1.Advances in Studies on Serum Biomarkers and Susceptibility Genes in Differential Diagnosis of Inflammatory Bowel Disease
Yuan CAO ; Jinlu TONG ; Zhihua RAN
Chinese Journal of Gastroenterology 2014;(5):297-300
Inflammatory bowel disease (IBD)includes Crohn’s disease (CD)and ulcerative colitis (UC).The differential diagnosis between CD and UC mainly depends on clinical symptoms,endoscopy,pathological biopsy,laboratory and imaging examinations.In recent years,studies with a variety of IBD-related biomarkers develop rapidly because of its non-invasiveness,simple and easily acceptable.With the development of genome-wide association study (GWAS),great progress has been achieved in studies of gene mutations and susceptibility genes related with CD and UC,which provides new approach for diagnosis of the disease.This article reviewed the advances in studies on serum biomarkers and susceptibility genes in differential diagnosis of IBD.
2.Concordance of endoscopic grading and scoring systems for inflammatory bowel diseases
Jun SHEN ; Zhihua RAN ; Jinlu TONG ; Xiang CHEN ; Shudong XIAO
Chinese Journal of Digestive Endoscopy 2008;25(5):239-244
Objective To assess the agreement of different endoscopy grading or scoring systems for inflammatory bowel diseases(IBD)including ulcerative colitis(UC)and Crohn's disease(CD).Methods A standardized table was prepared based on the searches for endoscopic grading or scoring systems on Medline and Chinese Biomedical Database,the data of 80 patients with UC and 31 with CD.who underwent colonoscopy in Shanghai Renji hospital from June 2006 to February 2007,were evaluated with each system by two physicians independently.Data were analyzed with SPSS 13.0.Results Six endoscopic grading and scoring systems of UC and three of CD were included for evaluation.For the systems of UC and CD,Kendall's coefficients of concordance were 0.71(P<0.01)and 0.34(P<0.01),respectively.There was no significant differenee between every two systems for UC.Nonetheless.Spearman's correlation coefficient between Chinese Grading System of Crohn's Disease(CGSCD)and Crohn's Disease Endoscopic Index of Severity(CDEIS)was 0.32(P=0.08).Significant differences in frequencies were detected in endoscopic systems for UC by Kruskal Wallis test(P<0.01).Conclusion There is satisfactory concordance among the endoscopic grading and scoring systems of UC,while CGSCD needs further improvement.Furthermore,Jeroen elassifieation inclines to severe category,while modified Baron scale tends to be a mild one.
3.Establishment and Optimization of Culture Technique for Enteroids
Dongjuan SONG ; Jinlu TONG ; Zhihua RAN ; Qing ZHENG
Chinese Journal of Gastroenterology 2016;21(2):75-79
Background:Enteroids are considered to be the best tool for studies on intestinal epithelium in vitro and have a widely application prospects,however,there are no associated reports in China. Aims:To establish and optimize the culture technique for enteroids and provide a fantastic platform for the basic research of small intestinal epithelial cells in China. Methods:L-WRN cells were cultured routinely and the conditioned medium with different concentrations of fetal bovine serum(FBS)was collected. Six to eight weeks old C57BL/ 6 mice were sacrificed and 15 cm small intestine from the terminal ileum was removed and cut longitudinally. Crypts were digested with EDTA and then collected and embedded in Matrigel? Matrix;after polymerization of Matrigel? Matrix,L-WRN conditioned medium at different concentration gradient was added. The budding ratio and length of buds were measured dynamically under microscope. The enteroids were re-embedded for subculture when certain length of buds was reached. Results:Compared with L-WRN conditioned medium containing 20% FBS,the conditioned medium containing 10% FBS was more favorable for enteroids culture in vitro. When conditioned medium accounted for 10% ,15% ,20% ,25% or 30% of the mixed medium,they all promoted the growth of enteroids and the 15% one seemed to yield better result. Conclusions:An enteroids culture technique was successfully established for the first time in China. When the L-WRN conditioned medium containing 10% FBS accounts for 15% of the mixed medium,it might promote budding better than the others.
4.MicroRNA expression profiling in hydroxycamptothecin-resistant human colon cancer cell line by microarray
Jinlu TONG ; Zhihua RAN ; Xiang CHEN ; Xitao XU ; Fang NIE ; Shudong XIAO
Chinese Journal of Digestion 2008;28(4):246-249
Objective To explore the role of a novel regulatory molecule-microRNA in the hydroxycamptothecin-resistant human colon cancer cell line SW1116/HCPT in order to provide a new reversal target for muhidrug resistance.Methods MicroRNA expression profiling in the hydroxycamptothecin-resistant human colon cancer cell line SW1116/HCPT were detected by microRNA array using microRCURYTM LNA Array V8.1 to screen multi-drug resistance(MDR)-related microRNAs.Specific stem-loop primers were used for reverse-transcribing cDNA and the expression of some MDR-related microRNAs were analyzed by the real-time PCR.Results The absorbance ratios of total RNA used for total RNA preparation was further confirmed by denaturing agarose gel electrophoresis.Compared to SW1116,28 microRNAs were down-regulated and 36 microRNAs were up-regulated in SW1116/HCPT cell line.The expression of two down-regulated microRNAs(hsa-miR-452 and hsa-miR-373*)and one up-regulated microRNA(hsa-miR-506)were confirmed by real-time PCR.The results of hsa-miR-452 and hsa-miR-506 were consistent with microRNA array nalysis,however,the expression of hsa-miR-373* may play a key role in the process of hydroxycamptothecin-resistant human colon cancer cell line SW1116/HCPT.
