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Objective:To determine a simpler and more practical scoring standard for predicting mucosal histological healing in ulcerative colitis (UC).Methods:From April 11, 2017 to February 8, 2021, 68 UC patients diagnosed with mucosal healing under endoscopy and hospitalized at Department of Gastroenterology, the Tenth People′s Hospital of Tongji University and during the same period 60 healthy individuals who underwent endoscopy for health checkup were retrospectively analyzed. Modified Mayo score and ulcerative colitis endoscopic index of severity (UCEIS), the modified Nancy index and Robarts histopathology index were determined based on the collected clinical data, endoscopic reports and histopathological evaluation. The proportions of neutrophils, eosinophils, and plasma cells in the colonic mucosal lamina propria were calculated. The proportions of activated neutrophils and T cells in the colonic mucosal lamina were calculated according to CD177 and CD40L, respectively. The new clinical and laboratory diagnostic formulas were determined by multivariate logistic regression analysis, the effectiveness of the equations was evaluated by receiver operating characteristic curve (ROC).Results:Among the 68 patients with UC, the modified Mayo score was 0.7 (0.4, 1.1), the UCEIS was 0.5 (0.3, 0.8), the Nancy index was 5.9±3.2, and the Robarts histopathology index was 2.6±1.7. According to multivariate logistic regression analysis, the formula for clinical diagnosis of histological healing was Y1=-21.09+ 355.9 X1+ 305.8 X2+ 44.91 X3 ( X1, X2 and X3 were the proportions of neutrophils, eosinophils, and plasma cells, respectively). The results of ROC analysis indicated that Y1<-0.747 was the cut-off value of diagnosis of histological healing, and the area under the curve (AUC) was 0.986 and 95% confidence interval ( CI) was 0.922 to 1.000 ( P<0.001), the sensitivity was 97.10% and the specificity was 91.20%. The formula of laboratory diagnosis of histological healing was Y2=-10.57+ 469.1 X1 + 132.7 X2 + 101.2 X3 + 18.56 X4 ( X1, X2, X3, and X4 were the proportions of CD177 + neutrophils, eosinophils, CD40L + T cells and plasma cells, respectively). The results of ROC analysis indicated that Y2<1.960 was the cut-off value of diagnosis of histological healing, and the AUC was 0.980, 95% CI was 0.913 to 0.999 ( P<0.001), the sensitivity was 84.78%, and the specificity was 100.00%. The new clinical and laboratory diagnostic criteria were positively correlated with the Nancy histological index ( r=0.411 and 0.308, P=0.001 and 0.011), and Robarts histopathology index ( r=0.311, 0.273, P=0.010 and 0.024). Conclusions:Compared with the Nancy index, the new clinical and laboratory diagnostic criteria are simpler and more practical. The new clinical diagnostic formula Y1<-0.747 and the new laboratory diagnosis formula Y2<1.960 are the independent factors for predicting histological healing in UC patients.
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Objective:To evaluate the efficacy and safety of adalimumab (ADA) in the treatment of Crohn′s disease (CD), and to analyze the predictive factors of ADA efficacy.Methods:From January 2020 to December 2020, 49 CD patients treated with ADA at the Department of Gastroenterology, Tenth People′s Hospital of Tongji University of Shanghai were enrolled. The clinical data before treatment were collected. During 12 weeks of ADA treatment, the patients were followed up every 2 weeks, the laboratory examinations were conducted every 4 weeks, and colonoscopy examination was rechecked at the 12th week. The improvement of the main symptoms of patients was assessed at 2nd, 4th, and 6th week during ADA treatment. At the 12th week after ADA treatment, the clinical response (Crohn′s disease activity index (CDAI) score decreased ≥70 points from baseline), clinical remission (CDAI score < 150 points), endoscopic response (simple endoscopic score for Crohn′s disease (SES-CD) decreased >50% from baseline) and endoscopic remission (SES-CD ≤2 points or Rutgeerts score ≤1 point), closure of anal fistula of CD patients complicated with anal fistula and occurrence of adverse reactions during treatment were recorded. The predictive factors of clinical remission of CD patients after ADA treatment for 12 weeks were analyzed. The Mann-Whitney U test and binary logistic regression analysis were used for statistical analysis. Results:The main symptom improved rates of 49 CD patients received ADA treatment at 2nd, 4th and 6th week were 75.5% (37/49), 95.9% (47/49) and 98.0% (48/49), respectively, and the main symptom improved time was 14.0 d (7.0 d, 17.0 d). After ADA treatment for 12 weeks, the clinical remission rate was 55.1% (27/49), the clinical response rate was 73.5% (36/49), the endoscopic remission rate was 43.3% (13/30), the endoscopic response rate was 55.6% (15/27), the anal fistula closure rate was 7/18, and the overall incidence of adverse reactions was 24.5% (12/49). The baseline of fecal calprotectin (FC) level of patients in the clinical remission group (27 cases) was lower than that of the patients in the active disease group (22 cases) (111.0 μg/g, 26.3 μg/g to 125.6 μg/g vs. 540.5 μg/g, 420.2 μg/g to 866.9 μg/g), and the difference was statistically significant ( Z=-4.44, P<0.001). The results of binary logistic regression analysis showed that baseline FC level was an independent predictive factor of clinical remission in CD patients treated with ADA for 12 weeks ( OR=1.08, 95%confidence interval 1.02 to 1.14, P=0.013). When the baseline FC cut-off value was 172.39 g/g, the sensitivity and specificity of it in predicting clinical remission in CD patients treated with ADA for 12 weeks were 81.48% and 90.91%, and the area under the receiver operator characteristic curve was 0.87 ( P<0.001). Conclusions:ADA is safe and effective in the treatment of CD. The baseline FC level is an independent predictive factor of clinical remission in CD patients treated with ADA for 12 weeks.
