Yimin Hua

Roles of planar cell polarity pathways in the development of neutral tube defects

Neural tube defects (NTDs) are the second most common birth defect in humans. Despite many advances in the understanding of NTDs and the identification of many genes related to NTDs, the fundamental etiology for the majority of cases of NTDs remains unclear. Planar cell polarity (PCP) signaling pathway, which is important for polarized cell movement (such as cell migration) and organ morphogenesis through the activation of cytoskeletal pathways, has been shown to play multiple roles during neural tube closure. The disrupted function of PCP pathway is connected with some NTDs. Here, we summarize our current understanding of how PCP factors affect the pathogenesis of NTDs.

Performance of Different Scan Protocols of Fetal Echocardiography in the Diagnosis of Fetal Congenital Heart Disease: A Systematic Review and Meta-Analysis

Objective The rapid progress in fetal echocardiography has lead to early detection of congenital heart diseases. Increasing evidences have shown that prenatal diagnosis could be life saving in certain cases. However, there is no agreement on which protocol is most adaptive diagnostic one. Thus, we use meta-analysis to conduct a pooled performance test on 5 diagnostic protocols. Methods We searched PUBMED, EMBASE, the Cochrane Central Register of Controlled Trials and WHO clinical trails registry center to identify relevant studies up to August, 2012. We performed meta-analysis in a fixed/random-effect model using Meta-disc 1.4. We used STATA 11.0 to estimate the publication bias and SPSS 17.0 to evaluate variance. Results We use results from 81 studies in 63 articles to analyze the pooled accuracy. The overall performance of pooled sensitivities of spatiotemporal image correlation (STIC), extend cardiac echography examination (ECEE) and 4 chambers view + outflow tract view + 3 vessels and trachea view (4 CV+OTV+3 VTV) were around 0.90, which was significant higher than that of 4 chambers view + outflow tract view or 3 vessels and trachea view (4 CV+OTV/3 VTV) and 4 chambers view (4 CV). Unfortunately the pooled specificity of STIC was 0.92, which was significant lower than that of other 4 protocols which reached at 1.00. The area under the summary receiver operating characteristic curves value of STIC, ECEE, 4 CV+OTV+3 VTV, 4 CV+OTV/3 VTV and 4 CV were 0.9700, 0.9971, 0.9983, 0.9929 and 0.9928 respectively. Conclusion These results suggest a great diagnostic potential for fetal echocardiography detection as a reliable method of fetal congenital heart disease. But at least 3 sections view (4 CV, OTV and 3 VTV) should be included in scan protocol, while the STIC can be used to provide more information for local details of defects, and can not be used to make a definite diagnosis alone with its low specificity.

Increased Risk for Congenital Heart Defects in Children Carrying the ABCB1 Gene C3435T Polymorphism and Maternal Periconceptional Toxicants Exposure

Backgrounds The etiology of congenital heart defect (CHD) is commonly believed to involve the interaction of multiple environmental and genetic factors. This study aimed to explore the joint effects of the ABCB1 gene C3435T polymorphism and maternal periconceptional toxicants exposure on the CHD risk in a Han Chinese population. Methods An age and gender matched case-control study with standardized data collection involving 201 pairs was conducted. Periconceptional toxicants exposure was obtained through a structured questionnaire. A job exposure matrix (JEM) was used for toxicants exposure assessment. Genotyping of the ABCB1 C3435T polymorphism was performed by sequencing. Logistic regression analysis was performed to assess the joint effects of the ABCB1 gene C3435T polymorphism and toxicants exposure on the risk of CHD. Placenta tissues and umbilical cords were collected to investigate the impact of C3435T polymorphism on the transcription and translation activities of ABCB1 gene. Results Maternal periconceptional exposures to phthalates (adjusted OR: 1.6; 95%CI: 1.0–2.6) and alkylphenolic compounds (adjusted OR:1.8; 95%CI:1.1–3.0) were associated with a higher incidence of CHDs in general. More cases were carriers of the ABCB1 CC/CT genotypes (OR: 2.0, 95%CI: 1.1–3.5, P-value: 0.021). Children carrying the CC/CT genotype and periconceptionally exposed to phthalates and alkylphenolic compounds suffered almost 3.5-fold increased risk of having CHD than non-exposed children with TT genotype (adjusted OR: 3.5, 95%CI: 1.5–7.9, P-value: 0.003), and the OR changed to 4.4 for septal defects (adjusted OR: 4.4,95%CI:1.8–10.9,P-value:0.001). The ABCB1 mRNA expression of the TT genotype was significantly higher than that of the CC genotype (Pu200a=u200a0.03). Compared with TT genotype, lower P-glycoprotein expression was observed for the CC/CT genotypes. Conclusion The C3435T polymorphism in the ABCB1 gene of fetus increases the risks of CHD in a Han Chinese population when the mothers are exposed to phthalates and alkylphenolic compounds during the periconceptional period, particularly for septal defects.

