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    28 September 2012, Volume 32 Issue 9 Previous Issue    Next Issue

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    Research progression on biologic function and effect of SUMO-specific proteinase
    CHENG Jin-ke, ZUO Yong
    2012, 32 (9):  1117. 
    doi: 10.3969/j.issn.1674-8115.2012.09.001

    Abstract ( 1866 )   PDF (352KB) ( 1433 )  

    SUMO, an ubiquitin-like protein, can covalently conjugate proteins and plays a role in the regulation of target protein functions and localizations. Similar to ubiquitin, SUMO modification is a dynamic process catalyzed by E1, E2, and E3 and reversed by Sentrin/SUMO-specific proteases (SENPs). To date, 6 SENP members have been defined in human cells, each of which has different cell localization and target specificity. However, the physiologic functions of SENPs are not fully understood. By analysis of SENPs knock-out mice, we find that SENP1 regulates hypoxia-HIF1α signaling or androgen receptor (AR) signaling through positive feedback loop, and plays an important role in HIF1α or AR-involved physiologic and pathologic processes. We also find that SENP2 is essential for suppression of polycomb group protein-mediated gene silencing during heart development. These results reveal the critical roles of SENPs in the regulation of targets-involved signaling.

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    Study on the mechanisms underlying that reactive oxygen species regulate post-translational modification of the proteins and affect the behaviors of cancer cells
    YI Jing, YANG Jie
    2012, 32 (9):  1122. 
    doi: 10.3969/j.issn.1674-8115.2012.09.002

    Abstract ( 1810 )   PDF (402KB) ( 1356 )  

    Reactive oxygen species (ROS) mainly comprised of super oxide, hydrogen peroxide and hydroxyl free radicals, are the side products of cell metabolism. The level of ROS brings complex impacts on cell fate, leading to complex impacts on the occurrence and progression of the oxidative stress-related human diseases such as cancer, diabetes, and neurodegeneration, but the underlying mechanism remain to be clarified. Our research group aimed in elucidating the mechanisms how different levels of ROS affect the biological events and the fate of cells, i.e. the regulatory role of ROS in signaling determining cell proliferation, differentiation and apoptosis. We specifically focus on the signaling role of ROS-regulated post-translational modifications of proteins, e.g. oxidation, ubiquitination and SUMOylation, and their links to formation, progression and remedy of cancers. Our major findings are: ①The sensitivity of cancer cells to arsenic trioxide, cisplatin and doxorubicin and other apoptosis-inducing drugs is positively correlated to the inherent cellular level of ROS. The increase of ROS level by using emodin and some other compounds, or enforced expression of Nox to cause severe oxidative stress can sensitize the apoptotic susceptibility of leukemic cells and solid tumor cells. The underlying mechanisms involve in an inhibition of RhoA, HIF-1, NF-κB and other pro-survival signaling pathways, and simultaneously an activation of caspase 9 by ROS. ②The mild oxidative stress existed in cancer cells promotes cancer genesis and progression, which may be via an induction of SENP3 to regulate the profiles of protein SUMOylation and gene expression. We ascertained for the first time that SUMO protease SENP3 is a redox sensing protein. Being induced by ROS, it is rapidly accumulated and thus regulates the sUMOylation status of a number of substrates in the nucleus, such as p300, PML and p53, leading to an adaptation of cancer cells to stressful environment and the more malignant phenotypes including survival, proliferation, angiogenesis and so on. Under this research direction we have dozens of paper published on the international journals and dozen of projects funded by NCSF. The academic achievement in this study is awarded by The Second Place Prize of The Education Ministry for Natural Science at 2011.

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    Autoimmune diseases: immuno-pathogenic dissection and strategy exploration for immune intervention
    SHEN Hao, WANG Ying, WANG Jia-qi, et al
    2012, 32 (9):  1128. 
    doi: 10.3969/j.issn.1674-8115.2012.09.003

    Abstract ( 1614 )   PDF (458KB) ( 1130 )  

    Autoimmune diseases arise from inappropriate immune responses against molecules and organs normally present in the body, resulting in tissue damage and functional defects. Supported by “211 Project”, the research groups from Shanghai Institute of Immunology and Shanghai Institute of Rheumatology have been working cooperatively to explore the immuno-regulation and immuno-pathogenesis of important autoimmune disorders including systemic lupus erythematosus (SLE), rheumatoid arthritis (RA) and psoriasis (PS), in which facilitate the diagnosis and intervention of the diseases. One of the research achievements, the pathogenesis of SLE and its novel therapeutic strategy, was awarded the second prize of 2009 National Science and Technology Progress Award.

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    Progress on the genomics and proteomics of Leptospira interrogans
    GUO Xiao-kui, QIN Jin-hong, HE Ping, et al
    2012, 32 (9):  1135. 
    doi: 10.3969/j.issn.1674-8115.2012.09.004

    Abstract ( 1223 )   PDF (431KB) ( 1184 )  

