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Zhou Q.,Fudan University | Zhou Q.,Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases | Acharya G.,University of Tromso | Acharya G.,Karolinska Institutet | And 6 more authors.
Acta Obstetricia et Gynecologica Scandinavica | Year: 2016

Many risk factors associated with adverse pregnancy outcomes can be identified and modified preconceptionally. Despite a broad consensus that preconception care should be provided to all couples of reproductive age, it has not been integrated in routine healthcare. There are several barriers to its implementation, and even in the most resourceful countries, it is only provided to some select high-risk groups, rather than being an organized healthcare service provision to all. Recently, China seems to be leading the way by implementing preconception care nationwide in all rural areas. Its National Free Preconception Health Examination Project is a unique model of comprehensive preconception care. Advantages of this ambitious project are now becoming evident and benefiting the most vulnerable sections of Chinese society. This commentary provides an overview of National Free Preconception Health Examination Project and highlights the concepts that could be further developed and adapted into a model of preconception care. © 2016 Nordic Federation of Societies of Obstetrics and Gynecology, Acta Obstetricia et Gynecologica Scandinavica. Source

Gu R.,Fudan University | Xu J.,Fudan University | Lin Y.,Fudan University | Zhang J.,Fudan University | And 11 more authors.
Pediatric Research | Year: 2016

Introduction:Retinoic acid X receptor alpha (RXRα) and Connexin 43 (Cx43) both play a crucial role in cardiogenesis. However, little is known about the interplay mechanism between the RXRα and Cx43.Methods:The activations of retinoic acid response element (RARE) in Cx43 were measured by luciferase transfection assay. Electrophoretic mobility shift assay (EMSA) and chromatin immunoprecipitation (ChIP) was performed to prove that RXRα can directly bind to the RARE sequence. Quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting were used to analyze the RXRα and Cx43 mRNA level and protein level in cells.Results:In this study, we confirmed the negative association of the gene expression between the RXRα and Cx43 in the cell level. Interestingly, a functional RARE was detected in the region from -1,426 to -314 base pairs upstream from the transcriptional start site of Cx43. Moreover, we also prove that RXRα can directly bind to this RARE sequence in vitro and in vivo.Conclusions:RXRα negatively regulates the transcription and expression by directly binding to the RARE in the promoter of Cx43. The RARE-like sequence harbored in the Cx43 promoter region may serve as a functional RARE in the retinoic acid (RA) signaling pathway. © Copyright 2016 International Pediatric Research Foundation, Inc. Source

Yuan Y.,Fudan University | Chen W.,Fudan University | Ma X.,Fudan University | Ma X.,Shanghai Key Laboratory of Birth Defects | And 6 more authors.
Early Human Development | Year: 2015

Background: Although congenital heart defect (CHD) pedigrees are rare, they are generally taken as evidence of the existence of a genetic etiologic mechanism or environmental factors common to family members, or a combination of both. Therefore, the analysis of CHD pedigrees is important for bridging the gap in our knowledge of its etiology. Aims: To assess the prevalence of CHD and evaluate the nongenetic factors in the CHD patients and healthy controls in the pedigrees. Study design: Observational retrospective study. Subjects: Twenty-three CHD pedigrees were involved in the prevalence statistics; thirty-nine CHD cases and fifty-two healthy controls in the CHD pedigrees were included in the family-based noninherited factors analysis. Outcome measures: The three-degree relatives and overall CHD prevalence were calculated. Thirty-four noninherited risk factors were compared between the CHD and control groups, first by univariate analysis and later by multivariable logistic stepwise regression analysis. Results: The CHD prevalence of the probands' relatives in all pedigrees was 8.0%, and it was 10.9%, 2.9% and 11.9% in first-, second- and third-degree relatives, respectively. The three risk factors, including maternal febrile illnesses (OR. = 14.2, 95%CI: [1.5 - 133.7]), influenza (OR = 6.9 [2.0 - 23.6]) and air pollution (OR = 13.5 [2.6 - 70.5]), were strongly associated with a higher risk of CHD in our sample. Conclusions: For the cluster and high prevalence of CHD in the collected pedigrees, our study confirms that genetic factors play a major role in the pathogenesis of CHD, while environmental factors, such as maternal febrile illnesses, influenza and air pollution, may also increase the burden of risk for CHD pathogenesis. © 2015 Elsevier Ireland Ltd. Source

