Quantitative proteomic analysis of down syndrome biomarkers in maternal serum using isobaric tags for relative and absolute quantification (iTRAQ).

Prenatal diagnosis of Down syndrome (DS) is based on calculated risk involving maternal age, biochemical and ultrasonographic markers, and, more recently, cell-free DNA (cfDNA). The present study was designed to identify Down Syndrome biomarkers in maternal serum. We quantified the changes in maternal serum protein levels between 10 non-pregnant women, 10 pregnant women with healthy fetuses, and 10 pregnant women with DS fetuses using isobaric tags for relative and absolute quantification (iTRAQ). We subsequently conducted a Gene Ontology (GO) analysis. A total of 470 proteins were identified, 11 of which had significantly different serum levels between the DS fetus group and Healthy fetuses group. Our data shows the identified proteins may be relevant to DS and constitute potential DS biomarkers.

p53 and Sp1 cooperate to regulate the expression of Epstein-Barr viral Zta protein.

Epstein-Barr virus (EBV) belongs to the gammaherpesvirus family. To produce infectious progeny, EBV reactivates from latency into the lytic cycle by expressing the determinative lytic transactivator, Zta. In the presence of histone deacetylase inhibitor (HDACi), p53 is a prerequisite for the initiation of the EBV lytic cycle by facilitating the expression of Zta. In this study, a serial mutational analysis of Zta promoter (Zp) indicated an important role for the ZID element in responding to HDACi induction and p53 binds to this ZID element together with Sp1, a universal transcription factor. Abolition of the DNA-binding ability of Sp1 reduces the inducibility of ZID by HDACi and also reduces the amount of p53 binding to ZID. Finally, it was shown that EBV in p53-positive-lymphoblastoid cell lines (LCLs) can enter into the lytic cycle spontaneously; however, knockdown of p53 in LCLs leads to retardation of EBV reactivation.

Effects of Modes and Timings of Delivery on Feto-Maternal Outcomes in Women with Severe Preeclampsia: A Multi-Center Survey in Mainland China.

BACKGROUND: Pregnancy termination is the only effective treatment for preeclampsia. However, there are controversies on the selection of modes of delivery. The objective was to evaluate whether mode of delivery in labor differentially affected the rate of adverse maternal outcomes related to severe preeclampsia. OBJECTIVE: This study aimed to evaluate whether the modes and timings of delivery affects adverse maternal outcomes in pre-eclampsia. METHODS: Clinical data from 2516 singleton pregnant women with severe preeclampsia were collected in a multicenter, large-sample, cross-sectional study in mainland China. The patients were divided into cesarean-delivery (CD) and vaginal-delivery (VD) categories and then into Group 1 (≤27+ 6 weeks), Group 2 (28-33+ 6 weeks), Group 3 (34-36+ 6 weeks), and Group 4 (≥37 weeks) according to the mode of delivery and gestational weeks. All data were exported into the SPSS software and analyzed by the Student's t-tests or Mann-Whitney U-tests and the chi-squared test. RESULTS: A total of 2516 singleton pregnant women with severe preeclampsia were collected and the overall cesarean section rate was 84.9%. The vaginal delivery rates among the four groups were significantly different with 70%, 19.7%, 6.6%, 15.1% in groups 1, 2, 3, 4, respectively (P<0.05), while perinatal mortality was lower in the CD groups than VD groups (3.3% vs 50.4%, P<0.05). The neonatal asphyxia rate was significantly higher with CD than with VD in Group 2 (36.4% vs 12.9%, P<0.05). The perinatal mortality with CD, 3, and 4 was significantly lower than with VD (10.0% vs 68.5% in Groups 2, 2.3% vs 28.3% in Groups 3, 0.8% vs 5.6% in Groups 4, all P<0.05). CONCLUSION: Most pregnant women with severe preeclampsia opted for a cesarean section in China. The lower perinatal mortality was associated with cesarean section, but the rate of maternal PPH or mortality was not related with the mode of delivery. So cesarean section is the safer delivery mode for the pregnant women complicated with severe preeclampsia.

Whole-exome sequencing reveals POLR3B variants associated with progeria-related Wiedemann-Rautenstrauch syndrome.

