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Objective To construct a folic acid deficient model in zebrafish and to observe the axial development in folic acid deficient embryos, so as to probe the mechanism by which folic acid deficiency induces abnormal development of axis. Methods We constructed the folic acid deficient zebrafish model by both using the antagonism of dihydrofolate reductase (MTX) and knocking-down dihydrofolate reductase gene. Then we observed the axial excursion of folic acid deficient embryos at 17 hpf under microscope. We labeled and observed the positions of liver, spleen and heart by using whole-mount in situ hybridization with specific antisense RNA probes. The expressions of some genes, which are down stream factors of Nodal signal pathway and important for axial development, were detected by whole-mount in situ hybridization and Real-time PCR. Results Parts of folic acid deficient embryos had axial excursion and abnormal positions of liver, spleen and heart. The expressing intensities of ntl and gsc appeared normal in folic acid deficient embryos, but the expressing spatial patterns were abnormal, which revealed the malformation of axial mesoderm. Conclusions Folic acid deficiency induced the abnormal development of axis and the malformation of axial mesoderm. Folic acid deficiency had no obviouse effect on Nodal pathway.

Objective To observe the development of hematopoietic stem cell and the apoptosis of ICM(intermediate cell mass) in folic acid deficient zebrafish embryos and investigate the mechanism by which folic acid deficiency induces abnormal hematopoiesis.Method The folic acid deficient zebrafish model was induced by both using the dihydrofolate reductase antagonism methotrexate(MTX) and knock-down dihydrofolate reductase gene.The development of embryos was observed under microscope.The blood cells were detected by O-dianisidine staining.Whole-mount in situ hybridization and real-time PCR were performed to examine the expression of FLK-1,GATA1and GATA2.Apoptosis in intermediate cell mass(ICM) was examined by TUNEL(terminal-deoxynucleotidyl transferase mediated nick end labeling) method.Results The abnormal developments of ICMs were observed both in MTX treated embryos and DHFR knock-down embryos.O-dianisidine staining revealed that folic acid deficiency resulted in the decreasing number of blood cells.In folic acid deficient embryos,the expression of FLK-1、GATA1and GATA2 was reduced and the apoptosis in ICMs was increased.Conclusion The abnormal hematopoiesis in zebrafish induced by folic acid deficiency is related with the increasing apoptosis in ICMs and decreasing expressions of FLK-1,GATA1and GATA2.

PurposeTo evaluate and describe fetal cardiac development and hemodynamics high risk pregnancy by using ultrasound technique. Methods Two-hundred and thirty-three pregnancies were prospectively studied by using the detailed fetal echocardiographic procedure( fetus gestational age from 19 weeks to 39 weeks). Cardiac chamber size, internal diameter of great arteries were documented together with the presence of inflow and outflow wave patterns. In utero diagnoses of variety of congenital heart defects were also conducted. ResultsCardiac chamber size and internal diameter of great arteries showed a positive correlation with the increasing of gestational age. Left and right ventricles were demonstrated the same size during whole fetal observational period. Blood flow through mitral valve and tricuspid valve were typically 'M' type. By comparing 'e' wave and 'a' wave, this inflow blood velocity pattern was dominant by 'a' wave, though the ratio of a/e gradually decreased during the fetal development period. Blood velocity in aorta and pulmonary artery remained steady along with the gestational age. The detection rate of verity types of congenital heart diseases in this sample population was 5.7% (13 cases) ,the major problem was the complex heart malformation. The occurrence of fetal cardiac arrhythmia was 14 cases (16 % ), with the majority of atrial premature beat. Conclusions Fetal echocardiography can be used to evaluate and monitor the change of cardiac anatomy, structure and hemodymanics during the different gestational age. This has provided a new approach to the further understanding of fetal cardiac development, and is importantto the screening of congenital heart disease during pregnancy.

Objective A retrospective study was undertaken to evaluate the outcomes of the newborns with pulmonary atresia with intact ventricular septum(PAIVS),in order to delineate strategies for the optimal management of PAIVS. Methods From July 2003 to July 2008,17 neonates with PAIVS underwent surgical treatment.The mean age at operation was(1 5.6±8.6)d and the mean weight was(3.54±0.44)kg.Initial surgical treatment included:Blalock-Taussig shunt (BT shunt)in 2 cases,closed pulmonary valvotomy and BT shunt in 1 case,right ventricular outlet tract reconstruction(RVOTR)in 2 cases,RVOTR and BT shunt in 11 cases. Results The mean duration of mechanical ventilation and intensive care unit stay were(35.5±35.1)h and(8.7±5.9)d,respectively.Two early deaths were reported inside the hospital(2/17,11.8%).Multivariable analysis demonstrated that mechanical ventilation before surgery was the risk factor for in-hospital mortality(r=1.02,P<0.01).The rest 15 cases were followed up with the average time of 19 months(2 months to 5 years)and no death was reported. Conclusions Neonates with PAIVS should be operated early.Individualized treatment strategy and regular follow-up are helpful to achieve better short-term outcome.

