Research progress of interleukin-1 and its receptor antagonist Anakinra in Kawasaki disease / 中华实用儿科临床杂志

Kawasaki disease (KD) is an acute vasculitis that often occurs in children under 5 years of age, leading to coronary artery aneurysms.It is the leading cause of acquired heart disease in children in many countries.Coronary artery stenosis, thrombosis, and even myocardial infarction may occur in the long-term course of KD, which seriously threaten the health of children.The etiology and pathogenesis of KD are complex, and it is recognized that KD is caused by the interaction of multiple factors like the heredity, immunity, inflammation, and environmental factors.Interleukin-1 plays an important role in the occurrence and progression of KD.This study mainly reviews the research progress of interleukin-1 and its receptor antagonist Anakinra in KD.

Research progress in influence of intrauterine hyper androgen on offspring health and mechanisms / 中华围产医学杂志

Maternal adverse endocrine environment severely affects the growth and development of offspring. This article reviews relevant cohort studies and animal experiments on the influence of intrauterine hyper androgen on offspring health and the mechanisms, aiming to provide a new perspective for further research, mechanism exploration, and early interventions in this field.

Comparison of inhaled nitric oxide and Iloprost in infants with moderate or severe pulmonary hypertension af-ter cardiac surgery:a prospective randomized trial / 中华实用儿科临床杂志

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.

Value of fetal cardiac axis measured in the fetal echocardiography of the second trimester / 中华超声影像学杂志

Objective To establish the reference ranges for fetal cardiac axis in the mid-second trimester and to evaluate the use of fetal cardiac axis in prenatal diagnosis.Methods 6744 unselected singleton pregnancies were enrolled from September 2008 to October 2010.Routine screening scan of second trimester and fetal echocardiography were performed at 18- 23+6 weeks gestation.Fetal cardiac axis was measured on the four-chamber view of the heart.Results The 6744 fetuses had a mean cardiac axis of (37.03 ± 6.10)°,ranging from 9.80° to 102.41°. Using above or below 95％ range of population (26.63° -49.40°) as a cut-off,there were significant difference of cardiac axis between normal group [(36.96 ± 5.91)°,P ＜0.01] and the group with heart defects [(43.12 ± 15.67)°,P ＜0.01],the group with intrathoricic anomalies or abdominal wall defect [(51.74 ± 15.97)°].ConclusionsThe reference ranges of fetal cardiac axis for local population in mid-second trimester may helpful for detecting congenital defects.Presence of an abnormal cardiac axis in the fetuses is associated with a substantial risk of congenital heart disease and/or other extra cardiac defects.

Changes of plasma corticotrophin releasing factor levels in the young rats with hypoxic-ischemic brain damage / 中国小儿急救医学

Objective To explore the changes of plasma corticotrophin releasing factor (CRF) levels in the young rats with hypoxic-ischemic brain damage.Methods Two hundred and forty young rats were randomly divided into three groups:hypoxic-ischemic brain damage group ( model group,n =80),sham-operated group ( n =80),and normal control group ( n =80).The plasma CRF levels of rats in three groups were detected at 1 h,3 h,6 h,12 h,l d,3 d,5 d and 18 d after hypoxia-ischemia,per ten rats for each time point.Plasma CRF levels were measured by radioimmunoassay.Results Plasma CRF levels of model group,shamoperated group and normal control group showed no significant difference in the young rats after 1 h,3 h,6 h,12 h of hypoxia-ischemia ( P ＞ 0.05 ).But plasma CRF levels in the model group were respectively significantly lower than those of sham-operated group and normal control group after 1 d and 3 d of hypoxia-ischemia ( P ＜0.001 ),and then recovered to the control group levels after 5 d and 18 d of hypoxia-ischemia ( P ＞0.05 ).Conclusion Hypoxia-ischemia affects plasma CRF levels in the young rats,which is related with the duration after hypoxia-ischemia.

