Chao Chen

Fudan University, Shanghai, Shanghai Shi, China

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Publications (83)160.03 Total impact

  • Jianguo Zhou · Vivek V Shukla · Denny John · Chao Chen ·
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    ABSTRACT: Context: Studies have suggested that human milk feeding decreases the incidence of retinopathy of prematurity (ROP); however, conflicting results have been reported. Objective: The aim of this meta-analysis was to pool currently available data on incidence of ROP in infants fed human milk versus formula. Data sources: Medline, PubMed, and EBSCO were searched for articles published through February 2015. Study selection: Longitudinal studies comparing the incidence of ROP in infants who were fed human milk and formula were selected. Studies involving donor milk were not included. Data extraction: Two independent reviewers conducted the searches and extracted data. Meta-analysis used odds ratios (ORs), and subgroup analyses were performed. Results: Five studies with 2208 preterm infants were included. Searches including various proportions of human milk versus formula, any-stage ROP, and severe ROP were defined to pool data for analyses. For any-stage ROP, the ORs (95% confidence intervals [CIs]) were as follows: exclusive human milk versus any formula, 0.29 (0.12 to 0.72); mainly human milk versus mainly formula, 0.51 (0.26 to 1.03); any human milk versus exclusive formula, 0.54 (0.15 to 1.96); and exclusive human milk versus exclusive formula, 0.25 (0.13 to 0.49). For severe ROP, they were 0.11 (0.04 to 0.30), 0.16 (0.06 to 0.43), 0.42 (0.08 to 2.18), and 0.10 (0.04 to 0.29), respectively. Limitations: Prospective randomized studies being impossible because of ethical issues, we chose observational studies for analysis. A few studies involving subgroup analyses presented high heterogeneity. Conclusions: Based on current limited evidence, in very preterm newborns, human milk feeding potentially plays a protective role in preventing any-stage ROP and severe ROP.
    PEDIATRICS 11/2015; DOI:10.1542/peds.2015-2372 · 5.47 Impact Factor
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    ABSTRACT: Objectives: To develop and validate a predischarge risk stratification model by using transcutaneous bilirubin (TcB) values and clinical factors to predict significant postdischarge hyperbilirubinemia in healthy term and late preterm Chinese neonates. Methods: In a prospective cohort study, 8215 healthy term and late preterm neonates in 8 hospitals in China underwent TcB measurement at <168 hours of age. TcB percentiles were calculated and used to develop an hour-specific nomogram, and 9 empirically weighted items were used to derive a prediction model. A risk stratification model was developed by combining the TcB nomogram with clinical risk scores to predict significant hyperbilirubinemia, defined as a postdischarge bilirubin level that exceeded the hour-specific recommended threshold value for phototherapy. Data from another 13 157 neonates were used to validate the model. Results: A TcB nomogram for every 12 hours of the studied interval was constructed from the development set. Gestational age, male gender, history of previous neonate who received phototherapy, bruising, feeding mode, weight loss, and early discharge were predictors of postdischarge significant hyperbilirubinemia. The combination of the TcB nomogram and clinical risk score provided the best prediction of significant hyperbilirubinemia with an area under the curve of 0.95 (95% confidence interval: 0.94-0.95) in the development data set and 0.94 (95% confidence interval: 0.93-0.94) in the validation data set. A risk stratification model with 6 distinct risk levels was developed and validated. Conclusions: A risk classification model, combining discharge transcutaneous bilirubin values and clinical risk factors, separated term and late preterm Chinese neonates into 6 risk classes for the timely follow-up of postdischarge hyperbilirubinemia detection.
    PEDIATRICS 09/2015; 136(4). DOI:10.1542/peds.2014-4058 · 5.47 Impact Factor
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  • Mingzhi Zhang · Yong Lu · Xiaobo Zhang · Aizhen Lu · Libo Wang · Chao Chen ·