    Leptospirosis is a globally important zoonosis which affects people life and health. Our research group sequenced a representative virulent serovar type strain 56601 of Leptospira interrogans serogroup Icterohaemorrhagiae in 2003. The result revealed that Leptospira contains two chromosomes which encoded 4 727 genes. After that, we rectify and reannotate its genome to encode 3 718 genes. In 2010, the virulence-attenuated Leptospira interrogans serovar Lai strain IPAV was sequenced based on the reference sequence of strain 56601. Aside from their highly similar genomic structure and gene order, a total of 101 mutant genes were detected throughout the genome of IPAV. Using DNA microarray of Leptospira, the comparative genomic and genome-wide transcriptional analysis were conducted.  Among the 11 strains tested, the common backbone of the L.interrogans genome was estimated to contain about 2 917 protein-coding sequences (CDSs), while 275 CDSs were found absent from at least one strain. Moreover, two genomic islands (GIs) were firstly reported in strain 56601. Mimic the temperature that Leptospira encountered during infection of a host from an environmental source, expression of 106 genes differed significantly according to temperatures change. The differentially expressed genes belonged to nine functional categories. Through the differential gene expression between Leptospira interrogans serovar Lai type strain 56601 and its corresponding attenuated strain IPAV, a 22-kb genomic island covering a cluster of 34 genes (i.e., genes LA0186 to LA0219) was included, which was further confirmed to be a defect prophage. Combining computational prediction and high-accuracy tandem mass spectra, 2 540 proteins were detected. Subsequently, multiple posttranslational modifications (PTMs) of L.interrogans serovar Lai strain 56601 were detected, containing in total 32 phosphorylated, 46 acetylated and 155 methylated proteins. The PTM systems in the serovar Lai show unique features which were eukaryotic-like. Comparative proteomic analysis between 56601 and IPAV strain revealed 1 627 pairs of orthologs, 174 genes in the IPAV strain were upregulated and 228 genes in strain 56601 were upregulated.Based on the genomic and proteomic studies, some genes were selected to be further studied  to confirm their potential function on pathogenesis, vaccine and diagnosis.

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    Pathogenesis of Mycobacterium tuberculosis and novel tools for diagnosis of tuberculosis
    YAO Yu-feng, ZHANG Shu-lin
    2012, 32 (9):  1141. 
    doi: 10.3969/j.issn.1674-8115.2012.09.005

    Abstract ( 1918 )   PDF (240KB) ( 1376 )  

    Mycobacterium tuberculosis (Mtb) has been a serious threat to human health globally. However, the diagnosis, therapy, prevention and increasing drug resistance remain to be major problems for tuberculosis control in China. Our group focused on the genome microevolution and pathogenesis of Mtb and the development of novel rapid diagnosis for tuberculosis and Mtb drug susceptibility test. So far, we have made some significant progress in the Mtb virulence evolution and tuberculosis clinical applications.

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    Chemical biology study for differentiation and apoptosis of leukemic cell
    CHEN Guo-qiang, ZHAO Qian, WU Ying-li, et al
    2012, 32 (9):  1145. 
    doi: 10.3969/j.issn.1674-8115.2012.09.006

    Abstract ( 1840 )   PDF (702KB) ( 1183 )  

    Chemical biology is a scientific interdiscipline spanning the fields of chemistry and biology that involves the application of chemical tools, often compounds, to the study and manipulation of biological systems. Remarkable achievements have been obtained on chemical biology which aims to study important biological events by using small molecular active compounds as a probe thus small active compound has become effective tools in the research of biomedicine. Our research group has achieved a series of results in the molecular mechanism study of leukemic cell differentiation and apoptosis through using small molecular active compounds. We discovered that adenanthin, a diterpenoid compound extracted from Rabdosia adenantha, induces APL-like cell differentiation, represses tumor growth in vivo and prolongs the survival of mouse APL models that are sensitive and resistant to retinoic acid. The chemical probe biotin-tagged adenanthin was designed on the basis of structure-activity relationship data. Further study demonstrated adenanthin directly targets the conserved resolving cysteines of PrxⅠ and Prx Ⅱ and inhibits their peroxidase activities. Consequently, cellular H2O2 is elevated, leading to the activation of extracellular signal regulated kinases and increased transcription of C/EBPβ, which contributes to adenanthin-induced differentiation. In another study we identified a novel natural ent-kaurene diterpenoid derived from I. pharicus leaves called pharicin B that can rapidly stabilize RARα as well as PML-RARα protein and enhances ATRA-dependent transcriptional activity of RARα. Additionally, pharicin B enhances differentiation-enhancing effect of ATRA in AML cell lines, some primary leukemic cells and overcomes retinoid resistance in ATRA-resistant subclones. The effectiveness of the ATRA/pharicin B combination warrants further investigation on their use as a therapeutic strategy for AML patients.Based on our previous study that NSC606985, a novel camptothecin analog, could effectively induce apoptosis in AML cells in a time- and concentration-dependent manner, sequentially through proteolytic activation of protein kinase Cδ (PKCδ), loss of mitochondrial Δψm and caspase-3 activation, we further employed NSC606985 as a molecule probe and systemically investigated the mechanisms of apoptotic induction in AML cells and the prospects of its clinical application in vitro and in vivo. We analyzed protein expression profiles of NSC606985-induced apoptotic AML cells by systematically using phosphoproteomics, quantitive proteomics as well as subcellular proteomics analytical strategy. As a result, we uncovered a series of deregulated proteins including translocated ones during apoptosis, most of which had not been reported previously. Among these apoptotic proteins we identified, the function of ANP32B as well as NDRG1 and their relationship with NSC606985-triggered AML cell apoptosis were further investigated respectively. Moreover, the in vivo study demonstrated that NSC606985 rapidly induced apoptosis of leukemic cells in peripheral blood, bone marrow, liver and spleen, and administration of NSC606985 significantly prolonged the survival of AML mice. The above results provide new leading compound for the acute leukemia therapy. The study of "New Mechanism for Differentiation and Apoptosis of Leukemic cell" wins the National Awards of Natural Sciences (Second prize) in 2010.

