Mucosal healing(MH)is vital in maintaining homeostasis within the gut and protecting against injury and infections.Multiple factors and signaling pathways contribute in a dynamic and coordinated manner to maintain int...Mucosal healing(MH)is vital in maintaining homeostasis within the gut and protecting against injury and infections.Multiple factors and signaling pathways contribute in a dynamic and coordinated manner to maintain intestinal homeostasis and mucosal regeneration/repair.However,when intestinal homeostasis becomes chronically disturbed and an inflammatory immune response is constitutively active due to impairment of the intestinal epithelial barrier autoimmune disease results,particularly inflammatory bowel disease(IBD).Many proteins and signaling pathways become dysregulated or impaired during these pathological conditions,with the mechanisms of regulation just beginning to be understood.Consequently,there remains a relative lack of broadly effective therapeutics that can restore MH due to the complexity of both the disease and healing processes,so tissue damage in the gastrointestinal tract of patients,even those in clinical remission,persists.With increased understanding of the molecular mechanisms of IBD and MH,tissue damage from autoimmune disease may in the future be ameliorated by developing therapeutics that enhance the body’s own healing response.In this review,we introduce the concept of mucosal healing and its relevance in IBD as well as discuss the mechanisms of IBD and potential strategies for altering these processes and inducing MH.展开更多
AIM To evaluate the utility of fecal calprotectin(FC) in predicting relapse and endoscopic activity during follow-up in an inflammatory bowel disease(IBD) cohort.METHODS All FC measurements that were obtained during a...AIM To evaluate the utility of fecal calprotectin(FC) in predicting relapse and endoscopic activity during follow-up in an inflammatory bowel disease(IBD) cohort.METHODS All FC measurements that were obtained during a 3-year period from patients with inflammatory bowel disease in clinical remission were identified. Data regarding the short-term(6 mo) course of the disease were extracted from the medical files. Exclusion criteria were defined as:(1) An established flare of the disease at the time of FC measurement,(2) Loss to follow up within 6 mo from baseline FC measurement, and,(3) Insufficient data on file. Statistical analysis was performed to evaluate whether baseline FC measurement could predict the short term clinical relapse and/or the presence of mucosal healing.RESULTS We included 149 [Crohn's disease(CD) = 113, Ulcerative colitis(UC) = 36, male = 77] IBD patients in our study. Within the determined 6-month period post-FC measurement, 47(31.5%) had a disease flare. Among 76 patients who underwent endoscopy, 39(51.3%) had mucosal healing. Baseline FC concentrations were significantly higher in those who had clinical relapse compared to those who remained in remission during follow up(481.0 μg/g, 286.0-600.0 vs 89.0, 36.0-180.8, P < 0.001). The significant predictive value of baseline median with IQR FC for clinical relapse was confirmed by multivariate Cox analysis [HR for 100μg/g: 1.75(95%CI: 1.28-2.39), P = 0.001]. Furthermore, lower FC baseline values significantly correlated to the presence of mucosal healing in endoscopy(69.0 μg/g, 30.0-128.0 vs 481.0, 278.0-600.0, in those with mucosal inflammation, median with IQR, P < 0.001). We were able to extract cut-off values for FC concentration with a high sensitivity and specificity for predicting clinical relapse(261 μg/g with AUC = 0.901, sensitivity 87.2%, specificity 85.3%, P < 0.001) or mucosal healing(174 μg/g with AUC = 0.956, sensitivity 91.9%, specificity 87.2%, P < 0.001). FC was better than CRP in predicting either outcome; nevertheless, having a pathological CRP(> 5 mg/L) in addition to the cutoffs for FC, significantly enhanced the specificity for predicting clinical relapse(95.1% from 85.3%) or endoscopic activity(100% from 87.2%). CONCLUSION Serial FC measurements may be useful in monitoring IBD patients in remission, as FC appears to be a reliable predictor of short-term relapse and endoscopic activity.展开更多