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    ABSTRACT: Respiratory syncytial virus (RSV) infection is a major health problem in young children. This study aimed to investigate whether the interleukin (IL)-4 -590C/T and -33 C/T polymorphisms were associated with the susceptibility to RSV infection in Chinese Han children and with the severity of the infection. The IL-4 -590C/T and -33 C/T SNPs were evaluated in 218 inpatients with RSV bronchiolitis and 303 healthy controls. The severity of RSV bronchiolitis was evaluated using a respiratory scoring system. The frequencies of IL-4 -590 CC, CT and TT in the 218 RSV bronchiolitis patients versus the 303 controls were 1.4% versus 1.7%, 21.1% versus 34% and 77.5% versus 64.4%, respectively. The frequencies of IL-4 -33 CC, CT and TT were 1.4%, 20.6% and 78%, respectively, in RSV bronchiolitis patients and 2.3%, 35.6% and 62%, respectively, in the controls. The frequencies of the IL-4 -590C/T and -33 C/T polymorphisms were significantly different between the two groups. There was a significant difference in the frequency of the T-T haplotype formed by -590C/T and -33C/T between the two groups. The respiratory score of the RSV bronchiolitis cases with -590TT was 3.02 ± 0.44, which was significantly higher than those with -590CT (2.80 ± 0.44). The score for patients with -33TT was 3.03 ± 0.43, which was significantly higher than the score of 2.78 ± 0.46 for patients with -33CT. In Chinese Han children, the IL-4 -590C/T and -33 C/T polymorphisms were associated with the susceptibility to RSV and the severity of the infection. © 2015 The Authors. Journal of Paediatrics and Child Health © 2015 Paediatrics and Child Health Division (Royal Australasian College of Physicians).
    Journal of Paediatrics and Child Health 08/2015; DOI:10.1111/jpc.12985 · 1.15 Impact Factor
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    ABSTRACT: The aim of the present study was to treat retinopathy of prematurity (ROP) with estrogen (E2) so as to elucidate the role of E2 in the pathogenesis of ROP. A total of 120 postnatal 7-day-old (P7) C57BL/6J mice were selected and raised in a high-oxygen environment (75% oxygen) for 5 days, followed by 5 days in normal room air. Different doses of E2 or normal saline (NS) were injected intraperitoneally during different time-periods, and the mice were divided into 14 groups according dose of E2 injection (0.5-1.5 µg/0.05 ml) and dosing time. Blood vessel changes and hyperplasia were evaluated in flat-mounted retina and retinal slices. All mice that were exposed to room air, whether they were administered E2 or NS, showed good vascular development in the flat-mounted retina at P17. No increase in the number of endothelial cell nuclei in the new blood vessels was observed. In ascending order of E2 dose the numbers of cell nuclei were as follows: 0.18±0.129, 0.28±0.086 and 0.55±0.110. The number in the NS group was 2.12±0.373. When the results of the room-air groups were compared with those of the hyperoxia groups, a highly significant difference was found in each comparison (P<0.0001). All mice showed varying degrees of neovascularization and vascular obstruction in the flat-mounted retina at P17, and it was difficult to compare the blood vessels morphologically among these groups. The number of endothelial cell nuclei decreased following E2 injection, and the difference from the NS group exposed to hyperoxia was highly significant (P<0.0001). For all dose levels, the number of cell nuclei was the lowest when the drug was administered during P7-16, and the difference from the other two time-periods was statistically significant (P<0.05). When E2 was administered during P7-16, the number of cell nuclei was 15.5±1.993 in the 0.5-µg group, 14.23±2.49 in the 1.0-µg group and 18.05±1.62 in the 1.5-µg group. No significant difference was found among these three groups (P>0.05). In conclusion, E2 treatment during the development of retinopathy can improve symptoms in neonatal mice, suggesting that E2 plays an important role at the two initial stages in the pathogenesis of ROP. This may indicate new pharmacological measures to prevent and treat ROP.
    Experimental and therapeutic medicine 06/2015; 10(2). DOI:10.3892/etm.2015.2554 · 1.27 Impact Factor
  • Mei Lyu · Xinzhu Lin · Chao Chen ·

