Zhejiang University Institute of Pediatrics
[Source]: [Author]: [Date]: 2010-12-09[Views]: 2664
Zhejiang University Institute of Pediatrics is located in the Children’s Hospital Zhejiang University School of Medicine. The institute comprises several well-equipped laboratories including the Gene Diagnostic Center, Neonatal Disease Prevention and Treatment Center, Pediatric Cardiovascular Disease Prevention and Treatment Center, Neonatal Screening Center, and Pediatric Hearing Screening Center. The laboratories occupy an area of 1500 square meters, with a real estate investment of 25,000,000 RMB. The institute was approved to start a master degree training program in 1981, a doctoral program in 1986, and a post-doctoral training program in 2000. The World Journal of Pediatrics, launched in 2005, is the first pediatric journal published in the English language in China, aiming to promote the international exchange between China and other countries.
The institute is equipped with a team of excellent staff, including 7 candidates of Zhejiang New Century 151 Talent Program, 31 professors, and 56 associate professors. There are 21 professors serving in the Chinese Medical Association (CMA) and other academic institutions. One professor serves as the Vice President of the Pediatric Branch of CMA and the Pediatric Branch of Chinese Medical Doctor Association. One professor serves as the Director of the Gastroenterology Committee of the Pediatric Branch in CMA. One professor serves as the Director of the Neonatal Screening Committee of the Chinese Pediatric Health Care Association. One professor serves as the Director of the Zhejiang Pediatric Association and Zhejaing Pediatric Health Care Association. One professor serves as the Associate Editor of Chinese Journal of Pediatrics, and another 27 professors serve as Editor-in-Chief, Associate Editor, or Editorial Members of several influential international and national academic journals.The subject features in neonatology, pediatric gastroenterology and infectious disease, pediatric hematology/oncology, pediatric cardiology, and pediatric health care. In the past six years, the institute has completed 437 research projects of different levels with a total funding sum of 17,260,000 RMB, including 12 programs supported by the National Natural Science Foundation of China and 15 programs honored by the National or provincial-ministry scientific and technological awards. Totally 1619 academic papers have been published, 79 of which were indexed by Science Citation Index (SCI). In the past two years, the institute publishes the most annual academic papers indexed by SCI compared with all other counterpart institutions.
Introduction to major research areas
1. The basic and clinical research on neonatal critical diseases
1) Clinical treatment and experimental studies on neonatal critical respiratory failure and persistent pulmonary hypertension of the newborn (PPHN): pre-clinical research on the pathogenic mechanism of PPHN, high-frequency ventilation, nitric oxide (NO) and ethyl nitrite aspiration mechanisms, effect and toxic side-effect. In 1997, the institute firstly reported the effect of NO in the treatment of PPHN in China. In 2002, the institute took charge in the establishment of PPHN routine treatment protocol, and reported the multi-centural research result of NO in the treatment of PPHN.
2) Early diagnosis of neonatal infection: based on the characteristics of 6SrRNA gene and with the use of reverse hybridization and gene chip technology, we established the method for early diagnosis of neonatal bacteria infection. In 1998, the institute firstly reported the results of early diagnosis of septicemia using 16SrRNA gene. In 2003, a practical diagnosis gene chip for detecting neonatal bacterial infection was developed.
3) Experimental studies on neonatal (preterm) brain damage: intervention research on NOS receptor inhibitor in neonatal hypoxic ischemic encephalopathy. The institute firstly elucidated the mechanisms of white matter damage in preterm newborns caused by uterus bacterial infection.4) The application and wide-spread of neonatal acute care: Since the set-up of NICU in 1983, the institute has trained 650 physicians engaged in neonatal intensive care in China. In the past six years, the neonatal acute care technology has been largely adopted by the basic-level hospitals, which improved the mode of neonatal acute care and lowered the mortality rate of neonatal asphyxia and respiratory failure. The institute is now cooperating with the University of Calgary in Canada with the Acute Care of at-Risk Newborns (ACoRN) program, in order to further improve the life quality of newborns.
2. Basic and clinical research on gastroenterology diseases and infectious diseases
1) The pathologic mechanism and treatment for pediatric diarrhea: The institute was the first in China to carry out transjugular mucosa biopsy, tissue light microscopy, electron microscopy, and intestinal mucosa enzyme activity analysis. Since 1986, the institute has published a series of reports on topics including the ultrastructural changes in the intestinal mucosa of patients suffering from diarrhea, the activities of lactase and brush border peptase, intestinal permeability changes and the relationship with lactase intolerance and protein metabolism. An oral nutritional formula self-prepared by the institute successfully controlled the chronic diarrhea in pediatric patients.