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Inflammatory bowel disease (IBD) is a non-specific chronic intestinal inflammatory disease with unknown etiology and pathogenesis and is often accompanied by extraintestinal manifestations involving multiple organs including the liver, the gallbladder, and the pancreas, with an important impact on the prognosis of IBD. Hepatobiliary and pancreatic complications mainly include primary sclerosing cholangitis, primary biliary cholangitis, autoimmune hepatitis, IgG4-associated sclerosing cholangitis, acute pancreatitis, chronic pancreatitis, autoimmune pancreatitis, and nonspecific increase in pancreatic enzyme. IBD-related hepatobiliary and pancreatic complications are caused by the combination of environmental and immune-mediated factors in individuals with genetic susceptibility, and this article summarizes the current research advances in the pathogenesis of such hepatobiliary inflammatory bowel disease;liver diseases;biliary tract diseases;pancreatic diseases;and pancreatic complications.
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Objective:To screen the risk factors of psychology problems and quality of life of patients with inflammatory bowel disease (IBD) by questionnaire, and to explore the impact of anxiety and depression on the quality of life and disease of IBD patients, in order to guide the treatment of IBD.Methods:From June 15 to July 15 in 2019, 171 IBD patients diagnosed in the Department of Gastroenterology, the Tenth People′s Hospital of Tongji University in Shanghai were investigated by internet questionnaire. Finally 136 IBD patients (IBD group) were enrolled. During the same period 121 healthy individuals with no difference in age and gender were selected as healthy control group. IBD clinical questionnaire, the generalized anxiety disorder (GAD)-7, patient health questionnare (PHQ)-9 depression screening and the short form 36-item health survey (SF-36) quality of life evaluation scale were used in IBD group. General situation questionnaire, GAD-7, PHQ-9 and SF-36 scale were conducted in healthy control group. Chi-square test, Binary logistic regression analysis, Ordinal logistic regression analysis, and Pearson correlation analysis were used for statistical analysis.Results:In IBD group, 87(64.0%) were males and 49(36.0%) were females; 25 cases (18.4%) were ulcerative colitis (UC) and 111 cases (81.6%) were Crohn′s disease (CD); and the median age was (32(26, 40)) years old. In healthy control group, 68 (56.2%) were males and 53(43.8%) were females; the median age was (32(26, 37)) years old. The incidence of anxiety in UC patients and CD patients was 64.0%(16/25) and 64.9%(72/111), respectively, and the incidence of depression in UC and CD was 72.0%(18/25) and 58.6%(65/111), respectively. There were no significant differences in the incidence of anxiety and depression between UC patients and CD patients (both P>0.05). Role-emotional (odds ratio ( OR)=0.965, 95% confidence interval ( CI) 0.937 to 0.994, P=0.017) and mental health ( OR=0.940, 95% CI 0.896 to 0.985, P=0.010) may be the independent factors of depression. Physiological function ( OR=1.040, 95% CI 1.010 to 2.730, P=0.022) was the independent factors of depression. There was no significant correlation between the duration of disease and the quality of life ( P>0.05). There was no significant correlation between disease activity and quality of life, however it was related to physiological function ( r=0.15, P=0.046). The physiological function of IBD patients in remission stage was better than that of patients in activity stage. Depression was negatively correlated with quality of life ( r=-0.55, P<0.01), and with a linear relationship ( r=19.429, intercept was 744.455, P<0.01). Anxiety was not correlated with quality of life ( P>0.05). Depression was negatively correlated with changes of physical function, role-physical function, physical pain, general health, vitality, social function, emotional function, mental health, and reported health transition ( r=-0.234, -0.358, -0.454, -0.449, -0.566, -0.485, -0.441, -0.597, and -0.193, all P<0.05). Conclusions:IBD patients are prone to anxiety and depression. Depression is negative correlated with quality of life. It is very important to screen and intervene mental disorders in IBD patients, especially in patients with depression. Controlling the activity of IBD and relieving the clinical symptoms of patients may be effective in improving anxiety and depression. The treatment of IBD itself is the basis of IBD psychotherapy.