BACKGROUND: Wiedemann-Rautenstrauch syndrome (WRS) is a rare autosomal recessive neonatal progeroid disorder characterized by prenatal and postnatal growth retardation, short stature, a progeroid appearance, hypotonia, and mental impairment. CASE PRESENTATION: A 6-year-old patient, who initially presented with multiple postnatal abnormalities, facial dysplasia, micrognathia, skull appearance, hallux valgus, and congenital dislocation of the hip, was recruited in this study. The patient was initially diagnosed with progeria. The mother of the patient had abnormal fetal development during her second pregnancy check-up, and the clinical phenotype of the fetus was similar to that of the patient. Whole-exome sequencing (WES) of the patient was performed, and POLR3B compound heterozygous variants-c.2191G > C:p.E731Q and c.3046G > A:p.V1016M-were identified in the patient. Using Sanger sequencing, we found that the phenotypes and genotypes were segregated within the pedigree. These two variants are novel and not found in the gnomAD and 1000 Genomes databases. The two mutation sites are highly conserved between humans and zebrafish. CONCLUSIONS: Our study not only identified a novel WRS-associated gene, POLR3B, but also broadened the mutational and phenotypic spectra of POLR3B. Furthermore, WES may be useful for identifying rare disease-related genetic variants.

[Risk factors of adverse pregnancy outcomes during expectant management of early onset severe pre-eclampsia].

OBJECTIVE: To identify the risk factors of adverse pregnancy outcomes in expectant management of pregnant women with early onset severe pre-eclampsia (EOSP). METHODS: Totally, 136 gravidas, who were diagnosed as ESOP and received expectant management from January 2007 to June 2008 in Beijing Obstetrics and Gynecology Hospital, were selected and divided into two groups: the favorable pregnancy outcome group (control, n = 101) and the adverse pregnancy outcome group (n = 35). The general clinical information, pregnancy outcomes, routine urine test, hemodynamic data, routine blood test, liver and renal function test on admission were collected and the risk factors for adverse outcomes were retrospectively analyzed. RESULTS: (1) General clinical information: more women complained of preeclamptic symptoms on admission in the adverse outcome group than in the control group (35.6% vs. 57.1%, P < 0.05). No significant differences was found between the two groups in the maternal age, times of previous pregnancies, prevalence of concurrent complications, pre-pregnant body mass index (BMI), proportion of women who had regular antenatal checks (P > 0.05). (2) Pregnant outcomes: the average duration of expectant management in the control group were similar to the adverse outcomes group [(6.5 +/- 8.2) days vs. (6.8 +/- 10.0) days, P > 0.05]. The main complications in the adverse outcome group included placental abruption (n = 13), heart failure and pulmonary edema (n = 10), hemolysis, elevated liver enzymes and low platelet syndrome (HELLP syndrome, n = 5), and no eclampsia was reported. However, none of these complications was reported from the control group. (3) Blood pressure and proteinuria: the gestation ages at the onset of EOSP and at delivery in the control group were earlier than those of the adverse outcome group [(31.3 +/- 3.4) weeks vs. (33.0 +/- 4.9) weeks, (32.1 +/- 3.0) weeks vs. (34.0 +/- 3.6) weeks, P < 0.05], the systolic blood pressure and urinary protein and the proportion of women with urinary protein of (+++) were also much higher in the adverse outcome group (all P < 0.05). (4) Hemodynamics and routine blood tests: the blood viscosity in the control group was obviously lower than that of the adverse outcome group (P < 0.05). But there was no significant difference in the cardiac output, cardiac index, peripheral resistance and vascular compliance between the two groups (P > 0.05). The adverse outcome group showed lower platelet (PLT) level and higher red blood cell (RBC) count and hematocrit compared with those of the control (all P < 0.01). (5) Liver and renal function: the alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), blood urea nitrogen (BUN) in the adverse outcome group were significantly higher than those of the control group (all P < 0.05), but the plasma level of total protein (TP), albumin (Alb), uric acid (UA) and creatinine (Cr) were similar between the two groups (P > 0.05). (6) Risk factor analysis: RBC count (OR = 3.68, 95%CI: 1.90-7.13), PLT count (OR = 0.99, 95%CI: 0.98-1.00) and the gestations at delivery (OR = 0.87, 95%CI: 0.80-0.94) were the risk factors of adverse pregnancy outcomes during the expectant management of EOSP. CONCLUSION: Elevated RBC count, reduced PLT count and earlier delivery weeks are the risk factors of adverse pregnancy outcomes during the expectant management of EOSP.

Intrapartum interventions that affect maternal and neonatal outcomes for vaginal birth after cesarean section.