2) Application of endoscopy in the diagnosis and treatment of gastroenterology diseases
: the first in China to employ endoscopy and colonoscopy for diagnosis and treatment of gastroenterology diseases. The institution was in charge of establishing “The routine procedures for pediatric endoscopy”, “Diagnostic criteria for pediatric chronic gastritis and digestive ulceration”, and “Treatment protocol for pediatric chronic gastritis and digestive ulceration” in China. The institution held several national continued education courses and trained 450 physicians in the field from 25 provinces.
3) Basic and clinical studies on pediatric functional gastrointestinal disorders and disorders of gastrointestinal motility: first in China to set up gastrointestinal motility laboratory to dynamically monitor esophageal and gastric pH values and Bilitec 2000 bilirubin levels, as well as performing upper and lower digestive tract motility examinations and biofeedback treatment. The institution firstly reported esophageal pH monitoring in the diagnosis of pediatric gastroenterology esophageal reflux (GER), systematically explaining the pediatric esophageal motility, GER pathologic mechanisms, relationships between GER and chronic respiratory diseases and the effect of anti-reflux drugs, and the motility characteristics of functional gastrointestinal disorders and Hirschsprung′s disease. The institution was also in charge of establishing “Treatment protocol for pediatric gastric esophageal reflux diseases” in China.
4) Early diagnosis and basic studies on pediatric infectious diseases: The institution seeks to establish genetic diagnostic technologies for pediatric infectious diseases. The gene chip for diagnosing bacterial and herpes virus infections has been established and got the national patent of utility model (No. ZL99256260.0 and 200520014022.X). Another national invention patent and patent of utility model are under approval.
3. Diagnosis, treatment and pathologic mechanism research on pediatric heart diseases
1) Basic and clinical studies on congenital heart diseases: focusing on early diagnosis of infantile complex heart diseases and the emergent operative management and experimental research. The intervention treatment has achieved a successful rate of 99%, and the successful rate for all heart surgeries is 99.5%, including 50% surgeries for infants and 40% for complex heart diseases. The institution has carried out a series of operations for complex heart diseases, including total anomalous pulmonary venous connection repair for small infants, pulmonary atresia, interrupted aortic arch, double outlet right ventricle repair, and primary repair of stenosis of the aortic valve associated with intracardiac abnormality by median incision, as well as minimally invasive cardiac surgery, all achieving satisfactory results. Staged operation and palliative operation for maldevelopment of the right heart also can be performed. In the recent three years, 150 cases of neonatal complex cardiac anomalies have been operated, including total transposition of the great artery with Switch operation, reaching a successful rate of 90%.
2) Basic and clinical studies on pulmonary hypertension (PH): pathologic mechanisms of PH, drug administration, and transgenic interference. The institution was the first in China to find out the curative effects of nebulized inhalation of nitroglycerin on rats with PH and those with ventricular septal defect associated with PH, and to find that VEGF transgene improves pulmonary arterial endothelial cell structure and the expressions of VEGF mRNA and eNOS mRNA in bleomycin-induced rabbits.
3) Basic and clinical studies on acquired pediatric heart diseases: the immune mechanism in pediatric viral myocarditis, the immune mechanism and early diagnosis of Kawasaki disease. The institution was the first in China to report the pathological changes of coronary artery in patients with Kawasaki disease, control studies on ultrasound and radiography characteristics, and coronary artery bypass in the treatment of Kawasaki disease patients associated with severe coronary artery changes. Also the institution firstly reported the increment of carotid intima thickness and decrease of endothelial dependent diastolic function in simple obesity children, complicated with hyperlipemia and hyperlipoproteinemia; hyperhomocysteinemia might be an important factor inducing early atherosclerotic diseases in obese children.
4. Basic and clinical studies on pediatric hematology/oncology
1) Clinical study: Studies on MICM typing of acute leukemia in children. More than 30 anti-HLA monoclonal antibodies and four-color flow cytometry (GCM) were used for immunological classification and diagnosis of leukemia in approximately 400 children as well as the minimal residual disease monitoring in more than 1000 cases. The immunological diagnosis protocol for leukemia has been established approaching to the international level. RT-PCR method is used to analyze the common fusion genes including TEL/AML1 and BCR/ABL, and the protocol on WT1 gene detection by real-time PCR has been established. A combination therapy with chemotherapy, immunotherapy and hemopoietic stem cell (HSC) were used to manage the children with hematology. FCM technique and real-time monitoring on MRD by fusion genes detection and individualized chemotherapy regimen were used for better the therapy efficiency. For children with ALL, the five-year overall survival rate is 82.1%, event free survival rate 70.7%. For children with AML, the five-year overall survival rate is 58.1%, event free survival rate 47.6%. The institution is one of the best for diagnosis and treatment of pediatric hematology and oncology in our country and is the first using CD45/CD56/ antiganglioside D2 and DCM technique for diagnosis and follow-up study on neuroblastoma in children in China. The total effective power of immune inhibitory therapy reaches 79% for management of aplastic anemia with antithymocyte globulin.