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    Progression of targeted therapy of anion exchanger 1 for gastric cancer
    FU Guo-hui, WANG Ting, SUO Wen-Hao
    2012, 32 (9):  1155. 
    doi: 10.3969/j.issn.1674-8115.2012.09.007

    Abstract ( 1103 )   PDF (419KB) ( 1174 )  

    Gastric cancer is the second leading cause of cancer-related death in China. Gastric adenocarcinoma comprises 95% of the total number of gastric malignancies which is often insensitive to chemo- and radiation therapy, and the 5-year survival rate of patients is only 15%-20%. Therefore, majority of studies have focused on early diagnosis and targeted therapy of gastric cancer. Our studies have found that human anion exchanger 1 (AE1), an erythrocyte membrane protein, is unexpectedly expressed in the gastric cancer with 83% frequency. Failure in negative feedback regulation between p65 and miR-24 is involved in aberrant expression of AE1. AE1 is accumulated in cytoplasm because the gastric epithelial cells do not have the ability for AE1 membrane trafficking. The cytoplasmic AE1 takes part in the gastric carcinogenesis through several signal pathways which communicate with each other: ①AE1 interacts with the tumor suppressor p16 and sequesters it in the cytoplasm, which leads to loss of negative cell cycle regulation. ②AE1 interrupts AE2 to traffick to the plasma membrane, resulting in intracellular alkalization and activation of Wnt/β-catenin pathway in gastric epithelium. The results have been included in Atlas of Genetics and Cytogenetics in Oncology and Haematology. Based on the premise that AE1 is a useful biomarker for gastric cancer, the AE1-targeted gastric cancer therapy has been carried out. The results showed that targeting of AE1 significantly inhibited the growth of gastric cancer cells. In drug-induced mouse gastric cancer model, the detection rate for gastric cancer was decreased from 62%-70% to 15.8% after knockdown of AE1. AE1 protein, as a target, has important value in diagnosis and treatment of gastric cancer.

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    Research on the pathogenesis, diagnosis and treatment of female reproductive disorders
    DI Wen, HONG Zu-bei
    2012, 32 (9):  1161. 
    doi: 10.3969/j.issn.1674-8115.2012.09.008

    Abstract ( 1193 )   PDF (353KB) ( 1101 )  

    Human reproduction health is the basis of race expand and nation´s prosperity, which involves fertilization, embryo implantation, fetal development and growth. Any relevant problems could result in reproductive disorders. Recurrent spontaneous abortion (RSA), 1%-5% incidence in pregnancy, is one of the most difficult infertility, which influences the female productive ability seriously. We major in the pathogenesis of RSA, and gained abundant experience in the diagnosis and treatment, which reached first class level at home and abroad. We are have gained National Scientific and Technological Progress second prize in 2008 and the National Population and Family Planning Outstanding Achievements first prize in 2011. Meanwhile, morbidity has changed with the development of social economy and improvement in living standard. Gynaecology oncology becomes more common and the age incidence is getting so lower that birth ability could be damaged. In recent years our research has concentrated on the pathogenesis and target treatment for epithelial ovarian tumor. Related findings have been published in the international journals, which bring us Ministry of Education Science and Technology Progress second prize, Shanghai Municipal Science and Technology Progress third prize, and Shanghai Medical Association Science and Technology Progress second prize in 2009. Also, we have applied for the patents based on the techniques developed during our research.

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    Progression of molecular mechanisms controlling self-renewal and differentiation of embryonic stem cells or induced pluripotent stem cells
    JIN Ying, REN Xiao-hui, LIU Xiao-fan
    2012, 32 (9):  1166. 
    doi: 10.3969/j.issn.1674-8115.2012.09.009

    Abstract ( 1188 )   PDF (359KB) ( 1228 )  

    During 2008 to 2011, affiliated project of genetic development and reproductive medicine key discipline— research project on molecular mechanisms controlling self-renewal and differentiation of embryonic stem cells or induced pluripotent stem cells, which was funded by 211 Project at the third stage, had gained many results, including establishment of the profiling of human embryos during early organogenesis; discovery of calcineurin-NFAT signaling critically regulating early lineage specification in mouse embryonic stem cells and embryos. Moreover, the regulatory mechanism of Oct4-centered core transcriptional circuitry for ES cell fate decision is elucidated: investigating the posttranslational modification of key transcription factor Oct4; discovering PARP1 Poly(ADP-ribosyl)ates Sox2 to control Sox2 protein levels and FGF4 expression during embryonic stem cell differentiation; finding that coactivator p300 in mouse embryonic stem cell differentiation and nanog expression have critical roles; demonstrating that Stk40 links the pluripotency factor Oct4 to the Erk/MAPK pathway and controls extraembryonic endoderm differentiation. In addition, the project discovers that Ly-1 antibody reactive clone is an important nucleolar protein for control of self-renewal and differentiation in embryonic stem cells. In 2011, the project of “Research of embryonic stem cell and early embryonic developmental molecular mechanism” received an award from Ministry of Education of Higher Education Scientific Research for the excellent achievement, the second prize of the natural science.

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    Research advances in cloning and functional studies on the genes causing human genetic disorders
    WANG Zhu-gang, GU Ming-min
    2012, 32 (9):  1171. 
    doi: 10.3969/j.issn.1674-8115.2012.09.010

    Abstract ( 1183 )   PDF (303KB) ( 1185 )  

    In the past 20 years, cloning and functional studies on the genes causing human genetic disorders has been developing repidly. However, the function of most disease genes still remains unknown. This paper briefly describes the basic characteristics of inherited diseases, then reviews the progress in disease gene cloning and pathogenic mechanism, and two achievements were presented, one is that the fibroblast growth factor 9 (FGF9) missense mutation (S99N) causes the multiple synostoses syndrome, another is that the disruption of palladin results in neural tube closure defects, herniation of intestine and liver, fetal liver atrophy, defects in definitive erythropoiesis, and embryonic lethality in mice.

