Pregnancy outcomes in women with heart disease / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>As the Shanghai Obstetrical Cardiology Intensive Care Center, our hospital has accumulated a large number of clinical data of pregnant women with heart disease. This paper is a retrospective analysis of 1142 pregnancies in women with heart disease so as to evaluate the maternal and fetal outcomes of these patients.</p><p><b>METHODS</b>A retrospective analysis was carried out for pregnancies in 1142 women with heart disease who delivered in Shanghai Obstetrical Cardiology Intensive Care Center between 1993 and 2007.</p><p><b>RESULTS</b>In this study, main heart diseases in pregnancy were arrhythmia (n = 359, 31.4%), congenital heart disease (CHD; n = 291, 25.5%), and myocarditis and its sequelae (n = 284, 24.9%); based on the functional classification criteria of New York Heart Association (NYHA), more than half (n = 678, 59.4%) of patients were classified NYHA Class I; pregnant women in NHYA Class I-II (n = 951, 83.3%) commonly had arrhythmia, myocarditis and its sequelae, while those in NHYA Class III-IV (n = 191, 16.7%) mainly had CHD, rheumatic heart disease (RHD), cardiopathy induced by hypertensive disorders complicating pregnancy, and peripartum cardiomyopathy (PPCM). Cardiac failure occurred in 97 (8.5%) patients, and 8 (0.7%) maternal deaths and 12 (1.1%) perinatal deaths were reported in this study. Compared with those in NHYA Class I-II, women in NHYA Class III-IV had a significantly lower gestational age at birth (P < 0.05), lower birth weight (P < 0.01), and higher incidence of preterm delivery, small for gestational age and perinatal death (P < 0.01). The incidence of cardiac failure in pregnant women with cardiopathy induced by hypertensive disorders complicating pregnancy and PPCM was relatively high, with a rate of 80% and 52.2%, respectively. After cardiac operation, 131 (90.3%) women were in classified NHYA Class I-II and 14 (9.7%) in NHYA Class III-IV.</p><p><b>CONCLUSIONS</b>Arrhythmia is the type of heart disease that has a highest incidence in patients with heart disease in pregnancy, while main types of heart disease that impair cardiac function are CHD and RHD; cardiac failure is more frequently caused by cardiopathy induced by hypertensive disorders complicating pregnancy and PPCM; impaired cardiac function increases perinatal morbidity; cardiac surgery before pregnancy could improve the cardiac function.</p>

Role of cyclooxygenase-2 signaling pathway dysfunction in unexplained recurrent spontaneous abortion / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Experimental evidence indicates that cyclooxygenase-2 (COX-2) plays a critical role in blastocyst implantation; however, little is known of the role of COX-2 in unexplained recurrent spontaneous abortion (URSA).</p><p><b>METHODS</b>We evaluated the expression level and potential signaling pathway of COX-2 in 30 cases of URSA who were excluded the abnormality of chromosomes, anatomy, endocrine, infectious, autoimmune diseases and in 30 normal pregnancies.</p><p><b>RESULTS</b>The mRNA and the protein expression level of COX-2 in the URSA group (-0.238 +/- 0.848, 0.368 +/- 0.089, respectively) were significantly lower than that in the control group (1.943 +/- 3.845, 1.046 +/- 0.108, respectively) (both, P < 0.01). The expression of prostaglandins PGF(2a), PGD(2), PGE(2), and PGI(2), in the URSA group ((2326.0 +/- 295.6) pg/ml, (2164.0 +/- 240.5) pg/ml, (238.7 +/- 26.4) pg/ml, (2337.0 +/- 263.0) pg/ml, respectively) were significantly lower than that in the control group ((3450.0 +/- 421.7) pg/ml, (3174.0 +/- 415.6) pg/ml, (323.5 +/- 43.8) pg/ml, (3623.0 +/- 460.4) pg/ml, respectively) (P < 0.05). The mRNA expression level of PPARbeta and RXRalpha (0.859 +/- 0.653, -0.172 +/- 0.752, respectively) in URSA group was significantly lower than that in the control group (1.554 +/- 1.735, 0.777 +/- 2.482, respectively) (both P< 0.05). The mRNA and protein expression levels of vascular endothelial growth factor-A (VEGF-A) in the URSA group (2.010 +/- 1.522, 0.35 +/- 0.46) was significantly lower than that in the control group (4.569 +/- 2.430, 0.750 +/- 0.350) (both P < 0.05).</p><p><b>CONCLUSIONS</b>COX-2 and the COX-2-derived PGI(2) signaling pathway possibly play an important role in successful embryo implantation, and their decreased expression may result in URSA. The decreased expression may influence the expression of VEGF-A which interferes with placental angiogenesis causing failure of embryo implantation, leading to spontaneous abortion.</p>

