Objective To investigate the role of tumor necrosis factor -?(TNF-?)in the pathogenesis of experimental murine colitis.Methods From Apr.1999 to May 2002,in the First Affiliated Hospital of Zhengzhou University,an experimental colitis model was established in which chronic colitis was induced by transfer of syngeneic CD45RB,CD~+_4T cells into severe combined immunodeficient(SCID)mice.These SCID recipients were treated with anti-TNF-? mAb,and the efficacy was observed and the mechanism was studied.Results Anti-TNF-? effectively prevented intestinal mucosal inflammation.Anti-TNF-? mAb also significantly suppressed leukocyte infiltration(e.g,CD~+_4 T cells,mononuclear macrophages)in the inflamed colon,and down-regulated production of proinflammatory cytokines interferon(IFN-?)and IL-2 of CD~+_4T cells in lamina propria.Conclusion The data suggests that administration of anti-TNF-? reverses mucosal inflammation via down-regulation of proinflammatory cytokines and decreases leukocyte infiltration in the bowel,thus providing additional support for TNF-?-targeted therapy in human Crohn's disease.

Objective To detect the expression of IL-23 receptor in T lymphocytes and NK cells in peripheral blood mononuclears(PBMC)from patients with inflammatory bowel disease(IBD)as well as its significance in the pathogenesis.Methods PBMC,isolated from 30 patients with UC,16 patients with CD and 30 healthy controls,were used to determine the expression of IL-23 receptor in T lymphocytes and NK cells by flow cytometry.The surface of lymphocytes was determined by three-colour flow cytometry in inflammatory bowel disease patients,and the results were compared with those of normal peripheral blood.Results The expression of IL-23R on peripheral CD4+ T,CD8+ T and CD56+ NK cells of patients was obviously higher than that in the control group.Conclusion The expression of IL-23R on T lymphocytes and NK cells of patients with IBD was increased,suggesting that IL-23 receptor plays an important role in the pathogenesis of IBD.

ObjectiveTo explore the therapeutic effects and value of endoscopic variceal ligation and tissue glue injection therapy in esophageal and gastric fundal varices.Methods184 patients with severe esophageal varices underwent endoscopic variceal ligation treatment,and 32 cases of those accompanied with gastric fundal varices were treated with tissue glue injection therapy.All patients were followed-up for 6-months to observe the therapeutic effects and complication of endoscopic variceal ligation and tissue glue injection therapy.ResultsThe effective rate of endoscopic variceal ligation in severe esophageal varices was 71.74 ％ ( 132/184 ),the rate of acute hemostasis was 95.00％(57/60)and the rate of complication was 2.17 ％ (4/184).The effective rate of tissue glue injection in gastric fundal varices was 100％ (32/32) and the rate of complication was 21.88％ (7/32) (7 cases with refractory ulcers in injection site,2 of refractory ulcers cases with bleeding).There was no perforation and severe infection complications.ConclusionEndoscopic variceal ligation and tissue glue injection therapy have good therapeutic effects in esophageal and gastric fundal varices.

Objective To investigate the impacts of S-ademetionine (SAM) on cell cycles,apoptosis and invasive capacity of gastric cancer cell lines,and its effects on methylation and expressions of c-myc and uPA.Methods MKN-28,SGC-7901 and MKN-45 cells were treated with gradient concentrations of SAM(0,2 and 4 mmol/L) for 72 hours.The changes of cell cycles and apoptosis were detected by flow eytometry,and invasion was detected by transwell assay.The expressions and methylations of c-myc and uPA were examined by RT-PCR and MSP,respectively.Results The cell apoptosis significantly increased and cell invasive capacity was restrained in three cell lines with increase of SAM concentration (all P values<0.01).In SGC-7901,the cell percentage of G0/G1 phase significantly increased [(74.53±2.49)% vs.(56.67±1.18)%,P<0.053,whereas the cell proliferation index (PI) decreased [(25.50±2.46)% vs.(43.33±1.18)%,P<0.05] in comparison with controls.The expressions of c-myc and uPA mRNA in SGC-7901,uPA mRNA in MKN-45 and in 4 mmol/L SAM treated MKN-28 significantly decreased.The methylations of c-myc gene in SGC-7901 and uPA gene in three cell lines were reversed after treated with SAM.Conclusions SAM reduces expressions of c-myc and uPA by reversing the methylations of c-myc in SGC-7901 and uPA in all three cell lines.However SAM,as methyl donor,can restrain the development and progression of tumor when hypomethylation widely presents in cancer.

