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Aims: To investigate the current situation of mental psychology and quality of life (QoL) in patients with inflammatory bowel disease (IBD) in China, and analyze the influencing factors., Methods: A unified questionnaire was developed to collect clinical data on IBD patients from 42 hospitals in 22 provinces from September 2021 to May 2022. Multivariate Logistic regression analysis was conducted, and independent influencing factors were screened out to construct nomogram. The consistency index (C-index), receiver operating characteristic (ROC) curve, area under the ROC curve (AUC), calibration curve, and decision curve analysis (DCA) were used to evaluate the discrimination, accuracy, and clinical utility of the nomogram model., Results: A total of 2478 IBD patients were surveyed, including 1371 patients with ulcerative colitis (UC) and 1107 patients with Crohn's disease (CD). Among them, 25.5%, 29.7%, 60.2%, and 37.7% of IBD patients had anxiety, depression, sleep disturbance and poor QoL, respectively. The proportion of anxiety, depression, and poor QoL in UC patients was significantly higher than that in CD patients (all p < 0.05), but there was no difference in sleep disturbance between them (p = 0.737). Female, higher disease activity and the first visit were independent risk factors for anxiety, depression and sleep disturbance in IBD patients (all p < 0.05). The first visit, higher disease activity, abdominal pain and diarrhea symptoms, anxiety, depression and sleep disturbance were independent risk factors for the poor QoL of patients (all p < 0.05). The AUC value of the nomogram prediction model for predicting poor QoL was 0.773 (95% CI: 0.754-0.792). The calibration diagram of the model showed that the calibration curve fit well with the ideal curve, and DCA showed that the nomogram model could bring clinical benefits., Conclusion: IBD patients have higher anxiety, depression, and sleep disturbance, which affect their QoL. The nomogram prediction model we constructed has high accuracy and performance when predicting QoL., (© 2024 The Authors. United European Gastroenterology Journal published by Wiley Periodicals LLC on behalf of United European Gastroenterology.)

Background: Approximately 10-15% of inflammatory bowel disease (IBD) patients with overlapping features of ulcerative colitis (UC) and Crohn's disease (CD) are termed as inflammatory bowel disease unclassified (IBDU). This study aimed to describe the clinical features of IBDU and evaluate the potential associated factors of reclassification., Methods: The clinical data of 37 IBDU patients were retrospectively analyzed from November 2012 to November 2020. 74 UC and 74 CD patients were randomly selected and age- and sex-matched with the 37 IBDU patients. Clinical characteristics were compared between the three patient groups. Potential factors associated with the IBDU reclassification were evaluated., Results: 60% of IBDU patients displayed rectal-sparing disease, and 70% of them displayed segmental disease. In comparison to UC and CD, the IBDU group demonstrated higher rates of gastrointestinal bleeding (32.4%), intestinal perforation (13.5%), spontaneous blood on endoscopy (51.4%), and progression (56.8%). The inflammation proceeded relatively slowly, manifesting as chronic alterations like pseudopolyps (78.4%) and haustra blunt or disappearance (56.8%). 60% of IBDU patients exhibited crypt abscess, and 16.7% of them exhibited fissuring ulcers or transmural lymphoid inflammation. The proportions of IBDU patients receiving immunosuppressants, surgery, and infliximab were basically the same as those of CD patients. During the 79 (66, 91) months of follow-up, 24.3% of IBDU patients were reclassified as UC, while 21.6% were reclassified as CD. The presence of intestinal hemorrhaging was associated with CD reclassification, while hypoalbuminemia was associated with UC reclassification., Conclusions: IBDU may evolve into UC or CD during follow-up, and hemorrhage was associated with CD reclassification. Different from the other two groups, IBDU exhibited a more acute onset and a gradual progression. When an IBD patient presents with transmural inflammation or crypt abscess but lacks transmural lymphoid aggregates or fissuring ulcers, the diagnosis of IBDU should be considered., (© 2024. The Author(s).)