Li J.,Fudan University | Cao Y.-Y.,Fudan University | Ma X.-J.,Fudan University | Ma X.-J.,Shanghai Key Laboratory of Birth Defects | And 11 more authors.
Frontiers in Bioscience - Landmark | Year: 2015

Ventricular septal defect (VSD) is a common congenital heart malformation. Several factors lead to the development of VSD, including familial causes, exposure to certain drugs, infectious agents, and maternal metabolic disturbances. We hypothesized that induced pluripotent stem (iPS) cells can be obtained from VSD patients to generate cardiomyocytes. Here, we show the generation and cardiomyocyte differentiation of iPS cells from the thymic epithelial cells of a patient with VSD (TECs-VSD) by overexpressing four transcription factors: OCT4, SOX2, NANOG, and LIN28 using lentiviral vectors. The self-renewal capacity and pluripotency of iPS cells was verified in vitro by expression of pluripotency markers and formation of teratoma in vivo. The results show that iPS cells can be derived from patients with VSD and they can be differentiated into cardiomyocytes. These cells can be used for understanding the pathogenesis of defect that causes VSD. © 2015, Frontiers in Bioscience. All rights reserved. Source

Zhao Q.-m.,Fudan University | Ma X.-j.,Fudan University | Ma X.-j.,Shanghai Key Laboratory of Birth Defects | Ge X.-l.,Fudan University | And 12 more authors.
The Lancet | Year: 2014

Background: Several pioneering studies have provided evidence for the introduction of universal pulse oximetry screening for critical congenital heart disease. However, whether the benefits of screening reported in studies from high-income countries would translate with similar success to low-income countries is unknown. We assessed the feasibility and reliability of pulse oximetry plus clinical assessment for detection of major congenital heart disease, especially critical congenital heart disease, in China. Methods: We did a pilot study at three hospitals in Shanghai to assess the accuracy of pulse oximetry plus clinical assessment for detection of congenital heart disease. We made a data collection plan before recruitment. We then undertook a large, prospective, and multicentre screening study in which we screened all consecutive newborn babies (aged 6-72 h) born at 18 hospitals in China between Aug 1, 2011, and Nov 30, 2012. Newborn babies with positive screen results (either an abnormal pulse oximetry or abnormal clinical assessment) were referred for echocardiography within 24 h of screening. We identified false-negative results by clinical follow-up and parents' feedback. We calculated sensitivity, specificity, positive and negative predictive values, and positive and negative likelihood ratios for pulse oximetry alone, and in combination with clinical assessment, for detection of major and critical congenital heart disease. Findings: In the pilot study, 6785 consecutive newborn babies were screened; 46 of 49 (94%) cases of asymptomatic major congenital heart disease and eight of eight (100%) cases of asymptomatic critical disease were detected by pulse oximetry and clinical assessment. In the prospective multicentre study, we screened 122 738 consecutive newborn babies (120 707 asymptomatic and 2031 symptomatic), and detected congenital heart disease in 1071 (157 critical and 330 major). In asymptomatic newborn babies, the sensitivity of pulse oximetry plus clinical assessment was 93·2% (95% CI 87·9-96·2) for critical congenital heart disease and 90·2% (86·4-93·0) for major disease. The addition of pulse oximetry to clinical assessment improved sensitivity for detection of critical congenital heart disease from 77·4% (95% CI 70·0-83·4) to 93·2% (87·9-96·2). The false-positive rate for detection of critical disease was 2·7% (3298 of 120 392) for clinical assessment alone and 0·3% (394 of 120 561) for pulse oximetry alone. Interpretation: Pulse oximetry plus clinical assessment is feasible and reliable for the detection of major congenital heart disease in newborn babies in China. This simple and accurate combined method should be used in maternity hospitals to screen for congenital heart disease. Funding: Key Clinical Research Project sponsored by Ministry of Health, Shanghai Public Health Three-Year Action Plan sponsored by Shanghai Municipal Government, and National Basic Research Project of China. © 2014 Elsevier Ltd. All rights reserved. Source

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