP (Ala197Thr) was increased in patients with CD compared with controls (59% vs 54% respectively) (OR = 1.25, CI = 1.08-1.45, P = 0.003), but not in UC (55%). The frequency of A and G (minor) alleles of Arg381Gln, rs11209026 and rs7517847 variants of IL23R were reduced significantly in CD (4%, OR = 0.62, CI = 0.45-0.87, P = 0.005; 28%, OR = 0.64, CI = 0.55-0.75, P < 0.01), compared with controls (6% and 38%, respectively). The A allele (but not G) was also reduced signifi cantly in UC (4%, OR = 0.69, CI = 0.5-0.94, P = 0.019). No association was demonstrated with sub-phenotypes and interaction with CARD15 , and OCTN1/2 genes, although both gene variants were associated with pediatric-onset disease. CONCLUSION: The present study confirms the association of IL23R polymorphisms with IBD, and ATG16L1 with CD, in both adult- and pediatric-onset subsets in our study population.展开更多
A 46-year-old female patient with terminal ileum Crohn’s disease and ankylosing spondylitis presented with recurrent angioedema and urticaria. Investigations ruled out hereditary angioedema, and environmental or food...A 46-year-old female patient with terminal ileum Crohn’s disease and ankylosing spondylitis presented with recurrent angioedema and urticaria. Investigations ruled out hereditary angioedema, and environmental or food allergen triggers. She was diagnosed with chronic idiopathic urticaria with angioedema, and was treated with a trial of intravenous immunoglobulin immunotherapy, danazol, prednisone and hydroxyzine. Due to ongoing bowel and arthritic complaints, she was started on infliximab infusions and within 2 treatments, she had complete resolution of the angioedema and urticaria, as well as of the bowel and arthritic symptoms. Unfortunately she developed allergic reactions to the infliximab and was switched to another anti-tumor necrosis factor （TNF）-a agent, adalimumab. Since then, she has had no further angioedema or urticaria, and her Crohn’s disease has been quiescent. This is the first known case report of chronic idiopathic urticaria with angioedema coexistent with Crohn’s disease that was successfully treated with anti-TNF-α agents.展开更多
基金Supported by INSERMFondation pour la Recherche Médicale No.DEQ2000326531 and Région Midi-PyrénéesSaoudi A is supported by the Centre National de la Recherche Scientifique
文摘In the gut, where billions of non-self-antigens from the food and the microbiota are present, the immune response must be tightly regulated to ensure both host protection against pathogenic microorganisms and the absence of immune-related pathologies. It has been well documented that regulatory T cells(Tregs) play a pivotal role in this context. Indeed, Tregs are able to prevent excessive inflammation, which can lead to the rupture of intestinal homeostasis observed in inflammatory bowel diseases(IBDs). Both the worldwide incidence and prevalence of such diseases have increased throughout the latter part of the 20^(th) century. Therefore, it is crucial to understand how Tregs suppress the colitogenic immune cells to establish new treatments for patients suffering from IBDs. In this review, we will first summarize the results obtained in animal model studies that highlight the importance of Tregs in maintaining intestinal homeostasis and describe the specific suppressive mechanisms involved. Next, our current knowledge about Tregs contribution to human IBDs will be reviewed, as well as the current therapeutic perspective on using Tregs for clinical IBD treatment and the challenges that remain to be resolved to ensure both the safety and effectiveness of these therapies in targeting this critical immune-regulatory cell population.
文摘Diagnostic imaging plays a key role in the diagnosis and management of inflammatory bowel disease(IBD). However due to the relapsing nature of IBD, there is growing concern that IBD patients may be exposed to potentially harmful cumulative levels of ionising radiation in their lifetime, increasing malignant potential in a population already at risk. In this review we explore the proportion of IBD patients exposed to high cumulative radiation doses, the risk factors associated with higher radiation exposures, and we compare conventional diagnostic imaging with newer radiation-free imaging techniques used in the evaluation of patients with IBD. While computed tomography(CT) performs well as an imaging modality for IBD, the effective radiation dose is considerably higher than other abdominal imaging modalities. It is increasingly recognised that CT imaging remains responsible for the majority of diagnostic medical radiation to which IBD patients are exposed. Magnetic resonance imaging(MRI) and small intestine contrast enhanced ultrasonography(SICUS) have now emerged as suitable radiation-free alternatives to CT imaging, with comparable diagnostic accuracy. The routine use of MRI and SICUS for the clinical evaluation of patients with known or suspected small bowel Crohn's disease is to be encouraged wherever possible. More provision is needed for out-of-hours radiation-free imaging modalities to reduce the need for CT.