Disease activity evaluation is important in Crohn's disease (CD). We aimed to establish new disease activity indices for CD based on noninvasive parameters. The data of 110 patients with CD were retrospectively analyzed. Parameters from bowel ultrasound and biomarkers were measured to select the variables included in the models by univariate analysis. Logistic regression analysis was performed to predict mucosal and transmural activities defined by ileocolonoscopy or computed tomography enterography, respectively. The models' performance was measured by the area under the receiver operating characteristic (ROC) curve (AUC). Leave-one-out cross validation (LOOCV) was applied to adjust for overconfidence in the newly established score models. To predict mucosal activity, erythrocyte sedimentation rate (ESR) and (LimG × BWT)-SUM (the sum of the product of Limberg grade [LimG] and bowel wall thickness [BWT] of each bowel segment) were selected for model A, and the equation was A = 2 × ESR + 9.3 × (LimG × BWT)-SUM. The AUC of ROC, sensitivity, and specificity were 0.927%, 89.8%, and 86.4%, respectively. The AUC of the ROC curve verified by LOOCV was 0.913. To predict transmural activity, albumin (ALB) and LimG-SUM (the sum of the LimG of all the bowel segments) were selected for model B, which was established as B = -1.3 × ALB +1.7 × LimG-SUM. The AUC of ROC, sensitivity, and specificity were 0.851%, 78.0%, and 84.2%, respectively. The AUC of the ROC curve verified by LOOCV was 0.833. Nomograms were developed for two score models. New score models based on noninvasive parameters established in this study showed good abilities in detecting active disease and performed well in the validation phase., (© 2023 The Authors. Clinical and Translational Science published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)

Background: Enteric fistula is one of the penetrating features in Crohn's disease (CD). This study aimed to clarify the prognostic factors for the efficacy of infliximab (IFX) treatment in luminal fistulizing CD patients., Methods: We retrospectively included 26 cases diagnosed with luminal fistulizing CD hospitalized in our medical center from 2013 to 2021. The primary outcome of our research was defined as death from all causes and undergoing of any relevant abdominal surgery. Kaplan-Meier survival curves were used to describe overall survival. Univariate and multivariate analyses were used to identify prognostic factors. A predictive model was constructed using Cox proportional hazard model., Results: The median follow-up time was 17.5 months (range 6-124 months). The 1- and 2-year surgery-free survival rates were 68.1% and 63.2%, respectively. In the univariate analysis, the efficacy of IFX treatment at 6 months after initiation (P < 0.001, HR 0.23, 95% CI 0.01-0.72) and the existence of complex fistula (P = 0.047, HR 4.11, 95% CI 1.01-16.71) was found significantly related to the overall surgery-free survival, while disease activity at baseline (P = 0.099) also showed predictive potential. The multivariate analysis showed that efficacy at 6 months (P = 0.010) was an independent prognostic factor. The C-index of the model for surgery-free survival was 0.923 (P < 0.001), indicating an acceptable predictive effect., Conclusion: Prognostic model including the existence of complex fistula, disease activity at baseline and efficacy of IFX at 6 months may be useful to predict long-term outcome of luminal fistulizing CD patients., (© 2023. The Author(s).)