Mucosal healing(MH)has emerged as a key therapeutic target in inflammatory bowel disease(IBD),and achievement of this goal is documented by endoscopy with biopsy.However,colonoscopy is burdensome and invasive,and subs...Mucosal healing(MH)has emerged as a key therapeutic target in inflammatory bowel disease(IBD),and achievement of this goal is documented by endoscopy with biopsy.However,colonoscopy is burdensome and invasive,and substitution with an accurate noninvasive biomarker is desirable.AIM To summarize published data regarding the performance of noninvasive biomarkers in assessing MH in IBD patients.METHODS We conducted a systematic review of studies that reported the performance of biomarkers in diagnosing MH in patients with IBD.The main outcome measure was to review the diagnostic accuracy of serum and fecal markers that showed promising utility in assessing MH.RESULTS We screened 1301 articles,retrieved 46 manuscripts and included 23 articles for full-text analysis.The majority of the included manuscripts referred to fecal markers(12/23),followed by circulatory markers(8/23);only 3/23 of the included manuscripts investigated combined markers(serum and/or fecal markers).Fecal calprotectin(FC)was the most investigated fecal marker for assessing MH.In ulcerative colitis,for cutoff levels ranging between 58 mcg/g and 490 mcg/g,the sensitivity was 89.7%-100%and the specificity was 62%-93.3%.For Crohn’s disease,the cutoff levels of FC ranged from 71 mcg/g to 918 mcg/g(sensitivity 50%-95.9%and specificity 52.3%-100%).The best performance for a serum marker was observed for the endoscopic healing index,which showed a comparable accuracy to the measurement of FC and a higher accuracy than the measurement of serum C-reactive protein.CONCLUSION Several promising biomarkers of MH are emerging but cannot yet substitute for endoscopy with biopsy due to issues with reproducibility and standardization assessing MH.In ulcerative colitis,for cutoff levels ranging between 58 mcg/g and 490 mcg/g,the sensitivity was 89.7%-100%and the specificity was 62%-93.3%.For Crohn’s disease,the cutoff levels of FC ranged from 71 mcg/g to 918 mcg/g(sensitivity 50%-95.9%and specificity 52.3%-100%).The best performance for a serum marker was observed for the endoscopic healing index,which showed a comparable accuracy to the measurement of FC and a higher accuracy than the measurement of serum C-reactive protein.CONCLUSION Several promising biomarkers of MH are emerging but cannot yet substitute for endoscopy with biopsy due to issues with reproducibility and standardization.展开更多
The latest guideline about ulcerative colitis(UC) clinical practice stresses that mucosal healing, rather than anti-inflammation, is the main target in UC clinical management. Current mucosal dysfunction mainly closel...The latest guideline about ulcerative colitis(UC) clinical practice stresses that mucosal healing, rather than anti-inflammation, is the main target in UC clinical management. Current mucosal dysfunction mainly closely relates to the endoscopic intestinal wall(mechanical barrier) injury with the imbalance between intestinal epithelial cells(IECs) regeneration and death, as well as tight junction(TJ) dysfunction. It is suggested that biological barrier(gut microbiota), chemical barrier(mucus protein layer, MUC) and immune barrier(immune cells) all take part in the imbalance, leading to mechanical barrier injury. Lots of experimental studies reported that acupuncture and moxibustion on UC recovery by adjusting the gut microbiota, MUC and immune cells on multiple targets and pathways, which contributes to the balance of IEC regeneration and death, as well as TJ structure recovery in animals. Moreover, the validity and superiority of acupuncture and moxibustion were also demonstrated in clinic. This paper aims to review the achievements of acupuncture and moxibustion on mucosal healing and analyse the underlying mechanisms.展开更多