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    Advances in research of digestive diseases
    FANG Jing-yuan, CHEN Ying-xuan
    2012, 32 (9):  1175. 
    doi: 10.3969/j.issn.1674-8115.2012.09.011

    Abstract ( 1283 )   PDF (434KB) ( 1369 )  

    On the basis of the achievements in the second phase of “211” project, the Department of Gastroenterology, Renji Hospital, Shanghai Jiaotong University School of Medicine has made lots of progresses in the original priority projects such as the generation, development, early diagnosis of gastrointestinal tumors, the diagnosis and treatment of chronic liver disease. In addition, we also open up new areas in terms of the diagnosis and treatment of intestinal diseases during the third phase construction. We studied systemically the molecular mechanisms, early diagnosis and prevention of gastric cancer and colorectal cancer, especially the role of epigenetic modifications (DNA methylation, histone modification and micro RNA, etc) and signaling pathways in the development of gastrointestinal tumors. To improve the diagnostic rate, we established the key technology of capsule endoscopy and double balloon endoscopy in the diagnosis of small bowel diseases, which popularized and promoted the application of the small intestine endoscopy in our country. In addition, we explored the innovative clinical therapy and its mechanism in the refractory gastrointestinal from vascular malformation. Moreover, we established non-invasive diagnosis model to predict liver fibrosis in chronic hepatitis B, and clarified the role and the mechanism of the nucleoside antivirals and oxymatrine in the inhibition of fibrosis and prevention its progress. Through the 5-year efforts, we have got two National Science and Technology Progress Awards, and have become the key national clinical specialist (Department of Gastroenterology) and the key national clinical specialist (Key Laboratory of Ministry of Health). The overall level of our discipline has been markedly improved.

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    Genetic and clinical study of hereditary endocrine and metabolic diseases
    NING Guang, LI Xiao-ying, WANG Wei-qing, et al
    2012, 32 (9):  1181. 
    doi: 10.3969/j.issn.1674-8115.2012.09.012

    Abstract ( 1262 )   PDF (306KB) ( 1126 )  

    Hereditary endocrine & metabolic diseases are an important group of diseases with complicated clinical manifestations. Clinically it has been bring numerous challenges to both diagnosis and treatment. Focusing the most demanding problems, in our project we established the molecular category system, the algorithm of genetic diagnosis and biobanks.

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    Mechanisms and translational research based on molecular biomarkers of gastric cancer
    ZHU Zheng-gang, FU Guo-hui, LIU Bing-ya, et al
    2012, 32 (9):  1185. 
    doi: 10.3969/j.issn.1674-8115.2012.09.013

    Abstract ( 1390 )   PDF (1000KB) ( 1145 )  

    With high-throughput omics techniques, the gastric cancer-related molecular markers were screened, and the biological functions of candidate gastric cancer molecular markers were studied. The results indicated that IPO-38, gastrin, IL-33, and FAM5C and MYLK methylation in circulation might serve as markers for early diagnosis of gastric cancer. It was also revealed that FRZB, TXNL2, PHF10, MPS-1 and PTP1B were highly expressed in tissues of gastric cancer, which was associated with the proliferation, differentiation, apoptosis and invasion of tumor cells. The high expression of AE1 in gastric cells might keep p16 in cytoplasm, and refrain it from entering nuclei, which served as proto-oncogene. IRX1 and miR-126 were weakly expressed in tissues of gastric cancer, which served as anti-oncogene. The research lays a good foundation for the clinical translational research of screening of candidate gastric cancer markers, development of diagnostics, molecular targets for therapeutics and prognosis prediction. The research findings have won the second prize of National Science Progress in 2008 and first prize of Shanghai Science Progress in 2012.

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    Key technologies and clinical applications of multimodality partial liver transplantation
    LI Hong-wei, PENG Cheng-hong, SHEN Bai-yong, et al
    2012, 32 (9):  1198. 
    doi: 10.3969/j.issn.1674-8115.2012.09.014

    Abstract ( 1031 )   PDF (396KB) ( 1148 )  

    Shortage of donors has been remaining a major obstacle in organ transplantation around the world for a long time. In the current study, a new pattern of liver transplantation, named partial liver transplantation, was established as a solution for deficiency of hepatic donor and a serial of original results has been achieved. After review and comparison with similar domestic and overseas investigations, some innovations and discoveries were found in this method. ①Establishment of the selection criteria of graft and the reconstruction pattern of right hemi hepatic grafts venous drainage. ②In living donor liver transplantation, the safety and necessity of using right hemi hepatic graft with middle hepatic vein in right hemi hepatic graft were determined by comparing the operational results with or without middle hepatic vein. ③This is the first time in China that split liver transplantation was adopted for the treatment of terminal liver diseases. The largest number of cases has been maintained in a single domestic transplantation center. ④It is also the first in China that one case of living donor liver transplantation using dual grafts was carried out successfully with non-identical blood types between donor and recipient. This modus operandi could provide recipient with a greater weight of liver graft and maximum safety of donor as well. ⑤The pharmacokinetics and pharmacodynamics of mycophenolic acid in Chinese liver transplant recipients were reported for the first time in this report. By monitoring of the full exposure of mycophenolic acid, abbreviated sampling strategy was adopted to determine the area under the curve. In addition, the pharmacokinetics of mycophenolic acid and its metabolites were compared between living donor liver transplant recipients and deceased donor liver transplant recipients. The research achievement has been awarded the second prize of National Science and Technology Progress.