Effect of antioxidants on amelioration of high-risk factors inducing hypertensive disorders in pregnancy / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>This is a prospective clinical study based on a large sample gathered from multiple centers in China, subordinating to 10th Five-Year Plan of National Science & Technology Progression. We analyzed the high-risk factors inducing hypertensive disorders in pregnancy (HDP) and estimated the potential effect of anti-oxidants administration, including vitamin C (VC), vitamin E (VE) and Salvia Miltiorrhiza L (SML), a Chinese herb medicine, in amelioration of the high-risk factors in pregnancy.</p><p><b>METHODS</b>From April 2005 to July 2006, 4814 pregnant women from 24 national wide cooperative hospitals were involved in this prospective research. The participants were randomly divided into two groups: 1607 cases were in anti-oxidants group with administration of vitamins and SML; 3207 cases were in control group without any medicine given. Every participant was under monitoring for the morbidity of HDP and the high-risk factors were investigated in HDP cases in each group.</p><p><b>RESULTS</b>(1) The morbidity of HDP was 3.55% in anti-oxidants group vs. 4.18% in control group. No statistical difference existed between the two groups (P > 0.05). (2) In anti-oxidants group, the HDP morbidities among three subgroups: VC + VE + SML, VC + VE and SML only, were 5.51%, 3.05% and 5% respectively. It showed no statistical difference among three remedies (P > 0.05). (3) The related index of factors affecting HDP showed in intensity sequence as follows: family HDP history > profession > education level > age > body weight. The incidence of HDP in normal population was 3.51%, and the incidence of HDP in high-risk pregnant women (family HDP history, heavy physical labor, low education level (middle school and below), age ≥ 40, body mass index ≥ 24) was 5.84%, which was obviously higher than that in normal population (P < 0.01). In anti-oxidants group, the probability of HDP in women with high-risk factors was 3.81%, which was obviously lower than that in control group with high-risk factors at 7.14% (P < 0.01). (4) In control group, the morbidity of HDP in women with family HDP history (especially with sisters'), heavy physical labor, middle school and below, age ≥ 35 was: 50.00%, 15.22%, 6.33%, 26.28% and 5.75%, respectively, and that in anti-oxidants group was 0, 7.69%, 3.74%, 9.27% and 2.67%, respectively, which was obviously lower than that in control group.</p><p><b>CONCLUSIONS</b>The high-risk factors prone to induce HDP included: family history of HDP, heavy physical labor, low education level, aging and obesity. No impressive effect of anti-oxidants application was found in preventing HDP in general population but the remedy demonstrated positive effect on preventing HDP in pregnant women with high-risk factors.</p>