Background: There is lack of real-world data for disease behavior and surgery of Crohn's disease (CD) from large-scale Chinese cohorts., Methods: Hospitalized patients diagnosed with CD in our center were consecutively included from January 2000 to December 2018. Disease behavior progression was defined as the initial classification of B1 to the progression of B2 or B3. Clinical characteristics including demographics, disease classification and activity, medical therapy, development of cancers, and death were collected., Results: Overall, 504 patients were included. Two hundred thirty-one (45.8%) patients were initially classified as B1; 30 (13.0%), 71 (30.7%), and 95 (41.1%) of them had disease progression at the 1-year follow-up, 5-year follow-up, and overall, respectively. Patients without location transition before behavior transition were less likely to experience behavior progression. However, patients without previous exposure to a corticosteroid, immunomodulator, or biological agent had a greater chance of experiencing behavior progression. When the long-term prognosis was evaluated, 211 (41.9%) patients underwent at least 1 CD-related surgery; 108 (21.4%) and 120 (23.8%) of these patients underwent surgery before and after their diagnosis, respectively. An initial classification as B1, no behavior transition, no surgery prior to diagnosis, and previous corticosteroid exposure during follow-up were associated with a lower risk of undergoing surgery., Conclusions: This study depicts the clinical features and factors associated with behavior progression and surgery among hospitalized CD patients in a Chinese center. Behavior progression is associated with a higher probability of CD-related surgery, and strengthened therapies are necessary for them in the early phase., (© The Author(s) 2021. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Cytomegalovirus (CMV) causes infection in patients with inflammatory bowel disease (IBD). This study investigated the prevalence of CMV colitis, the current status of laboratory testing equipment, and physicians' opinions regarding CMV and IBD in China., Methods: This retrospective multicenter study was conducted by Chinese members of the Asian Organization for Crohn's and Colitis and included 36 hospitals/institutes divided according to municipality, provincial capital city, and prefectural-level city. A survey questionnaire was administered, and chi-square and Fisher's exact tests were performed., Results: A total of 4823 inpatients with ulcerative colitis (UC) and 4622 inpatients with Crohn's disease (CD) were included. The percentages of patients with moderate UC in the provincial capital city and municipality were significantly higher than that in the prefectural-level city (38.3% vs 29.1% and 40.1% vs 29.1%, respectively). The percentage of patients with mild CD was significantly lower in the provincial capital city than in the prefectural-level city and municipality (30.4% vs 40.3%; 30.4% vs 39.3%, respectively). There were 3.1% patients with UC and 0.8% patients with CD who had CMV colitis. The prevalence of CMV colitis was lower in patients with CD than in patients with UC (0.8% vs 3.1%). Of the 150 patients with UC and concurrent CMV colitis, 17.3% patients underwent surgery, 2.0% died, and 23.3% experienced complications. Punched-out ulcerations were the major characteristic features for detecting CMV colitis. Approximately 77.8% of hospitals possessed testing facilities capable of conducting CMV immunohistochemistry., Conclusions: CMV colitis is an important issue during the disease progression of IBD. However, improvement in knowledge and facilities is required to enhance the prognosis of patients., (© The Author(s) 2022. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Inflammatory bowel disease (IBD) is a complex chronic disorder characterized by systemic inflammation, which may cause abnormal state of coagulation, resulting in cardiac events. This study aimed to investigate the incidences and risks of cardiac events in patients with IBD in China., Methods: A retrospective cohort study was performed comprising 1435 patients with IBD from 12 IBD centers in China. Cases were matched with 1588 eligible participants without IBD from 12 medical centers according to age, sex, and laboratory parameters., Results: Patients with IBD in China exhibited significantly higher incidences of ischemic heart disease (IHD; coronary heart disease included) but lower frequencies of right bundle branch block and premature contraction than those of matched controls. The risk of IHD increased in patients with IBD, peaking at the age of 18-35 years. Female patients with IBD were more likely to experience IHD than male patients. The C-reactive protein (CRP) levels and neutrophil count in the peripheral blood were positively related with the risk of IHD among patients with Crohn's disease, whereas plasma fibrinogen levels were negatively related with the risk of IHD both in patients with Crohn's disease and ulcerative colitis., Conclusions: The risk of IHD is increased in patients with IBD, especially in young female patients with IBD when compared with matched non-IBD subjects. The CRP and plasma fibrinogen levels and neutrophil count in the peripheral blood may be potential predictors associated with the occurrence of IHD in patients with IBD. The study's findings have significant implications for the management and prevention of cardiac events in patients with IBD., (© The Author(s) 2021. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Prevalence of inflammatory bowel disease (IBD) is increasing in China. The EXPLORE study evaluated the incidence and indicators of suboptimal responses to first-line anti-tumor necrosis factor (TNF) in patients with ulcerative colitis (UC) or Crohn's disease (CD). We present results for the mainland China subgroup., Methods: A retrospective chart review was performed in adults with IBD at 10 centers in mainland China who initiated anti-TNF therapy between 01 March 2010 and 01 March 2015. The cumulative incidence of suboptimal response to first-line anti-TNF therapy was assessed over 24 months using the Kaplan-Meier method. Indicators of suboptimal response were: dose escalation, discontinuation, augmentation with non-biologic therapy, or IBD-related surgery/hospitalization. At site initiation, a survey was conducted with participating physicians to identify barriers to anti-TNF use., Results: Of 287 patients (72% male) examined, 16/35 (45.7%) with UC and 123/252 (48.8%) with CD experienced a suboptimal response to first-line anti-TNF therapy at any point during the observation period (median 27.6 and 40.0 months, respectively). At 1 and 2 years post anti-TNF initiation, the cumulative incidence of suboptimal response was 51.4% and 75.7% for UC and 45.4% and 57.0% for CD, respectively. Median time to first suboptimal response was 7.2 months for UC and 14.3 months for CD. The most frequent indicator of suboptimal response was discontinuation of anti-TNF therapy (9/16, 56.3%) for UC and IBD-related hospitalization for CD (69/123, 56.1%) followed by augmentation with non-biologic therapy for both cohorts (5/16, 31.3% for UC and 28/123, 22.8% for CD). Dose escalation was the least frequent indicator of suboptimal response to anti-TNF therapy (CD: 4/123, 3.3%; UC: not cited as an indicator). The cumulative incidence of suboptimal response within 4 months of first-line anti-TNF therapy (primary non-response) was over 30% in both cohorts. Financial reasons and reimbursement were identified by surveyed physicians as the most common barriers to prescribing an anti-TNF therapy., Conclusions: Over one-half of patients with IBD are at risk of experiencing a suboptimal response to first-line anti-TNF therapy at 2 years post-initiation in China. This study highlights a substantial unmet need associated with anti-TNF therapies in China. (Clinicaltrials.gov identifier: NCT03090139)., (© 2022. The Author(s).)