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    Basic research and clinical study of diagnosis and treatment of complex urethral stricture and its complications
    XU Yue-min, FU Qiang, SA Ying-long, et al
    2012, 32 (9):  1203. 
    doi: 10.3969/j.issn.1674-8115.2012.09.015

    Abstract ( 1303 )   PDF (518KB) ( 1228 )  

    Complex urethral stricture or obliteration is always a great challenge to most urologists. It is very difficult to treat those patients suffered from panurethral stricture or obliteration (>14 cm). To patients with previous failure in urethroplasty, the strategy selection will become a dilemma. In this field, we have obtained several original achievements in recent years. Comparing with those similar investigations in the world, many creative ideas or conceptions can be concluded in our study. Firstly, we have proved that the colonic mucosa could be an alterative material for urethroplasty. Up till now, 55 patients have undergone this procedure. The mean length of stricture in those patients was 15.2 cm. The clinic results demonstrated that the colonic mucosa has several advantages, such as abundant resource, easy to harvest, strong ability of anti-infection and low contractive rate. Therefore, this material is suitable for patients with panurethral stricture (>14 cm), especially for those with previous failure in operation. Secondly, we established the new conception of treating panurethral stricture or obliteration using three stages operation. Totally, 11 cases accepted this procedure, all of them obtained satisfied results. The strategy provides a new idea to treat patients with ultra-long segment of urethral stricture and obliteration between anterior and posterior urethra. Thirdly, we firstly described the pathologic characteristics and transformation rule of urethra in patients who accepted the lingual mucosa substitution in the world. And, we have invented the new technique to harvest the large area lingual mucosa. After that, we firstly performed the clinical lingual mucosa urethroplasty in China. With the effort over 10 years, we have collected the largest database about lingual mucosa urethroplasty in the world. Fourthly, we have established the objective quantitative criteria of urethral pressure (90 cmH2O or 40-50 cmH2O over baseline) in the world, which is to evaluate the effectiveness of bulbar urethral sling procedure during the operation. After using this criterion during the operation, the operative successive rate obviously increased. The related complications could be minimized. The results were encouragement. Due to those achievements, we have obtained several first prize and second prize of provincial and ministerial scientific and technical progress rewards.

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    Study on the effect of sleep on children´s growth development and its application
    SHEN Xiao-ming, JIANG Fan, LI Sheng-hui, et al
    2012, 32 (9):  1209. 
    doi: 10.3969/j.issn.1674-8115.2012.09.016

    Abstract ( 1302 )   PDF (422KB) ( 1737 )  

    Sleep plays an very important role in children´s growth and development, but insufficient sleep as well as sleep disorders turns to be common in modern society. This research project is the first series research in the field of sleep which was designed to address below questions. ①Chinese children´s sleep ever have “quality” and “quantity” problem? ②If those kinds of sleep problems affect children´s health? ③How these kinds of harm effect children’s health? ④How to prevent such hazards. This project was designed to carry out the systematic evaluation of children´s sleep and its related factors by multidisciplinary teams from epidemiology, pediatrics, neurobiology, and pedagogy. It was valued as filling the blank of national children sleep foundation information. In addition, it was further explored the effects and mechanism of sleep on children physical growth and nervous system development such as obesity and learning and memories. Finally, this study was translated into health policy to advocate the government postpone the school start time based on the results from well designed studies. From the perspective of sleep health, make policy recommendations and intervention programme on the current daily routine of primary and secondary schools. This policy was later proved to not only increase children´s sleep time but also improve their sleep quality. This was kind of translational research to use medical research results into health policy, eventually benefits children´s health. This research project obtained the National Scientific and Technological Progress Second Prize in 2011.

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    Progression of basic research and clinical practice for nutrition support in the critically ill neonates
    CAI Wei, TANG Qing-ya, WU Jiang
    2012, 32 (9):  1214. 
    doi: 10.3969/j.issn.1674-8115.2012.09.017

    Abstract ( 1138 )   PDF (307KB) ( 1208 )  

    At present, over 1million critically ill newborn infants (including premature neonates, low birth weight babies and those with congenital malformation) each year need medical therapy shortly after birth, and most of them need nutrition support which is not only an essential part of the whole treatment but also important for their later health. Our research group carried out a series of basic and clinical research focusing on nutrition support in critically ill neonate ever since 1985. We found that the energy expenditure in neonates was lower than formula predicted value, and changed the energy recommendation to the value of 60-80 kcal/(kg·d) for parenteral nutrition. We also successfully developed the first domestic pediatric amino acid preparation based on the analysis of serum amino acid characteristics in Chinese neonates. We help to introduce new techniques for nutrition support in neonates, including jejunal puncture ostomy and percutaneous endoscopic gastrostomy for enteral nutrition, as well as the use of peripherally inserted central venous catheters for parenteral nutrition. Liver injury is a severe complication of parenteral nutrition, and our studies revealed that oxidative stress related mitochondrial apoptotic pathway might be an important mechanism, while glutamine showed protective effect not only in animal study but also in our clinical trial. In addition, we successful implemented intestinal rehabilitation therapy in 46 neonates with short bowel syndrome from all around the country, including one case with residual small intestine of only 25 cm.In the year 2005 and 2010, we formulated evidence-based Chinese guidelines of clinical nutrition support in neonates and pediatric patients, which help to improve the application of adequate nutrition support in the field of neonatology and pediatrics. The research achievement won the second prize of National Science and Technology Progress Award.