Relationship between expression of chemokine receptors CCR3, CCR5 and CXCR3 on CD4(+) T cells and spontaneous abortion in mice / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Previous studies have shown that local immune cells in the feto-maternal interface are recruited from peripheral blood, and that chemokines and their receptors play an initial and key role in this recruitment process. In this study, we aimed to determine whether spontaneous abortion is associated with the expression of chemokine receptors CCR3, CCR5, and CXCR3 on CD4(+) T cells.</p><p><b>METHODS</b>Peripheral blood, spleen, and thymus were collected from the spontaneous abortion mouse model CBA/JxDBA/2 (SA group, n = 14), the normal pregnant mouse model CBA/JxBALB/c (NP group, n = 13), and normal non-pregnant CBA/J mice (NNP group, n = 11). The number of chemokine receptors CCR3, CCR5, and CXCR3 expressed on CD4(+) T cells was measured by double-label flow cytometry (FCM) method.</p><p><b>RESULTS</b>In peripheral blood, the SA group had significantly lower CCR3 expression (P < 0.01) and higher CCR5 and CXCR3 expression (P < 0.01) on CD4(+) T cells than did the NP group. But comparing these chemokines between the SA and NNP groups, there was no significant difference (P > 0.05). In spleen, the SA group expressed significantly lower CCR3 expression (P < 0.01) and higher CCR5 and CXCR3 expression (P < 0.05) on CD4(+) T cells than did the NP group. When compared with the NNP group, the SA group had significantly higher CCR3 expression (P < 0.01), but was not statistically different with regards to the other two chemokines (P > 0.05). In thymus, the SA group had significantly lower CCR3 expression (P < 0.05) and higher CXCR3 expression (P < 0.05) on CD4(+) T cells than the NP group, with no significant difference in CCR5 expression (P > 0.05). Compared with the NNP group, the SA group had higher CCR3 expression (P < 0.01), but there was no statistical difference in CXCR3 and CCR5 expression (P > 0.05) between the two groups.</p><p><b>CONCLUSION</b>The abnormal expression of CCR3, CCR5 and CXCR3 on CD4(+) T cells may play an important role in the pathogenesis of spontaneous abortion.</p>

Research advances in biomarkers for early prediction of preeclampsia / 上海第二医科大学学报

Preeclampsia is a leading cause of maternal and infant morbidity and mortality. It is very important to explore the biomarkers for the early prediction of preeclampsia. Some peptides released from placenta, such as soluble Flt-1 and placenta growth factor (PlGF), have been revealed for definite prospects of application. Meanwhile, the recent advances in proteomics, metabolomics and microRNA shed light on searching of new biomarkers for preeclampsia prediction.

Pathogenesis,diagnosis and treatment of recurrent spontaneous abortion with immune type / 上海第二医科大学学报

Recurrent spontaneous abortion (RSA),which affects 1% to 5% of women of reproductive age,is difficult to treat in the clinical setting. In the investigations of immunopathogenesis,diagnosis and treatment of RSA since the late 1980s,it was found that RSA was associated with abnormal maternal local or systemic immune response,the pathogenesis of autoimmune RSA was mainly associated with antiphosphlipid antibody (APA),while that of alloimmune RSA was due to the disturbance of maternofetal immunological tolerance. Systemic etiological screening process and diagnosis systems of RSA with immune type were developed,and anticardiolipin (ACL)+? 2-GP1 combining multiple assay for effective diagnosis of RSA with immune type was initially established. According to dynamic monitoring clinical parameters before and during gestation,low-dose,short-course and individual immunosuppressive therapy and lymphocyte immunotherapy for RSA with immune type were initiated. The outcomes of the offsprings of patients with RSA were followed up,and the safety and validity of the therapies were confirmed. The research achievement leads to great progress in the diagnosis and treatment of RSA in China.

Mechanism of pregnancy immune tolerance induced by adoptive transfer of FasL gene-modified dendritic cells / 上海第二医科大学学报

Objective To study the mechanism of pregnancy immune tolerance induced by adoptive transferring of FasL gene-modified dendritic cells(DC). Methods The mouse models of spontaneous abortion(CBA/J ? DBA/2) and normal pregnancy(CBA/J ? BALB/c) were established.Five different experimental groups were included: mice of normal pregnancy(CBA/J?BALB/c)(n=17),served as control group;mice of spontaneous abortion without treatment(CBA/J?DBA/2)(n=37),mice injected with DC culture medium(DCCM)(n=25);mice immunized with empty plasmid pcDNA3.1-DC(n=6);and mice immunized with pcDNA3.1-FasL-DC(n=5).Embryo resorption rates of pregnant mice in each groups were observed.Annexin V-FITC was used to detect the apoptosis of T cells.Immunohistochemical staining(SABC) was used to detect the expression of FasL in decidual membranes of pregnant mice. ResultsThe embryo resorption rate of mice immunized with FasL-DC was decreased significantly as compared with that of mice of spontaneous abortion without treatment,DCCM group and immunized with pcDNA3.1-DC(P0.05). Conclusion The decreased apoptosis rate of peripheral T cells and the reduced expression of FasL in decidual membranes may be an important mechanism for the pathogenesis of abortion.Adoptive transfer of FasL gene-modified DC may induce pregnancy immune tolerance by increasing FasL expression of maternal-fetal interface and decreasing embryo resorption rate.