Abstract: Persistent disease activity is associated with a poor prognosis in patients with inflammatory bowel disease (IBD). This study aims to explore the accuracy of the highly sensitive C-reactive protein/albumin ratio (CAR) in determining IBD activity.The clinical data of 231 IBD patients treated at Peking Union Medical College Hospital from 2012 to 2018 were analyzed retrospectively. The patients were classified as having active disease or remission according to the Crohn disease activity index scores for patients with Crohn disease (CD) and partial Mayo scores for patients with ulcerative colitis (UC).This study included 231 IBD patients (137 CD and 94 UC). From these groups, 182 patients had active disease, while 49 patients were in remission. The platelet counts, erythrocyte sedimentation rates, high-sensitivity C-reactive protein levels, and CAR scores were significantly higher, while hemoglobin levels, ALB, and body mass indexes were significantly lower in patients with active disease (P < 0.01). The hsCRP, CAR, and ALB significantly correlated with disease activity for both CD and UC (P < 0.001). The area under the curve (AUC) of CAR was highest among the laboratory indexes at 0.829, and the AUC of CAR in the UC patients was larger than that of the CD patients. Also, CAR with cutoff value of 0.06 displayed the highest sensitivity among the indexes for IBD activity at 83.05%.CAR is a useful biomarker for identifying disease activity in patients with CD and UC. Higher CAR levels are indicative of increased IBD activity. CAR may be more valuable in UC than that in CD for assessing the degree of IBD activity., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Inflammatory bowel disease (IBD) has increased in incidence and prevalence in Asian countries since the end of the 20th century. Moreover, differences in the cause, phenotypes, and natural history of IBD between the East and West have been recognized. Therefore, the Asian Organization for Crohn's and Colitis and the Asia Pacific Association of Gastroenterology have established recommendations on medical management of IBD in Asia. Initially, the committee members drafted 40 recommendations, which were then assessed according to Grading of Recommendations Assessment, Development and Evaluation. Eight statements were rejected as this indicated that consensus had not been reached. The recommendations encompass pretreatment evaluation; medical management of active IBD; medical management of IBD in remission; management of IBD during the periconception period and pregnancy; surveillance strategies for colitis-associated cancer; monitoring side effects of thiopurines and methotrexate; and infections in IBD., (© 2020 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Background: Being a rare disease, cryptogenic multifocal ulcerous stenosing enteritis (CMUSE) is easily misdiagnosed as small bowel Crohn's disease (SBCD)., Aims: This study was aimed to compare clinical features of CMUSE to SBCD., Methods: Fourteen patients with CMUSE and 61 patients with SBCD were retrospectively analyzed., Results: Hematochezia was more frequent in CMUSE patients (10, 71.4% vs 23, 37.7%, P = 0.022), while diarrhea was more common in SBCD patients (23, 37.7% vs 0, 0.0%, P = 0.015). More patients with CMUSE developed intestinal stenosis than with SBCD (14, 100% vs 37, 60.7%, P = 0.011). 30 (50.0%) SBCD patients and none CMUSE patients had an elevated erythrocyte sedimentation rate level (P = 0.001). Extra-enteric findings found by computed tomography enterography were significantly more prevalent in SBCD patients than in CMUSE patients (25,71.4% vs 3,25%, P = 0.013). Longitudinal ulcers found by endoscopy were more common in SBCD patients (16, 37.2% vs 0, 0.0%, P = 0.041), while circumferential ulcers were more common in CMUSE patients (6, 54.6% vs 8, 18.6%, P = 0.041). All ulcers observed in CMUSE patients were within mucosal and submucosal layers, but 8 (44.4%) SBCD patients had deep ulcers that reached beyond submucosal layers (P = 0.003). Ulcers were located at strictures in 9 (90.0%) CMUSE patients but only in 1 (5.6%) SBCD patient (P = 0.000)., Conclusions: Gastrointestinal symptoms, erythrocyte sedimentation rate levels, radiologic, endoscopic and pathologic features help to distinguish CMUSE from SBCD.