    Zhonghua er ke za zhi. Chinese journal of pediatrics 05/2015; 53(5):383-4.
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    ABSTRACT: Phenylalanine, which is an essential aromatic amino acid, is either used for protein synthesis or irreversibly hydroxylated to tyrosine. The provision of optimal amounts of dietary phenylalanine is not only important for growth and development but might also influence catecholamine synthesis and release rates. The current recommended aromatic amino acid requirement for infants aged 0-6 mo is based on the amino acid content of human milk. We quantified the requirements for phenylalanine in the presence of excess tyrosine (166 or 177 mg/kg per day for term and preterm infants, respectively) for term and preterm neonates by using the indicator amino acid oxidation method with l-[1-(13)C]lysine 2HCl as an indicator. Hence, we determined the minimum obligatory phenylalanine requirement. Fully enterally fed term and preterm infants received randomly graded amounts of phenylalanine (5-177 mg/kg per day) as part of an elemental formula. Data are expressed as means ± SDs. Twenty term (birth weight: 3.19 ± 0.34 kg; gestational age: 38.9 ± 1 wk) and 16 preterm (birth weight: 1.75 ± 0.17 kg; gestational age: 32.5 ± 0.6 wk) Asian infants participated at a postnatal age of 17 ± 8 d. In total, 44 studies were performed. The minimum obligatory phenylalanine requirement was 58 mg/kg per day (95% CI: 38-78 mg/kg per day) and 80 mg/kg per day (95% CI: 40-119 mg/kg per day) for term and preterm infants, respectively. The determined mean phenylalanine-requirement estimates are lower than the contents of term and preterm formulas currently on the market. This trial was registered at as NTR1610. © 2015 American Society for Nutrition.
    American Journal of Clinical Nutrition 04/2015; 101(6). DOI:10.3945/ajcn.114.089664 · 6.77 Impact Factor
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    ABSTRACT: Hypomyelination is the major cause of neurodevelopmental deficits that are associated with perinatal white matter injury. Chondroitin sulfate proteoglycans (CSPGs) are known to exert inhibitory effects on the migration and differentiation of oligodendrocytes (OLs). However, few studies describe the roles of CSPGs in myelination by OLs and the cognitive dysfunction (CD) that follows perinatal white matter injury. Here, we examined the alterations in the expression of CSPGs and their functional impact on the maturation of OLs and myelination in a neonatal rat model of hypoxic-ischemic (HI) brain injury. Three-day-old Sprague-Dawley (SD) rats underwent a right common carotid artery ligation and were exposed to hypoxia (6% oxygen for 2.5h). Rats were given cABC via an intracerebroventricular injection to digest CSPGs. Animals were sacrificed at 7, 14, 28 and 56days after HI injury and the accompanying surgical procedure. We found that the expression of CSPGs was significantly up-regulated in the cortical regions surrounding the white matter after HI injury. cABC successfully degraded CSPGs in the rats that received cABC. Immunostaining showed decreased expression of the pre-oligodendrocyte marker O4 in the cingulum, external capsule (EC) and corpus callosum (CC) in HI+cABC rats compared to HI rats. However HI+cABC rats exhibited greater maturation of OLs than did HI rats, with increased expression of O1 and myelin basic protein (MBP) in the white matter. Furthermore, using electron microscopy, we demonstrated that myelin formation was enhanced in HI+cABC rats, which had an increased number of myelinated axons and decreased G-ratios of myelin compared to HI rats. Finally, HI+cABC rats performed better in the Morris water maze task than HI rats, which indicates an improvement in cognitive ability. Our results suggest that CSPGs inhibit both the maturation of OLs and the process of myelination after neonatal HI brain injury. The data also raise the possibility that modifying CSPGs may repair this type of lesion associated with demyelination. Copyright © 2015. Published by Elsevier Inc.
    Experimental Neurology 04/2015; 269. DOI:10.1016/j.expneurol.2015.03.026 · 4.70 Impact Factor
  • Jin-ping Zhang · Jianguo Zhou · Chao Chen · Wenjing Shi ·

