Background::Histological healing is closely associated with improved long-term clinical outcomes and lowered relapses in patients with ulcerative colitis (UC). Here, we developed a novel diagnostic criterion for assessing histological healing in UC patients.Methods::We conducted a retrospective cohort study in UC patients, whose treatment was iteratively optimized to achieve mucosal healing at Shanghai Tenth People’s Hospital of Tongji University from January 2017 to May 2022. We identified an inflammatory cell enumeration index (ICEI) for assessing histological healing based on the proportions of eosinophils, CD177 + neutrophils, and CD40L + T cells in the colonic lamina propria under high power field (HPF), and the outcomes (risks of symptomatic relapses) of achieving histological remission vs. persistent histological inflammation using Kaplan-Meier curves. Intrareader reliability and inter-reader reliability were evaluated by each reader. The relationships to the changes in the Nancy index and the Geboes score were also assessed for responsiveness. The ICEI was further validated in a new cohort of UC patients from other nine university hospitals. Results::We developed an ICEI for clinical diagnosis of histological healing, i.e., Y = 1.701X 1 + 0.758X 2 + 1.347X 3 - 7.745 (X 1, X 2, and X 3 represent the proportions of CD177 + neutrophils, eosinophils, and CD40L + T cells, respectively, in the colonic lamina propria under HPF). The receiver operating characteristics curve (ROC) analysis revealed that Y <-0.391 was the cutoff value for the diagnosis of histological healing and that an area under the curve (AUC) was 0.942 (95% confidence interval [CI]: 0.905-0.979) with a sensitivity of 92.5% and a specificity of 83.6% ( P <0.001). The intraclass correlation coefficient (ICC) for the intrareader reliability was 0.855 (95% CI: 0.781-0.909), and ICEI had good inter-reader reliability of 0.832 (95% CI: 0.748-0.894). During an 18-month follow-up, patients with histological healing had a substantially better outcome compared with those with unachieved histological healing ( P <0.001) using ICEI. During a 12-month follow-up from other nine hospitals, patients with histological healing also had a lower risk of relapse than patients with unachieved histological healing. Conclusions::ICEI can be used to predict histological healing and identify patients with a risk of relapse 12 months and 18 months after clinical therapy. Therefore, ICEI provides a promising, simplified approach to monitor histological healing and to predict the prognosis of UC.Registration::Chinese Clinical Trial Registry, No. ChiCTR2300077792.

Inflammatory bowel disease(IBD)is a disease characterized by chronic,recurrent intestinal inflammation,includ-ing Crohn's disease(CD)and ulcerative colitis(UC).Etiology and pathogenesis of IBD are unknown,and the treatment is difficult.In recent years,immunocellular therapy represented by regulatory T(Treg)cell therapy and dendritic cell(DC)therapy has developed rapidly in the field of immune-related disease treatment,and some progress has also been made in the treatment of IBD.This review will introduce application and progression of Treg cell therapy and DC therapy in IBD treatment.

Objective:To investigate the differences in cell-free DNA (cfDNA) concentrations between the inflammatory bowel disease (IBD) patients with different disease severities and the significance.Methods:Cross-sectional study was conducted. Ninety-one patients with IBD were included in the Second Affiliated Hospital of Zhengzhou Univesity from April 2021 to May 2022, including 48 patients with ulcerative colitis (UC) and 43 patients with Crohn′s disease (CD). Fifteen healthy people were assigned as healthy control group. The differences in cfDNA concentration between IBD group and healthy control group and between IBD patients with different disease severities were compared. The correlations between cfDNA concentration and laboratory indicators of IBD patients were analyzed.Results:The cfDNA concentration of IBD patients was higher than that of healthy control group [ (86.7±22.6) ng/ml vs. (52.6±15.8) ng/ml, P<0.001], and the cfDNA concentrations of UC and CD patients were higher than that of healthy control group (both P<0.001), the differences were statistically significant. The cfDNA concentration of mild, moderate and severe UC patients increased successively, and the differences were statistically significant [ (62.9±11.1) ng/ml vs. (83.6±17.1) ng/ml vs. (103.9±19.1) ng/ml, all P<0.01]. cfDNA concentration of UC patients was positively correlated with disease activity ( r = 0.74, P<0.001). cfDNA concentration of active CD patients was significantly higher than that in remission stage [ (104.2±17.2) ng/ml vs. (78.6±18.6) ng/ml, P<0.001]. cfDNA concentration in CD patients was positively correlated with disease activity ( r = 0.58, P<0.001). cfDNA concentration in UC patients was positively correlated with C-reactive protein (CRP) ( r = 0.4, P<0.01) and erythrocyte sedimentation rate (ESR) ( r = 0.37, P<0.01), and negatively correlated with hemoglobin ( r = -0.46, P<0.01) and albumin ( r = -0.51, P<0.01). cfDNA concentration in CD patients was positively correlated with CRP ( r = 0.48, P<0.01) and ESR ( r = 0.38, P<0.05), and negatively correlated with hemoglobin ( r = -0.45, P<0.01) and albumin ( r = -0.32, P<0.05) . Conclusion:cfDNA concentration closely correlates with disease severity of IBD patients and is a new indicator to evaluate disease severity of IBD patients.