Inflammatory bowel disease(IBD),consisting primarily of ulcerative colitis and Crohn’s disease,is a group of debilitating auto-immune disorders,which also increases the risk of colitis-associated cancer.However,due t...Inflammatory bowel disease(IBD),consisting primarily of ulcerative colitis and Crohn’s disease,is a group of debilitating auto-immune disorders,which also increases the risk of colitis-associated cancer.However,due to the chronic nature of the disease and inconsistent treatment outcomes of current anti-IBD drugs(e.g.,approximately 30%non-responders to anti-TNFαagents),and related serious side effects,about half of all IBD patients(in millions)turn to alternative treatment options.In this regard,mucosal healing is gaining acceptance as a measure of disease activity in IBD patients as recent studies have correlated the success of mucosal healing with improved prognosis.However,despite the increasing clinical realization of the significance of the concept of mucosal healing,its regulation and means of therapeutic targeting remain largely unclear.Here,stemcell therapy,which uses hematopoietic stem cells or mesenchymal stem cells,remains a promising option.Stem cells are the pluripotent cells with ability to differentiate into the epithelial and/or immune-modulatory cells.The overreaching concept is that the stem cells can migrate to the damaged areas of the intestine to provide curative help in the mucosal healing process.Moreover,by differentiating into the mature intestinal epithelial cells,the stem cells also help in restoring the barrier integrity of the intestinal lining and hence prevent the immunomodulatory induction,the root cause of the IBD.In this article,we elaborate upon the current status of the clinical management of IBD and potential role of the stem cell therapy in improving IBD therapy and patient’s quality of life.展开更多
BACKGROUND Although expression of interleukin(IL)-34 is upregulated in active ulcerative colitis(UC),the molecular function and underlying mechanism are largely unclear.AIM To investigate the function of IL-34 in acut...BACKGROUND Although expression of interleukin(IL)-34 is upregulated in active ulcerative colitis(UC),the molecular function and underlying mechanism are largely unclear.AIM To investigate the function of IL-34 in acute colitis,in a wound healing model and in colitis-associated cancer in IL-34-deficient mice.METHODS Colitis was induced by administration of dextran sodium sulfate(DSS),and carcinogenesis was induced by azoxymethane(AOM).Whether the impact of IL-34 on colitis was dependent on macrophages was validated by depletion of macrophages in a murine model.The association between IL-34 expression and epithelial proliferation was studied in patients with active UC.RESULTS IL-34 deficiency aggravated murine colitis in acute colitis and in wound healing phase.The effect of IL-34 on experimental colitis was not dependent on macrophage differentiation and polarization.IL-34-deficient mice developed more tumors than wild-type mice following administration of AOM and DSS.No significant difference was shown in degree of cellular differentiation in tumors between wild-type and IL-34-deficient mice.IL-34 was dramatically increased in the active UC patients as previously reported.More importantly,expression of IL-34 was positively correlated with epithelial cell proliferation in patients with UC.CONCLUSION IL-34 deficiency exacerbates colonic inflammation and accelerates colitis-associated carcinogenesis in mice.It might be served as a potential therapeutic target in UC.展开更多