基金Supported by Science and Technology Project of Liaoning ProvinceNo.2013225303+1 种基金Science and Technology Project of Shenyang CityNo.F13-316-1-40
文摘AIM: To investigate the effect of chymase inhibitor TY-51469 in the therapy of inflammatory bowel disease and the underlying mechanism. METHODS: Seventy-five healthy Sprague-Dawley rats were randomly assigned to one of the three groups(control group, model group and TY-51469 experiment group) and each group had twenty-five rats. The rats of the model group and experiment group were subjected to treatment with 3.5% dextran sulfate sodium(DSS) 10 mg/kg to induce colitis. The control group and model group were subjected to intraperitoneal injection of saline, while the experiment group was subjected to intraperitoneal injection of 10 mg/kg TY-51469 each day. Five rats of each group were sacrificed on 0, 7, 14, 21 and 28 d, respectively. The degree of inflammation was assessed by histopathological scoring; flow cytometry was performed to detect the proportion of CD4+CD25+ Tregs in peripheral blood; colon tissues of rats were collected to measure m RNA and protein expression by PCR, Western blot and immunohistochemistry; serum levels of interleukin(IL)-10, transforming growth factor(TGF)-β1 and IL-17A were detected by ELISA. RESULTS: The rats in the experiment group and model group had significantly more severe colitis than the ones in the control group(P < 0.05) before treatment on day 0; no significant difference was observed between the experiment group and model group(P > 0.05). After treatment with TY-51469, the rats in the experiment group had significantly less severe colitis compared with the model group on 7, 14, 21 and 28 d(P < 0.05). The proportion of CD4+CD25+ Tregs was lower in the model group and experiment group than in the control group; the experiment group had a significantly higher proportion of CD4+CD25+ Tregs than that in the model group(P < 0.05). The model group and experiment group demonstrated lower expression of Foxp3 than the control group; the experiment group had higher Foxp3 expression than the model group(P < 0.05). Cytokines IL-10, TGF-β1 and IL-17 A were lower in the model group and experiment group than in the control group; the experiment group had higher expression than the model group(P < 0.05). CONCLUSION: After treatment with chymase inhibitor TY-51469, the experiment group demonstrated more significantly reduced intestinal inflammation and higher expression of immune tolerance related cytokines(IL-10, TGF-β1, IL-17A) and Foxp3 which is specifically expressed in Tregs compared with the model group. Therefore, chymase inhibitor TY-51469 might ameliorate the progression of DSS-induced colitis possibly by increasing the expression of Tregs and cytokines.