Parental Occupational Exposures to Endocrine Disruptors and the Risk of Simple Isolated Congenital Heart Defects

This study aims to explore the associations between parental occupational exposures to endocrine disruptors (EDs) and simple isolated congenital heart defects (CHDs). A case–control study with standardized data collection involving 761 children with isolated CHDs and 609 children without any congenital malformations was conducted in Sichuan Province of China from March in 2012 to August in 2013. An adjusted job exposure matrix was used for occupational EDs exposure assessment. Logistic regression analysis was performed to assess the associations between parental occupational EDs exposures and CHDs. Maternal age at births, maternal education level, gravity, parity, induced abortion, folic acid use, medication use, drinking capacity and area of residence periconceptionally were selected as confounding factors for mothers. For fathers, we selected the following confounding factors: paternal education level, smoking, drinking frequencies and drinking capacity periconceptionally. Maternal occupational exposures to phthalates are associated with perimembranous ventricular septal defect (PmVSD) (Pxa0=xa00.001, adjusted OR 3.7, 95xa0% CI 1.7–8.0), patent ductus arteriosus (PDA) (Pxa0=xa00.002, adjusted OR 3.8, 95xa0% CI 1.6–8.9), secundum atrial septal defect (s-ASD) (Pxa0=xa00.008, adjusted OR 3.5, 95xa0% CI 1.4–8.7) and pulmonary valve stenosis (PS) (Pxa0=xa00.035, adjusted OR 4.2, 95xa0% CI 1.1–16.0), to alkylphenolic compounds and PmVSD (Pxa0=xa00.003, adjusted OR 2.2, 95xa0% CI 1.3–3.6), PDA (Pxa0=xa00.005, adjusted OR 2.0, 95xa0% CI 1.1–3.5) and PS (Pxa0=xa00.004, adjusted OR 3.8, 95xa0% CI 1.5–9.4), to heavy metals with PmVSD (Pxa0=xa00.003, adjusted OR 7.3, 95xa0% CI 2.0–27.6) and s-ASD (Pxa0=xa00.034, adjusted OR 6.5, 95xa0% CI 1.1–36.7). Paternal occupational exposures to phthalates are associated with PmVSD (Pxa0=xa00.035, adjusted OR 1.6, 95xa0% CI 1.0–2.4) and PS (Pxa0=xa00.026, adjusted OR 2.4, 95xa0% CI 1.1–5.2), to alkylphenolic compounds (Pxa0=xa00.027, adjusted OR 1.5, 95xa0% CI 1.0–2.2) with PmVSD. In conclusion, parental occupational exposures to some specific EDs, in particular phthalates and alkylphenolic compounds, are associated with an increased risk of some CHD phenotypes. However, the findings need to be considered more circumspectly regarding a crude measure of exposure probabilities and small numbers.

Planar Cell Polarity Signaling Pathway in Congenital Heart Diseases

Congenital heart disease (CHD) is a common cardiac disorder in humans. Despite many advances in the understanding of CHD and the identification of many associated genes, the fundamental etiology for the majority of cases remains unclear. The planar cell polarity (PCP) signaling pathway, responsible for tissue polarity in Drosophila and gastrulation movements and cardiogenesis in vertebrates, has been shown to play multiple roles during cardiac differentiation and development. The disrupted function of PCP signaling is connected to some CHDs. Here, we summarize our current understanding of how PCP factors affect the pathogenesis of CHD.

Neurodevelopmental delay with critical congenital heart disease is mainly from prenatal injury not infant cardiac surgery: current evidence based on a meta‐analysis of functional magnetic resonance imaging

No consensus has been reached regarding whether brain injury related to congenital heart disease (CHD) is caused by infant cardiac surgery and/or prenatal injury resulting from the CHD. We performed this meta‐analysis to identify the likely cause of neurodevelopmental delay in CHD patients.

Evaluation of therapeutic effect and cytokine change during transplacental Digoxin treatment for fetal heart failure associated with fetal tachycardia, a case–control study

a Dept. of Pediatric Cardiology, West China Second University Hospital, Sichuan University, Chengdu 610041, PR China b Dept. of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University, Chengdu 610041, PR China c Dept. of Ultrasound Cardiography, West China Second University Hospital, Sichuan University, Chengdu 610041, PR China d Dept. of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu 610041, PR China e Key Laboratory of Ob&G and Pediatric Diseases and Birth Defects of Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu 610041, PR China f Program for Yangtze River Scholars and Innovative Research Team in University, West China Medical Center, West China Second University Hospital, Sichuan University, Chengdu 610041, PR China