AIM To evaluate the role of oral curcumin in inducing clinical remission in patients with mild to moderate ulcerative colitis(UC).METHODS A prospective randomized double-blind placebo-controlled trial comparing the re...AIM To evaluate the role of oral curcumin in inducing clinical remission in patients with mild to moderate ulcerative colitis(UC).METHODS A prospective randomized double-blind placebo-controlled trial comparing the remission inducing effect of oral curcumin and mesalamine 2.4 g with placebo and mesalamine 2.4 g in patients of ulcerative colitis with mild to moderate severity was conducted from January 2003 to March 2005. The included patients received 1 capsule thrice a day of placebo or curcumin(150 mg) for 8 wk. Patients were evaluated clinically and endoscopically at 0,4 and 8 wk. The primary outcome was clinical remission at 8 wk and secondary outcomes were clinical response, mucosal healing and treatment failure at 8 wk. The primary analysis was intention to treat worst case scenario(ITT-WCS).RESULTS Of 300 patients with UC, 62 patients(curcumin: 29, placebo: 33) fulfilled the inclusion criteria and were randomized at baseline. Of these, 21 patients did not complete the trial, 41 patients(curcumin: 16, placebo: 25) finally completed 8 wk. There was no significant difference in rates of clinical remission(31.3% vs 27.3%, P = 0.75), clinical response(20.7% vs 36.4%, P = 0.18), mucosal healing(34.5% vs 30.3%, P = 0.72), and treatment failure(25% vs 18.5%, P = 0.59) between curcumin and placebo at 8 wk.CONCLUSION Low dose oral curcumin at a dose of 450 mg/d was ineffective in inducing remission in mild to moderate cases of UC.展开更多
Advancements in murine modeling systems for ulcerative colitis have diversified our understanding of the pathophysiological factors involved in disease onset and progression.This has fueled the identification of molec...Advancements in murine modeling systems for ulcerative colitis have diversified our understanding of the pathophysiological factors involved in disease onset and progression.This has fueled the identification of molecular targets,resulting in a rapidly expanding therapeutic armamentarium.Subsequently,management strategies have evolved from symptomatic resolution to well-defined objective endpoints,including clinical remission,endoscopic remission and mucosal healing.While the incorporation of these assessment modalities has permitted targeted intervention in the context of a natural disease history and the prevention of complications,studies have consistently depicted discrepancies associated with ascertaining disease status through clinical and endoscopic measures.Current recommendations lack consideration of histological healing.The simultaneous achievement of clinical,endoscopic,and histologic remission has not been fully investigated.This has laid the groundwork for a novel therapeutic outcome termed disease clearance(DC).This article summarizes the concept of DC and its current evidence.展开更多
Colonoscopic evaluation is an important tool in the evaluation of ulcerative colitis(UC).UC is divided by disease extent into proctitis,proctosigmoiditis,left-sided colitis,and pan-colitis.In addition,a cecal or peri-...Colonoscopic evaluation is an important tool in the evaluation of ulcerative colitis(UC).UC is divided by disease extent into proctitis,proctosigmoiditis,left-sided colitis,and pan-colitis.In addition,a cecal or peri-appendiceal patch and backwash ileitis are associated with UC.The extent and behavior of UC has been characterized further using various indices and scoring systems;among these systems is the Mayo Score,which is widely used in current clinical trials for new medications.As these medical therapies for UC have developed,achieving mucosal healing with medications has become an important therapeutic objective.展开更多
背景:黏膜愈合被认为是克罗恩病(CD)的一个临床终点,而全壁愈合则是一个深度缓解的概念。目前的CD治疗方法对于诱导黏膜愈合及全层愈合的效果并不理想。全肠内营养(EEN)这种治疗方式尚未引起足够的重视,其治疗价值也没有得到充分的评估...背景:黏膜愈合被认为是克罗恩病(CD)的一个临床终点,而全壁愈合则是一个深度缓解的概念。目前的CD治疗方法对于诱导黏膜愈合及全层愈合的效果并不理想。全肠内营养(EEN)这种治疗方式尚未引起足够的重视,其治疗价值也没有得到充分的评估。本研究旨在评价经口EEN在诱导CD患者黏膜和全壁愈合中的作用。方法:这是一项单中心前瞻性开放研究,研究对象来自中山大学附属第六医院2015年1月至2016年12月间收治的儿童和成人CD患者。所有入组患者接受经口EEN治疗,并在治疗前和治疗完成后评估其C反应蛋白水平、红细胞沉降率、血小板计数、血红蛋白、体质指数、CD活动度指数、单纯CD内镜评分及肠道超声结果。联合应用硫唑嘌呤以预防复发。结果:29例CD患者纳入此次前瞻性观察研究,患者平均年龄28.9岁。在经口EEN治疗后,23例(79%)患者获得了完全黏膜愈合,平均愈合时间123(50-212)天。尽管只有5例(17%)患者获得了全壁愈合,但肠道超声显示其肠壁厚度明显减少(9.4163.06 vs 4.9761.76mm,P<0.001),肠道并发症(包括瘘、脓肿、腹水、狭窄)显著改善(均P<0.05)。结论:经口EEN可有效诱导CD患者的黏膜愈合。无论是活动期还是缓解期的CD患者,都对EEN治疗呈现出良好的临床应答。展开更多