文摘目的:评估炎症性肠病(inflammatory bowel disease,IBD)患者腹部双能量CT(dual-energy CT,DECT)扫描不同能级噪声优化的虚拟单能量图像(noise-optimized virtual monoenergetic imaging,VMI+)的主观和客观图像质量,得出最佳重建参数,提高IBD诊断准确率。方法:选取2016年4月到2017年6月确诊为IBD的32名患者腹部DECT扫描图像进行线性融合(M_0.6)、VMI+、传统虚拟单能量图像(virtual monoenergetic imaging,VMI)重建,虚拟能级为40~100 ke V,间隔为10 ke V。以病变肠段部位的图像信噪比(signal-to-noise ratio,SNR)和对比噪声比(contrast-to-noise ratio,CNR)作为客观图像质量评价标准,主观图像质量评价由3名放射科医生对总体图像质量、锐利度、病变轮廓、噪声4个方面进行双盲评估。结果:客观图像质量评价最佳重建参数为40 ke V VMI+(SNR 8.28±2.34;CNR 5.10±2.10),优于线性融合图像(SNR 5.82±1.44;CNR 1.53±0.86)和传统VMI(P<0.01)。主观图像质量评价中,50 ke V VMI+总体图像质量(均值4.80)高于其他图像(P<0.01),40和50 ke V VMI+锐利度最高(均值分别为4.14和4.25,P=0.415),40 ke V VMI+显示病变轮廓能力评分高于其他图像(均值4.52,P<0.01)。100 ke V VMI+和100 ke V VMI噪声最低(均值分别为4.58和4.40,P≥0.11)。结论:相比于线性融合和传统VMI重建,低能级VMI+可显著提高IBD病变部位的腹部DECT扫描图像的主观和客观图像质量。
文摘自滤泡辅助性T细胞(follicular helper T cells,Tfh细胞)发现以来,大量证据表明与炎症性肠病的发病有关.Tfh细胞及其亚群分泌不同细胞因子皆可在炎症性肠病的发病过程中扮演重要角色,为靶向治疗炎症性肠病提供重要思路.BCL-6信号作为Tfh细胞分化途径上的关键性转录因子,可调控Tfh细胞的增殖、分化.在BCL-6信号缺乏时无法产生Tfh细胞,且BCL-6信号也可通过正性调控、负性调控以及表观遗传学等多种途径有效调控Tfh细胞的分化.在BCL-6信号调控异常时可导致Tfh的分化异常导致炎症性肠病的发生.因此可以通过干预BCL-6信号来调控Tfh细胞分化来作为治疗炎症性肠病新的有效靶点.
基金supported by in part by a grant from the Japan Ministry of Health and Welfare
文摘AIM: to evaluate the effectiveness of probiotic therapy for suppressing relapse in patients with inactive ulcerative colitis(UC).METHODS: Bio-Three tablets, each containing 2 mg of lactomin(Streptococcus faecalis T-110), 10 mg of Clostridium butyricum TO-A, and 10 mg of Bacillus mesentericus TO-A, were used as probiotic therapy.Sixty outpatients with UC in remission were randomly assigned to receive 9 Bio-Three tablets/day(BioThree group) or 9 placebo tablets/day(placebo group)for 12 mo in addition to their ongoing medications.Clinical symptoms were evaluated monthly or on the exacerbation of symptoms or need for additional medication. Fecal samples were collected to analyze bacterial DNA at baseline and 3-mo intervals. Terminal restriction fragment length polymorphism and cluster analyses were done to examine bacterial components of the fecal microflora.RESULTS: Forty-six patients, 23 in each group,completed the study, and 14 were excluded. The relapse rates in the Bio-Three and placebo groups were respectively 0.0% vs 17.4% at 3 mo(P = 0.036), 8.7%vs 26.1% at 6 mo(P = 0.119), and 21.7% vs 34.8%(P = 0.326) at 9 mo. At 12 mo, the remission rate was 69.5% in the Bio-Three group and 56.6% in the placebo group(P = 0.248). On cluster analysis of fecal flora, 7 patients belonged to cluster Ⅰ, 32 to cluster Ⅱ,and 7 to cluster Ⅲ.CONCLUSION: Probiotics may be effective formaintaining clinical remission in patients with quiescent UC, especially those who belong to cluster Ⅰ on fecal bacterial analysis.
文摘Inflammatory bowel diseases(IBD), including ulcerative colitis and Crohn's disease are chronic, life-long, and relapsing diseases of the gastrointestinal tract. Currently, there are no complete cure possibilities, but combined pharmacological and nutritional therapy may induce remission of the disease. Malnutrition and specific nutritional deficiencies are frequent among IBD patients, so the majority of them need nutritional treatment, which not only improves the state of nutrition of the patients but has strong anti-inflammatory activity as well. Moreover, some nutrients, from early stages of life are suspected as triggering factors in the etiopathogenesis of IBD. Both parenteral and enteral nutrition is used in IBD therapy, but their practical utility in different populations and in different countries is not clearly established, and there are sometimes conflicting theories concerning the role of nutrition in IBD. This review presents the actual data from research studies on the influence of nutrition on the etiopathogenesis of IBD and the latest findings regarding its mechanisms of action. The use of both parenteral and enteral nutrition as therapeutic methods in induction and maintenance therapy in IBD treatment is also extensively discussed. Comparison of the latest research data, scientific theories concerning the role of nutrition in IBD, and different opinions about them are also presented and discussed. Additionally, some potential future perspectives for nutritional therapy are highlighted.