Influence of Oral Antigens on Expression of Costimulatory Molecules CD80/CD86 on Surface of M? / 上海第二医科大学学报

Objective To study the influence of oral antigens on the expression of costimulatory molecules CD80/CD86 on the surface of M and to investigate the genesis of pregnancy immunological tolerance induced by oral antigens through CD80/CD86. Methods Mice of spontaneous abortion(CBA/J?DBA/2) were divided into two groups: immune group and non-immune group.Trophoblast membrane antigen-2(TMA2)or ovum albumin(OVA) was administered orally to the mice in the immune group.Mice of normal pregnancy(CBA/J?BALB/c) were served as controls.The number of CD80/CD86 M of spleen and mesenteric lymph node(MLN) were determined by double-label FCM method. Results In the MLN,CD80 M of non-immune group was increased significantly as compared with that of the control group(P

Association of HLA-DQB1 coding region with unexplained recurrent spontaneous abortion / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>DNA analysis has shown a lack of significant compatibility between couples affected by unexplained recurrent spontaneous abortion (URSA) compared with normal fertile couples, [8] although one study that made use of a PCR-sequence-specific oligonucleotide (SSO) method did observe evidence of significant compatibility in the HLA-DQA1 and DQB1 alleles between patients and aborted fetuses. [9] This study was designed to investigate whether URSA were associated with particular DQ alleles or promoter alleles.</p><p><b>METHODS</b>Thirty-two patients with URSA and 54 women who had had at least one successful pregnancy were included in this study. HLA-DQ genotyping was performed by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. The HLA-DQB1 promoter was detected by the SSO and sequence-specific primer (SSP) methods. The DQA1, DQB1, and DQB1 promoter (QBP) gene frequencies in the patients were compared with the gene frequencies in normal controls. The data were analyzed statistically with the chi(2) and Fisher's exact tests.</p><p><b>RESULTS</b>The results showed that the frequency of DQB1 * 0604/0605 was significantly higher and the frequency of DQB1 * 0501/0502 was significantly lower in the patient group as compared with the normal controls. In addition, the frequencies of the DQA1 * 01-DQB1 * 0604/0605 and QBP6.2-DQB1 * 0604/0605 haplotypes were overrepresented in the patients relative to the controls. Our results did not show any differences between URSA patients and the controls with regard to DQA1 and QBP allele frequencies.</p><p><b>CONCLUSIONS</b>Our data suggest that URSA is associated with the HLA-DQB1 coding region, and is not associated with its upstream regulatory region. The DQB1 * 0604/0605, DQA1 * 01-DQB1 * 0604/0605, and QBP6.2-DQB1 * 0604/0605 haplotypes may confer susceptibility to URSA, while the DQB1 * 0501/0502 allele may protect women from URSA.</p>

Study on the expression of transcription factor GATA-3 and T-bet mRNA in decidua of women with unexplained recurrent spontaneous abortion / 中华妇产科杂志

Objective To investigate the roles of transcription factor GATA-3 and T-bet at the fetal- maternal interface in the pathogenesis of unexplained recurrent spontaneous abortion(URSA).Methods The expression of GATA-3 and T-bet mRNA was examined by in situ hybridization.Decidua was obtained from 20 women with URSA and 20 normal pregnant(NP)women.Results(1)The number of GATA-3 positive cells per high power field in women with URSA(25?16)was significantly lower than those in NP women(38?16)(P