Juan Xiao

The complication and mode of delivery in Chinese women with severe preeclampsia: a retrospective study

Objective: Severe preeclampsia is a serious threat for pregnant women and fetuses. The complications of severe preeclampsia greatly affect perinatal outcome. This study aimed to investigate the complication and delivery mode of Chinese pregnant women with severe preeclampsia, and analyze the change in these aspects in the past decades. Methods: Clinical data of 1713 pregnant women with severe preeclampsia were collected and analyzed. The patients were divided into two groups: early period (1985–1997) and later period (1998–2010). Results: The complications for severe preeclampsia included preterm birth, fetal distress, postpartum hemorrhage, fetal growth restriction (FGR). Compared to early period, the rates of preterm birth, FGR, oligohydramnios, abnormal pregnancy outcome increased while the rates of fetal distress, postpartum hemorrhage and eclampsia decreased in later period. The rate of cesarean section was 73.073% in the early period and increased to 88.258% in the later period. Accordingly, the rate of natural childbirth, forceps extraction, vacuum extraction and breech extraction decreased in the later period. Conclusions: Our data provide important information on the complication and mode of delivery in Chinese women with severe preeclampsia in the past decades, which may be helpful for clinical management of severe preeclampsia in Chinese women.

Long-term Impact of Intrauterine MCMV Infection on Development of Offspring Nervous System

SummaryThis study examined the impacts of intrauterine murine cytomegalovirus (MCMV) infection on the long-term learning and memory of offspring. Sexually matured male and female BALB/C mice without MCMV infection were identified by ELISA and then mated. Seventy pregnant mice were randomly divided into the virus group (n=40) and the control group (n=30), in which the pregnant mice were subjected to placenta inoculation of MCMV suspension (1 μL, 1×106 PFU) or the same amount of cell culture medium, respectively, at gestational age of 12.5 days. Some pregnant mice [virus group (n=20), control group (n=15)] were sacrificed by cervical dislocation at gestational age of 18.5 days, and the head circumference and brain weight of the mouse fetuses were measured, and the MCMV infection in their brain tissues was detected by PCR. The other pregnant mice [virus group (n=20), control group (n=15)] delivered naturally, and the learning and memory capability of the offspring at 70-day-old was analyzed by Morris water maze test. The results showed that 28.57% mouse fetuses in the virus group developed viral infection in the brain. Their head circumference and brain weight were significantly reduced as compared with those in the control group (P<0.01). The Morris water maze test revealed that the mouse offspring in the control group found the platform with straight-line trajectories after training. In contrast, the counterparts in the virus group intended to enter the central area, but looked for the platform with a circular trajectory. And the infected mice exhibited prolonged swimming distance and swimming latency (P<0.01). It was concluded that: (1) placenta inoculation of MCMV can cause fetal brain infection and intrauterine development retardation; (2) the offspring of MCMV placenta inoculation mice showed a long-term decline in learning and memory capability.This study examined the impacts of intrauterine murine cytomegalovirus (MCMV) infection on the long-term learning and memory of offspring. Sexually matured male and female BALB/C mice without MCMV infection were identified by ELISA and then mated. Seventy pregnant mice were randomly divided into the virus group (n=40) and the control group (n=30), in which the pregnant mice were subjected to placenta inoculation of MCMV suspension (1 μL, 1×106 PFU) or the same amount of cell culture medium, respectively, at gestational age of 12.5 days. Some pregnant mice [virus group (n=20), control group (n=15)] were sacrificed by cervical dislocation at gestational age of 18.5 days, and the head circumference and brain weight of the mouse fetuses were measured, and the MCMV infection in their brain tissues was detected by PCR. The other pregnant mice [virus group (n=20), control group (n=15)] delivered naturally, and the learning and memory capability of the offspring at 70-day-old was analyzed by Morris water maze test. The results showed that 28.57% mouse fetuses in the virus group developed viral infection in the brain. Their head circumference and brain weight were significantly reduced as compared with those in the control group (P<0.01). The Morris water maze test revealed that the mouse offspring in the control group found the platform with straight-line trajectories after training. In contrast, the counterparts in the virus group intended to enter the central area, but looked for the platform with a circular trajectory. And the infected mice exhibited prolonged swimming distance and swimming latency (P<0.01). It was concluded that: (1) placenta inoculation of MCMV can cause fetal brain infection and intrauterine development retardation; (2) the offspring of MCMV placenta inoculation mice showed a long-term decline in learning and memory capability.

In vitro study on human trophoblast cells infected with HCMV

Human trophoblast cells were isolated and cultured in vitro in order to investigate possible pathogenesis of intrauterine infection caused by HCMV. Trophoblast cells were obtained by compound enzymes digestion and discontinuous percoll gradient. Cells and purity were identified by using immunocytochemistry assay with anti-CK7, Vim and β-hCG antibodies. HCMV AD169 strain replication in isolated trophoblast cells and cell apoptosis were detected at different time points post infection (p.i.). The results showed that highly purified trophoblast cells were obtained. Specific virus replication was increased dramatically at the 24th h p.i., and then increased slowly during 48 h and 72 h. Apoptosis rate of trophoblast cells infected with HCMV was (34.68±3.14)% at 24th h p.i., while that in control group was (15.32±2.34)% (P<0.05). It was suggested that highly purified trophoblast cells can be isolated by the simplified cell purification method. HCMV can infect human trophoblast cells, and be quickly replicated, resulting in the accelerated apoptosis of human trophoblast cells during early time.SummaryHuman trophoblast cells were isolated and cultured in vitro in order to investigate possible pathogenesis of intrauterine infection caused by HCMV. Trophoblast cells were obtained by compound enzymes digestion and discontinuous percoll gradient. Cells and purity were identified by using immunocytochemistry assay with anti-CK7, Vim and β-hCG antibodies. HCMV AD169 strain replication in isolated trophoblast cells and cell apoptosis were detected at different time points post infection (p.i.). The results showed that highly purified trophoblast cells were obtained. Specific virus replication was increased dramatically at the 24th h p.i., and then increased slowly during 48 h and 72 h. Apoptosis rate of trophoblast cells infected with HCMV was (34.68±3.14)% at 24th h p.i., while that in control group was (15.32±2.34)% (P<0.05). It was suggested that highly purified trophoblast cells can be isolated by the simplified cell purification method. HCMV can infect human trophoblast cells, and be quickly replicated, resulting in the accelerated apoptosis of human trophoblast cells during early time.