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    Protection of selective cerebral deep hypothermia and clinical values
    JIANG Ji-yao
    2012, 32 (9):  1218. 
    doi: 10.3969/j.issn.1674-8115.2012.09.018

    Abstract ( 1258 )   PDF (223KB) ( 1180 )  

    Selective cerebral deep hypothermia in monkeys has been successfully established and transfer this technique to surgically treat the patients with complex and major cardio-vascular diseases during anesthesia. The mechanisms have been explored. Our work has made creative contribution for clinical usage of selective cerebral deep hypothermia.

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    Basic and clinical research on the pathogenesis, diagnosis and treatment of Parkinson´s disease
    CHEN Sheng-di, WANG Gang, LIU Jun, et al
    2012, 32 (9):  1221. 
    doi: 10.3969/j.issn.1674-8115.2012.09.019

    Abstract ( 1475 )   PDF (406KB) ( 1467 )  

    Parkinson´s disease (PD) is one of the most common neurodegenerative diseases, Because of high prevalence, severe disability and chronic course of disease, it becomes one of research focus in modern medicine from diagnosis to treatment and prevention. Based on our previous studies, we further extended our investigation into the field of pathogenesis, diagnosis and treatment in PD with characteristics of translational medicine. We found that: ①Serum IgG and C5a from PD patients could activate the microglia and produce the damage effects in turn; and lysosome enzyme released by early microglia activation was harmful for the dopaminergic neurons; ②Three kinds of traditional Chinese herbal medicine—curcumin, salidroside and tripchlorolide (TW397) had neuroprotective and therapeutic effects in cellular and animal models of PD; ③Two types of neuron stem cells (c17.2 neuron stem cell transfected with neurturin or IL-10, or bone marrow stem cell transfected with neurturin) were proved exerting neuroprotective and therapeutic effects in rat models of PD; ④We investigated the economic burden of PD in China and provided the first data of the current pharmacoeconomics situation in Chinese PD patients. Furthermore, we presided the first and second version “Chinese guidelines for the treatment of Parkinson´s disease”, which intended to standardize the clinical treatment of PD in China. The research achievement won the first prize of Natural Science Award of Ministry of Education in 2010.

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    Research progress on endophenotype characteristics of psychopathology, early recognition and optimized treatment on anxiety disorder
    XIAO Ze-ping, ZHANG Tian-hong
    2012, 32 (9):  1227. 
    doi: 10.3969/j.issn.1674-8115.2012.09.020

    Abstract ( 1277 )   PDF (551KB) ( 1232 )  

    Along with China´s economic and social development, the incidence of anxiety disorder has been increasing. According to the reports in 2009, the prevalence of anxiety disorder reached 5.6% in general population. The etiology of anxiety disorder is very complicated, and the overall remission rate is quite low, but apt to relapse, especially for the obsessive compulsive disorder which is one of the most severe and disabling type of diseases. Therefore, it is time for us to conduct an evidence based study to explore the endophenotype characteristics of psychopathology, early recognition and optimized treatment of anxiety disorder.Our studies focused on the biological pathogenesis and clinical features of anxiety disorder, picked the most essential elements and simplified as a toolkit for the early recognition, and applied to a successful promotion of general hospital to help the general practitioners identify anxiety disorder. The genetics, EEG, MRI and biochemistry research methods were used to explore the etiology of anxiety disorder. Our results show that a number of factors contribute to the risk of anxiety disorder: amplification or lack of copy number of 1p1.1 and 20p13 area of euchromosome, the increased N-acetylaspartate level relative to creatine in the medial prefrontal cortex, error-related negativity abnormalities, level of brain-derived neurotrophic factor (BDNF), et al. Those abnormal tests may help to early identify anxiety disorder through biological way. What´s more, we formulated the multi-dimension evaluation system and optimized treatment for anxiety disorder based on years of clinical experiences and research practice, which were proved as accurate and efficient methods for clinical practice.

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    Accelerate the translational research and promote the systems biology study on hematology
    CHEN Sai-juan, ZHAO Wei-li, ZHANG Xiao-wei, et al
    2012, 32 (9):  1234. 
    doi: 10.3969/j.issn.1674-8115.2012.09.021

    Abstract ( 1187 )   PDF (492KB) ( 1260 )  

    Leukemia is a malignancy of serious harm to human health and its pathogenesis needs to be further clarified. With the rapid development of science and technology, study on disease mechanism is no longer limited to a single point of view, but aim to integrate the different levels of information, focus on mutual relations and interactions between molecules, in order to understand the systems biological dysfunction in the disease. Thus, using systems biological methods to study in depth the leukemia development, and in this setting, applying the idea of translational medicine to explore the targeted therapy of leukemia, has an important significance for the final capture of the disease. During the construction of the “211 Project”, Shanghai Institute of Hematology has made a major breakthrough in the basic and clinical studies of differentiation and apoptosis-induced targeted therapy of acute promyelocytic leukemia (APL), making APL the first curable acute myeloid leukemia, and the successful example of leukemia gene product-based targeted therapy. This will be further extended to other types of leukemia. Also, our group has made a significant progress on leukemia systems biology research, being the first to carry out the Leukemia Genome Anatomy Project. Using exome sequencing of acute monocytic leukemia, we identify the mutations and epigenetic changes of DNA methyltransferase 3A (DNMT3A) gene, which is closely related to the clinical diagnosis and prognosis of leukemia patients. We also study at the genome-wide level the APL pathogenesis and illustrate the target genes transcriptionally repressed by PML-RARα oncoprotein. These results not only provide guidance on leukemia pathogenesis, molecular typing and standardized clinical pathway of leukemia, but also deepen the theoretical connotations of “translational medical research” and use target therapy to save thousands of leukemia patients world-wide.