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Objective:To explore the role of infliximab (IFX) in the repairation of intestinal mucosal barrier in Crohn′s disease (CD).Methods:From January 2018 to October 2019, in Shanghai Tenth People′s Hospital, 382 CD patients were selected. All the patients were treated with IFX. And 103 individuals who underwent colonoscopy were selected as healthy control group. The general clinical data, fasting blood samples and intestinal mucosa tissue samples of CD patients and healthy controls were collected. The body mass index (BMI), hemoglobin, albumin, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and relative inflammation factors, including tumor necrosis factor (TNF)-α, interferon (IFN)-γ, interleukin (IL)-1, IL-2, IL-6, IL-8, IL-10 and IL-17A, and their mRNA expression levels were detected. Crohn′s disease activity index (CDAI) and simplified endoscopic score for Crohn′s disease (SES-CD) were used to evaluate the disease activity of CD patients. The expression levels of occudin, claudin-1, zonula occluden-1 (ZO-1) and junctional adhesion molecule-A (JAM-A) were measured by Western blotting. The intestinal mucosal epithelial cells were observed by transmission electron microscope. T test was used for statistical analysis. Results:Before treatment, BMI, and hemoglobin and albumin levels of CD patients were all lower than those of healthy control group ((18.3±1.8) kg/m 2 vs. (20.2±1.2) kg/m 2, (95.3±8.4) g/L vs. (129.2±5.7) g/L, (33.2±5.4) g/L vs. (50.3±3.2) g/L), and the differences were statistically significant ( t=3.457, 5.342 and 2.674, all P<0.05). After treatment the BMI and hemoglobin levels of CD patients were higher than those before treatment ((19.5±2.1) kg/m 2 vs. (18.3±1.8) kg/m 2, (117.2±10.3) g/L vs. (95.3±8.4) g/L), and the CRP level, CDAI score and SES-CD score were lower than those before treatment ((16.3±2.3) mg/L vs. (47.2±9.3) mg/L, 113.2±12.5 vs. 245.2±23.5, 5.0±2.1 vs. 10.0±4.3), and the differences were statistically significant ( t=2.090, 2.339, 2.432, 6.345 and 5.234, all P<0.05). The expression levels of TNF-α, IFN-γ, IL-2, IL-6, IL-8, IL-17A and their mRNA levels of healthy control group were lower than those of CD patients before treatment ((1.1±0.4) ng/L vs.(158.2±38.3) ng/L, (3.2±0.8) ng/L vs. (28.3±13.4) ng/L, (2.7±1.3) ng/L vs. (3.3±2.4) ng/L, (5.2±0.3) ng/L vs. (16.3±7.4) ng/L, (16.3±6.3) ng/L vs. (18.9±10.2) ng/L, (10.5±2.3) ng/L vs. (38.5±11.2) ng/L; 1.00±0.00 vs. 4.68±0.34, 7.83±0.32, 1.25±0.46, 8.36±0.44, 2.01±0.89 and 6.83±0.53, respectively), and the differences were statistically significant ( t=2.345, 6.456, 3.008, 4.009, 7.045, 10.223, 8.345, 11.235, 1.114, 12.334, 5.304 and 5.678, all P<0.05). After treatment the TNF-α, IFN-γ, IL-2, IL-6, IL-8, IL-17A expression levels and their mRNA levels of CD patients were lower than those before treatment ((106.4±29.9) ng/L vs. (158.2±38.3) ng/L, (25.7±10.8) ng/L vs. (28.3±13.4) ng/L, (2.9±1.7) ng/L vs. (3.3±2.4) ng/L, (15.4±4.2) ng/L vs. (16.3±7.4) ng/L, (17.2±8.7) ng/L vs. (18.9±10.2) ng/L, (29.9±12.7) ng/L vs. (38.5±11.2) ng/L, 2.45±0.21 vs. 4.68±0.34, 3.75±0.18 vs. 7.83±0.32, 1.09±0.22 vs. 1.25±0.46, 3.78±0.21 vs. 8.36±0.44, 1.67±0.33 vs. 2.01±0.89, 2.96±0.11 vs. 6.83±0.53), and the differences were statistically significant ( t=9.345, 2.456, 2.334, 2.090, 3.009, 8.345, 4.567, 6.445, 2.046, 7.774, 3.008 and 8.867, all P<0.05). The results of Western blotting showed that the expression levels of occudin, claudin-1, ZO-1 and JAM-A in the intestinal mucosa of CD patients before treatment were lower than those of the healthy control group (0.21±0.03 vs. 1.00±0.02, 0.17±0.07 vs. 1.00±0.01, 0.16±0.06 vs. 1.00±0.04, 0.26±0.08 vs. 1.03±0.04). After treatment the expression levels of occudin, claudin-1, ZO-1 and JAM- A mRNA in the intestinal mucosa of CD patients were higher than those before treatment (0.77±0.08 vs. 0.21±0.03, 0.69±0.08 vs. 0.17±0.07, 0.78±0.09 vs. 0.16 ±0.06, 0.72±0.07 vs. 0.26±0.08), and the differences were statistically significant ( t=4.567, 6.346, 5.557, 8.456, 9.678, 8.671, 10.456 and 7.456, all P<0.05). Conclusions:IFX can effectively relieve the disease activity and improve the nutritional status of CD patients. IFX maintains the expression of intestinal epithelial tight junction protein by reducing inflammatory response, and repairs the intestinal mucosal barrier of CD patients.
