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Effect of lipoxin A4 on interleukin-1β production of human monocytes from severe preeclamptic women and its relationship with cytoplasm free calcium concentration-an in vitro study

Jianfang WANG ; Yinping HUANG ; Yanjun HUANG ; Xiaoli LIU ; Jie ZHOU ; Jing WANG

Chinese Journal of Perinatal Medicine.2010;13(3):191-195. doi:10.3760/cma.j.issn.1007-9408.2010.03.005

Objective To investigate the effect of lipoxin A4(LXA4) on interleukin-1β(IL-1β)production of monocytes in maternal peripheral blood from severe preeelampsia women and its relationship with cytosolic free calcium([Ca2+]i)concentration. Methods Peripheral venous blood was drawn from 15 women with severe preeelampsia(SPE group)and 20 normal pregnant women (control group)who were admitted to the First Affiliated Hospital of Wenzhou Medical College from October 2008 to May 2009.Monoeytes were obtained from peripheral blood with Ficolt density gradient centrifugation and then were suspended in RPMI-1640 culture supplemented with LXA4 at the final concentrations of 0,10 and 100 nmol/L,respectively.IL-1β levels in monocytes supernatant were detected by enzyme-linked immunosorbent assay.The cytoplasma[Ca2+]i of cultured monocytes and its variations affected by LXA4 were measured by laser scanning confocal microscope. Results (1) After incubation with different concentrations of LXA4(0,10,100 nmol/L)for 24 h,the levels of IL-1β in SPE group were(63.16±8.20)pg/L,(53.71±8.08)pg/L and(43.16±6.89)pg/L,respectively, indicating a significant inhibition effect on IL-1β level in a dose-dependent manner (P<0. 05). The IL-1β levels in the control group were (19.22±7.43) pg/L, (16.99±6.32) pg/L and (15. 18±5.24) pg/L, correspondingly (P>0.05). (2) Without LXA4, the [Ca2+ ]i concentrations of monocytes in the SPE group were higher than that of the control (1028.09 ± 160. 52 vs 323.61 ±87.86, P<0. 05). After treatment with 100 nmol/L LXA4, the [Ca2+ ]i concentration of monocytes significantly decreased in the SPE group (409.67± 116.73, P<0. 05). Conclusions In vitro LXA4 may inhibit the IL-1β production in monoeytes of SPE patients through decrease of the cytoplama [Ca2+ ]i concentration.

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mRNA expression and promoter methylation of paternally expressed gene 1 and paternally expressed gene 3 in human placenta of abnormal birth weight fetuses

Ying WANG ; Weiwei SONG ; Lili WANG ; Lin YANG

Chinese Journal of Perinatal Medicine.2010;13(3):187-190. doi:10.3760/cma.j.issn.1007-9408.2010.03.004

Objective To study the mRNA expression of two imprinted genes,paternally expressed gene 1(PEG1) and paternally expressed gene 3(PEG3),and their promoter methylation in human placenta of abnormal birth weight(BW)neonates. Methods Placentas were obtained after full term delivery,without any maternal complications during pregnancy,and were divided into 3 groups according to BW:high BW group(n=22,BW≥4000 g),normal BW group(n=14,BW>2500 g and<4000 g)and low BW group(n=24,BW≤2500 g).The mRNA expression of PEG1 and PEG3 were determined by real-time quantitative polymerase chain reaction.Promoter methylation was measured by the bisulfite genomic sequencing method.Results among different groups were compared. Results (1)The mRNA expression of PEGl and PEG3 were 11.66±9.01 and 16.45±10.13 in the high BW group,0.84±0.49 and 0.85±0.67 in the low BW group and 1.10±0.77 and 1.11±0.60 in the normal BW group,respectively.Both genes were significantly up-regulated in the high BW group compared to the normal BW group(P<0.05),but no significant difference was found between the normal and low BW group (P>0.05). (2) The levels of PEG1 promoter methylation were (49. 7± 2. 3) %, (50. 2 ± 2. 1 )% and (50. 3 ± 1.9)% in the high, low and normal BW group (P>0.05), while the levels of PEG3 promoter methylation in the high BW was significantly lower than in the normal BW group [(13.1± 2. 7) % vs (16.2 ±1.8)%, P<0. 05], but no difference was shown between the low BW group (16.7± 3.5)% and the normal BW group (P>0.05). (3)Negative correlation was detected between the expression of PEG:3 and DNA methylation level within the objective fragment of promoter region (r= -0. 963, P<0. 01). Conclusions The up-regulation of PEG1 and PEG3 may be associated with high BW. The reduction of methylation pattern in the promoter region of PEG3 might be involved in the up-regulation of PEG3 and contribute to the mechanism of high BW fetus in turn.