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    Recent progress in tissue engineering
    CAO Yi-lin, LIU Wei, ZHANG Wen-jie, et al
    2012, 32 (9):  1241. 
    doi: 10.3969/j.issn.1674-8115.2012.09.022

    Abstract ( 1707 )   PDF (673KB) ( 1165 )  

    Tissue damage and organ disfunction caused by trauma or variety of diseases have become major threatens to human health. The restoring, maintaining, or enhancing tissue and organ function have been a great challenge in medical science. Tissue engineering, a new approach that use the combination of cells, engineering and materials methods, and suitable biochemical and physio-chemical factors to repair or restore the biological functions of damaged tissue/organ, is changing the traditional therapeutic strategy from tissue/organ graft to tissue/organ regeneration. With the progresses on seeding cells, biomaterials and engineering techniques, we have successfully constructed tissue engineered bone, cartilage and tendon to repair the related defects in large mammals. In addition, tissue engineered bone has been applied in clinic with satisfied results. The successful works in large animal studies and clinical trials demonstrated the potential power of this approach in tissue/organ regeneration. These works have been awarded for National Award for Technological Invention 2nd Prize in 2008.

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    Appearance repair and functional reconstruction of severe post-traumatic deformity
    LI Qing-feng
    2012, 32 (9):  1251. 
    doi: 10.3969/j.issn.1674-8115.2012.09.023

    Abstract ( 1171 )   PDF (200KB) ( 1220 )  

    Severe post-traumatic deformities are defined as severe superficial organs defect, deformity and dysfunction that result from burn, traffic injury, industrial injury or blast injury. This kind of disease has two general characteristics: high incidence and grave harmfulness. In the field of plastic and reconstructive surgery which is the main subject for the restoration of post-traumatic deformities, the weaknesses and limitation of main reconstructive techniques at present is obvious: current treatments aim for recovery of defect, far from the reconstruction of function and appearance. This project has created new more effective treatments by means of the combination of molecular biology, stem cells technology and digital medicine with conventional plastic and reconstructive surgery techniques. The main progress is as follows: (1) Flap prefabrication is a frontier technique for treatment of severe posttraumatic deformities. However, insufficient neovascularization and subsequent necrosis remain difficult problems in applications of the technique. It is found that “therapeutic vasculogenesis” with stem cell transplantation is superior to “therapeutic angiogenesis” with vascular endothelial growth factor (VEGF) administration in improving revascularization during flap prefabrication in our research. The therapeutic vasculogenesis effect of somatic stem cells can be enhanced by VEGF gene transfection, which means a reduced quantity of stem cells would be needed for treatment after VEGF gene transfection. The further founding is that application of hypoxia-mimetic could promote the directional migration and homing of transplanted stem cells. (2) Series methods and revolution of superficial tissue and organ reconstruction with flap prefabrication and tissue expansion. (3) The 3-d digital dynamic mechanics analysis of soft tissue is accomplished. And 3-d digital simulation software has been applied in the treatment of 2-3 types of typical craniofacial deformities successfully. (4) Some treatment methods are established or improved such as facial nerve reconstruction by masseter-facial nerve coaptation, transposition of pedicled sternocleidomastoid muscle for repair of facial paralysis, etc. By the development and application of these new techniques and methods mentioned above, the therapeutic effects were well improved.

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    Progress of diagnosis and treatment in scarring, vascular anomalies and lymphedema
    LIU Wei, LIN Xiao-xi, LIU Ning-fei
    2012, 32 (9):  1254. 
    doi: 10.3969/j.issn.1674-8115.2012.09.024

    Abstract ( 1273 )   PDF (270KB) ( 1112 )  

    Scar, vascular anomalies and lymphedema are the common diseases that are difficult to treat, which severely affect patients´ psychological and physical fitness. Therefore, further defining the disease mechanism and improving the diagnosis and therapeutic efficiency are the important topics of this area. In this project, our group has: ①revealed the role of keloid stem cells, drug resistance and GDF-9 differentiation in keloid development; ②established low dose chemotherapy of keloid with increased cure rate and reduced recurrence rate; ③established engineered epidermis to treat wound bed to inhibit scar formation; ④established diagnosis and therapy system in infantile hemangioma; ⑤established clinical classification of port wine stains; ⑥established diagnosis and therapy of venous malformations; ⑦established diagnosis and therapy methods for arteriovenous malformations; ⑧preliminarily defined the molecular mechanism of lymphedema; ⑨established MRI diagnosis for lymphedema; ⑩development of specialized traditional Chinese medicine for lymphedema.

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    Diagnosis and treatment for vascular anomalies in head and neck region
    ZHANG Zhi-yuan, WANG Yan-an, ZHENG Jia-wei, et al
    2012, 32 (9):  1258. 
    doi: 10.3969/j.issn.1674-8115.2012.09.025

    Abstract ( 1179 )   PDF (436KB) ( 1191 )  

    Vascular anomalies include hemangioma and vascular malformation, and about 60% of the lesions are found in the head and neck region. Although there are many treatment modalities reported for vascular disease, great challenges still exist for clinicians because of their unknown etiology and difficulties in management. The classification of vascular disease plays an important role in the selection of treatment modalities. This paper summarized the classification and terminology, as well as the treatment principles for vascular disease, emphasizing the importance of comprehensive and sequential approaches based on the authors´ experience and relevant literatures. The related research achievements gained the first prize of Shanghai Science and Technology Progress and the second prize of National Science and Technology Progress.