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Objective:To investigate the clinical characteristics and change trend of patients with perianal lesions before or after Crohn′s disease (CD) diagnosed.Methods:From January 2008 to September 2018, at The Tenth People′s Hospital Affiliated to Tongji University, the clinical data of 747 hospitalized CD patients were retrospectively collected, 293 patients were PCD patients. The clinical characteristics of PCD patients before or after CD diagnosed were analyzed and the change trend was followed. T test, Mann-Whitney U test, and Chi-square test were performed for statistical analysis. Multivariate logistic regression analysis was used to analyze factors associated with perianal lesions onset time. Spearman correlation analysis was used to analyze the change trend of clinical characteristics. Results:Before CD diagnosis, 86.3% (253/293) PCD patients had perianal lesions. The median follow-up time (range) was 72 months (36 to 108 months). Compared with the patients presented with perianal lesions after CD diagnosis, the onset age of patients with perianal lesions before CD diagnosis was younger ((36.0±12.6) years vs. (24.2±10.2) years), and the rates of male (62.5%, 25/40 vs. 77.9%, 197/253), non-structuring and non-penetrating type (32.5%, 13/40 vs. 56.9%, 144/253) and perianal surgery (55.0%, 22/40 vs.76.7%, 194/253) were high, but low rate of abdominal surgery (37.5%, 15/40 vs. 13.0%, 33/253), and the differences were statistically significant ( t=2.630, χ2=4.442, 8.379, 8.379 and 15.081; all P<0.05). The results of logistic multivariate analysis showed that before CD diagnosis, non-structuring and non-penetrating type was more common than structuring type (odds ratio ( OR)=0.447, 95% confidence interval ( CI) 0.207 to 0.962, P=0.039) and penetrating type ( OR=0.264, 95% CI 0.089 to 0.780, P=0.016). The short disease duration of CD ( OR=0.981, 95% CI 0.968 to 0.995, P=0.008), structuring type ( OR=2.239, 95% CI 1.040 to 4.822, P=0.039) and penetrating type ( OR=3.788, 95% CI 1.281 to 11.198, P=0.016) were the risk factors of perianal lesions after CD diagnosed. The number of PCD patients ( r=0.964, P<0.01) and the proportion of biological agents ( r=0.879, P<0.01) increased with years, while PCD duration ( r=-0.828, P<0.01) and the rate of abdominal surgery significantly decreased with years ( r=-0.882, P<0.01). The proportion of biological agents was negatively correlated with the rate of abdominal surgery ( r=-0.770, P=0.006). Conclusions:The perianal lesions should be closely monitored in adult CD patients with short disease duration, structuring type and penetrating type for early diagnosis and treatment. Biological agents can improve the clinical outcomes of PCD.
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Inflammatory bowel disease (IBD) is an idiopathic and chronic non-specific inflammatory disease of gastrointestinal tract. Abnormal immune response in intestinal mucosa toward commensal microbiota together with intestinal mucosal barrier defects, genetic and environmental factors might be associated with the pathogenesis of human IBD. In recent years, great progress has been made in genetic study of IBD, providing important help for clinical translation and application. Genetic analysis will help us to explain the etiology and lesional areas of IBD, predict the disease behaviors and effectiveness of treatment, thereby benefits the clinical diagnosis and treatment of the disease. This review summarizes the latest achievements and new progresses in genetic study and clarifies the potential value of genetic study in management of IBD.
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Mesentery is the connective tissue membrane that fixes the intestinal tract in retroperitoneum,and plays an important role in maintaining the physiological function of intestine.Inflammatory bowel disease (IBD) is a chronic and non-specific inflammatory disease of digestive tract.Its etiology and pathogenic mechanism are still not entirely clarified.Characteristic pathological changes of mesentery such as creeping fat could be observed in Crohn's disease (CD) and might affect the disease progression.In this article,the relationship between mesentery and CD was reviewed.
