Shuping Han

Nanjing Medical University, Nanjing, Jiangsu Sheng, China

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Publications (13)22.92 Total impact

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    ABSTRACT: Polychlorinated biphenyls (PCBs) are ubiquitous environmental pollutants that may pose significant health-risks to various organisms including humans. Although the mixed PCB Aroclor 1254 is widespread in the environment, its potential toxic effect on heart development and the mechanism underlying its developmental toxicity have not been previously studied. Here, we used the zebrafish as a toxicogenomic model to examine the effects of Aroclor 1254 on heart development. We found that PCB exposure during zebrafish development induced heart abnormalities including pericardial edema and cardiac looping defects. Further malformations of the zebrafish embryo were observed and death of the larvae occurred in a time- and dose-dependent manner. Our mechanistic studies revealed that abnormalities in the arylhydrocarbon receptor, Wnt and retinoic acid signaling pathways may underlie the effects of PCBs on zebrafish heart development. Interestingly, co-administration of Aroclor 1254 and diethylaminobenzaldehyde, an inhibitor of retinaldehyde dehydrogenase, partially rescued the toxic effects of PCBs on zebrafish heart development. In conclusion, PCBs can induce developmental defects in the zebrafish heart, which may be mediated by abnormal RA signaling.
    Molecular Biology Reports 08/2014; · 2.51 Impact Factor
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    ABSTRACT: Background: MicroRNAs are broadly accepted as crucial regulators of cardiovascular development, and dysregulation of their expression has been linked to cardiac disease. MicroRNA cluster miR-17-92 has been implicated in cardiac development and function, yet its defined mechanisms of action in this context are uncertain. Here, we focused on miR-19b, a key component of the miR-17-92 cluster proven to induce cardiomyocyte proliferation in vitro. We aimed to identify the biological significance of miR-19b in cardiac development and its underlying molecular mechanism of action in vivo. Methods: We micro-injected zebrafish embryos with different concentrations (0, 2, 4 and 8 μm) of miR-19b mimics or a negative control, and assessed the embryo malformation rate, mortality rate, hatching rate and heart abnormalities at 72 hours post-fertilization (72 hpf). Results: We found that overexpression of miR-19b impacted left-right symmetry and cardiac development of zebrafish embryos, characterized by pericardial edema, slower heart rate and cardiac looping defects in a dose-dependent manner. Moreover, several important signaling molecules in the Wnt signaling pathway were abnormally expressed, suggesting that overexpression of miR-19b induces the inhibition of the Wnt signaling pathway by directly targeting ctnnb1. Interestingly, the deformed cardiac phenotype was partially rescued by treatment with the GSK3β inhibitor lithium chloride. Conclusion: Our findings suggest that miR-19b regulates laterality development and heart looping in zebrafish embryos by targeting ctnnb1. © 2014 S. Karger AG, Basel.
    01/2014; 33(6):1988-2002.
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    ABSTRACT: Objetivo validar de forma prospectiva um nomograma de bilirrubina transcutânea (BTc) para identificar hiperbilirrubinemia grave em neonatos a termo e pré‐termo tardios saudáveis na China. Métodos foi realizado um estudo multicêntrico que incluiu 9174 neonatos a termo e pré‐termo tardios saudáveis em oito unidades da China. Foram realizadas dosagens de BTc utilizando um bilirrubinômetro. Os valores de BTc foram traçados em um nomograma de BTc para identificar a capacidade de predição de hiperbilirrubinemia significativa. Resultados 972 recém‐nascidos (10,6%) desenvolveram hiperbilirrubinemia significativa. O percentil 40 de nosso nomograma pode identificar todos os recém‐nascidos com risco de hiperbilirrubinemia significativa, porém com baixo valor preditivo positivo (VPP) (18,9%). De 453 recém‐nascidos acima do percentil 95, 275 recém‐nascidos desenvolveram posteriormente hiperbilirrubinemia significativa, com VPP elevado (60,7%), porém com baixa sensibilidade (28,3%). O percentil de 75 foi altamente específico (81,9%) e moderadamente sensível (79,8%). A área sob a curva (ASC) de nosso nomograma de BTc foi de 0,875. Conclusões este estudo validou o nomograma de BTc, que pode ser utilizado para prever hiperbilirrubinemia significativa em neonatos a termo e pré‐termo tardios saudáveis na China. Contudo, combinar o nomograma de BTc e fatores de risco clínicos pode melhorar a precisão de predição da hiperbilirrubinemia grave, o que não foi avaliado neste estudo. São necessários estudos adicionais para confirmar essa combinação.