5.Activation of CD40-CD154 co-stimulatory pathway and its correlation with disease activity in patients with inflammatory bowel disease
Jun SHEN ; Zhihua RAN ; Qing ZHENG ; Jinlu TONG ; Qing CAI ; Mingming ZHU ; Meilan HUANG ; Tianrong WANG
Chinese Journal of Digestive Endoscopy 2010;27(2):80-84
Objective To investigate the expression of CD40-CD154 co-stimulatory pathway in peripheral circulation and intestinal mucosa in patients with inflammatory bowel disease (IBD),the difference between the expression of CD40-CD154 in patients with IBD and that in healthy controls,and the correlation between CD40-CD154 levels and disease activity. Methods A total of 62 patients with Crohn's disease (CD),64 patients with ulcerative colitis (UC) and 56 healthy controls were enrolled. Enzyme-Linked Immuno Sorbent Assay (ELISA),SYBR-green real time PCR and immunohistochemical assay were respectively applied to evaluate expression of CD40-CD154 in plasma,mononuclear cells of peripheral blood and intestinal mucosa. Results Levels of CD40 (P=0. 000) and CD154 (P=0. 001) in plasma,mononuclear cells of peripheral blood and intestinal mucosa were significantly higher in patients with CD and UC than in healthy controls. However,no correlation between disease activity and CD40-CD154 expression in peripheral circulation or intestinal mucosa was detected (P > 0. 05 ). Conclusion CD40-CD154 pathway activation is found in plasma,peripheral blood mononuclear cells and intestinal mucosa in patients with IBD,but is not correlated with disease activity.
6.Study on activation of CD27-CD70 co-stimulatory pathway in patients with inflammatory bowel disease
Zhihua RAN ; Jun SHEN ; Qing ZHENG ; Fang NIE ; Jinlu TONG ; Xiaoxian QIAN ; Qing CAI ; Feng ZHANG ; Meilan HUANG ; Tianrong WANG ; Shudong XIAO
Chinese Journal of Digestion 2009;29(12):803-807
Objective To investigate the expression of CD27-CD70 co-stimulatory pathway in peripheral circulation and intestinal mucosa of patients with inflammatory bowel disease, and to find the difference between the expression of CD27-CD70 in patients with inflammatory bowel disease and in healthy controls. Methods A total of 62 patients with Crohn's disease, 64 patients with ulcerative colitis and 56 healthy controls were enrolled. Enzyme-linked immunosorbent assay was applied to evaluate plasma CD27-CD70 protein expression in patients with inflammatory bowel disease and healthy controls. SYBR-green real time PCR was applied to access CD27-CD70 mRNA expression in peripheral blood mononuclear cells in patients with inflammatory bowel disease and healthy controls.And CD27-CD70 protein expression in intestinal mucosa was determined by immunohitochemistry.Results Plasma levels of CD27 (P=0. 025) and CD70 (P=0. 000) were significantly higher in patients with Crohn's disease than in healthy controls. However, CD27 (r= 0. 055, P= 0. 673) and CD70 (r= 0. 024, P = 0. 852) were not significantly associated with endoscopic disease activity in patients with Crohn's disease. Similarly, CD27 (P=0. 001) and CD70 (P=0. 000) were significantly higher in patients with ulcerative colitis than in healthy controls. And CD27 (r=0. 077, P=0. 547)and CDT0 (r=0.021, P=0. 869) were not significantly associated with endoscopic disease activity in patients with ulcerative colitis. Moreover, CD27 and CD70 mRNA expression in peripheral blood mononuclear cells were significantly higher in patients with Crohn's disease and ulcerative colitis than in healthy controls (all P=0. 000), and immunostaining indicated that CD27 and CD70 expression in intestinal mucosa were significantly higher in patients with Crohn's disease and ulcerative colitis than in healthy controls (all P=0. 000). Conclusions CD27-CD70 pathway activated in plasma, peripheral blood mononuclear cells and intestinal mucosa of patients with inflammatory bowel disease. However,plasma levels of CD27 and CD70 can not reflect endoscopic disease activity.