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    Advances in research on the role and mechanism of microRNAs in hepatic carcinogenesis
    HE Xiang-huo, LIANG Lin-hui, DING Jie, et al
    2012, 32 (9):  1264. 
    doi: 10.3969/j.issn.1674-8115.2012.09.026

    Abstract ( 1416 )   PDF (392KB) ( 1255 )  

    MicroRNAs (miRNAs) are small, non-coding RNAs that can act as oncogenes or tumor suppressors in human cancer. Recently we identified 129 known miRNA genes in the recurrent chromosomal aberration regions of hepatocellular carcinoma (HCC). Further analysis showed that 22 miRNAs are often amplified or deleted in HCC. MicroRNA-151 (miR-151), a frequently amplified miRNA on 8q24.3, is often expressed together with its host gene FAK, and significantly increases HCC cell migration and invasion in vitro and in vivo by directly targeting RhoGDIA, a putative metastasis suppressor in HCC, thus leading to the activation of Rac1, Cdc42 and Rho GTPases. In addition, we analyzed the miRNA profiles in HCC and found that 69 miRNAs were differentially expressed between HCC and corresponding noncancerous liver tissues. The set of differentially expressed miRNAs could distinctly classify HCC and noncancerous liver tissues. Moreover, some of these differentially expressed miRNAs were related to the clinical features of HCC patients such as metastasis and recurrence. Importantly, the expression level of individual miRNA miR-125b was correlated with the survival time of HCC patients. These results revealed the diagnostic and prognostic implications of miRNAs in HCC. Furthermore, we showed that miR-125b could function as a candidate tumor suppressor in HCC through directly targeting oncogene LIN28B, thus resulting in the increase of p21Cip1/Waf1 expression and cell cycle arrest at G1/S transition. Moreover, we analyzed the function and mechanism of metastasis-related miR-30d in HCC and found that miR-30d could promote HCC cell migration and invasion by downregulating Galphai2 (GNAI2) expression. Intriguingly, we found that miRNA can target the coding region of mRNA other than its 3’ UTR; and experimentally showed that one mRNA could be simultaneously regulated by multiple miRNAs.

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    Development of postgraduates´|innovative abilities in medical education
    GU Qin-long, LIU Wei
    2012, 32 (9):  1269. 
    doi: 10.3969/j.issn.1674-8115.2012.09.027

    Abstract ( 1222 )   PDF (357KB) ( 1217 )  

    Accompanying with the unusual course of rapid development of degree and postgraduate education from scratch in China over the past thirty years, the postgraduate education of Shanghai Jiaotong University School of Medicine has also achieved tremendous development and great progress. In particular, after the merger of former Shanghai Jiaotong University and Shanghai Second Medical University in 2005, Shanghai Jiaotong University School of Medicine has been building on strength and making a step-change in its postgraduate education. From then on, the number of postgraduate students enrolled has increased to over 1 000 each year. Meanwhile, the basic conditions of postgraduate education, scientific research, abilities of advisors to guide students, level of training and quality of education have been fully upgraded. Since 2008, with the support of third construction phase of “211 Project”, School of Medicine takes “quality and innovation” as its theme and pays close attention to connotation construction. By implementation of the projects of “Experimental Skills in Information Technology Platform”, “Outbound Learning and Enhancing Plan” and “National Excellent Doctoral Dissertation Incubation Program”, School of Medicine efforts to improve the educational “soft power” which intends to improve innovation abilities of postgraduate students. Great performance has been made in various aspects. The quantity and quality of published papers from postgraduate students have significantly improved, and award of National Excellent Doctoral Dissertation, Shanghai Graduate Outstanding Achievements as well as national First-Class Discipline Assessment are now in the forefront among the domestic medical schools.

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    Construction and practice of innovative medical undergraduate training system
    HUANG Gang, ZHANG Yan-ping, LU Bin-jie, et al
    2012, 32 (9):  1274. 
    doi: 10.3969/j.issn.1674-8115.2012.09.028

    Abstract ( 909 )   PDF (236KB) ( 1028 )  

    In recent years, with the continuous deepening and advancing of the reform of medical education, the theoretical research and practical work in medical education in China has also entered a leap stage. In particular, the long schooling medical education reform since 2004 marks our medical education into a new era. This paper summarizes the progress of the practice of innovative medical undergraduate training system, in terms of teaching philosophy, curriculum, teaching methods and assessment system.

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    Establish innovative policy to promote talent strategy for school development
    LU Yang, ZHU Hai-ying
    2012, 32 (9):  1277. 
    doi: 10.3969/j.issn.1674-8115.2012.09.029

    Abstract ( 1183 )   PDF (427KB) ( 1132 )  

    Since the creation of Shanghai Jiaotong University School of Medicine from 1952, especially from the merge of former Shanghai Jiaotong University and Shanghai Second Medical University in 2005, the comprehensive strength of School of Medicine has being improved rapidly. The rapid development depends on a variety of factors, and the important one is to firmly promote talent recruitment and personnel training for the faculty based on the concept that talents are the first important resource in school. This report sums up the achievement bout the establishment of innovative policy for promoting talent strategy for school development during the third phase of “211 Project”.

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