Changes of hypothalamus corticotropin releasing factor levels in children with acute brain injury / 中国小儿急救医学

Objective To explore the changes of corticotropin releasing factor (CRF) levels secreted by hypothalamus neuron in children with acute brain injury. Methods Fifty-one intracranial-infection children with brain injury and 11 intracranial-noninfection children with brain injury were chosen from pediatric intensive care unit of our hospital. Severities of their brain damage were evaluated by Glasgow score,and CRF level in cerebrospinal fluid (CSF) and serum TNF-α and IL-6 levels were measured by radioimmunoassay. Results There was no significant difference of Glasgow scores between the intracranial infection group and intracranial-noninfection group ( P = 0. 302 6 ), CSF CRF level of intracranial infection group was significantly lower than that of intracranial-noninfection group ( P ＜ 0. 01 ), serum TNF-α and IL-6 levels of intracranial infection group were significantly higher than those of intracranial-noninfection group ( P ＜ 0. 01,P ＜0. 001 ). As comparing to the children with Glasgow score of 6 ～ 7, the levels of CSF CRF and serum TNF-α and IL-6 in children with Glasgow score of 4 ～ 5 were significantly increased ( P ＜ 0. 05, P ＜ 0. 001 ).Conclusion CSF CRF level of the children with acute brain injury is changing, which may be concerned with the secretion of hypothalamus CRF neuron stimulated by TNF-α, IL-6 and hypoxia stress in children with brain injury.

Diurnal temperature range as a novel risk factor for sudden infant death / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>To assess the relationship between diurnal temperature range (DTR) and sudden infant death (SID) between 2001 and 2004 in Shanghai, China.</p><p><b>METHODS</b>We conducted a time-stratified case-crossover analysis to estimate the percent increase of SID associated with changes in DTR after adjustment for daily weather conditions (temperature and relative humidity) and outdoor air pollution.</p><p><b>RESULTS</b>DTR was significantly associated with daily SID. An increase of 1 °C in the current-day (L0) and in the 2-day moving average (L01) DTR corresponds to a 1.56% (95% CI: 0.97%, 2.15%) and a 1.89% (95% CI: 1.17%, 2.60%) increase in SID, respectively.</p><p><b>CONCLUSION</b>An increased DTR was associated with an increased risk of SID in Shanghai. More studies are needed to understand the effect of DTR on infant deaths.</p>

The experimental research for contribution of insulin-like growth factor binding protein-2 during zebrafish embryonic cardiovascular development / 复旦学报（医学版）