7. Construction and application of inflammatory bowel disease cohort database
Xiaoping WU ; Tao ZHENG ; Jingyuan FANG ; Jinlu TONG ; Zhijun CAO ; Yuqi QIAO
Chinese Journal of Gastroenterology 2023;28(4):237-242
Under the organization of Renji Hospital, Shanghai Jiao Tong University School of Medicine, a specialized disease database of inflammatory bowel disease (IBD) cohort was deployed, and a brief introduction of the database was made in this article. The IBD data set was established by referring to domestic and foreign standards. Through data extraction, cleaning, normalization and other information processing technologies, data from multi‑source heterogeneous platform were arranged to form a specialized major disease database of IBD cohort and the efficiency and quality of data collection in clinical practice, teaching and scientific research were guaranteed. The display and personalized export capacities of the database can promote the researches on IBD and assist the clinical decision‑making. It provides not only efficient, comprehensive and reliable research‑level data support for scientific research, but also a precise guidance for diagnosis and treatment of the disease. Furthermore, it can excavate the potential clinical principles based on medical big data.
8.Drug therapy and monitoring for inflammatory bowel disease: a multinational questionnaire investigation in Asia
Chenwen CAI ; Juntao LU ; Lijie LAI ; Dongjuan SONG ; Jun SHEN ; Jinlu TONG ; Qing ZHENG ; Kaichun WU ; Jiaming QIAN ; Zhihua RAN
Intestinal Research 2022;20(2):213-223
Background/Aims:
The incidence and prevalence of inflammatory bowel disease (IBD) is rising in Asia recently. The study aimed to obtain a comprehensive understanding of the current status of drug therapy and monitoring for IBD in Asia.
Methods:
A questionnaire investigation on drug therapy and monitoring for IBD was conducted right before the 6th Annual Meeting of Asian Organization for Crohn’s & Colitis. Questionnaires were provided to Asian physicians to fill out via emails between March and May 2018.
Results:
In total, responses of 166 physicians from 129 medical centers were included for analysis. Among the surveyed regions, the most average number of IBD specialist gastroenterologists and nurses was 4.8 per center in Taiwan and 2.5 per center in Mainland China, respectively. 5-Aminosalicylic acid/sulfasalazine (99.4%) was the most preferred first-line choice for mild-moderate ulcerative colitis (UC), meanwhile corticosteroid (83.7%) was widely applied for severe UC. The first-line medication for Crohn’s disease (CD) markedly varied as corticosteroid (68.1%) was the most favored in Mainland China, Japan, and South Korea, followed by infliximab (52.4%) and azathioprine (47.0%). Step-up strategy was preferred in mild-moderate UC (96.4%), while 51.8% of the physicians selected top-down treatment for CD. Only 25.9% and 17.5% of the physicians could test blood concentration of infliximab and antibody to infliximab in their hospitals, respectively.
Conclusions
The current status of drug therapy and monitoring for IBD in Asia possesses commonalities as well as differences. Asian recommendations, IBD specialist teams and practice of therapeutic drug monitoring are required to improve IBD management in Asia.
9. Risk Factors for Relapse of Perianal Fistulizing Crohn's Disease After Discontinuation of Infliximab Therapy
Xitao XU ; Juntao LU ; Mingming ZHU ; Tianrong WANG ; Zhanghan DAI ; Jinlu TONG ; Zhihua RAN
Chinese Journal of Gastroenterology 2021;26(9):513-518
Background: Some of the active perianal fistulizing Crohn's disease (CD) patients achieving remission with infliximab (IFX) therapy would develop relapse of perianal fistula within weeks to years after discontinuation of IFX therapy. Aims: To assess the outcomes of patients with perianal fistulizing CD after discontinuation of IFX therapy and the risk factors for relapse of perianal fistula. Methods: The clinical data of patients with perianal fistulizing CD who received IFX therapy at Shanghai Renji Hospital between June 2013 and May 2019 and stopped IFX therapy after achieving complete or partial radiological remission were collected retrospectively and analyzed. Demographic data, clinical and imaging characteristics, as well as data of IFX treatment and relapse of perianal fistula were extracted. Kaplan-Meier analysis was performed to calculate the cumulative probabilities of perianal and luminal relapse, while Cox proportional hazards model was applied to identify the risk factors for relapse. Results: A total of 56 perianal fistulizing CD patients who had been treated with IFX and stopped IFX therapy were included. Of them 26 achieved complete radiological remission and 30 achieved partial radiological remission. The median follow-up time was 20.5 months. Twenty-one patients (37.5%) had relapse of perianal fistula. The cumulative probabilities of perianal relapse were 29.0%, 33.7% and 42.8% at 12, 24 and 60 months after IFX discontinuation, respectively; and the cumulative probabilities of luminal relapse were 21.7%, 31.2% and 56.4% at 12, 24 and 60 months after IFX discontinuation, respectively. Multivariate analysis showed that non-stricturing and non-penetrating type (HR=9.711, 95% CI: 1.210-77.939, P=0.032) and involvement of rectum (HR=3.034, 95% CI: 1.119-8.231, P=0.029) were independent risk factors for relapse of perianal fistula, while the frequency of using of IFX therapy was a protective factor (HR=0.885, 95% CI: 0.792-0.990, P=0.032). Conclusions: There is a high risk of relapse of perianal fistulizing CD after discontinuation of IFX therapy. Non-stricturing and non-penetrating type and rectal involvement are risk factors for relapse of perianal fistula, and increasing the frequencies of using IFX therapy is crucial for the maintenance of remission.