Sodium tanshinone IIA sulfonate and sodium danshensu open the placental barrier through down-regulation of placental P-glycoprotein in mice: Implications in the transplacental digoxin treatment for fetal heart failure

a Department of Pediatric Cardiology, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, China b The Pulmonary Vascular Remodeling Research Unit, West China Institute of Women and Childrens Health, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, China c West China Medical School of Sichuan University, Chengdu, Sichuan, China d Key Laboratory of Obstetric & Gynecologic and Pediatric Diseases and Birth Defects of Ministry of Education,West China Second University Hospital, Sichuan University, Chengdu, Sichuan, China

mirnas as biomarkers for diagnosis of heart failure: A systematic review and meta-analysis

Background: With the rapid development of molecular biology, the kind of mircoRNA (miRNA) has been introduced into emerging role both in cardiac development and pathological procedure. Thus, we conduct this meta-analysis to find out the role of circulating miRNA as a biomarker in detecting heart failure. Methods: We searched PubMed, EMBASE, the Cochrane Central Register of Controlled Trials, and World Health Organization clinical trials registry center to identify relevant studies up to August 2016. We performed meta-analysis in a fixed/random-effect model using Meta-disc 1.4. We used STATA 14.0 to estimate the publication bias and meta-regression. Besides, we took use of SPSS 17.0 to evaluate variance between several groups. Information on true positive, false positive, false negative, and true negative, as well as the quality of research was extracted. Results: We use results from 10 articles to analyze the pooled accuracy. The overall performance of total mixed miRNAs (TmiRs) detection was: pooled sensitivity, 0.74 (95% confidence interval [CI], 0.72 to 0.75); pooled specificity, 0.69 (95%CI, 0.67 to 0.71); and area under the summary receiver operating characteristic curves value (SROC), 0.7991. The miRNA-423-5p (miR-423-5p) detection was: pooled sensitivity, 0.81 (95%CI, 0.76 to 0.85); pooled specificity, 0.67 (95%CI, 0.61 to 0.73); and SROC, 0.8600. However, taken the same patients population, we extracted the data of BNP for detecting heart failure and performed meta-analysis with acceptable SROC as 0.9291. Among the variance analysis, the diagnostic performance of miR-423-5p claimed significant advantages of other pooled results. However, the combination of miRNAs and BNP could increase the accuracy of detecting of heart failure. Unfortunately, there was no dramatic advantage of miR-423-5p compared to BNP protocol. Conclusion: Despite interstudy variability, the performance test of miRNA for detecting heart failure revealed that miR-423-5p demonstrated the potential to be a biomarker. However, other miRNAs were not able to provide enough evidence on promising diagnostic value for heart failure based on the current data. Moreover, the combination of miRNAs and BNP could work as a better method to detection. Unfortunately, BNP was still the most convinced biomarker for such disease.

Amplatzer occluder versus CardioSEAL/STARFlex occluder: a meta-analysis of the efficacy and safety of transcatheter occlusion for patent foramen ovale and atrial septal defect

OBJECTIVEnPercutaneous transcatheter occlusion has benefited thousands of patients suffering from patent foramen ovale and atrial septal defect. However, no general agreement has been reached on the superiority among occluders. Thus, a meta-analysis between the two most commonly adopted types of occluders was conducted.nnnMETHODSnThe literature review has identified relevant studies up to May, 2011 in the databases of PubMed, EMBASE, the Cochrane Central Register of Controlled Trials, and World Health Organization clinical trials registry centre. Meta-analysis was performed in a fixed/random effects model using Revman 5.1.1. Information on complications and outcomes was extracted.nnnRESULTSnAnalysis from included studies reports an outcome in favour of the Amplatzer. The Amplatzer has proven its superiority in efficacy with a significantly lower risk of early (95% confidence interval = 0.09-0.34) and long-term (95% confidence interval = 0.14-0.97) residual shunt rate for atrial septal defect occlusion, although no significant difference in performance has been reported for patent foramen ovale. In addition, the Amplatzer has also remarkably reduced the risk of embolisation by the device (95% confidence interval = 0.07-0.45) for atrial septal defect and new-set atrial fibrillation (95% confidence interval = 0.18-0.48) for patent foramen ovale. On evaluation of recurrent thrombotic events, it was found that the Amplatzer greatly lowered the rate of thrombus formation on the device (95% confidence interval = 0.02-0.21) for patent foramen ovale; however, no statistical difference was found on atrial septal defect evaluation. However, the result indicated no statistically significant difference between the two kinds of occluders in stroke and transient ischaemic attack of patent foramen ovale.nnnCONCLUSIONnThe meta-analysis has proven the Amplatzer to be the superior occluder, serving better prognosis with more fluent procedure and less complications.