Background: This study aimed to understand the disease characteristics and treatment outcomes of Crohn's disease (CD) in a real-world setting in China., Methods: In this prospective, non-interventional, multicenter disease registry, adults (≥18 years) with existing and newly diagnosed CD were recruited from 14 medical centers across China from January 2015 to January 2017. The study consisted of the enrollment and follow-up periods, of 12 months each. Demographic, clinical characteristics, diagnostic duration and management of CD at enrollment were evaluated. Logistic regression analysis and stepwise multivariate logistic regression analysis used to assess the relationship between the risk factors and CD., Results: Of 504 enrolled patients, 499 (99.0%) were eligible for analysis. The mean (SD) age at study enrollment was 32.3 (11.43) years and the majority (69.7%) of participants were male. In the past 15 years, a sustained decrease of the period of time in the diagnosis of CD was observed, at about 39.4 (24.11) months in 2010, which decreased to 3.1 (2.13) months in 2015. The most common presenting symptoms of CD included abdominal pain (78.0%), diarrhea (58.1%), weight loss (52.9%) and fever (30.1%). Oral ulcer (19.4%) and arthritis (9.8%) were the most common extra-intestinal manifestations. Non-stricturing non-penetrating (B1) (49.9%) behavior and ileocolonic involvement (L3) (56.2%) location were more frequent. Perianal disease was observed in 29.1% of the patients. Around 23.8% (119/499) patients had CD-related surgery other than perianal disease surgery. Older age at enrollment, longer disease course, complicated disease behavior and absence of perianal disease were all surgery risk factors (p < 0.05). The most common medications was immunomodulators (e.g., azathioprine) (41.5%), anti-TNFα agents (32.9%) and aminosalicylates (20.6%). The mean (SD) Crohn's Disease Active Index (CDAI) score was 159.1 (91.45) and almost half of the patients (49.1%, 81/165) were in remission., Conclusions: This study demonstrated the CD-disease characteristics, risk factors of CD-related surgery and perianal disease, and treatment strategies in a real-world setting in China and may help in developing programs to diagnose and manage patients with CD.

To determine the effect of prior corticosteroid treatment on the results of infliximab (IFX) therapy in patients with Crohn disease (CD).Patients with CD treated with at least 3 IFX infusions between March 2009 and April 2017 were divided into steroid group (n = 43) and nonsteroid group (n = 22) and analyzed retrospectively.The cumulative probabilities of clinical remission and response to IFX at weeks 14, 30, 54, and 78 were higher in the steroid group, though this difference was not statistical significant. At the mean interval of 11.7 months following the initiation of IFX treatment, the mucosal healing rate was significantly higher in the steroid group (71.0% vs 22.2%, P < .01). There was no statistical difference in the incidence of adverse reactions between the 2 groups.In CD, patients with prior corticosteroid treatment may increase the response rate to IFX therapy.

Objectives: Differentiating Crohn's disease (CD) from intestinal tuberculosis (ITB) remains a diagnostic challenge. Misdiagnosis carries potential grave implications. We aimed to develop and validate a novel diagnostic nomogram for differentiating them., Methods: In total, 310 eligible patients were recruited from 6 tertiary inflammatory bowel disease centers. Among them, 212 consecutive patients (143 CD and 69 ITB) were used in the derivation cohort for the establishment of diagnostic equation and nomogram; 7 investigative modalities including clinical manifestations, laboratory results, endoscopic findings, computed tomography enterography features, and histology results were used to derive the diagnostic model and nomogram. Ninety-eight consecutive patients (76 CD and 22 ITB) were included for validation of the diagnostic model., Results: Eight out of total 79 parameters were identified as valuable parameters used for establishing diagnostic equations. Two regression models were built based on 7 differential variables: age, transverse ulcer, rectum involvement, skipped involvement of the small bowel, target sign, comb sign, and interferon-gamma release assays (for model 1) or purified protein derivative (for model 2), respectively. Accordingly, 2 nomograms of the above 2 models were developed for clinical practical use, respectively. Further validation test verified the efficacy of the nomogram 1 with 90.9% specificity, 86.8% sensitivity, 97.1% PPV, 66.7% negative predictive value (NPV), and 87.8% accuracy for identifying CD, and the efficacy of the nomogram 2 with 100% specificity, 84.2% sensitivity, 100% positive predictive value, 64.7% NPV, and 87.8% accuracy for diagnosing CD., Conclusions: The derivation and validation cohorts identified and validated 2 highly accurate and practical diagnostic nomograms for differentiating CD from ITB. These diagnostic nomograms can be conveniently used to identify some difficult CD or ITB cases, allowing for decision-making in a clinical setting.