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Objective To explore the expression and its clinical significance of immunoglobulin G4 (IgG4) in inflammatory bowel disease (IBD) by detecting the expression of IgG4 in the serum and intestinal mucosa of patients with IBD.Methods From March 2015 to August 2016,68 patients with ulcerative colitis (UC),132 patients with Crohn's disease (CD) and 52 healthy controls were collected.The serum levels of IgG4 were detected by immunonephelometry.The expression of IgG4 in intestinal mucosa was analyzed by immunohistochemistry.Five high power fields (HPF) were randomly selected in each specimen.C-reaction protein (CRP) and erythrocyte sedimentation rate (ESR) of patients with UC,patients with CD and healthy controls were detected.The extent of disease,clinical type,disease activity scores (UC scored by Mayo score system,CD scored by Crohn's disease activity index (CDAI)) and current treatment were collected.The correlation between IgG4 expression and CRP,ESR,Mayo score and CDAI were analyzed.Independent sample t test,Chi square test and Pearson's correlation were performed for statistical analysis.Results The results of immunonephelometry indicated that the serum levels of IgG4 of patients with UC,CD and healthy controls were (0.79±-0.61),(0.69±0.59) and (0.41±0.32) g/L,respectively;all were lower than standard level 1.35 g/L.The results of immunohistochemistry revealed that the number of IgG4 positive cells in the colonic mucosa of active UC and CD patients were higher than that of healthy controls ((15.42±12.47)/HPF,(18.65±12.46)/HPF and (4.71±4.14)/HPF),and the differences were statistically significant (t=5.392 and 8.450,both P＜0.05).There was no statistically significant difference in mucosal IgG4 expression between UC,CD patients at remission phase and healthy controls ((4.72±4.23)/HPF,(5.30±4.87)/HPF and (4.71±4.14)/HPF,both P＞0.05).There was no statistically significant difference in mucosal IgG4 expression between UC and CD patients at active phase and remission phase (both P＞0.05).The case number of active patients,CRP,ESR and Mayo scores of IgG4 positive UC patients were all higher than those of IgG4 negative group(x2 =5.499,t=2.811,3.471 and 4.676;all P＜0.05).The number of active patients,CRP,ESR and CDAI of IgG4 positive CD patients were all higher than those of IgG4 negative group(x2 =4.341,t=3.842,3.892 and 2.935,all P＜ 0.05).In UC patients,the number of IgG4 positive cells was positively correlated with CRP,ESR and Mayo scores (r=0.382,0.381 and 0.470;P=0.001,0.003 and P＜0.01).The number of IgG4 positive cells was positively correlated with CRP,ESR and CDAI in CD patients (r=0.199,0.209 and 0.201;P=0.022,0.016 and 0.021).Conclusions The expression level of IgG4 significantly increased in the intestinal mucosa of IBD patients correlated with the activity of disease.The expression level of [gG4 may be one of the parameters to evaluate the activity of IBD.
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The prevalence of functional constipation (FC) is increased in elderly population, and seeking for a simple, safe and effective treatment modality is of great importance.Aims: To assess the clinical efficacy and safety of abdominal acupoint massage in elderly FC patients.Methods: A total of 151 elderly patients with FC were enrolled and randomly assigned into three groups: group A was treated with bisacodyl 5 mg once a day orally, group B with massage on Guanyuan, Zhongwan and Tianshu acupoints three times a day and group C with their combination.The treatment course was 4 weeks.The stool frequency per week was recorded, and the Patient Assessment of Constipation Symptoms scale (PAC-SYM) was scored.Results: The baseline data were comparable among the three groups (P>0.05).When compared with those before treatment, there was an increase in stool frequency per week and decrease in overall and dimensional scores of PAC-SYM at 1, 2, and 4 weeks after the beginning of treatment in all the three groups (P<0.05).Bisacodyl was superior to acupoint massage for improving stool frequency, consistency and rectal symptoms (P<0.05), while acupoint massage was superior to bisacodyl for alleviating abdominal symptoms (P<0.05).Mild adverse effects were recorded in patients receiving oral bisacodyl, and no adverse effects were observed in patients receiving acupoint massage.Conclusions: Abdominal acupoint massage is safe and effective for improving stool frequency and constipation-associated symptoms especially abdominal symptoms such as abdominal pain and distention in elderly FC patients.
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Background:Malnutrition is common in inflammatory bowel disease,especially in Crohn' s disease (CD).Combined partial enteral and parenteral nutrition is effective for nutritional support in patients with severe CD.Aims:To investigate the effect of combined enteral and parenteral nutritional support on body composition and disease activity in severe active CD patients.Methods:A total of 72 patients with severe active CD admitted from July 2015 to August 2016 at Shanghai Tenth People' s Hospital were enrolled.In addition to conventional antibacterial and remission induction therapy,a combined partial enteral and parenteral nutritional support was given after admission.The nutritional status,body composition parameters and disease activity were evaluated and compared on admission and week 1,week 2 and week 3 of hospitalization.Results:The malnutrition rate was 100％ on admission,of which 90.3％ were severe malnutrition.After a 3-week combined enteral and parenteral nutritional support,the proportion of severe malnutrition decreased from 90.3％ to 34.7％ (P ＜0.05).Meanwhile,the body weight,body mass index,muscle mass,fat mass,protein content,and basal metabolic rate gradually increased and the disease activity index gradually decreased (P all ＜ 0.05).Conclusions:Combined enteral and parenteral nutritional support can improve the nutritional status and body composition parameters,reduce disease activity and induce remission effectively in severe active CD patients.