OBJECTIVE: To investigate maternal and neonatal outcomes after different intrapartum interventions for vaginal birth after cesarean section (VBAC) in mainland China. METHODS: A retrospective study was performed on 143 VBAC cases from Beijing Obstetrics and Gynecology Hospital between January 2015 and November 2016. These cases were divided into two groups on the basis of different intrapartum interventions. Maternal and neonatal outcomes were compared. RESULTS: The durations of the first stage and total labor after oxytocin were significantly longer than those before oxytocin use. The proportion of operative vaginal delivery with oxytocin was significantly higher than that without oxytocin (43.9% vs. 11.8%). The times of the first stage, second stage, and total labor with analgesia were significantly longer than those without analgesia (548.4±198.1 vs. 341.8±233.0 minutes, 52.0±38.9 vs. 36.0± 29.1 minutes, and 606.3±212.1 vs. 387.3±233.0 minutes, respectively). Postpartum hemorrhage and operative vaginal delivery occurred significantly more frequently in women with epidural analgesia than in those without epidural analgesia (29.7% vs. 12.3 and 35.1% vs. 16.0%, respectively). CONCLUSIONS: Induction can increase the rate of operative vaginal delivery in VBAC. Oxytocin and epidural analgesia may increase the risk of operative vaginal delivery, and may be associated with a prolonged duration of labor.

Labor Onset, Oxytocin Use, and Epidural Anesthesia for Vaginal Birth after Cesarean Section and Associated Effects on Maternal and Neonatal Outcomes in a Tertiary Hospital in China: A Retrospective Study.

BACKGROUND: In the mainland of China, the trial of labor after cesarean section is still a relatively new technique. In this study, we aimed to investigate the effects of labor onset, oxytocin use, and epidural anesthesia on maternal and neonatal outcomes for vaginal birth after cesarean section (VBAC) in a tertiary hospital in China. METHODS: This was a retrospective study carried out on 212 VBAC cases between January 2015 and June 2017 in Beijing Obstetrics and Gynecology Hospital, Capital Medical University. Relevant data were acquired on a form, including maternal age, gravidity and parity, body mass index before pregnancy, weight gain during pregnancy, type of labor onset, gestational age, the use of oxytocin and epidural anesthesia, birth mode, the duration of labor, and neonatal weight. The factors affecting maternal and neonatal outcomes for cases involving VBAC, especially with regards to postpartum hemorrhage (PPH) and fetal distress, were evaluated by univariate analysis and multivariable logistic regression. RESULTS: Data showed that 36 women (17.0%) had postpartum hemorrhage (PPH) and 51 cases (24.1%) featured fetal distress. Normal delivery took place for 163 infants (76.9%) while 49 infants (23.1%) underwent operative vaginal deliveries with forceps. There were 178 cases (84.0%) of spontaneous labor and 34 cases (16.0%) required induction. Oxytocin was used in 54 cases (25.5%) to strengthen uterine contraction, and 65 cases (30.7%) received epidural anesthesia. The rate of normal delivery in cases involving PPH was significantly lower than those without PPH (61.1% vs. 80.1%; χ2 = 6.07, P = 0.01). Multivariate logistic analysis showed that the intrapartum administration of oxytocin (odds ratio [OR] = 2.47; 95% confidence interval [CI] = 1.07-5.74; P = 0.04) and birth mode (OR = 0.40; 95% CI = 0.18-0.87; P = 0.02) was significantly associated with PPH in VBAC cases. Operative vaginal delivery occurred more frequently in the group with fetal distress than the group without (49.0% vs. 14.9%, χ2 = 25.36, P = 0.00). Multivariate logistic analysis also revealed that the duration of total labor (OR = 1.01; 95% CI = 1.00-1.03; P = 0.04) and the gestational week of delivery (OR = 1.08; 95% CI = 1.05-1.11; P = 0.00) were significantly associated with fetal distress in VBAC. CONCLUSIONS: The administration of oxytocin during labor and birth was identified as a protective factor for PPH in VBAC while birth mode was identified as a risk factor. Finally, the duration of total labor and the gestational week of delivery were identified as risk factors for fetal distress in cases of VBAC. This information might help obstetricians provide appropriate interventions during labor and birth for VBAC.

Novel expression and regulation of TIMP-1 in Epstein Barr virus-infected cells and its impact on cell survival.

Epstein Barr virus (EBV) uses various strategies to manipulate host cytokine production in favor of the survival of infected B-cells. Microarray and cytokine protein array assays revealed that tissue inhibitor of metalloproteinase-1 (TIMP-1) was significantly up-regulated in EBV-infected primary B cells and maintained in abundance in EBV-immortalized lymphoblastoid cell lines (LCLs). TIMP-1 plays critical roles in extracellular matrix homeostasis and regulates signaling pathways. In this study, we demonstrated that the EBV-encoded immediate early lytic protein, Zta, upregulates mainly TIMP-1 expression by binding to the AP-1 site within the TIMP-1 promoter. Moreover, knockdown of TIMP-1 expression promoted cisplastin and cold shock-induced death of LCLs. This study provides a mechanistic link between EBV-induced TIMP-1 expression and its impact on LCL survival.