文摘Mucosal healing(MH)is vital in maintaining homeostasis within the gut and protecting against injury and infections.Multiple factors and signaling pathways contribute in a dynamic and coordinated manner to maintain intestinal homeostasis and mucosal regeneration/repair.However,when intestinal homeostasis becomes chronically disturbed and an inflammatory immune response is constitutively active due to impairment of the intestinal epithelial barrier autoimmune disease results,particularly inflammatory bowel disease(IBD).Many proteins and signaling pathways become dysregulated or impaired during these pathological conditions,with the mechanisms of regulation just beginning to be understood.Consequently,there remains a relative lack of broadly effective therapeutics that can restore MH due to the complexity of both the disease and healing processes,so tissue damage in the gastrointestinal tract of patients,even those in clinical remission,persists.With increased understanding of the molecular mechanisms of IBD and MH,tissue damage from autoimmune disease may in the future be ameliorated by developing therapeutics that enhance the body’s own healing response.In this review,we introduce the concept of mucosal healing and its relevance in IBD as well as discuss the mechanisms of IBD and potential strategies for altering these processes and inducing MH.
文摘AIM To evaluate the utility of fecal calprotectin(FC) in predicting relapse and endoscopic activity during follow-up in an inflammatory bowel disease(IBD) cohort.METHODS All FC measurements that were obtained during a 3-year period from patients with inflammatory bowel disease in clinical remission were identified. Data regarding the short-term(6 mo) course of the disease were extracted from the medical files. Exclusion criteria were defined as:(1) An established flare of the disease at the time of FC measurement,(2) Loss to follow up within 6 mo from baseline FC measurement, and,(3) Insufficient data on file. Statistical analysis was performed to evaluate whether baseline FC measurement could predict the short term clinical relapse and/or the presence of mucosal healing.RESULTS We included 149 [Crohn's disease(CD) = 113, Ulcerative colitis(UC) = 36, male = 77] IBD patients in our study. Within the determined 6-month period post-FC measurement, 47(31.5%) had a disease flare. Among 76 patients who underwent endoscopy, 39(51.3%) had mucosal healing. Baseline FC concentrations were significantly higher in those who had clinical relapse compared to those who remained in remission during follow up(481.0 μg/g, 286.0-600.0 vs 89.0, 36.0-180.8, P < 0.001). The significant predictive value of baseline median with IQR FC for clinical relapse was confirmed by multivariate Cox analysis [HR for 100μg/g: 1.75(95%CI: 1.28-2.39), P = 0.001]. Furthermore, lower FC baseline values significantly correlated to the presence of mucosal healing in endoscopy(69.0 μg/g, 30.0-128.0 vs 481.0, 278.0-600.0, in those with mucosal inflammation, median with IQR, P < 0.001). We were able to extract cut-off values for FC concentration with a high sensitivity and specificity for predicting clinical relapse(261 μg/g with AUC = 0.901, sensitivity 87.2%, specificity 85.3%, P < 0.001) or mucosal healing(174 μg/g with AUC = 0.956, sensitivity 91.9%, specificity 87.2%, P < 0.001). FC was better than CRP in predicting either outcome; nevertheless, having a pathological CRP(> 5 mg/L) in addition to the cutoffs for FC, significantly enhanced the specificity for predicting clinical relapse(95.1% from 85.3%) or endoscopic activity(100% from 87.2%). CONCLUSION Serial FC measurements may be useful in monitoring IBD patients in remission, as FC appears to be a reliable predictor of short-term relapse and endoscopic activity.