Objective To evaluate the diagnosis and application values of endoscopic ultrasonography (EUS) with micro-probe in duodenal lesions.Methods Clinical data of 37 patients with duodenal lesions and underwent EUS with micro-probe were analyzed retrospectively.All lesions were treated with endoscopic mucosal resection or surgical resection to get the pathological diagnosis.The diagnostic accuracy of EUS with microprobe and endoscopic biopsy was analyzed respectively.Results The overall diagnosis accuracy of EUS with micro-probe on duodenal lesions was 78.38％ (29/37),with a higher diagnostic rate in duodenal lipoma 4/4and duodenal adenomas 10/12 than in early duodenal cancer 2/4 or inflammatory hyperplasia 3/8.The overall diagnostic accuracy of biopsy on duodenal lesions was 40.54％ (15/37),with a higher diagnosis rate on duodenal carcinoid 1/1 and adenoma 7/12 than on duodenal stromal tumor 1/10 and lipoma 1/4.Conclusion Pathological evaluation of endoscopic biopsy sample is not a golden standard for the diagnosis of duodenal lesions,while EUS with micro-probe has better diagnostic and application value.

Objective To investigate the role of bacterial flagellin and CD98 in ulcerative colitis (UC).Methods A total of 60 first episode patients with active UC were recruited,including 30 mild and 30 moderate to severe UC cases.The serum of 30 healthy volunteers and normal intestinal tissues surgically removed from 15 colon cancer patients (more than 5 cm away from surgical margins) were collected as control.The content of bacterial flagellin antibodies in peripheral blood were measured with enzyme-linked immunosorbent assay (ELISA).The expression of CD98 in peripheral blood T lymphocyte was measured by flow cytometry (FACS).The expression of bacterial flagellin protein in intestinal mucosa and CD98 in intestinal epithelial basement membrane was tested by immunohistochemistry (IHC).The comparison between two groups was performed with the SNK-q method,the R×C table x2 test was used to analyze the counted data,and the Spearman correlation was used to analyze the rank materials.Results The peripheral blood concentration of bacteria flagella protein antibody of control group,mild UC group and moderate to severe group showed an upward trend,which was (7.603±2.118) pg/ml,(13.702±3.131) pg/ml and (20.813±3.004) pg/ml respectively,and the differences among groups were statistically significant (F=13.57,P＜0.01).The expression percentage of bacteria flagella protein in intestinal mucosa of the three groups also showed an upward trend,which was 3/15,56.67％ and 73.33％ respectively,and the differences among groups were statistically significant (x2 =11.553,P=0.003).The positive rate of CD98 expression in peripheral blood T lymphocytes of the three groups showed an upward trend,which was (28.42±4.31)％,(32.45±6.71)％ and (43.40±5.09) ％ respectively,and the differences among groups were statistically significant (x2 =10.110,P=0.007).The positive rate of CD98 expression in intestinal epithelial cells of the three groups also showed an upward trend,which was 1/15,36.67 ％ and 66.67％ respectively,and the differences among groups were statistically significant (x2 =5.400,P＜0.05).There was positive correlation between the peripheral blood concentration of bacteria flagella protein antibody and the expression of CD98 in peripheral blood T lymphocytes (r=0.548,P＜0.05).Conclusion Bacterial flagellin and CD98 may be important factors causing inflammatory reaction activity in UC.

Inflammatory bowel disease (IBD)is an autoimmune disease leading to diarrhea,abdominal pain,and weight loss. The pathogenesis of diarrhea remains unclear,however,increasing evidence has shown that the epithelial sodium channel (ENaC)is associated with diarrhea. ENaC is crucial in the control of sodium homeostasis,extracellular fluid volume,blood pressure. This article reviewed advances in study on relationship between ENaC and IBD.

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.

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 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.