2) Development and identification of anti-HLA monoclonal antibody: More than 40 anti-HLA monoclonal antibodies developed and named as ACH series. Nineteen of them have been certificated and CD defined by the HLDA. ACH-2B8a is the only self-made anti-HLA monoclonal antibody in the world up to now. Co-immunoprecipitation study has been carried out to analyze the ACH-2B8a recognizing antigen, and the molecular weight of the antigen is 52kDa with sequence under analyzing. ACH-2B8a is a new antibody as the pediatric hematology treatment target.
3) Reinstruction of humanized self-made monoclonal: Cloning and sequencing of the genes of heavy and light chains in the variable region of mouse anti-HLA CD14 monoclonal antibody (ZCH-7-2F9) and anti-HLA CD19 monoclonal antibody (ZCH-4-2E8). The eukaryotic expression vectors of these monoclonal antibodies have been constructed and the proteins expressed in CHO cells. These proteins are monoclonal antibodies having similar bioactivity with the parent mouse derived. Three national invention patents obtained.
5. Integrative study on child health care
1) Serial studies on newborn screening: Newborn screening for congenital hypothyroidism (CH) and phenylketonuria (PKU) was initiated in Zhejiang Province in 1998. After more than one decade of efforts, we have established the only centralized provincial screening newborn screening network and follow-up treatment system in our country. The number of newborns screened annually reaches 480,000 and a total of 2,600,000 newborns have been screened up to now. Totally 1517 children were diagnosed with CH and 73 with PKU. All the children diagnosed by newborn screening had normal physical and mental development after standard treatment and close follow-up by our center. The incidence of mental retardation in the whole province reduced dramatically after the implementation of newborn screening program. Meanwhile, we carried out a serial of basic studies on the genetics of the CH and PKU and the pathogenesis of CH on the brain and heart injury in our population. We obtained the gene mutation spectrum of TSHR
in Han ethnicity
children in Zhejiang Province and found three novel mutations. The research results help to reduce of the rate of birth defects.
2) Monitoring the mortality of children under five years old: Monitoring the mortality of children under five years old among the population of more than 5,000,000 by collecting data from 22 monitoring centers throughout the whole province for 15 years successively. The quality control system was established and data were obtained on the mortality of newborns, infants and children under five years, causes of death and the child health care before death. All these provide a scientific evidence for policy making for the medical governors. After intervention, the mortality of
newborns reduced from 7.34‰ in 2000 to 4.28‰ in 2005, infants from 9.95‰ to 6.46‰ and children under five years from 12.66‰ to 8.43‰. The coverage rate of the well child care for children at 7 years old increased from 89.52% to 92.20%. The provincial maternal and child heath care level takes leading position in the country.
3) Epidemiological investigation and basic and clinical research on lead poisoning: By analyzing risks of lead poisoning in Zhejiang Province and epidemiological study on the blood lead level of children pre- and post-intervention, practical evidences were provided for health policy making of public health administration. The research outcome on the lead poisoning revealed the toxicology of various lead levels on cognition and the neurophysiology of auditory pathway in children. First elucidate the effects of lead poisoning on immune system in children and the toxicology of lead poisoning on the leucocytes.
4) Studies on cognition and its neuromechanism of children with inherited mental retardation: Use the facial three-dimension engineering to screen inherited mental retardation. More than 100 children were diagnosed with William’s syndrome (WS), Fragile X syndrome (FXS) and DiGeorge syndrome (DGS); First carry out the research of disease related genes, cognition phenotype and inner neuromechanism on WS, FXS, DGS and Down’s syndrome children by multiple visual searching tasks and advanced event related potential (ERP), and to elucidate the complicated relation of gene-nerve-cognition and the gene deficit related neurologic development process.
5) Nutritional deficiency related with cognition and behavior of developing brain: Based on the studies of Vitamin A deficiency and anemia, firstly investigate the key stage of iron deficiency on developing brain and its reversibility and elucidate its pathogenesis. A serial studies on the perinatal iron deficiency animal model and the motor, emotion, behavior and cognition of the children with iron deficiency in different stages are investigated.
6) Basic and clinical studies on growth and development discrepancy: Researches on the glucose, lipid and bone metabolite disorders in the children with dwarfism and investigate the possible mechanism of improved glucose, lipid and bone metabolites in children with growth hormone deficiency managed with rhGH. Researches on pathogenesis of precocious puberty, psychological and behavior problems and adrenosterone and bone metabolite changes before and after GnRHa treatment.
The Institute of Pediatrics is affiliated to one of the largest children’s hospital in China. The institute has very rich pediatric clinical and basic research resources and personnel reserve; meanwhile, we can carry out multi-disciplinary collaborations through the platform of Zhejiang University and establish the partnership with many famous universities from USA, England, Germany, Japan and Sweden with broad development perspectives.