    Journal of microbiology, immunology, and infection = Wei mian yu gan ran za zhi 04/2015; 48(2):S48. DOI:10.1016/j.jmii.2015.02.089 · 2.35 Impact Factor
  • Jinping Zhang · Jianguo Zhou · Baogan Xu · Chao Chen · Wenjing Shi ·
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    ABSTRACT: TLR insufficiency increases newborn's susceptibility to infectious disease. The peripheral blood of four premature births has been collected weekly from the 28(th) gestational week (GW) until maturity at 36(th) GW. Microarray assays were used to derive dynamic follow-up data of TLR1-10 and other TLR signaling pathway associated factor changes. The follow-up results showed that the transcription level of TLR1 increased at the 36(th), TLR 3 decreased at the 33(rd) and TLR7 increased at the 34(th) GW significantly, whereas NFkB and its activator TBK1 were highest transcribed in the 28(th) and 32(nd) GW. Low TLR4 transcription in addition to late MD-2 maturation (33(rd) GW) indicated a lack of defense mechanisms against bacterial infections in preterm births particular in the first weeks after birth. Late transcriptional enhancements of TLR1 and MYD88 (35(th) week) as well as β 2 microglobulin (35(th) GW) also indicated a weak immune system in the early maturation stages. The transcription levels of TLR1, 3, 7 and the signaling pathway associated cofactors were different transcribed during the 28(th) and 36(th) GWs of the premature newborns. In the early stage after preterm birth, beside peak transcriptions of NFkB and TBK1, the immune system is not fully developed and maturation takes place mainly between the 33th and 35(th) GW.
    International Journal of Clinical and Experimental Medicine 03/2015; 8(3):4108-14. · 1.28 Impact Factor
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    ABSTRACT: Few data are available on central-line associated bloodstream infections (CLABSIs) in Chinese neonatal intensive care units (NICUs). The aims of this study were to characterize CLABSIs among neonates in a Chinese NICU and evaluate the impact of a multifaceted evidence-based practice for improving quality program to decrease CLABSI. We conducted a prospective before-after intervention study with a 1-year follow-up among patients with central lines at the NICU of the Children's Hospital of Fudan University between January 2008 and December 2010. The study was conducted in 3 phases: before, during, and after the intervention. A multifaceted infection control program was introduced in phase 2 with successive surveillance. CLABSIs were prospectively monitored and compared. A total of 171 patients with central lines (CLs) were observed; 29 of them developed CLABSI corresponding to 7.35 per 1,000 catheter days, with a CL utilization ratio of 37.9%. Overall CLABSI rate decreased gradually from 16.7 per 1,000 CL days in phase 1 to 7.6 per 1,000 CL days in phase 2 (P = .08) to 5.2 per 1,000 CL days in phase 3 (P < .01). Gram-negative bacterium (54.5%) was the predominant pathogen in CLABSIs. A multifaceted infection control program is effective in reducing the CLABSI rate among neonates. Such interventions could be extended to other resource-limited countries. Copyright © 2015 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.
    American Journal of Infection Control 03/2015; 43(3):275-9. DOI:10.1016/j.ajic.2014.12.001 · 2.21 Impact Factor
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    ABSTRACT: Since 1986, the reference of birth weight for gestational age has not been updated. The aim of this study was to set up Chinese neonatal network to investigate the current situation of birth weight in China, especially preterm birth weight, to develop the new reference for birth weight for gestational age and birth weight curve. A nationwide neonatology network was established in China. This survey was carried out in 63 hospitals of 23 provinces, municipalities and autonomous regions. We continuously collected the information of live births in participating hospitals during the study period of 2011-2014. Data describing birth weight and gestational age were collected prospectively. Newborn's birth weight was measured by electronic scale within 2 hours after birth when baby was undressed. The evaluation of gestational age was based on the combination of mother's last menstrual period, ultrasound in first trimester and gestational age estimation by gestational age scoring system. the growth curve was drawn by using LMSP method, which was conducted in GAMLSS 1.9-4 software package in R software 2.11.1. A total of 159 334 newborn infants were enrolled in this study. There were 84 447 male and 74 907 female. The mean birth weight was (3 232 ± 555) g, the mean birth weight of male newborn was (3 271 ± 576) g, the mean weight of female newborn was (3 188 ± 528) g. The test of the variables' distribution suggested that the distribution of gestational age and birth weight did not fit the normal distribution, the optimal distribution for them was BCT distribution. The Q-Q plot test and worm plot test suggested that this curve fitted the distribution optimally. The male and female neonatal birth weight curve was developed using the same method. Using GAMLSS method to establish nationwide neonatal birth weight curve, and the first time to update the birth weight reference in recent 28 years.
    Zhonghua er ke za zhi. Chinese journal of pediatrics 02/2015; 53(2):97-103.
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    ABSTRACT: Low birth weight is associated with an increased risk of adverse outcomes in many diseases in adult life. We investigated the expression of IGF-II and the status of differentially methylated regions (DMR) in small for gestational age (SGA) infants after birth. Plasma IGF-II, IGF-II receptor (IGF2R), IGF-I, and IGF-binding protein 3 (IGFBP3) levels were measured after birth in 150 newborn infants. These included 30 term appropriate for gestational age (AGA), 30 term SGA, 30 term large for gestational age (LGA), 30 preterm AGA, and 30 preterm SGA infants. Plasma IGF-II levels after birth were lower in both term SGA (435.1±33.82 vs. 620.4±44.79, p=0.002) and LGA infants (483.7±33.8 vs. 620.42±44.79, p=0.018) than in term AGA infants. The expression of IGF-II was associated with birth weight and expressed at high levels, which suggests that IGF-II may continue to play an important role after birth.
    Journal of pediatric endocrinology & metabolism: JPEM 12/2014; 28(5-6). DOI:10.1515/jpem-2014-0269 · 1.00 Impact Factor
  • Weiwei Lin · Chao Chen ·