文摘Mucosal healing(MH)has emerged as a key therapeutic target in inflammatory bowel disease(IBD),and achievement of this goal is documented by endoscopy with biopsy.However,colonoscopy is burdensome and invasive,and substitution with an accurate noninvasive biomarker is desirable.AIM To summarize published data regarding the performance of noninvasive biomarkers in assessing MH in IBD patients.METHODS We conducted a systematic review of studies that reported the performance of biomarkers in diagnosing MH in patients with IBD.The main outcome measure was to review the diagnostic accuracy of serum and fecal markers that showed promising utility in assessing MH.RESULTS We screened 1301 articles,retrieved 46 manuscripts and included 23 articles for full-text analysis.The majority of the included manuscripts referred to fecal markers(12/23),followed by circulatory markers(8/23);only 3/23 of the included manuscripts investigated combined markers(serum and/or fecal markers).Fecal calprotectin(FC)was the most investigated fecal marker for assessing MH.In ulcerative colitis,for cutoff levels ranging between 58 mcg/g and 490 mcg/g,the sensitivity was 89.7%-100%and the specificity was 62%-93.3%.For Crohn’s disease,the cutoff levels of FC ranged from 71 mcg/g to 918 mcg/g(sensitivity 50%-95.9%and specificity 52.3%-100%).The best performance for a serum marker was observed for the endoscopic healing index,which showed a comparable accuracy to the measurement of FC and a higher accuracy than the measurement of serum C-reactive protein.CONCLUSION Several promising biomarkers of MH are emerging but cannot yet substitute for endoscopy with biopsy due to issues with reproducibility and standardization assessing MH.In ulcerative colitis,for cutoff levels ranging between 58 mcg/g and 490 mcg/g,the sensitivity was 89.7%-100%and the specificity was 62%-93.3%.For Crohn’s disease,the cutoff levels of FC ranged from 71 mcg/g to 918 mcg/g(sensitivity 50%-95.9%and specificity 52.3%-100%).The best performance for a serum marker was observed for the endoscopic healing index,which showed a comparable accuracy to the measurement of FC and a higher accuracy than the measurement of serum C-reactive protein.CONCLUSION Several promising biomarkers of MH are emerging but cannot yet substitute for endoscopy with biopsy due to issues with reproducibility and standardization.
基金Supported by National Key Research and Development Program of China(No.2019YFC1709002)National Natural Science Foundation of China(No.81973947 and 82004453)+4 种基金Natural Science Foundation of Nanjing University of Chinese Medicine(No.XZR2020043)Jiangsu Province Chinese Medicine Science and Technology Development Program(No.YB201951)Changzhou Science and Technology Program(No.CJ20190070)Changzhou Municipal Health Commission Science and Technology Program(No.QN 201939)Changzhou Municipal Health Qing Miao Talent Training Program(No.CZQM2020083)。
文摘The latest guideline about ulcerative colitis(UC) clinical practice stresses that mucosal healing, rather than anti-inflammation, is the main target in UC clinical management. Current mucosal dysfunction mainly closely relates to the endoscopic intestinal wall(mechanical barrier) injury with the imbalance between intestinal epithelial cells(IECs) regeneration and death, as well as tight junction(TJ) dysfunction. It is suggested that biological barrier(gut microbiota), chemical barrier(mucus protein layer, MUC) and immune barrier(immune cells) all take part in the imbalance, leading to mechanical barrier injury. Lots of experimental studies reported that acupuncture and moxibustion on UC recovery by adjusting the gut microbiota, MUC and immune cells on multiple targets and pathways, which contributes to the balance of IEC regeneration and death, as well as TJ structure recovery in animals. Moreover, the validity and superiority of acupuncture and moxibustion were also demonstrated in clinic. This paper aims to review the achievements of acupuncture and moxibustion on mucosal healing and analyse the underlying mechanisms.
基金Department of Veterans Affairs,No.2I01BX002761-05 and No.2I01BX002086-06A1The National Institutes of Health,No.1R01DK124095-01A1 and No.1R21CA216746-01A1.