Objective:To investigate the differences in cell-free DNA (cfDNA) concentrations between the inflammatory bowel disease (IBD) patients with different disease severities and the significance.Methods:Cross-sectional study was conducted. Ninety-one patients with IBD were included in the Second Affiliated Hospital of Zhengzhou Univesity from April 2021 to May 2022, including 48 patients with ulcerative colitis (UC) and 43 patients with Crohn′s disease (CD). Fifteen healthy people were assigned as healthy control group. The differences in cfDNA concentration between IBD group and healthy control group and between IBD patients with different disease severities were compared. The correlations between cfDNA concentration and laboratory indicators of IBD patients were analyzed.Results:The cfDNA concentration of IBD patients was higher than that of healthy control group [ (86.7±22.6) ng/ml vs. (52.6±15.8) ng/ml, P<0.001], and the cfDNA concentrations of UC and CD patients were higher than that of healthy control group (both P<0.001), the differences were statistically significant. The cfDNA concentration of mild, moderate and severe UC patients increased successively, and the differences were statistically significant [ (62.9±11.1) ng/ml vs. (83.6±17.1) ng/ml vs. (103.9±19.1) ng/ml, all P<0.01]. cfDNA concentration of UC patients was positively correlated with disease activity ( r = 0.74, P<0.001). cfDNA concentration of active CD patients was significantly higher than that in remission stage [ (104.2±17.2) ng/ml vs. (78.6±18.6) ng/ml, P<0.001]. cfDNA concentration in CD patients was positively correlated with disease activity ( r = 0.58, P<0.001). cfDNA concentration in UC patients was positively correlated with C-reactive protein (CRP) ( r = 0.4, P<0.01) and erythrocyte sedimentation rate (ESR) ( r = 0.37, P<0.01), and negatively correlated with hemoglobin ( r = -0.46, P<0.01) and albumin ( r = -0.51, P<0.01). cfDNA concentration in CD patients was positively correlated with CRP ( r = 0.48, P<0.01) and ESR ( r = 0.38, P<0.05), and negatively correlated with hemoglobin ( r = -0.45, P<0.01) and albumin ( r = -0.32, P<0.05) . Conclusion:cfDNA concentration closely correlates with disease severity of IBD patients and is a new indicator to evaluate disease severity of IBD patients.

Galectin⁃3 is an endogenous lectin with extensive immunomodulatory effects, and plays an important role in inflammatory response, autoimmunity and tumorigenesis. However, the expression of galectin⁃3 in ulcerative colitis (UC) and its relationship with disease activity of UC are unclear. Aims: To detect the expression of galectin⁃3 in colon tissue and serum in UC patients, and explore the relationship between galectin⁃3 and disease activity. Methods: Thirty⁃ three patients with UC diagnosed and treated from March 2019 to December 2019 at the Second Affiliated Hospital of Zhengzhou University were recruited, and 20 paracancerous normal tissue of colon cancer patients were served as controls. The expression of galectin ⁃ 3 in colon tissue was detected by immunohistochemistry SABC. Serum samples of 24 UC patients and 20 healthy controls were collected. Serum level of galectin⁃3 was detected by ELISA. Results: The positive expression rate of galectin⁃3 in colon tissue in UC patients was significantly lower than that in paracancerous normal tissue, and the difference was statistically significant (P<0.05). The positive expression rate in mild UC patients was higher than that in moderate to severe UC patients, and the difference was statistically significant (P<0.05). The positive expression rate in remission stage was higher than that in active stage, and the difference was statistically significant (P<0.05). Serum galectin⁃3 level in UC patients was higher than that in healthy control group, and the difference was statistically significant (P<0.05). Serum galectin ⁃ 3 level in moderate to severe UC patients was higher than that in mild UC group, and the difference was statistically significant (P<0.05). Serum galectin ⁃ 3 level in active UC patients was higher than that in remission UC patients, and the difference was statistically significant (P<0.05). Conclusions: In UC patients, the expression of galectin⁃3 in colon tissue and serum are dysregulated, and the expression of galectin⁃3 in colon tissue is decreased, especially in moderate to severe UC, while the serum galectin⁃3 level is opposite to the tissue expression.