    Zhonghua er ke za zhi. Chinese journal of pediatrics 10/2014; 52(10):763-6.
  • Bi Ze · Chao Chen ·

    Zhonghua er ke za zhi. Chinese journal of pediatrics 10/2014; 52(10):760-3.
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    ABSTRACT: Objectives: To investigate plasma ghrelin and obestatin levels, and ghrelin/obestatin prepropeptide gene polymorphisms, in sequentially enrolled small for gestational age (SGA) infants. Methods: Neonates were sequentially enrolled into this study and were then subdivided into different groups, according to different study aims and availability of study materials. Consequently, plasma ghrelin and obestatin levels were measured in term SGA, term appropriate for gestational age (AGA), term large for gestational age (LGA), preterm SGA and preterm AGA neonates. Levels of both peptides were also measured in AGA infants of different gestational ages, and in term AGA neonates at different days following birth. Three ghrelin/obestatin prepropeptide gene single nucleotide polymorphisms (SNPs), Arg51Gln, Leu72Met, and Gln90Leu, were measured in neonates. Results: The study involved a total cohort of 581 neonates. Out of 150 neonates (30 term AGA, 30 term SGA, 30 term LGA, 30 preterm AGA, and 30 preterm SGA), plasma obestatin levels were significantly higher in term SGA versus term LGA neonates (0.21 ± 0.02 ng/ml versus 0.17 ± 0.01 ng/ml, respectively). Out of a wider cohort, there were no significant differences in genotypes and allele frequencies of Arg51Gln, Leu72Met, and Gln90Leu SNPs between term SGA and AGA neonates, or between preterm SGA and AGA neonates. Conclusions: Ghrelin/obestatin prepropeptide polymorphisms were not found to be associated with SGA status in neonates; however, ghrelin and obestatin levels may be involved in growth and development. Further studies are required to understand the relationship between ghrelin, obestatin and prenatal development.
    The Journal of international medical research 09/2014; 42(6). DOI:10.1177/0300060514533525 · 1.44 Impact Factor
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    ABSTRACT: Background: Human toll-like receptor 4 (TLR4) is an important receptor in innate immunity, particularly against gram-negative bacterial infection (GNBI). In our study, we evaluated associations of TLR4 single nucleotide polymorphisms (SNPs) with GNBI in Han Chinese neonates. Patients and methods: Polymorphisms in TLR4 were genotyped in 201 neonates with GNBI and 279 gestational age and birth weight-matched controls without GNBI. Polymorphism analyses were applied to allele frequencies of the detected TLR4 SNPs and their associations with various clinical entities, including premature birth and GNBI were assessed. Results: A total of six SNPs with more than 5% frequency were found in several promoter sequences, including rs10759931, rs2737190, rs10116253, rs10983755, rs1927914, and rs10759932. Mutation allele frequencies ranged from 23 to 41%. There were no SNPs with a frequency greater than 5% in exon analyses. Allele G rs2737190 mutations and GGCGGC haplotypes were more frequent among preterm GNBI neonates (odds ratio [OR], 1.32; 95% confidence interval [CI], 1.02-1.71 and OR, 1.89; 95% CI, 1.19-3.00, respectively). No specific alleles or haplotypes were associated with GNBI status among term neonates. Conclusion: In this study population of Han Chinese, there was a significant association between an ethnical unique SNP in the TLR4 promoter region and preterm neonatal GNBIs.
    American Journal of Perinatology 09/2014; 32(04). DOI:10.1055/s-0034-1387929 · 1.91 Impact Factor
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    ABSTRACT: Objectives: Tryptophan not only is an amino acid essential to protein synthesis but also serves as a precursor in 2 important metabolic pathways: the serotonin and the kynurenine pathways. Tryptophan is related to sleeping patterns. The objective of the present study was to determine the tryptophan requirement of term infants using the indicator amino acid oxidation (IAAO) method with L-[1-C]phenylalanine as the indicator. Methods: Enterally fed infants were randomly assigned to tryptophan intakes ranging from 0.5 to 73 mg · kg · day as part of an elemental diet. After 1-day adaptation to the test diet, [C]bicarbonate and L-[1-C]phenylalanine tracers were given enterally. Breath samples were collected at baseline and during isotopic plateaus. The mean tryptophan requirement was determined by using the biphasic linear regression crossover analysis on the fraction of CO2 recovery from L-[1-C]phenylalanine oxidation (FCO2). Data are presented as mean ± standard deviation. Results: A total of 30 term neonates (gestational age 39 ± 1 weeks) were studied at 9 ± 4 days. FCO2 decreased until a tryptophan intake of 15 mg · kg · day; additional increases in tryptophan intake did not affect FCO2. Mean requirement was determined to be 15 mg · kg · day. Conclusions: The mean tryptophan requirement for elemental formula-fed term infants is 15 mg · kg · day. This requirement is lower than the present recommended intake of 29 mg · kg · day, which is based on the average intake of a breastfed infant.
    Journal of Pediatric Gastroenterology and Nutrition 09/2014; 59(3):374-379. DOI:10.1097/MPG.0000000000000434 · 2.63 Impact Factor
  • Bo Sun · Dongyang Liu · Guoyan Zhou · Chao Chen · Fengxiang Ge ·