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Expression of apoptosis signal-regulating kinase 1 in pulmonary tissue of premature newborn rat exposed to hyperoxia

Ruiyan SHAN ; Liwen CHANG ; Yan CHEN ; Wenbin LI ; Cheng CAI ; Wei LIU

Chinese Journal of Perinatal Medicine.2010;13(3):217-221. doi:10.3760/cma.j.issn.1007-9408.2010.03.010

Objective To investigate the changes and potential roles of the expression of apoptosis signal-regulating kinase 1(ASK1),thioredoxin(Trx)and thioredoxin reductase(TrxR)in the pathogenesis of lung injury of premature newborn rats exposed to hyperoxia. Methods In the first day after delivery,preterm SD rats were randomly divided into air group and hyperoxia group with 64 rats in each.The rats were respectively sacrificed at 1,4,7,10 and 14 days after air or hyperoxia exposure.Sections of 1ungs were stained with HE to observe the histologic changes.Trx and TrxR mRNA were detected by reverse transcription-polymerase chain reaction(RT-PCR).Immunohistochemistry was used to detect the expression and distribution of ASK1.Western blot was used to detect the expression of ASK1 protein. Results Rats in hyperoxia group showed typical lung injury,which was characterized by alveolitis and delayed of lung development.Immunohistochemistry detected that ASK1 expressed generally in the cytoplasm of both alveolar epithelial cells and vascular endothelial cells:ASK1 protein expression in hyperoxia group at 1th and 4th day were 0.4382±0.0227 and 0.5270±0.0432,higher than in the air group(0.3458±0.0263 and 0.3760±0.0058)(P<0.01),and it was until 7th day that the expression became weaker(0.4343±0.0254),but still higher compared with the air group(0.3473±0.0220)(P<0.01).Compared with the air group,Trx and TrxR mRNA of the hyperoxia group increased significantly and peaked at lOth day(0.6860±0.0811)and 7th day(2.0351±0.1600),respectively(P<0.05).ASK1 protein expressions resulting

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Combination of ultrasonography and magnetic resonance image in diagnosing monochorionic multifetal malformations-report of 14 cases

Xia ZHU ; Xinlin CHEN ; Xiaohong YANG ; Ziyan SUN ; Mei XIAO ; Liming XIA ; Xiaohong ZHU

Chinese Journal of Perinatal Medicine.2010;13(3):196-200. doi:10.3760/cma.j.issn.1007-9408.2010.03.006

Objective To demonstrate the value of eombined application of prenatal ultrasonography with fetal magnetic resonance imaging(MRI) in the diagnosis of monochorionic muhifetal realformations. Methods Fourteen cases of muhifetal malformations,detected by prenatal ultrasonography,received MRI within 48 h afterwards.All diagnosis were confirmed after delivery or mid-term termination.All imaging results of the 14 cases were retrospectively reviewed. Results Among the 14 cases,there were 7 acardias,5 Conjoined twins and 2 demise of multifetuses.Comparing ultrasound with MRI,we found that:(1)In cases with acardia and demise of multifetusea,ultrasound could diagnose correctly and be an important tool for follow-up,while MRI could demonstrate organs and structures of the acardiac recipient more clearly and detect the secondary changes of brain in the donor and survived fetus.(2)In Conjoined twins,ultrasound was superior to MRI in demonstrating the structure and function of cardiovascular system : and equivalent to MRI in identifying stomach,kidney,bladder and limbs;but inferior to MRI in identifying esophagus,lung,liver and intestinal,especially in the brain. And MRI could demonstrate two fetuses and the relationship between them in COnjoined twins simultaneously. Conclusions Prenatal ultrasonography and MRI have their own advantages and disadvantages in diagnosing monochorionic multifetal malformations.But the combination of prenatal ultrasonography and fetal MRI may be more valuable.