    Jornal de pediatria 01/2014; · 1.07 Impact Factor
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    ABSTRACT: Many long non-coding RNAs (lncRNAs) are species specific and seem to be less conserved than protein-coding genes. Some of them are involved in the development of the lateral mesoderm in the heart and in the differentiation of cardiomyocytes. The purpose of the study was to investigate the expression profiles of lncRNAs during the differentiation of P19 cells into cardiomyocytes, with a view to studying the biological function of lncRNAs and their involvement in the mechanism of heart development. First, we observed the morphology of P19 cells during differentiation using an inverted microscope. Then, cardiac troponin T (cTnT) expression was detected to validate that the cells had successfully differentiated into cardiac myocytes by real-time reverse transcriptase polymerase chain reaction (real-time RT-PCR) and western blotting. Lastly, the expression profile of lncRNA genes was obtained using an lncRNA microarray and real-time RT-PCR analyses. The microarray results showed that 40 lncRNAs were differentially expressed, of which 28 were upregulated and 12 were downregulated in differentiated cardiomyocytes. The differentially expressed lncRNAs were further validated. Our results illustrated a critical role of lncRNAs during the differentiation of P19 cells into cardiac myocytes, which will provide the foundation for further study of the biological functions of lncRNAs and the mechanism of heart development.
    International journal of medical sciences 01/2014; 11(5):500-7. · 2.07 Impact Factor
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    ABSTRACT: BACKGROUND: Congenital heart defects (CHD) are the most common form of malformation during embryonic development. Circulating miRNAs have recently been shown to serve as diagnostic/prognostic biomarkers in patients with cancers. Our current study focused on the altered expression of maternal serum miRNAs and their correlation with fetal CHD. Methodology/Principle Findings We systematically performed SOLiD sequencing followed by individual quantitative reverse transcription polymerase chain reaction (qRT-PCR) assays to identify and validate the expression of maternal serum miRNAs at 18-22 weeks of gestation. Four miRNAs (miR-19b, miR-22, miR-29c and miR-375) were found to be significantly upregulated in pregnant women with fetal CHD, with an area under the receiver operating characteristic (ROC) curve (AUC) of 0.79, 0.671, 0.767 and 0.693, respectively. Furthermore, the combination of the four miRNAs using multiple logistic regression analysis showed a larger AUC (0.813) that was more efficient for the early detection of fetal CHD. CONCLUSIONS/SIGNIFICANCE: We identified and validated a class of four maternal serum miRNAs which could act as novel non-invasive biomarkers for the prenatal detection of fetal CHD.
    Clinica chimica acta; international journal of clinical chemistry 05/2013; · 2.54 Impact Factor
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    ABSTRACT: To detect potential mutations of OTC gene in a male infant affected with ornithine transcarbamylase deficiency. Genomic DNA were isolated from peripheral blood samples of family members and 100 healthy individuals. Potential mutations of the 10 exons of OTC gene were screened with PCR and Sanger sequencing. A homozygous missense mutation c.917G>C in exon 9, which results in p.R306T, was identified in the infant. Sequencing of the mother and two female members of the family indicated a heterozygous status for the same mutation. The same mutation was not found in other members of the family and 100 healthy controls. A missense mutation c.917G>C in the OTC gene is responsible for the pathogenesis of the disease. Identification of the mutation can facilitate prenatal diagnosis and genetic counseling for the family.
    Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical genetics 04/2013; 30(2):195-8.
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    ABSTRACT: Overweight/obesity in women of childbearing age is a serious public-health problem. In China, the incidence of maternal overweight/obesity has been increasing. However, there is not a meta-analysis to determine if pre-pregnancy body mass index (BMI) is related to infant birth weight (BW) and offspring overweight/obesity. Three electronic bibliographic databases (MEDLINE, EMBASE and CINAHL) were searched systematically from January 1970 to November 2012. The dichotomous data on pre-pregnancy overweight/obesity and BW or offspring overweight/obesity were extracted. Summary statistics (odds ratios, ORs) were used by Review Manager, version 5.1.7. After screening 665 citations from three electronic databases, we included 45 studies (most of high or medium quality). Compared with normal-weight mothers, pre-pregnancy underweight increased the risk of small for gestational age (SGA) (odds ratios [OR], 1.81; 95% confidence interval [CI], 1.76-1.87); low BW (OR, 1.47; 95% CI, 1.27-1.71). Pre-pregnancy overweight/obesity increased the risk of being large for gestational age (LGA) (OR, 1.53; 95% CI, 1.44-1.63; and OR, 2.08; 95% CI; 1.95-2.23), high BW (OR, 1.53; 95% CI, 1.44-1.63; and OR, 2.00; 95% CI; 1.84-2.18), macrosomia (OR, 1.67; 95% CI, 1.42-1.97; and OR, 3.23; 95% CI, 2.39-4.37), and subsequent offspring overweight/obesity (OR, 1.95; 95% CI, 1.77-2.13; and OR, 3.06; 95% CI, 2.68-3.49), respectively. Sensitivity analyses revealed that sample size, study method, quality grade of study, source of pre-pregnancy BMI or BW had a strong impact on the association between pre-pregnancy obesity and LGA. No significant evidence of publication bias was observed. Pre-pregnancy underweight increases the risk of SGA and LBW; pre-pregnancy overweight/obesity increases the risk of LGA, HBW, macrosomia, and subsequent offspring overweight/obesity. A potential effect modification by maternal age, ethnicity, gestational weight gain, as well as the role of gestational diseases should be addressed in future studies.