Background: Inflammatory bowel disease [IBD] results particularly from an aberrance of CD4+ helper and regulatory T cells and comprises histopathologically chronic active enterocolitis with features reflecting both activity and chronicity of mucosal inflammation. The exact immunological-histological correlation in IBD is not understood., Methods: We studied the correlation between colonic mucosal CD4+ T cell subsets [Th1, Th2, Th17, Th22 and Treg] and mucosal histological changes in ulcerative colitis [UC] and Crohn's disease [CD]. CD4+ T cell subtyping and enumeration were achieved by flow cytometry. Histological features were categorized and assessed semi-quantitatively using three validated histological scoring schemes [ECAP, RHI and D'Haens]. Correlations between prevalence [%] of CD4+ T cell subsets and histological scores were analysed., Results: Treg cells were correlated with ECAP category A [activity] as well as RHI scores. Treg cell were increased particularly in mucosa with severe neutrophilic infiltration in the cryptal/surface epithelium and in lamina propria, and with basal plasmacytosis. Th17 cells were also increased in cases with extensive neutrophil infiltrate in lamina propria, whereas RORc+ cells were increased in cases with severe lymphoplasmacytic infiltration in lamina propria. In both UC and CD, mucosa with marked crypt architectural alteration had increased IL-22+ and Th22 cells. UC with Paneth cell metaplasia had higher Th17 cells. CD with granuloma had increased IL-22+ and IL-22+IFN-γ+ cells., Conclusions: The Treg subset appears to be associated with the overall severity of IBD histopathology, particularly with active inflammation. Th17 is also associated with activity. By contrast, IL-22+ cells are associated with chronicity and granuloma formation in CD.

Background: Hovhannisyan et al. first showed evidence of plasticity between Treg and Th17 in the inflamed intestine of Crohn's disease (CD) patients. Our previous report suggests that the inflammatory cytokine milieu generates IL-17 + Foxp3 + CD4 + T lymphocytes which is a crossover population converting Treg subset to Th17 in the peripheral blood of IBD patients. This is considered as an evidence of Treg/Th17 plasticity., Aim: The aim of this study was to characterize a variety of helper T cell crossover population, not limited to IL-17 + Foxp3 + CD4 + T lymphocytes, in the lamina propria (LP) of IBD patients., Methods: Fresh colonoscopic biopsies were obtained from patients with CD (n = 50) and ulcerative colitis (UC, n = 32) and from healthy controls (HC, n = 25). LP mononuclear cells were assessed for intracellular cytokines and transcription factors such as IFNγ, IL-13, IL-17, IL-22, T-bet, Gata-3, RORγt, and Foxp3 using multicolor flow cytometry to detect subsets of LP CD4 + T lymphocytes., Results: Patients with IBD demonstrated increased crossover populations in IL-17 + Foxp3 + , T-bet + Foxp3 + , Gata3 + Foxp3 + , RORγt + Foxp3 + populations compared to HC. There was an inverse correlation of Harvey-Bradshaw index with Gata3 + Foxp3 + population in CD patients, while IL-13 + Foxp3 + population was directly correlated with Mayo clinical scores in UC patients. Furthermore, total IL-22 expressing cells as well as Th22 and IL-22 + Th1 populations were decreased in UC compared to CD and HC., Conclusion: IBD patients exhibit the increased crossover populations in LP Treg cells toward Th2 and Th17 compared to HC. The prevalence of Treg/Th2 crossover populations is associated with clinical disease score of IBD.

Background: This study aimed at evaluating whether leukocyte differentials could serve as effective biomarkers for disease activity in IBD., Methods: A total of 100 subjects were prospectively enrolled, including 36 patients with CD, 34 patients with UC, and 30 healthy controls (HC). Leukocyte differentials were determined by CytoDiff Flow Cytometry analysis., Results: Total neutrophil counts, monocyte/lymphocyte ratio (M/L), and CD16 - monocyte/lymphocyte ratio (CD16 - M/L) were significantly higher in active UC patients compared with quiescent UC patients and HC. A cut-off value of 0.25 in M/L exhibited the best overall accuracy of 82.4% with an AUC of 0.846 in differentiating active UC from quiescent UC. Total leukocyte counts were significantly decreased in active CD patients, while total monocyte counts and total CD16 - monocyte counts were significantly increased in active CD patients compared with quiescent CD patients and HC. A cut-off value of 0.25 in CD16 - M/L displayed the best AUC of 0.886 (overall accuracy of 86.1%) in differentiating active CD from quiescent CD., Conclusions: Our data suggest that CD16 - M/L could serve as promising biomarkers for distinguishing active disease from quiescent disease in both UC and CD. In addition, they could be used as supplements to other disease activity indicators, such as hsCRP and ESR., (Copyright © 2017. Published by Elsevier B.V.)