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Inhibition of maternal antibody to hepatitis B surface antigen on antibody response to hepatitis B vaccine in infants

Yali HU ; Qiaozhen WU ; Quanlin GENG ; Hong CHEN ; Zhiqun WANG ; Zhenxian HOU ; Ying LI ; Yihua ZHOU

Chinese Journal of Perinatal Medicine.2010;13(3):181-186. doi:10.3760/cma.j.issn.1007-9408.2010.03.002

Objective To investigate whether maternal antibody to hepatitis B surface antigen (anti-HBs)in infants may interfere with the antibody response to hepatitis B vaccine. Methods Infants from singleton pregnant mothers,who delivered at full term at the Affiliated Drum Tower Hospital of Nanjing University Medical School from October 2006 to January 2007,were divided into two groups based on their mothers'status of anti-HBs(43 positive and 29 negative).All infants were vaccinated with hepatitis B vaccine at birth and one month thereafter.Serum anti-HBs were quantitatively determined for the mothers before delivery and for infants in cord blood at delivery and in serum at the age of 1 and 3.5 months. Results Anti-HBs of all 43 newborns in the positive group were positive in cord blood with the coefficiency of 0.98 to the maternal serum anti-HBs level(t=39.05,P<0.01).Forty-two out of the 43 infants remained anti-HBs positive at the age of 1 month.Anti-HBs was negative both at birth and 1 month old in infants of the negative group.However,all infants in both groups were anti-HBs positive at 3.5 months of age,while the average concentration of anti-HBs in infants of the negative group was significantly higher than that of the positive group [(466.9±86.7)mIU/ml vs(151.2±23.1)mIU/ml,t=2.72,P=0.011].Among the 5 infants whose maternal anti-HBs level>1000 mIU/ml,3 did not produce active antibodies against two doses of hepatitis B vaccination. Conclusions Passively acquired maternal anti-HBs in infants can inhibit the active antibody response to hepatitis B vaccine,and the extent of this effect is associated with maternal anti-HBs level.

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Management for neonatal pulmonary atresia with intact ventricular septum

Jingjing HUANG ; Yaping MI ; Bing JIA ; Zhanggen CHEN ; Yonghao GUI

Chinese Journal of Perinatal Medicine.2010;13(3):213-216. doi:10.3760/cma.j.issn.1007-9408.2010.03.009

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.

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Oral erythromycin for the prevention and treatment of feeding intolerance in preterm infants-meta analysis of randomized controlled trials

Zhiqun ZHANG ; Huiping LI ; Xianmei HUANG ; Jianxing ZHU

Chinese Journal of Perinatal Medicine.2010;13(3):201-208. doi:10.3760/cma.j.issn.1007-9408.2010.03.007

Objective To evaluate the efficacy and safety of oral erythromycin in the prevention and treatment of feeding intolerance in preterm infants. Methods The Cochrane Library,PubMed,EMBASE,CBMdise,VIP,WartFang and CNKl were searched up to the year of 2008.Randomized controlled trials (RCT) of erythmmycin for feeding intolerance in preterm infants were included.According to the dosage (low-dose,3-15 mg/kg and high dose,>15 mg/kg)and gestational age(≤32 weeks vs>32 weeks),all infants were divided into several subgroups.Meta-analysis was performed with the Cochrane Collaboration's software RevMan. Results Nine RCrs involving 542 premature infants were included.(1)In preventive studies,low-dose erythromycin could significantly decrease the duration of total parenteral nutrition compared with the high-dose erythmmycin (WMD=-2.99,95%CI:-3.99--1.98).(2)Intreatment studies,highdose erythromycin could significantly decrease the duration of total parenteral nutrition (WMD=-7.06.95%CI:-7.91--6.20,P<0.01)and hospital stay (WMD=-8.10,95%CI:-14.02--2.18,P=0.007)compared with the placebo when gestational age≤32 weeks. Erythromydn could decrease the incidence of iaundice(RR=0.36,95%CI:0.21-0.63,P=0.0003)which might be the effect of bigh-dose erytromycin. Conclusions Compared with placebo,oral erythromycin of different dosage might help to achieve full enteral feeding,shorten the duration of parenteral nutrition and hospital stay,and reduce the associated cholestasis jaundice of preterm infants with different gestational age respectively.

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Effect of retinal dehydrogenase type 2 inhibitor on embryonic cardiac development of zebrafish

Jia HOU ; Yonghao GUI ; Yuexiang WANG ; Lifeng ZHANG ; Houyan SONG

Chinese Journal of Perinatal Medicine.2010;13(2):117-122. doi:10.3760/cma.j.issn.1007-9408.2010.02.009

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.