文摘The purpose of this work was to assess the evidence for effectiveness of acupuncture （AC） treatment in gastrointestinal diseases. A systematic review of the Medline-cited literature for clinical trials was performed up to May 2006. Controlled trials assessing acupuncture point stimulation for patients with gastrointestinal diseases were considered for inclusion. The search identified 18 relevant trials meeting the inclusion criteria. Two irritable bowel syndrome （IBS） trials, 1 Crohn＇s disease and 1 colitis ulcerosa trial had a robust random controlled trial （RCT） design. In regard to other gastrointestinal disorders, study quality was poor. In all trials, quality of life （QoL） improved significantly independently from the kind of acupuncture, real or sham. Real AC was significantly superior to sham acupuncture with regard to disease activity scores in the Crohn and Colitis trials. Efficacy of acupuncture related to QoL in IBS may be explained by unspecific effects. This is the same for QoL in inflammatory bowel diseases （IBD）, whereas specific acupuncture effects may be found in clinical scores. Further trials for IBDs and in particular for all other gastrointestinal disorders would be necessary to evaluate the efficacy of acupuncture treatment. However, it must be discussed on what terms patients benefit when this harmless and obviously powerful therapy with regard to QoL is demystified by further placebo controlled trials.
文摘Utilization of mesenchymal stromal cells(MSCs) for the treatment of Crohn's disease and ulcerative colitis is of translational interest.Safety of MSC therapy has been well demonstrated in early phase clinical trials but efficacy in randomized clinical trials needs to be demonstrated.Understanding MSC mechanisms of action to reduce gut injury and inflammation is necessary to improve current ongoing and future clinical trials.However, two major hurdles impede the direct translation of data derived from animal experiments to the clinical situation:(1) limitations of the currently available animal models of colitis that reflect human inflammatory bowel diseases(IBD).The etiology and progression of human IBD are multifactorial and hence a challenge to mimic in animal models; and(2) Species specific differences in the functionality of MSCs derived from mice versus humans.MSCs derived from mice and humans are not identical in their mechanisms of action in suppressing inflammation.Thus, preclinical animal studies with murine derived MSCs cannot be considered as an exact replica of human MSC based clinical trials.In the present review, we discuss the therapeutic properties of MSCs in preclinical and clinical studies of IBD.We also discuss the challenges and approaches of using appropriate animal models of colitis, not only to study putative MSC therapeutic efficacy and their mechanisms of action, but also the suitability of translating findings derived from such studies to the clinic.
文摘AIM： To investigate the influence of infliximab （Remicade） on experimental colitis produced by 2,4,6,trinitrobenzene sulfonic add （TNBS） in rats. METHODS： Thirty-six Wistar rats were allocated into four groups （three groups of six animals each and a fourth of 12 animals）. Six more healthy animals served as normal controls （Group 5）. Group 1： colitis was induced by intracolonic installation of 25 mg of TNBS dissolved in 0.25 mL of 50% ethanol and infliximab was subcutaneously administered at a dose of 5 mg/kg BW; Group 2： colitis was induced and infliximab was subcutaneously administered at a dose of 10 mg/kg BW; Group 3： colitis was induced and infliximab was subcutaneously administered at a dose of 15 mg/kg BW; Group 4： colitis was induced without treatment with infliximab. Infliximab was administered on d 2-6. On the 7^th d, all animals were killed. The colon was fixed in 10% buffered formalin and examined by light microscopy for the presence and activity of colitis and the extent of tissue damage. Tumor necrosis factor-alpha （TNF-α） and malondialdehyde （MDA） were also measured. RESULTS： Significant differences concerning the presence of reparable lesions and the extent of bowel mucosa without active inflammation in all groups of animals treated with infliximab compared with controls were found. Significant reduction of the tissue levels of TNF-α in all groups of treated animals as compared with the untreated ones was found （0.47＋0.44, 1.09＋0.86, 0.43＋0.31 vs 18.73＋10.53 respectively）. Significant reduction in the tissue levels of MDA was noticed in group 1 as compared to group 4, as well as between groups 2 and 4. CONCLUSION： Subcutaneous administration of infliximab reduces the inflammatory activity as well as tissue TNF-α and MDA levels in chemical colitis in rats. Infliximab at a dose of 5 mg/kg BW achieves better histological results and produces higher reduction of the levels of TNF-α than at a dose of 10 mg/kg BW. Infliximab at a dose of 5 mg/kg BW produces higher reduction of tissue MDA levels than at a dose of 15 mg/ kg BW.