    International Conference of Information Science and Management Engineering; 09/2014
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    ABSTRACT: AimIFN-γ, an essential cytokine in the viral cell-mediated immune response, has been associated with the pathogenesis of respiratory syncytial virus (RSV) bronchiolitis and to the severity of the infection. The aim of this study was to investigate whether IFN-γ CA microsatellite (rs3138557) polymorphism was associated with susceptibility to RSV in Chinese Han children and with the severity of the infection.Methods The IFN-γ CA microsatellite was tested in 218 RSV bronchiolitis inpatients and 303 healthy controls and the severity of the RSV bronchiolitis was evaluated using a standardised respiratory scoring system.ResultsThe frequencies of CA12+/CA12+, CA12+/CA12- and CA12-/CA12- in the 218 RSV bronchiolitis patients and 303 controls were approximately 11% versus 19%, 55% versus 53% and 34% versus 28% respectively. The gene polymorphism of IFN-γ CA repeats between the two groups was statistically different. The clinical respiratory scores of RSV bronchiolitis cases with CA12+/CA12+ and CA12+/CA12- were 2.84±0.40(SD) and 2.95±0.44(SD), respectively, and these were significantly lower than the 3.1±0.36 (SD) score for those with CA12-/CA12-.ConclusionIFN-γ CA microsatellite polymorphism was associated with the susceptibility of Chinese Han children to RSV and the severity of the infection.This article is protected by copyright. All rights reserved.
    Acta Paediatrica 08/2014; 103(12). DOI:10.1111/apa.12767 · 1.67 Impact Factor

Publication Stats

382 Citations
160.03 Total Impact Points


  • 2003-2015
    • Fudan University
      • Department of Pediatrics
      Shanghai, Shanghai Shi, China
  • 2014
    • The University of Warwick
      • Department of Computer Science
      Coventry, England, United Kingdom
  • 2013
    • Shanghai Children's Hospital
      Shanghai, Shanghai Shi, China