文摘Inflammatory bowel disease(IBD),consisting primarily of ulcerative colitis and Crohn’s disease,is a group of debilitating auto-immune disorders,which also increases the risk of colitis-associated cancer.However,due to the chronic nature of the disease and inconsistent treatment outcomes of current anti-IBD drugs(e.g.,approximately 30%non-responders to anti-TNFαagents),and related serious side effects,about half of all IBD patients(in millions)turn to alternative treatment options.In this regard,mucosal healing is gaining acceptance as a measure of disease activity in IBD patients as recent studies have correlated the success of mucosal healing with improved prognosis.However,despite the increasing clinical realization of the significance of the concept of mucosal healing,its regulation and means of therapeutic targeting remain largely unclear.Here,stemcell therapy,which uses hematopoietic stem cells or mesenchymal stem cells,remains a promising option.Stem cells are the pluripotent cells with ability to differentiate into the epithelial and/or immune-modulatory cells.The overreaching concept is that the stem cells can migrate to the damaged areas of the intestine to provide curative help in the mucosal healing process.Moreover,by differentiating into the mature intestinal epithelial cells,the stem cells also help in restoring the barrier integrity of the intestinal lining and hence prevent the immunomodulatory induction,the root cause of the IBD.In this article,we elaborate upon the current status of the clinical management of IBD and potential role of the stem cell therapy in improving IBD therapy and patient’s quality of life.
基金the Science and Technology Bureau,No.MS22018007Six Peak Talents in Jiangsu Province,No.YY-177+4 种基金Project of Jiangsu Province Youth Medical Talent Development,No.QNRC2016400 and No.QNRC2016697Project of Nantong Youth Medical Talent Development,No.05Youth Fund of the National Natural Science Foundation of China,No.82000497Youth Fund of the Natural Science Foundation of Jiangsu Province,No.BK20200965Scientific Research Fund of Nantong Health Commission,No.MB2020037.
文摘BACKGROUND Although expression of interleukin(IL)-34 is upregulated in active ulcerative colitis(UC),the molecular function and underlying mechanism are largely unclear.AIM To investigate the function of IL-34 in acute colitis,in a wound healing model and in colitis-associated cancer in IL-34-deficient mice.METHODS Colitis was induced by administration of dextran sodium sulfate(DSS),and carcinogenesis was induced by azoxymethane(AOM).Whether the impact of IL-34 on colitis was dependent on macrophages was validated by depletion of macrophages in a murine model.The association between IL-34 expression and epithelial proliferation was studied in patients with active UC.RESULTS IL-34 deficiency aggravated murine colitis in acute colitis and in wound healing phase.The effect of IL-34 on experimental colitis was not dependent on macrophage differentiation and polarization.IL-34-deficient mice developed more tumors than wild-type mice following administration of AOM and DSS.No significant difference was shown in degree of cellular differentiation in tumors between wild-type and IL-34-deficient mice.IL-34 was dramatically increased in the active UC patients as previously reported.More importantly,expression of IL-34 was positively correlated with epithelial cell proliferation in patients with UC.CONCLUSION IL-34 deficiency exacerbates colonic inflammation and accelerates colitis-associated carcinogenesis in mice.It might be served as a potential therapeutic target in UC.