    PLoS ONE 01/2013; 8(4):e61627. · 3.53 Impact Factor
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    ABSTRACT: Overweight/obesity is a serious public health problem that affects a large part of the world population across all age and racial/ethnic groups. However, there has not been a meta-analysis of the prevalence of childhood and adolescent overweight/obesity in China during the past 30 years. The China National Knowledge Infrastructure and Wanfang DATA, MEDLINE, EMBASE and Cumulative Index to Nursing and Allied Health Literature were searched for relevant studies published between January 1970 and June 2012. The prevalence of overweight/obesity over time was pooled using Stata/SE, version 9. Summary statistics (odds ratios, ORs) were used to compare sex-specific and urban-rural preponderance of overweight/obesity using Review Manager. After screening 1326 papers, we included 35 papers (41 studies), most of medium quality. The prevalence of overweight/obesity increased from 1.8% (95% confidence interval [CI], 0.4%-3.1%) and 0.4% (95% CI, -0.1% to -0.8%) respectively in 1981-1985 to 13.1% (95% CI, 11.2%-15.0%) and 7.5% (95% CI, 6.6%-8.4%) respectively in 2006-2010. The average annual increase was 8.3% and 12.4% respectively. Boys were more likely to be overweight/obese than girls (OR, 1.36; 95% CI, 1.24-1.49 and OR, 1.68; 95% CI, 1.52-1.86 respectively). The prevalence of overweight/obesity was higher in urban areas than in rural areas (OR, 1.66; 95% CI, 1.54-1.79 and OR, 1.97; 95% CI, 1.68-2.30 respectively). For age-specific subgroup analyses, both overweight and obesity increased more rapidly in the toddler stage than in other developmental stages. Sensitivity analyses showed that sample-size differences, study quality, overweight/obesity criteria and geographical distribution affected overweight/obesity prevalence. Toddlers and urban boys were at particularly high risk; the prevalence in these groups increased more rapidly than in their counterparts. Public health prevention strategies are urgently needed to modify health behaviors of children and adolescents and control overweight/obesity in China.
    PLoS ONE 01/2012; 7(12):e51949. · 3.53 Impact Factor
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    ABSTRACT: The pre- and postnatal detection rate, incidence, clinical characteristics and outcomes of congenital heart disease (CHD) have been studied in developed countries for many years, but rarely have large-scale studies been reported in Chinese populations. The aim of the present study was to investigate the pre- and postnatal detection rates, incidence, clinical characteristics and outcomes of CHD in a Chinese hospital in order to improve the future screening and treatment of CHD. Fetuses without risk factors for CHD were screened using basic cardiac ultrasound examination (BCUE). Fetuses with suspected cardiac malformation revealed by BCUE and fetuses with risk factors were screened using extended cardiac ultrasound examination. Outcomes recorded from fetal, neonatal and postmortem records over 4 years (2006-2009) included: therapeutic termination of pregnancy, spontaneous abortions or stillbirths, deaths at birth or in the neonatal period (before 28 days of age), and rate of birth and clinical characteristics of newborns. A total of 34,071 fetuses were screened for CHD during a period of 4 years, of which 173 fetuses were screened for CHD using BCUE and 301 fetuses were screened using extended cardiac ultrasound examination. The incidence of fetal CHD increased from 1.1% in 2006 to 2.4% in 2009 (P < 0.05), yielding an overall incidence of 1.5% (523/34,071). Of the fetuses with CHD, 48.2% (252/523) died before 28 days of age (including intra-uterine death and termination of pregnancy), 51.8% (271/523) lived more than 28 days and the incidence of live newborns with CHD was 0.80% (271/34071). The prevalence of CHD was quite common in this Chinese hospital. Detailed profiles of CHD suggest that, while training programs in obstetric screening at this hospital were beneficial, prenatal intervention, treatment and care of fetal CHD were inefficient and should be strengthened in China.