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Objective To investigate the percentage of CD177+ neutrophils in peripheral blood and inflamed mucosa of the intestine in patients with inflammatory bowel disease(IBD)and in healthy controls, and to investigate the correlation between CD177+ neutrophils and mucosal impairment as well as clinical characteristics. Methods A total of 54 patients with ulcerative colitis(UC),62 patients with Crohn disease (CD),and 48 healthy controls were enrolled. SYBR-green Realtime PCR was applied to determine the ex-pression proportion of CD177+ neutrophils in peripheral blood and in inflamed intestinal mucosa to investigate the correlation between CD177+ neutrophils and endoscopic and clinical disease activity. Results In periph-eral blood and inflamed mucosa of the intestine,the expression of CD177+ neutrophils was significantly higher than that in health controls or patients in remission stage(P< 0. 05),with higher proportion( P<0. 05). The expression of CD177+ neutrophils in peripheral blood and inflamed mucosa of the intestine was positively correlated with both endoscopic disease activity index and clinical severity of the disease( P <0. 05). Conclusion CD177+ neutrophils increase in peripheral blood and intestinal mucosa of patients with IBD. The percentage of CD177+ neutrophils is a favorable marker for both endoscopic disease activity and clinical severity of the disease. CD177+ neutrophils may play a vital role in the immune response in the intes-tinal mucosa,as a new subset of effector neutrophils.
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<p><b>OBJECTIVE</b>To investigate the association between receptor-interacting kinase protein 4 (RIPK4) relative copy number (RCN) and prognosis of stage III( colorectal cancer (CRC) patients treated with oxaliplatin-based chemotherapy.</p><p><b>METHODS</b>RIPK4 RCN was determined by real-time PCR and then dichotomized into high RIPK4 RCN group(n=35) and low RIPK4 RCN group (n=104) using the third quartile as the cut-off point. Overall survival (OS) and recurrence-free survival (RFS) were compared between high and low RIPK4 RCN groups. The subgroup prognostic analysis was also conducted based on tumor site.</p><p><b>RESULTS</b>The median follow-up period was 49 months (ranged 4 to 98 months). Patients with high RIPK4 RCN had poorer OS than those with low RIPK4 RCN, which reached marginal significance(median OS, 43.0 months vs. 53.5 months, P=0.074). Meanwhile there was no significant difference of RFS between two groups (P=0.352). In colon cancer subgroup, high RIPK4 RCN was significantly associated with poor OS (median OS, 31.5 months vs. 56.6 months, P=0.015) but not with RFS (P=0.135). In rectal cancer subgroup, RIPK4 RCN was not associated with both OS and RFS (P=0.981, P=0.738). Multivariate analysis revealed that high RIPK4 RCN was an independent prognostic factor of OS in stage III( CRC patients treated with oxaliplatin-based chemotherapy (HR=2.903, 95% CI: 1.275 to 6.610).</p><p><b>CONCLUSION</b>RIPK4 RCN is significantly associated with OS in stage III( colon cancer patients receiving oxaliplatin-based chemotherapy and may be a novel biomarker that can predict the efficacy of oxaliplatin in colon cancer patients.</p>
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Objective To investigate the role and significance of miRNA-21 in the pathogenesis and development of inflammatory bowel disease (IBD).Methods The expressions of microRNA-21 (miRNA-21) in colonic mucosa and peripheral blood CD4+T cells were analyzed by fluorescence quantitative polymerase chain reaction (PCR) in 26 patients with active Crohn's disease (CD), 23 patients with active ulcerative colitis (UC) and 19 healthy controls.The relative expression amount of miRNA-21 in colonic mucosal and peripheral blood CD4+ T cells in 11 patients with CD was compared before and after infliximab (IFX) treatment, and its correlation with tumor necrosis factor (TNF)-α was analyzed.t-test was performed for comparison between groups.The correlation between miRNA-21 expression in peripheral blood CD4+ T cells and serum TNF-α was analyzed by Spearman correlation analysis.Results The expression of miRNA-21 in colonic mucosa of CD patients and UC patients was 4.720 ± 0.397 and 4.993±-0.415, respectively, which were both higher than that of healthy control group (1.101±-0.284),and the differences were statistically significant (t =7.657 and 8.356, both P＜0.01).The expression of miRNA-21 in peripheral blood CD4+ T cells of CD patients and UC patients was 3.254 ± 0.323 and 3.450±0.311, which were both higher than that of healthy control group (0.891 ±0.220), and the differences were statistically significant (t=6.007 and 7.098, both P＜0.01).After 12 weeks of IFX treatment, simple endoscopic score for Crohn's disease (SES-CD) of CD patients was 8.019 ± 0.349,which was lower than that before treatment (21.502 ± 1.185), and the difference was statistically significant (t=10.910, P＜0.01).The serum TNF-α level was 61.570±6.252, which was lower than that before treatment (173.500 ± 12.670), and the difference was statistically significant (t=7.926, P＜0.01).The results of correlation analysis indicated that serum TNF-α level was positively correlated with miRNA-21 expression in peripheral blood CD4+ T cells (r =0.780 4, P ＜ 0.01).Conclusions The increasing of miRNA-21 expression in IBD was closely correlated with the serum TNF-α level and severity of inflammation.miRNA-21 might be a new target for IBD treatment.
