Shanghai Institute of Digestive Disease (SIDD) was founded in 1984. Since then SIDD has developed arduously and extensively by conforming to the motto of "Austerity, Practicality, Unity and Creativity", and has become one of the top research institutes in China. SIDD has more than 100 staff members, including 10 professors and 16 associated professors. Professor Jiang Shaoji (Academician, Chinese Academy of Engineering), a distinguished hepato-gastroenterologist, was the first director of SIDD. Currently, Professor Xiao Shudong serves as honorary director, and Professor Fang Jingyuan as director.
At SIDD, there are two research divisions, Gastroenterology and Hepatology, and several laboratories working on molecular pathology, cell biology, molecular biology, biochemistry, immunology, gut hormones, gastrointerstinal physiology, pharmacology, microbiology (Parvovirus H-1 and H.pylori) and flow cytometry. The endoscopy center was established this year.
The research interest mainly focuses on chronic gastric disease and chronic liver disease. About 50 grants were gained and 30 prizes of science and technology were awarded by the State, the Ministry of Public Health and/or the Shanghai Municipality in the past ten years. More than 400 papers and 20 books were published in English and Chinese. Over 100 students who studied for Ph.D. or master's degree have completed their training courses and research programs.
SIDD has academic contacts with many universities and institutes in USA, Japan, Australia, Netherlands, France, German and Norway. Six international conferences on gastroenterology were successfully organized by SIDD in 1988, 1992, 1996, 2000, 2005 and 2009.
Professor Fang Jingyuan, M.D, Ph.D.
Professor Qiu Dekai, M.D, Ph.D.
Professor Xiao Shudong
Professor Zeng Minde
Professor Qiu Dekai
Professor Liu Wenzhong
Professor Ge Zhizheng
Professor Ran Zhihua
Professor Wu Shuming
Professor Ma Xiong
The research program demonstrated that: 1) High dose folic acid prevented the gastric carcinogenesis induced by ENNG in beagles. Folic acid can treat chronic atrphic gastritis and prevent gastric carcinogenesis, which is related to maintaining the DNA methylation. 2) Abnormalities in the DNA methylation and histone acetylation are involved in the tumorigenesis and development of gastric and colorectal carcinoma. 3) JAK/STAT3/STAT5 are implicated in colorectal cancer cells growth, cell cycle regulation and invasion. 5-aza-dc suppresses growth of CRC cells, and induces G2 cell cycle arrest and apoptosis through regulation of downstream targets of JAK2/STAT3/STAT5 signaling. 4) We found mTOR signaling components, including mTOR, p70s6 K, and 4EBP1 are important factors involved in colorectal tumorigenesis. 5) A new class of regulatory RNA, microRNAs (miRNAs) have been found deregulated in human colorectal cancer, and some of them may function as tumor suppressor genes. We found mir-345 is a novel methylation-sensitive miRNA in CRC. The methylation-mediated downregulation of mir-345 may be involved in CRC pathogenesis through its targets.
Over the past years, in this field we have made several prize-winning achievements including the second prize of National Science and Technology Progress Award in 2008, the first prize of the Chinese Medical Sciences and Technology Award in 2007 and the first prize of Shanghai Science and Technology Progress Award and the second prize of Science and Technology Progress Award from National Ministry of Education in 2005. And treatment of chronic atrophic gastritis with folic acid has been broadly used by a lot of hospitals nationwide.
As one of the biggest institute studies on helicobacter pylori, we started to culture the bacterium in the early 1990s. The work of our study group involves helicobacter pylori's virulent factors and pathogenesis, its diagnosis, treatment and clinical perspectives. We are the first in the world to uncover that: 1) One-week regimens containing furazolidone are well tolerated and effective for the eradication of Hp. 2) The prevalence of cagA-positive Hp populations in Chinese patients is almost universally high. CagA cannot be used as a marker for the presence of PUD in Chinese patients, which is quite different from Western Europe. 3) CpG-ODN given intranasally is a potent adjuvant for development of a Hp vaccine. Th1-type response and IFN-gamma are involved in the protection. 4) DupA is a novel marker associated with an increased risk for DU and reduced risk for gastric atrophy and cancer. Different pathways by the cag PAI and OipA lead to the IL-8 and IL-6 induction. During the last 30 years, we have published many papers about Hp in journals of Gastroenterology, JBC, MBC, Helicobacter, APT and Cancer. Grants on Hp study including four from National Natural Science Foundation of China were awarded to Prof. Xiao Shudong, Prof. Liu Wenzhong and Dr. Lu Hong. We have a patent regarding development of diagnostic tests（Rapid Urease Test）for Helicobacter pylori infection. Our group won the second prize of National Science and Technology Progress Award in 1998, the second prize of Shanghai Science and Technology Progress Award in 2003 and the second prize of Science and Technology Progress Award from National Ministry of Education in 2001.