    Pediatrics International 08/2011; 53(6):1059-65. · 0.88 Impact Factor
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    ABSTRACT: Polymorphisms in adipokine genes, such as leptin (LEP), leptin receptor (LEPR), resistin (RETN), adiponectin (ADIPOQ), interleukin-1β (IL-1β), IL-6 (IL-6), and tumor necrosis factor-α (TNF-α) may be involved in the development of obesity. We conducted a systematic review of published evidence on the association between different adipokine genes and the risk of obesity. Librarian-designed searches of PubMed and HuGeNet, review of reference lists from published reviews and content expert advice identified potentially eligible studies. The genotyping information and polymorphisms of different adipokine genes, numbers of genotyped cases and controls and frequencies of genotypes were extracted from 48 eligible studies included in this review. Twenty-one polymorphisms each associated with obesity in at least one study were identified. Polymorphisms in the adipokine genes, LEP, LEPR, and RETN were not associated with obesity susceptibility, whereas ADIPOQ G276T (T vs. G: odds ratio (OR), 1.59; 95% confidence interval (CI), 1.39-1.81), IL-1β C3953T (CC vs. CT+TT: OR, 1.61; 95% CI, 1.18-2.20), and TNF-α G308A (GG vs. GA+AA: OR, 1.19; 95% CI, 1.02-1.39) polymorphisms were associated with an increased risk of obesity. The IL-6 G174C polymorphism was also associated obesity when using allelic comparisons, the recessive genetic model and the dominant genetic model with OR (95% CI) of 1.95 (1.37-2.77), 1.44 (1.15-1.80), and 1.36 (1.16-1.59), respectively. No significant evidence of publication bias was present. However, these "null" results were underpowered due to a small pooled sample size, and analysis of additional case-control studies with larger sample sizes should provide further clarifications.
    Obesity 06/2011; 20(2):396-406. · 3.92 Impact Factor
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    ABSTRACT: Congenital heart defects (CHD) are the most common form of major birth defect, affecting almost 1% of live births. These defects place a significant economic burden on the National Health Service and on the psychological wellbeing of affected families. The early screening and identification of neonates with CHD could reduce morbidity and mortality by allowing proactive medical treatment and parental counseling about options during pregnancy, including termination. Fetal echocardiography is the principal screening tool for the identification of CHD, but its accuracy mainly depends on the skill and experience of the operator. Various biomarkers of screening for fetal CHD are currently available, such as nuchal translucency (NT), β-hCG and PAPP-A; however, these are non-specific indexes with high incidences of false positive results. Certain specific microRNAs (miRNAs) of cardiogenesis have been identified, which correlate positively with placental miRNA expression. These miRNAs of placental origin can be detected in maternal peripheral blood. Therefore, we postulate that these maternal serum miRNAs may be a potential biomarker for fetal CHD.
    Medical Hypotheses 03/2011; 76(3):424-6. · 1.18 Impact Factor
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    ABSTRACT: A meta-analysis was performed to assess the accuracy of the procalcitonin (PCT) test for diagnosing neonatal sepsis. The major databases, MEDLINE, EMBASE and the Cochrane Library were searched for studies published between January 1996 and May 2009 that evaluated PCT as a diagnostic marker for neonatal sepsis and provided sufficient data to calculate sensitivity and specificity. Twenty-two studies were included in the analysis. Trials that evaluated the PCT test for the diagnosis of early-onset neonatal sepsis at different time points (birth, 0-12 h, 12-24 h, and 24-48 h) and late-onset neonatal sepsis (LONS) all showed moderate accuracy (Q* = 0.79, 0.86, 0.81, 0.82, and 0.77, respectively). The PCT test was more accurate than the C-reactive protein (CRP) test for the diagnosis of LONS. A sensitivity analysis found that differences in PCT assay producer, gestational age and severity of sepsis in the study population may partially explain the between-studies heterogeneity. The PCT test showed moderate accuracy in diagnosing neonatal sepsis, regardless of differences in diagnostic criteria and time points for testing. For the diagnosis of LONS, the PCT test showed better accuracy than the CRP test. PCT is a valuable additional tool for the diagnosis of neonatal sepsis.
    Scandinavian Journal of Infectious Diseases 10/2010; 42(10):723-33. · 1.71 Impact Factor
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