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Human intestinal microbial flora has complex interaction with intestinal mucosal immune system,which maintains intestinal homeostasis. Inflammatory bowel disease( IBD)is a chronic and nonspecific intestinal inflammatory disease,the etiology and pathogenic mechanisms have not yet been fully clarified. Dysbiosis of intestinal microbiota is an important factor in the pathogenesis of IBD,and modulation of intestinal microbiota can be one of the measures for treatment of IBD. This article reviewed the dysbiosis of intestinal microbiota in IBD.
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Background:Lipopolysaccharide( LPS)and(1,3)-β-D glucan( BG)are involved in the process of Crohn’s disease(CD)by activating immune cells in gut to produce inflammatory cytokines. Aims:To investigate the relationship between LPS,BG and disease activity of CD. Methods:Sixty-eight patients with CD from April 2013 to July 2014 at Shanghai Tenth People’s Hospital were enrolled,of them 41 cases were active-CD( A-CD group)and 27 cases were remission-CD(R-CD group). Twenty healthy subjects were served as normal controls. Crohn’s disease activity index (CDAI)and simple endoscopic score for Crohn’s disease(SES-CD)were used to assess the disease activity and severity. Serum levels of LPS,BG,ESR and CRP were determined,and their relationships were analyzed. Results:Serum levels of LPS and BG in A-CD group were significantly higher than those in R-CD and control groups(P all 0. 05). Levels of LPS and BG were positively correlated with CDAI,SES-CD and ESR(P all 0. 05). Conclusions:Serum levels of LPS and BG can be used to assess the disease activity and severity of endoscopic mucosal lesions in CD.
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Objective To test and evaluate the lung function of patients with inflammatory bowel disease (IBD),and to explore the correlation and characteristics between IBD and abnormal lung function.Methods From January 2012 to June 2013,74 hospitalized patients with IBD were collected,among them 34 cases were ulcerative colitis (UC) and 40 cases were Crohn's disease (CD).At the same period,74 healthy individuals were enrolled as controls.The database of history was established.The general state,chemical examinations,lung function,chest X-ray,the diagnosis and treatment were statistically analyzed separately.T test was performed for comparison between groups of measurement data,chi square test was for comparison between groups of count data,rank-sum test was for comparison between groups of ordinal data,and Logistic regression was for multivariate analysis.Results Among the 74 patients with IBD,56 patients (75.68％) were found with abnormal lung function.The percentage of abnormal residual volume of IBD and CD group was 51.35％(38/74) and 60.00％(24/40),which were higher than that of control group [31.08％ (23/74)] and the differences were statistically significant (t=-2.557,P=0.013; t=2.236,P=0.031).There were no significant difference between UC and CD group (P＞0.05).There was no significant correlation between abnormal pulmonary function and the severity of IBD (F=0.744,P=0.690) or extent of lesion (F-2.796,P=0.424).The course of disease ≥five years was a possible protecitive actor (OR=0.824,95％CI:0.687-0.987),and elevated erythrocyte sedimentation rate (ESR) was a possible risk factor (OR=1.093,95％CI:0.994-1.202).Conclusions Most IBD patients are complicated with impaired lung function.It might occur regardless of severity or extent of disease.Course of the disease and ESR may he the influence factors in abnormal lung function.