Objective To study the effect of retinal dehydrogenase type 2 inhibitor (4-diethylaminobenzaldehyde,DEAB) on embryonic CSrdiac develclpment of zebrafish model with retinoic acid(RA)deficiency. Methods Zebrafish embryos were treated with DEAB at various concentrations including 1×10~(-6),5×10~(-6),10×10~(-6),25×10~(-6)mol/L at 5,8 and 10.3 hours post fertilization,respectively.The effects of DEAB on the embryonic development were assessed under microscope.1×10~(-9)mol/L exogenous RA was then added to detect the antagonistic effect against DEAB.The abnormal cardiac phenotype,heart rate and ventricular systolic fraction were observed and analyzed between wild type and DEAB treated groups.The expression of specific cardiac gene, natriuretic peptide precursor A,was monitored by whole-mount in situ hybridization to demonstrate the effect of RA signaling on early cardiac development. Results The survival rate of zebrafish embryos declined with the increase of DEAB concentration at different developmental stage.The percentage of abnormal embryos reached 100% when DEAB over 5×10~(-6)mol/L.1×10~(-9) mol/L exogenous RA could eliminate the teratogenic effect of DEAB(≥5×10~(-6)mol/L).DEAB treated embryos presented abnormal cardiac phenotype,including tubular heart,incomplete D-loop,abnormal atrioventricular development,regurgitation,slow blood flow and weak heart beat.The difference of heart rate and ventrieular systolic fraction between wild type and RA deficiency embryos was of statistical significance(P<0.05).The natriuretic peptide precursor A expression remained in the ventricle,but reduced obviously in the atrium with RA signaling deficiency. Conclusions The effects of DEAB on the embryonic development are dose-dependent and time-dependent,and could be rescued by exogenous RA.RA signaling plays a critical role in several key stages of early cardiac development and natriuretie peptide precursor A expression.

Objective To follow up the changes of postnatal cardiac sizes and function in infants of mothers with gestational diabetes mellitus (GDM). Methods Eighteen GDM mothers with euglycemia (GDM group) and 24 gestational age-matched normal pregnant women (control group),having prenatal examination and delivered in Women's Hospital of Fudan University from January to August in 2007, received fetal echocardiographic examination in late pregnancy. Infants of these GDM mothers and 24 age-matched healthy infants of normal pregnancy (control group) received sonographic follow up. Cardiac sizes and function were evaluated and compared. Results At birth, there were six (33.3%) infants of large for gestational age (LGA) and 12(66.7%) appropriate for gestational age(AGA) in GDM group, while in the control group, there were two LGA (8. 3%) and 22(91.7%)AGA infants (x2 =3. 840, P= 0. 05). Both the interventricular septum and left ventricular walls in GDM fetuses were thicker than in control fetuses (P ＜ 0.05). No increase in the thickness of ventricular walls was observed till infantile period. However, the end-systolic thickness of left ventricular walls in LGA infants was still larger than in control infants [(4.55 ± 0.37) mm vs (4. 13±0.39)mm, P＜0. 05], and end-diastolic left ventricular long-diameters were also larger [(37. 3±2.3) mm vs (34.6±2.6) mm] (P＜0. 05). In GDM fetuses, the peak velocities of aorta and pulmonary artery and left cardiac output were higher than in the controls (P＜ 0. 01 ), and right/left cardiac outputs ratios were lower (1.198±0.206 vs 1. 430±0. 321, t= -2.668,P=0. 011). Till infantile period, only right/left cardiac outputs ratios in AGA infants of GDM group were larger than in controls (P＜0. 05). GDM fetuses' left atrial shortening fraction and tricuspid E/A ratios were smaller (P＜0. 05). In infantile period, only left atrial shortening fraction in GDM infants was still smaller than in controls (0. 356 ± 0. 040 vs 0. 386 ± 0. 041, t = - 2. 332, P = 0. 025). Left and right ventricular Tei index in GDM fetuses were 0. 482±0. 129 and 0. 414±0. 094, both larger than those of control fetuses (0. 309 ± 0. 074 and 0. 283 ± 0. 072) (t = 5. 075 and 5. 129, P = 0. 000 ). Till infantile period they both became significantly lower and no differences were found among LGA, AGA and control infants. Conclusions The cardiac sizes and function at 2-3 months of age, in infants of GDM mothers with good glucose control, became better than that in uterus.

Objective To compare the efficacy of inhaled Iloprost and nitric oxide( NO)in infants with moderate or severe pulmonary hypertension(PH)after congenital heart disease surgery. Methods This was a prospec-tive randomized study in Children's Hospital of Fudan University from January 2011 to January 2014,including 40 in-fants who suffered from moderate to severe PH after heart surgery. Their ages ranged from 1 to 24 months. Their weight ranged from 3. 2 to 11. 0 kg. They were randomly allocated to inhale NO( NO group,n = 20)or Iloprost( Iloprost group,n = 20). Iloprost group was given Iloprost with 50 ng/(kg·min)for 10 min and then combined with NO 20 × 10 - 6 for 10 min;NO group was first given 20 × 10 - 6 of NO for 10 min,then combined with Iloprost 50 ng/(kg·min) for 10 min. Heart rate,systolic blood pressure,pulmonary artery pressure(PAP)and central venous pressure were recor-ded continuously. At the same time,the concentration of nitrogen dioxide and methemoglobin after inhaling NO was de-tected. Results Inhaled Iloprost and NO caused significant reduction in PAP(t = 4. 670,P = 0. 009;t = 3. 762,P =0. 004)and pulmonary - to - systemic pressure ratio(Pp/ Ps)(t = 16. 974,P = 0. 000;t = 9. 682,P = 0. 000)but signifi-cant increase in oxygen index separately. The combination had no additional effect compared with single application. In term of the reduction of PAP,there was no significant difference between inhaled Iloprost and NO(F = 2. 742,P =0. 129). The levels of nitrogen dioxide and methemoglobin were not above the normal limits. Conclusions Moderate to severe PH after cardiac surgery was significantly reduced by inhaled NO and Iloprost. They had similar effects. However, the combination of both vasodilators failed to prove more potent than either substance alone. Compared with the potential toxicity of NO,the individual differences and the complex transmission,Iloprost may be more reasonable and feasible for the postoperative treatment of PH.