基金Supported by SNUH Research Fund,No.06-2011-1770Basic Science Research Program through the National Research Foundation of Korea(NRF)funded by the Ministry of Education,No.NRF-2014R1A1A2057695
文摘AIM:To investigate the effects of restraint stress on chronic colitis in interleukin(IL)-10 deficient(IL-10^(-/-))mice.METHODS:The first experiment compared the effect of restraint stress on the development of intestinal inflammation in wild-type and IL-10^(-/-) mice.Both wildtype and IL-10^(-/-) mice were physically restrained in a well-ventilated,50 cm3 conical polypropylene tube for2 h per day for three consecutive days.The second experiment was performed to assess the effect of restraint stress on exacerbation of colitis induced by piroxicam in IL-10^(-/-) mice.The IL-10^(-/-) mice were exposed to restraint stress for 2 h per day for 3consecutive days,and then treated with piroxicam for4 d at a dose of 200 ppm administered in the rodent chow.RESULTS:In the first experiment,none of the wildtype mice with or without restraint stress showed clinical and histopathological abnormality in the gut.However,IL-10^(-/-) mice exposed to restraint stress exhibited histologically significant intestinal inflammation as compared to those without restraint stress.In the second experiment,restraint stress significantly reduced body weight and increased the severity of intestinal inflammation assessed by histopathologic grading in IL-10^(-/-) mice.Colonic IL12p40 mRNA expression was strongly increased in mice exposed to restraint stress.CONCLUSION:This novel animal model could be useful in future study of psychological stress in the pathogenesis of inflammatory bowel disease.
文摘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.
基金The National Minister of Health grant, No. RC0702GA35
文摘AIM: To investigate gene variants in a large Italian inflammatory bowel disease (IBD) cohort, and to analyze the correlation of sub-phenotypes (including age at diagnosis) and epistatic interaction with other IBD genes. METHODS: Total of 763 patients with Crohn's disease (CD, 189 diagnosed at age < 19 years), 843 with ulcerative colitis (UC, 179 diagnosed <19 years), 749 healthy controls, and 546 healthy parents (273 trios) were included in the study. The rs2241880 [autophagy-related 16-like 1 (ATG16L1)], rs11209026 and rs7517847 [interleukin 23 receptor (IL23R)], rs2066844, rs2066845, rs2066847 (CARD15), rs1050152 (OCTN1), and rs2631367 (OCTN2) gene variants were genotyped. RESULTS: The frequency of G allele of ATG16L1 SNP (Ala197Thr) was increased in patients with CD compared with controls (59% vs 54% respectively) (OR = 1.25, CI = 1.08-1.45, P = 0.003), but not in UC (55%). The frequency of A and G (minor) alleles of Arg381Gln, rs11209026 and rs7517847 variants of IL23R were reduced significantly in CD (4%, OR = 0.62, CI = 0.45-0.87, P = 0.005; 28%, OR = 0.64, CI = 0.55-0.75, P < 0.01), compared with controls (6% and 38%, respectively). The A allele (but not G) was also reduced signifi cantly in UC (4%, OR = 0.69, CI = 0.5-0.94, P = 0.019). No association was demonstrated with sub-phenotypes and interaction with CARD15 , and OCTN1/2 genes, although both gene variants were associated with pediatric-onset disease. CONCLUSION: The present study confirms the association of IL23R polymorphisms with IBD, and ATG16L1 with CD, in both adult- and pediatric-onset subsets in our study population.