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Objective To investigate the expression of microRNA (miRNA)-10a in the intestinal mucosa,serum and peripheral blood mononuclear cell (PBMC) of patients with inflammatory bowel disease (IBD) and explore its role and relevance in the pathogenesis of the disease.Methods The intestinal or colonic mucosal biopsy specimens of nine active ulcerative colitis (UC) patients,11 active Crohn's disease (CD) patients and eight patients with negative colonoscopy result as control were collected.The sera of 12 active UC patients,13 active CD patients and nine healthy controls were collected.The PBMC of nine active UC patients,11 active CD patients and eight healthy controls were collected.The expression of miRNA-10a in the intestinal mucosa,sera and PBMC and the expression of IL-12/IL-23 p40 in the intestinal mucosa were detected by real-time polymerase chain reaction (PCR).Each 8 cases of active UC and CD patients were collected.The intestinal mucosa before infliximab (IFX) treatment and six weeks after three times of IFX treatment were collected.And at same time,the intestinal mucosa of 11 active UC patients and 10 active CD patients were collected and cultured for 18 hours stimulated with IFX in vitro and then the expression of miRNA-10a in the intestinal mucosa was tested.One-way analysis of variance was used for comparison in three samples.Paired t-test was used for two samples comparison.Spearman test was used for correlation analysis.Results Compared with healthy controls,the expression of miRNA-10a in the intestinal mucosa,serum and PBMC of UC and CD patients significantly decreased (F=38.45,30.46 and 14.74,all P＜0.05).There was no statistic significance between UC and CD groups.The expression of IL-12/IL-23 p40 in the intestinal mucosa of UC and CD patients significantly increased (F=32.90,P＜0.05).The expression of IL-12/IL-23 p40 was negatively correlated with the expression of miRNA-10a in the intestinal mucosa of CD patients.After three times of IFX treatment,the expression of miR-10a in the intestinal mucosa of IBD patients significantly increased (t=3.341,3.382,both P＜0.05).After stimulated with IFX in vitro,the expression of miRNA-10a in the intestinal mucosa significantly increased (t=3.095,7.193,both P＜0.05).Conclusions miRNA-10a was closely correlated with the inflammation of IBD patients and with the role of targeting IL-12/IL-23 p40.miRNA-10a might be a new target for the IBD treatment.
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Objective To create Mucin gene 1 (MUC1) antisense peptide nucleic acid (PNA),and to observe its effects on MKN-45 cell invasion and explore the mechanism. Methods The sequence of antisense PNA was designed according to MUC1 gene sequence and transfected into human gastric cancer cells (MKN-45) by liposome,and the empty vector group (randomized control group)and blank control group (negative control group) were involved. The expression of MUC1 was detected by real time quantitative PCR and the changes of E-cadherin expression were also observed.The effects on gastric cancer cell invasion were tested with transwell chamber assays.Results The expression of MUC1 gene was effectively suppressed by the 3 created antisense PNA,and their expression level (0.62±0.18,0.49±0.12 and 0.60±0.21) was significantly lower than that of negative control group (1.18 ± 0.03,P ＜ 0.01). There was no significant difference between radomized control group and negative control group (1.00±0.04,P=0.657).After MUC1 PNA transfected,the capability of gastric cancer cell invasion decreased significantly (P=0.005).And the expression of E-cadherin at mRNA and protein level was up-regulated.Conclusions There is negative correlation between MUC1 and E-cadherin expression in gastric cancer cell MKN-45.The capability of tumor cell invasion is significantly inhibited by suppressing MUC1 gene expression.
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Objective To investigate the changes of interleukin-21 (IL 21) and interleukin-21 receptor (IL 21R) expression level in Crohn's disease (CD) patients before and after accepted infliximab (IFX) treatment.Methods From June 2009 to July 2011,twenty-two CD patients met the research criteria were recruited at Tenth People's Hospital of Tongji University.Patients were treated with infliximab at weeks 0,2,6,and 16 healthy individuals were set as healthy control group at same time.Peripheral blood of healthy control group was taken at regular physical examination and blood of CD patients was taken before treatment and 10 weeks after treatment,intestinal mucosa biopsy samples were taken under colon endoscopy examination.The changes of Crohn's disease activity index (CDAI),erythrocyte sedimentation rate (ESR),C-reactive protein (CRP) in CD patients were observed.The change of IL-21R in peripheral blood CD4+ T lymphocytes was detected by flow cytometry.The change of IL-21 expression at mRNA level in intestinal mucosa was determined by realtime quantitative polymerase chain reaction (PCR).The data were analyzed by t test.Results Before treatment,the level of IL21R in peripheral blood CD4+ T lymphocytes of CD patients (12.25％±3.25％) and the expression of IL-21 at mRNA level in inflamed intestinal mucosa (1.38±0.32) were both significantly higher than those of healthy controls (4.25 ％ ± 1.41％,0.44±0.18),the differences were statistically significant (F=15.88,6.75 ; both P＜0.05).At 10th week,the level of IL-21R in peripheral blood CD4+ T lymphocytes of CD patients (8.12％ ± 2.05％) and the expression of IL-21 at mRNA level in intestinal mucosa (0.77 ± 0.24) were both significantly lower than those before treatment,the differences were statistically significant ( t=4.880,8.019; both P＜0.01).Before treatment,ESR,CRP and CDAI of CD patients was (46.8±11.4) mm/1 h,(52.4±11.5) mg/L and 319±74,which was (23.5±9.0) mm/1 h,(11.6±4.6) mg/L and 113±42 after treatment,the differences were statistically significant (t=9.485,16.458,11.100; all P＜0.05).Conclusion The IL-21 expression of active CD patients decreases after IFX treatment,which indicates that IL-21 may involve in IFX induced clinical remission of active CD.