① Noninvasive Daignossis of Liver Fibrosis. A model was constructed consisting of clinical and serum variables to discriminate between hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) patients with and without significant fibrosis (stages 2-4 vs. stages 0-1). Multivariate analysis identified a2-macroglobulin, age, gamma glutamyl transpeptidase, and hyaluronic acid as independent predictors of fibrosis. The area under the receiver operating characteristic curve was 0.84 for the training group and 0.77 for the validation group. Therefore, the predictive model with a combination of easily accessible variables identified HBeAg-positive CHB patients with and without significant fibrosis with a high degree of accuracy. Application of this model may decrease the need for liver biopsy in staging of 35.5% CHB. (Zeng Minde, et. al. HEPATOLOGY 2005)
② Antiviral Therapy of Chronic Hepatitis B. Four hundred and eighty Chinese subjects with hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) were enrolled in a multicenter, double-blind, randomized, placebo-controlled study of adefovir dipivoxil (ADV) 10 mg once daily. Treatment with ADV 10mg daily over 52 weeks was safe and effective in Chinese subjects with HBeAg-positive CHB and did not lead to the emergence of drug resistance. The study is continuing for an additional 4 years with all subjects on open-label ADV 10 mg daily. (Zeng Minde, et al. Hepatology 2006)
③ The pathogenesis of Nonalcoholic Steatohepatitits. In nonalcoholic fatty liver disease, the pathogenesis of progression from simple steatosis to steatohepatitis has not been fully clarified. HF-induced steatosis was associated with the depletion of hepatic Regualtory T cells (Tregs) and led to up-regulation of the inflammatory tumor necrosis factor-a signaling pathway. When challenged by exogenous lipopolysaccharide, the HF-fed mice developed liver inflammation. In contrast, the adoptive transfer of Tregs decreased inflammation in HF-fed mice. Our results indicate that increased oxidative stress in a fatty liver causes the apoptosis of Tregs, reduces the number of hepatic Tregs, and leads to a lowered suppression of inflammatory responses. This scenario is likely to be one of the pathogenetic mechanisms that facilitate the transformation of simple steatosis into steatohepatitis when a fatty liver is exposed to second or third hits. (Ma Xiong, et al. Hapatology 2007)
We also showed that probiotics improve high fat diet-induced steatosis and insulin resistance. These effects of probiotics are likely due to increased hepatic NKT cell numbers and reduced inflammatory signaling. (Ma Xiong, et al. Journal of Hepatology 2008)
④ The Diagnosis and Management of Autoimmune Liver Diseases. International Autoimmune Hepatitis Group (IAIHG) revised the diagnostic criteria of autoimmune hepatitis (AIH) in 1999, and developed the simplified criteria in 2008 to enhance its clinical applicability. We validated two diagnostic criteria in Chinese patients with diverse liver diseases in 405 patients with diverse liver diseases. Our results suggest that the simplified criteria have high sensitivity and specificity for diagnosis of AIH in Chinese patients. Liver histology is critical for the diagnosis of AIH especially when using the simplified criteria. Further study or prospective evaluation is needed to confirm these observations, due to the small group of CHC and no PSC patient in our study. (Qiu Dekai, Ma Xiong, et al. Journal of Hepatology, In press)
SIDD had academic contacts with Johns Hopkins University Hospital in 2004. Since then, the fifth and sixth Shanghai International Conferences of Gastroenterology were organized by both our institute and Johns Hopkins University Hospital. In addition, both departments collaborated to sponsor "the Winning Concepts of Gastroenterology and Hepatology: the view of international experts". There is a researcher exchange program in the field of endoscopy and liver disease between the two departments.
Three members in our institute were graduated from the joint PhD program. And there is a cooperation relationship in the field of Hp and its related diseases.
Two scholars in our institute have been to the University of Michigan and co-published several papers with researchers in UM. Now we have established scientific collaboration with Professor Zou Weiping, a famous tumor immunologist in Cancer Center.