Background: Antibodies to saccharomyces cerevisiae (ASCA), antibodies to perinuclear anti-neutrophil cytoplasmic (pANCA), pancreatic autoantibodies (PAB) and antibodies against intestinal goblet cells (GAB) are important in diagnosing Crohn's disease (CD) and ulcerative colitis (UC). However, little is known about their diagnostic value in real clinical practice in China. This retrospective study aimed to present our 2-year clinical experience with those biomarkers in diagnosis of CD and UC., Methods: A total of 140 patients with UC, 128 patients with CD, and 224 patients with intestinal associated diseases as disease controls were included. Serum ASCA were determined by ELISA. Serum pANCA, GAB, and PAB were tested by indirect immunofluorescent assay. Retrospective review of laboratory results and clinical information was performed., Results: ASCA and ASCA+/pANCA- showed poor abilities in differentiating CD from UC, CD from intestinal Behçet's disease (BD), or CD from intestinal tuberculosis (ITB). In contrast, PAB exhibited good capacities in differentiating CD from UC, CD from intestinal BD, and CD from ITB. IgG pANCA demonstrated a high sensitivity and specificity in differentiating UC from CD. pANCA+/ASCA- or pANCA+/PAB- displayed a high sensitivity and specificity in differentiating UC from CD. GAB showed poor potential in differentiating UC from CD. PAB were positively correlated with early disease onset, ileocolonic disease, and perianal disease in CD patients., Conclusions: Our data suggest that pANCA and PAB are helpful in diagnosis of UC and CD, respectively, while ASCA and GAB were not. Our findings indicate a clear need for additional biomarkers for diagnosis of CD in China.

Background: Distinction between 2 forms of inflammatory bowel disease (IBD), ulcerative colitis (UC) and Crohn's disease (CD), can be challenging. Aberrant mucosal immunity suggests that CD is a T helper type 1 cell (Th1)-driven disease, whereas UC as Th2-driven response. However, whether this paradigm truly distinguishes CD from UC is controversial. We aimed to clarify the discriminating potential of lamina propria Th subsets in patients with IBD., Methods: Biopsies from 79 patients with IBD and 20 healthy controls were collected for Th subsets analysis (Th1:interferon γ [IFN-γ], T-bet; Th2:interleukin 13 [IL-13], Gata3; Th17:IL-17, RORγt; Treg:FoxP3). The receiver-operating characteristic curves were constructed to assess the discriminating ability by calculating the area under the receiver-operating characteristic curve. The equation with the highest area under the receiver-operating characteristic curve was applied to newly diagnosed patients to evaluate discriminating ability., Results: Patients with CD showed increased IFN-γ or T-bet cells and decreased IL-13 or Gata3 cells compared with UC. A discriminant equation composed of 4 markers (IFN-γ, T-bet, IL-13, and Gata3) yielded the highest area under the receiver-operating characteristic curve. In 36 established CD or UC, the sensitivity, specificity, positive and negative predictive probabilities were 92.6%, 55.6%, 86.2%, and 71.4% and in 14 newly diagnosed patients were 100.0%, 42.9%, 63.6%, and 100.0%. Furthermore, Gata3 cells were increased in tumor necrosis factor inhibitor therapy nonresponders compared with responders in CD. IFN-γ cells were directly and inversely proportional to disease activity in patients with CD and UC, respectively., Conclusions: The Th1/Th2 paradigm can distinguish CD from UC and may be further associated with response to tumor necrosis factor inhibitor in CD and disease activity in patients with IBD.