Inflammatory bowel disease (IBD) is a chronic and recurrent inflammatory disease of gastrointestinal tract, including Crohn's disease and ulcerative colitis. The exact etiology and pathogenesis of IBD are still not clear. Neutrophil gelatinase-associated lipocalin (NGAL) plays an important role in regulating intestinal immunity, maintaining intestinal epithelial cell barrier, and coordinating the composition of intestinal flora. In addition, NGAL is useful for helping the clinical testing of IBD. This article reviewed the research progress of NGAL in IBD.

Background: Matrix metalloproteinase-7 (MMP-7) is a proteolytic enzyme involved in wound healing, tissue remodeling by regulating a variety of extracellular matrix and non-matrix substrates, and is an important mediator of tissue damage during inflammation in inflammatory bowel disease (IBD). Aims: To investigate the clinical significance of MMP-7 in IBD. Methods: A total of 38 cases of colon biopsy samples from patients with IBD from January 2019 to January 2021 at the Second Affiliated Hospital of Zhengzhou University were collected, including 20 ulcerative colitis (UC) and 18 Crohn's disease (CD). The paracancerous tissues of 5 patients with colon cancer were served as the control group. The expression of MMP-7 in colon tissue was detected by immunohistochemical staining, and its correlation with C-reactive protein (CRP) and white blood cell (WBC) was analyzed. Results: Compared with the control group, the expression of MMP-7 was significantly up-regulated in both active UC group and severe CD group (P<0.05). The expression of MMP-7 was gradually up-regulated with the increase of severity. The expression of MMP-7 in severe UC and CD group was significantly increased than that in remission UC and CD group (P<0.05). No significant difference in the expression of MMP-7 was found between patients with different gender, age, and whether treated with anti-TNF-α agents (P>0.05). The expression of MMP-7 in colon tissue of patients with active IBD was positively correlated with CRP and WBC (P<0.001). Conclusions: The expression of MMP-7 is correlated with the activity and severity of IBD, but not correlated with gender, age, and whether treated with anti-TNF-α agents. To some extent, MMP-7 can indicate the severity of intestinal inflammation, and may be an important indicator of inflammatory activity in IBD.

Background: The prevalence of inflammatory bowel disease (IBD) is increasing worldwide, and anemia, one of the most prevalent extraintestinal manifestations of IBD, is still often underdiagnosed and undertreated. Aims: To analyze the correlations of clinical factors with anemia in patients with ulcerative colitis (UC). Methods: A retrospective analysis was conducted in 60 cases of UC admitted from September 2019 to May 2020 at the Second Affiliated Hospital of Zhengzhou University. Sixty healthy subjects were served as controls. Data of fasting venous blood sample analysis on admission were collected, and the correlations of indicators for anemia with the clinical factors were analyzed. Results: The indicators for anemia, including red blood cell (RBC) count, hemoglobin (Hb), hematocrit (HCT), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH) etc. were significantly decreased in UC patients than in healthy controls (all P<0.05). RBC was lower in females than in males (P<0.05); RBC and HCT were lower in patients with pancolitis than in those with proctitis or left hemi-colon colitis (all P<0.05); RBC, Hb and HCT were lower in severe active UC than in mild active UC (all P<0.05). RBC, Hb, HCT and MCH were negatively correlated with two disease activity indicators for IBD, C-reactive protein (CRP) and/or erythrocyte sedimentation rate (ESR) (all P<0.05). Conclusions: Gender, as well as the disease extent, activity and severity are important clinical factors for anemia in patients with UC.

Exosomes are extracellular vesicles with a diameter of 30-150 nm, which exist in multi-vesicular bodies in the form of intraluminal vesicles. Exosomes can be secreted by a variety of immune cells. Studies have shown that exosomes might play an important role in IBD through their components, such as annexin-A1 (ANXA1), the miRNAs and lipids. As a carrier of antigen presentation, it can affect the signaling pathways related to IBD, regulate the immune response and intestinal homeostasis. This article reviewed the relationship between exosomes and IBD.

MicroRNAs (miRNAs) are a group of short non-coding RNAs consisting of about 22 nucleotides that downregulate gene expression at posttranscriptional level through binding to the 3'-untranslated region (3'-UTR) of target mRNAs. With the increase in research about miRNAs, it is found that miRNAs could modulate the differentiation and secretion of immunocytes as well as the function of intestinal mucosal barrier. Besides, miRNAs could regulate the composition of intestinal microbiome, and could be used as crucial biomarkers for the diagnosis of inflammatory bowel disease (IBD). In this paper, the roles of miRNAs in the pathogenesis of IBD were reviewed through intestinal immunity and barrier function.