Objective To establish a zebrafish IGFBP-2 gene knock-down model by morphilino modified antisense oligonucleotide injection, so as to investigate the abnormal phenotypes of heart and vessels in early stage of zebrafish development and the expression of zebrafish cardiogenesis related genes. Methods The spatiotemporal expression of IGFBP-2 gene in early stage of zebrafish development was testified by whole mount in situ hybridization with antisense RNA IGFBP-2 probe. The IGFBP-2 morpholino (IGFBP-2 MO) that especially inhibited the gene promoter and standard control morpholino (Con-MO) were designed and synthesized by Gene-tools Corporation. Four different concentration gradients (0.05, 0.10, 0.25 and 1.0 mmol/L) were set as IGFBP-MO injection groups with 0.25 mmol/L Con-MO injection group and wild type group as controls. Contribution to the incidence of heart abnormal phenotypes and mortality rate induced by 4 different IGFBP-2 concentrations injection group was recorded and compared with 2 control groups. Heart abnormal phenotypes at different developmental stages in 0.25 mmol/L IGFBP-2 injection group were observed in detail. To validate the effectiveness of IGFBP-2 MO, the expression of enhanced green fluorescence presented by wild type zebrafish embryos at 12hpf which received single injection of IGFBP-2 EGFP recombinant plasmid and those co-injected with Con-MO or IGFBP-2 MO were detected. To investigate the regulation relationship between IGFBP-2 gene and other cardiogenesis related genes, expression of atrium specific marker gene Amhc was detected in IGFBP-2 MO and wild type group by in situ hybridization. Ventricle specific green fluorescence of Vmhc-EGFP transgenic zebrafish embryos whose IGFBP-2 gene was knocked-down were compared with those untreated. Zebrafish peripheral vascular development in the IGFBP-2 MO group was also checked out by micro-angiography. Results Whole mount in situ hybridization revealed that IGFBP-2 gene expressed in turn at eyes, midbrain and then focused on liver in early stage of zebrafish development. The micro-injection of 0.25 mmol/L IGFBP-2 MO resulted in heart malformation in nearly 60% of all injected zebrafish embryos. Heart malformation phenotypes included slow heart beat, pericardial edema, weak ventricle systole contraction and heart tube looping disorder. Some of them represented atria dilation, blood regurgitation and ciculation obstruction. Wild type zebrafish embryos that received single injection of IGFBP-2 EGFP plasmid DNA or co-injected with Con-MO presented strong enhanced green fluorescence at 12hpf, meanwhile, the fluorescence was barely seen in the embryos co-injected with IGFBP-2 MO. This strongly validated the gene specific knock-down effect of IGFBP-2 MO. Amhc was down-regulated at 48hpf in IGFBP-2 MO group. Vmhc-EGFP transgenic zebrafish down-regulated by IGFBP-2 gene also resulted in attenuated expression of ventriclar-specific green fluorescence protein at 48hpf. Intersegmental blood vessels of IGFBP-2 MO group by micro-angiography at 60hpf demonstrated an sparsate and chaos image, which suggested that IGFBP-2 gene expression was involved in the regulation of normal vascular development. Conclusions Micro-injection of IGFBP-2 MO is an efficient way to knock-down IGFBP-2 gene in zebrafish embryos. IGFBP-2 gene expression down-regulation leads to heart and vessels maldevelopment and have an impact on the expression of cardiogenesis related genes of zebrafish embryos as well. In short, IGFBP-2 plays a critical role in the normal cardiovascular development of zebrafish embryos.

Effect of retinal dehydrogenase type 2 inhibitor on embryonic cardiac development of zebrafish / 中华围产医学杂志

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.

Management for neonatal pulmonary atresia with intact ventricular septum / 中华围产医学杂志

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.

Follow-up of cardiac function in infants of mothers with gestational diabetes mellitus / 中华围产医学杂志

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.

The effects of folic acid deficiency on the axial development of zebrafish / 复旦学报（医学版）

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.

Cardiac/coronary artery lesion in Kawasaki disease treated with different kind of intravenous immunoglobulin therapy in Shanghai from 1998-2008 / 临床儿科杂志

Objective To evaluate the effect of different kind of intravenous immunoglobulin (IVIG) therapy in treating Kawasaki disease (KD) and preventing cardiac consequences (coronary artery lesion, CAL). Methods A questionnaire form and guideline for KD diagnosis were sent to 50 hospitals providing pediatric medical care in Shanghai. The data from a total of 1 682 KD patients were collected. It included 1 064 males and 618 females from 1998 through 2008 in Shanghai. The average age of the KD patients was (2.57±2.33) years old (0.1-18.8 years).The patients had been divided into 6 groups for different IVIG therapy, which included 1 g/kg once, 2 g/kg once, 0.4-0.5 g/kg five times, 1 g/kg twice, 2 g/kg twice and others. SAS 6.12 software was used for statistical analysis. Results In all KD patients, the patients treated with IV1G in 5th-10th day of illness has the least cardiac complication and CAL incidence and the group with IVIG therapy of 1 g/kg twice also has the least cardiac complication and CAL incidence. Conclusions The best doses of IVIG in treating KD is 1 g/kg twice and the IVIG therapy should be used in 5th-10th day of KD illness.