文摘A 46-year-old female patient with terminal ileum Crohn’s disease and ankylosing spondylitis presented with recurrent angioedema and urticaria. Investigations ruled out hereditary angioedema, and environmental or food allergen triggers. She was diagnosed with chronic idiopathic urticaria with angioedema, and was treated with a trial of intravenous immunoglobulin immunotherapy, danazol, prednisone and hydroxyzine. Due to ongoing bowel and arthritic complaints, she was started on infliximab infusions and within 2 treatments, she had complete resolution of the angioedema and urticaria, as well as of the bowel and arthritic symptoms. Unfortunately she developed allergic reactions to the infliximab and was switched to another anti-tumor necrosis factor （TNF）-a agent, adalimumab. Since then, she has had no further angioedema or urticaria, and her Crohn’s disease has been quiescent. This is the first known case report of chronic idiopathic urticaria with angioedema coexistent with Crohn’s disease that was successfully treated with anti-TNF-α agents.
文摘目的:探讨宁夏医科大学总医院不同年龄组炎症性肠病(inflammatory bowel diseases,IBD)特点,为临床诊治提供客观依据.方法:收集2002-01/2014-12宁夏医科大学总医院收治的IBD患者共567例,按患者年龄不同分为<17岁组、17-39岁组、40-59岁组、>60岁组,统计患者性别、发病年龄、病程等一般资料、临床症状、肠外表现及并发症等,回顾性分析各组患者的疾病特点.结果:各组IBD住院率均呈上升趋势,发病高峰年龄未发生改变,以男性多见.>60岁组UC患者较其他组病情较重,疾病严重程度分型多为重度(85.39%);各组CD患者疾病活动度指数(Crohn's disease activity index,C D A I)评分结果较为一致,均以缓解期、中度活动期.就疾病部位,<17岁组和17-39岁组UC以直肠型最为常见(100%,53.25%),40-59岁组以左半结肠型为主(57.69%),>60岁组多为广泛结肠型(79.78%);<17岁组和>60岁组CD病变部位一致,以回肠末端型最为常见(50%,46.67%),中间年龄组以结肠型最多(51.52%,46.67%).结论:<17岁组及>60岁不同年龄组的临床特点及疾病特征与中间年龄组不尽一致,应给予更细致全面的研究,从而提高对IBD的诊治水平.
文摘目的:比较英夫利昔(infliximab,IFX)与硫唑嘌呤(azathioprine,AZA)联合用药与单药治疗中重度炎症性肠病(inflammatory bowel disease,IBD)的疗效及安全性,用以指导IBD药物方案的选择.方法:从MEDLINE、EMBASE、Pub Med、Ovid、谷歌、万方数据库、中国维普数据库、中国知网数据库以及中国生物医学文献数据库检索有关IFX与AZA联用及单药治疗IBD的随机对照试验.并对纳入文献进行质量评价和数据提取进行Meta分析.结果:按照入选标准,共纳入6篇随机对照试验文献,Meta分析结果显示:IFX与A Z A联合用药治疗I B D的临床症状缓解率(RR=1.33,95%CI:1.13-1.56,Z=3.40,P=0.0007)、内镜检测有效率(R R=1.29,95%C I:1.05-1.58,Z=2.43,P=0.02)均优于IFX单药,但两组间总体不良反应(RR=1.01,95%CI:0.91-1.10,Z=0.11,P=0.91)差异无统计学意义.联合用药治疗IBD临床症状缓解率(RR=1.84,95%CI:1.53-2.20,Z=6.54,P<0.001)、内镜检测有效率(RR=2.06,95%CI:1.65-2.62,Z=5.96,P<0.0001)均优于AZA单药,但两组间总体不良反应(RR=0.94,95%CI:0.86-1.03,Z=1.34,P=0.18)差异无统计学意义.结论:对于一线治疗无效的中重度IBD,IFX与AZA联合用药优于IFX或AZA单药治疗.联合用药对临床缓解、内镜黏膜愈合均有明显的疗效,且总不良反应与单药治疗比较差异无统计学意义.