文摘AIM To evaluate the role of oral curcumin in inducing clinical remission in patients with mild to moderate ulcerative colitis(UC).METHODS A prospective randomized double-blind placebo-controlled trial comparing the remission inducing effect of oral curcumin and mesalamine 2.4 g with placebo and mesalamine 2.4 g in patients of ulcerative colitis with mild to moderate severity was conducted from January 2003 to March 2005. The included patients received 1 capsule thrice a day of placebo or curcumin(150 mg) for 8 wk. Patients were evaluated clinically and endoscopically at 0,4 and 8 wk. The primary outcome was clinical remission at 8 wk and secondary outcomes were clinical response, mucosal healing and treatment failure at 8 wk. The primary analysis was intention to treat worst case scenario(ITT-WCS).RESULTS Of 300 patients with UC, 62 patients(curcumin: 29, placebo: 33) fulfilled the inclusion criteria and were randomized at baseline. Of these, 21 patients did not complete the trial, 41 patients(curcumin: 16, placebo: 25) finally completed 8 wk. There was no significant difference in rates of clinical remission(31.3% vs 27.3%, P = 0.75), clinical response(20.7% vs 36.4%, P = 0.18), mucosal healing(34.5% vs 30.3%, P = 0.72), and treatment failure(25% vs 18.5%, P = 0.59) between curcumin and placebo at 8 wk.CONCLUSION Low dose oral curcumin at a dose of 450 mg/d was ineffective in inducing remission in mild to moderate cases of UC.
文摘Advancements in murine modeling systems for ulcerative colitis have diversified our understanding of the pathophysiological factors involved in disease onset and progression.This has fueled the identification of molecular targets,resulting in a rapidly expanding therapeutic armamentarium.Subsequently,management strategies have evolved from symptomatic resolution to well-defined objective endpoints,including clinical remission,endoscopic remission and mucosal healing.While the incorporation of these assessment modalities has permitted targeted intervention in the context of a natural disease history and the prevention of complications,studies have consistently depicted discrepancies associated with ascertaining disease status through clinical and endoscopic measures.Current recommendations lack consideration of histological healing.The simultaneous achievement of clinical,endoscopic,and histologic remission has not been fully investigated.This has laid the groundwork for a novel therapeutic outcome termed disease clearance(DC).This article summarizes the concept of DC and its current evidence.
文摘Colonoscopic evaluation is an important tool in the evaluation of ulcerative colitis(UC).UC is divided by disease extent into proctitis,proctosigmoiditis,left-sided colitis,and pan-colitis.In addition,a cecal or peri-appendiceal patch and backwash ileitis are associated with UC.The extent and behavior of UC has been characterized further using various indices and scoring systems;among these systems is the Mayo Score,which is widely used in current clinical trials for new medications.As these medical therapies for UC have developed,achieving mucosal healing with medications has become an important therapeutic objective.
基金supported by the National Natural Science Foundation of China(81470795)the Science and Technology Planning Project of Guangdong Province,China(2013B022000035).
文摘背景:黏膜愈合被认为是克罗恩病(CD)的一个临床终点,而全壁愈合则是一个深度缓解的概念。目前的CD治疗方法对于诱导黏膜愈合及全层愈合的效果并不理想。全肠内营养(EEN)这种治疗方式尚未引起足够的重视,其治疗价值也没有得到充分的评估。本研究旨在评价经口EEN在诱导CD患者黏膜和全壁愈合中的作用。方法:这是一项单中心前瞻性开放研究,研究对象来自中山大学附属第六医院2015年1月至2016年12月间收治的儿童和成人CD患者。所有入组患者接受经口EEN治疗,并在治疗前和治疗完成后评估其C反应蛋白水平、红细胞沉降率、血小板计数、血红蛋白、体质指数、CD活动度指数、单纯CD内镜评分及肠道超声结果。联合应用硫唑嘌呤以预防复发。结果:29例CD患者纳入此次前瞻性观察研究,患者平均年龄28.9岁。在经口EEN治疗后,23例(79%)患者获得了完全黏膜愈合,平均愈合时间123(50-212)天。尽管只有5例(17%)患者获得了全壁愈合,但肠道超声显示其肠壁厚度明显减少(9.4163.06 vs 4.9761.76mm,P<0.001),肠道并发症(包括瘘、脓肿、腹水、狭窄)显著改善(均P<0.05)。结论:经口EEN可有效诱导CD患者的黏膜愈合。无论是活动期还是缓解期的CD患者,都对EEN治疗呈现出良好的临床应答。