Evaluation of the prenatal screening mode for fetal congenital heart diseases by ultrasound / 中华妇产科杂志

Objective To assess prenatal heart disease screening program by ultrasound. Methods A total of 11 544 second-trimester screening scans were performed before 24 weeks′ gestation on 11 410 women between February 2004 and May 2007 in Obstetrics and Gynecology Hospital of Fudan University. Fetal heart screening was based on four-chamber and outflow tract views( left ventricular outflow + three vessel view). The sensitivity and specificity of different views were evaluated. Follow-up data of newborns was obstained. Results (1) Among 11 544 cases, 48 cases of congenital heart disease (CHD) were diagnosed in utero. Six cases were false negative, and 2 cases were false positive. The incidence of CHD was 0.47% (54/11 544). (2) Thirty-three CHDs were detected based on the four-chamber view, including 18 ventricular septal defect (9 with conotroncal anomalies),6 anomalous atrioventricle valve, 9 disproportion of left/right ventricle. The sensitivity of the four-chamber view alone was 61.11% (33/54), and the specificity was 99. 98% ( 11 488/11 490). Fifteen CHDs were detected based on the left ventricular outflow and three vessel views, including 1 pulmonary atresia, 3 pulmonary valve stenosis, 2 transposition of the great arteries ( TGA ), 1 pulmonary stanosis with TGA, 6 tetralogy of Fallot, and 2 pulmonary stenosis. The sensitivity of the combination of the four-chamber and outflow tract views was 88. 89% (48/54), and the specificity was 99. 98% (11 488/11 490). (3)Of 48 CHDs,11 cases were eceompanied by other malformations. Eleven cases were performed amniocentesis, amony whom 5 cases were trisemy 21. Conclusion The screening program based on four-chamber and outflow tract views shows good sensitivity and excellent specificity. Our prenatal heart screening program is clinically feasible.

Construction of the Top-quality Course of Pediatrics / 中华医学教育探索杂志

The article sums up the thinking and methods of the top-quality courses of Pediatrics constructed by the pediatric bed-sided teaching(PBL courses) and clinical training.The aim of the courses is to combine gradually lecture,question,discussion and practice,encourage active discussion,emphasize clinical ability and establish a new teaching method of pediatrics.

Construction of Pediatrics Curriculum in Conformance with New Medical Mode / 中华医学教育探索杂志

Facing a transformation of society and new problems of health care system in the twenty-first century,traditional medical modals have many challenges.The new modes of modern medicine have been formed.The medical education reform must adapt new medical modes to cultivate high quality medical talents.And at the same time the course of pediatrics should be constantly innovated to construct the first class teaching staff,first-rank teaching contents,teaching methods,teaching material and teaching administration.

The Development of Medical Bilingual Teaching and its Model and Strategy / 中华医学教育探索杂志

Bilingual teaching is a new measure to enhance the quality of education in universities and to meet the requirement for a WTO member.Conducting bilingual teaching in medical schools is to aim at cultivating high-quality doctors and improving Chinese medical science.This article interprets the concept and goal of bilingual teaching and analyzes the history and mode of bilingual teaching in China.The methods of conducting medical bilingual teaching,the construction of the teaching resource and the evaluation of the curriculum have also been discussed.

PBL Practice in Pediatrics Teaching / 中华医学教育探索杂志

Pediatrics is a medical discipline,studying children health,growth and development,health care and disease prevention.To ignite medical students' interest in pediatrics,cultivate their creativity and ability in clinical practice,since February 2004,Pediatric Department in Children's Hospital of Fudan University has implemented the teaching pattern that combines traditional teaching practice with problem based learning(PBL) in students of seven-year medical training program,which has received positive feedback and wide approval from the students.

Ultrasound Evaluation of Fetal Cardiac Development and Hemodynamics / 复旦学报（医学版）

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.

EFFECT OF FOLIC ACID DEFICIENCY ON ZEBRAFISH HEMATOPOIESIS / 营养学报

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.