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Relationship between Tei index and the myocardial enzymes in newborns after asphyxia LEI Xiao-yan,

Xiaoyan LEI ; Yonghong SUN ; Jiao DONG ; Sanping WANG

Chinese Journal of Perinatal Medicine.2010;13(3):209-212. doi:10.3760/cma.j.issn.1007-9408.2010.03.008

Objective To study the relationship between Tei index and the myocardial enzymes in newborns with myocardial damage due to asphyxia. Methods Forty-four newborns with mild asphyxia,27 newborns with severe asphyxia and 20 healthy newborns hospitalized in our hospital from January 2005 to December 2008 were enrolled in this study.The peak E and peak A and E/A ratio at mitral valve,the ejection fraction,isovolumetric contraction time,isovolumetric relaxation time and Tei index were measured by conventional echocardiography,and aspartate aminotransferase,creatine kinase,lactate dehydrogenase,hydroxybutyrate dehydrogenase and creatine phosphate kinase isoenzyme,and cardiac troponin T were tested also.One-way ANOVA was used to analyze the difference between groups. Results Tei index,isovolumetric contraction time and isovolumetric relaxation time in the severe asphyxia newborns were 0.62±0.13,(47±7)ms and(52±8)ms,higher than those in the mild asphyxia newborns[0.51±0.14,(41±6)ms and(43±6)ms],those in the mild asphyxia newborns were higher than in the healthy newborns[0.39±0.12,(34±6)ms and (37±6)ms] (all P<0.01).Aspartate aminotransferase,lactate dehydrogenase,hydroxybutyrate dehydrogenase,creatine kinase and its isoenzymes and cardiac troponin T in the severe asphyxia newborns were higher than in the mild asphyxia newborns and healthy group(P<0.01).Tei index,isovolumetric contraction time and isovolumetric relaxation time were positively related to the myocardial enzymes.The positive relationships were more statistically significant in Tel index,creatine kinase,its isoenzymes and cardiac troponin T(r=0.762,0.821,0.778,P<0.01).Conclusions Combination of Tei index and myocardial enzymes can not only be applied to assess the cardiac function in newborns with myocardial damage due to asphyxia,but also to evaluate the degree of cardiac dysfunction accurately and dynamically.

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Retrmpective analysis of 1340 women with intrahepatic cholestasis of pregnancy

Anping LIN ; Chundong LU ; Lin WANG ; Yuanli YANG ; Wei WANG ; Qing CHANG

Chinese Journal of Perinatal Medicine.2010;13(2):102-106. doi:10.3760/cma.j.issn.1007-9408.2010.02.005

Objective To evaluate the clinieal significance of classification for intrahepatic cholestasis of pregnancy (ICP) on diagnosis and management of ICP. Methods A retrospective analysis was conducted on 1340 cases of ICP admitted to our hospitaI from January 2000 to December 2007.AIl subiects were divided to mild and severe ICP groups.AIl clinical data were retrieved,and clinical manifestations,biochemicsl indicators,mode of delivery,perinatal outcomes were analyzed between the two groups. Results These 1340 ICP cases occupied 8.58% of all the maternity inpatients during the study period.Among those delivered in the hospital(n=1058),including 52 twin pregnancies,the preterm birth rate was 11.72 oA(124/1058),the neonatal asphyxia rate was 2.07%(23/1110),and the perinatal mortality rate was 1.08%(12/1110).Skin pruritus was the main symptom in 75.97%(1018/1340) of all cases and no significant difference was found in theproportion of women with skin pruititus between mild and severe ICP cases [74.89%(522/697) vs 77.14%(496/643),X~2=0.94,P>0.05].The perinatal mortality rate(1.02%vs 1.46%),neonatal asphyxia rate(2.30% vs 1.82%)and preterrn birth rate(11.61 vs 12.04%)showed no difference between women with and without skin pruritus among those delivered in the hospital(all P>0.05).Comparisons between those women with CG≥64.43 μmol/L vs CG<64.43μmol/L,those with AST and/or ALT≥250 U/L vs both AST and ALT<250 U/L,those with TBA≥40 μmol/L vs DOI:10.3760/cma.j.issn.1007-9408.2010.02.005 TBA<40 μmol/L,the perinatal mortality rate,neonatal asphyxia rate and preterm birth rate were all lower in the former groups(all P<0.05).The average gestations at delivery was later in mild ICP women than in the severe ones[(38.3±1.9)weeks vs(36.1±1.7)weeks,P<0.05].And the cesarean section rate(73.73%va 97.33%),preterm birth rate(6.13 0A vs 18.28%),neonatal asphyxia rate(1.05%vs 3.49%) and perinatal mortality rate (0.18% vs 2.26%)in the mild ICP cases were all lower than in the severe ICP women(all P<0.05). Conclusions It ia helpful for the management of ICP by dividing ICP cases into mild or severe ones.Cesarean section ia recommended for severe ICP,and trial of labor may be possible for mild cases under close monitoring.

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