The need for reliable biomarkers for distinguishing Crohn disease (CD) from ulcerative colitis (UC) is increasing. This study aimed at evaluating the diagnostic potential of anti-GP2 antibodies as a biomarker in Chinese patients with CD. In addition, a variety of autoantibodies, including anti-saccharomyces cerevisiae antibodies (ASCA), perinuclear anti-neutrophil cytoplasmic antibodies (PANCA), anti-intestinal goblet cell autoantibodies (GAB), and anti-pancreatic autoantibodies (PAB), were evaluated.A total of 91 subjects were prospectively enrolled in this study, including 35 patients with CD, 35 patients with UC, 13 patients with non-IBD gastrointestinal diseases as disease controls (non-IBD DC), and 8 healthy controls (HC). The diagnosis of IBD was determined based on the Lennard-Jones criteria, and the clinical phenotypes of the IBD patients were determined based on the Montreal Classification.Anti-GP2 IgG antibodies were significantly elevated in patients with CD, compared with patients with UC (P = 0.0038), HC (P = 0.0055), and non-IBD DC (P = 0.0063). The prevalence of anti-GP2 IgG, anti-GP2 IgA and anti-GP2 IgA, or IgG antibodies in patients with CD was 40.0%, 37.1%, and 54.3%, respectively, which were higher than those in non-IBD DC (anti-GP2 IgG, 15.4%; anti-GP2 IgA, 7.7%; and anti-GP2 IgA or IgG, 23.1%) and those in patients with UC (anti-GP2 IgG, 11.4%; anti-GP2 IgA, 2.9%; and anti-GP2 IgA or IgG, 14.3%). For distinguishing CD from UC, the sensitivity, specificity, positive predictive value (PPV) and positive likelihood ratios (LR+) were 40%, 88.6%, 77.8%, and 3.51 for anti-GP2 IgG, 37.1%, 97.1%, 92.9%, and 13.0 for anti-GP2 IgA, and 54.3%, 85.3%, 79.2%, and 3.69 for anti-GP2 IgA or IgG. For CD diagnosis, the combination of anti-GP2 antibodies with ASCA IgA increased the sensitivity to 68.6% with moderate loss of specificity to 74.3%. Spearman's rank of order revealed a significantly positive correlation of anti-GP2 IgG with ileocolonic location of disease (L3) (P = 0.043) and a negative correlation of anti-GP2 IgA with biologic therapy (P = 0.012).Our findings suggest that anti-GP2 antibodies could serve as a biomarker for distinguishing patients with CD from patients with UC, and the combination of anti-GP2 antibodies with ASCA IgA may improve the predictive power.

This study analyzed IL-23p19 expression in inflamed mucosa of IBD and the role in the induction of IEL and NK cell activation as well as Th17 cell differentiation. Expression of IL-23p19 was performed by immunohistochemistry and quantitative real-time PCR. Expression of IL-23R was assessed by flow cytometry. Cytolytic activities of IEL and NK cells by IL-23 were determined by a standard (51)Cr-release assay. Cytokine levels were analyzed by ELISA and quantitative real-time PCR. Expression of IL-23p19 was increased significantly in inflamed mucosa of CD compared with that in UC and healthy controls. Double-staining confirmed that IL-23p19(+) cells were mainly CD68(+) macrophages/DCs. IL-23R(+) cells were increased significantly in PB- and LP-CD4(+) and -CD8(+) T and NK cells. IL-23 markedly promoted IBD IEL and NK cell activation and cytotoxicity and triggered IBD PB- and LP-T cells to secrete significantly higher levels of IFN-γ, TNF, IL-2, and IL-17A compared with controls. Importantly, IL-23 promoted IBD PB- or LP-CD4(+) T cells to differentiate into Th17 cells, characterized by increased expression of IL-17A and RORC. Anti-TNF treatment could markedly reduce IL-23 expression and Th17 cell infiltration in inflamed mucosa of CD patients. These data indicate that IL-23 is highly expressed in inflamed mucosa of IBD and plays an important role in the induction of IEL, NK, and T cell activation, proinflammatory cytokine secretion, and Th17 cell differentiation. Targeted therapy directed against IL-23p19 may have a therapeutic role in treatment of IBD.

Objective: To probe the relationship between location and extent of ulcerative colitis (UC) by analyzing its extra-intestinal manifestations., Methods: 392 UC cases in Peking Union Medical College Hospital from 1976 to 2000 were reviewed retrospectively. Chi-square test was used to test the difference between groups., Results: 82 of 392 patients (20.9%) with UC had extra-intestinal manifestations, 34 (8.7%) of these patients had more than one extra-colonic organ involvement; It shows that the extensive colitis has highest incidence of extra-intestinal manifestations with UC than that of the left-sided colitis did, while the proctitis had the lowest incidence. There were no significant difference (P > 0.05) between the group of extensive colitis and that of left-side colitis; The incidence of extra-intestinal manifestations in severe cases was significantly greater than that in mild cases. There was a trend of increasing incidence from severe to moderate to mild type (P < 0.05); Most of the extra-intestinal manifestations were associated with active UC, except for AS, PSC, healed during SASP and/or steroid treatment., Conclusions: Extra-intestinal manifestations had a high incidence in UC. The most frequently involved organs were joints, hepatobiliary system, skin, mouth and eyes. The majority of them were associated with the active UC. The incidence of extra-intestinal manifestations with UC was closely related with the extent and severity of the lesions, and the most of the extra-intestinal manifestations occurred in the active phase of UC. But the incidence of extra-intestinal manifestations was not related to prognosis.