ADAMTS13: more than a regulator of thrombosis

ADAMTS13, a plasma reprolysin-like metalloprotease, proteolyzes von Willebrand factor (VWF). ADAMTS13 is primarily synthesized by hepatic stellate cells (HSCs), and mainly regulates thrombogenesis by cleaving VWF. Recent studies demonstrate that ADAMTS13 also plays a role in the down-regulation of inflammation, regulation angiogenesis, and degradation of extracellular matrix. The purpose of this review is to introduce the state of progress with respect to some of the theorized roles of ADAMTS13.

Effect of Human Cytomegalovirus on Invasive Capability of Early Pregnant Extravillous Cytotrophoblasts

SummaryThe effect of human cytomegalovirus (HCMV) on invasive capability of early pregnant extravillous cytotrophoblasts (EVTs) was investigated in vitro. Primary EVTs were obtained by complex phosphoesterasum digestion and gradient centrifugation from villous tissue aseptically taken from healthy pregnant women. Cytokeratin7 (CK7), vimentin (Vim) and c-erbB-2 were immunocytochemically detected to identify source of cells, and HCMVpp65 antigen was assayed to determine the infection state of primary EVTs by immunocytochemical staining. The EVTs were divided into two groups: control group and HCMV group, and the expression of c-erbB-2, matrix metalloproteinase-2 (MMP-2) and MMP-9 proteins was detected in two groups by immunocytochemistry and Western blotting. Enzymic activity changes of MMP-2 and MMP-9 were tested by gelatin zymography in primary EVTs infected with HCMV. The invasion of primary EVTs was detected by cell invasion assay in vitro after they were infected by HCMV. The cell source identification showed that the cells obtained were highly-pure primary EVTs, and primary EVTs could be infected by HCMV. Primary EVTs could express c-erbB-2, MMP-2 and MMP-9 proteins, and as compared with control group, the protein expression was decreased significantly in HCMV groups (P<0.05). Primary EVTs could secrete active MMP-2 and MMP-9 in vitro, and the activity of two MMPs was decreased significantly in HCMV groups (P<0.05). The in vitro cell invasion assay showed that the number of primary EVTs permeating Matrigel in HCMV group was decreased (P<0.05). We are led to conclude that HCMV can infect primary EVTs and inhibit their invasion capability, suggesting that the impaired EVT’s invasion capability might be related to the abnormal expression of c-erbB-2, MMP-2 and MMP-9 proteins.The effect of human cytomegalovirus (HCMV) on invasive capability of early pregnant extravillous cytotrophoblasts (EVTs) was investigated in vitro. Primary EVTs were obtained by complex phosphoesterasum digestion and gradient centrifugation from villous tissue aseptically taken from healthy pregnant women. Cytokeratin7 (CK7), vimentin (Vim) and c-erbB-2 were immunocytochemically detected to identify source of cells, and HCMVpp65 antigen was assayed to determine the infection state of primary EVTs by immunocytochemical staining. The EVTs were divided into two groups: control group and HCMV group, and the expression of c-erbB-2, matrix metalloproteinase-2 (MMP-2) and MMP-9 proteins was detected in two groups by immunocytochemistry and Western blotting. Enzymic activity changes of MMP-2 and MMP-9 were tested by gelatin zymography in primary EVTs infected with HCMV. The invasion of primary EVTs was detected by cell invasion assay in vitro after they were infected by HCMV. The cell source identification showed that the cells obtained were highly-pure primary EVTs, and primary EVTs could be infected by HCMV. Primary EVTs could express c-erbB-2, MMP-2 and MMP-9 proteins, and as compared with control group, the protein expression was decreased significantly in HCMV groups (P<0.05). Primary EVTs could secrete active MMP-2 and MMP-9 in vitro, and the activity of two MMPs was decreased significantly in HCMV groups (P<0.05). The in vitro cell invasion assay showed that the number of primary EVTs permeating Matrigel in HCMV group was decreased (P<0.05). We are led to conclude that HCMV can infect primary EVTs and inhibit their invasion capability, suggesting that the impaired EVT’s invasion capability might be related to the abnormal expression of c-erbB-2, MMP-2 and MMP-9 proteins.

Effect of baicalein on the expression of VIP in extravillous cytotrophoblasts infected with human cytomegalovirus in vitro

SummaryThis paper aimed to study the ability of baicalein to block human cytomegalovirus (HCMV) infection in extravillous cytotrophoblasts (EVT) and its effect on the vasoactive intestinal peptide (VIP) expression in HCMV-infected EVT in vitro. A human trophoblast cell line (HPT-8) was chosen in this study. HCMV with 100 TCID50 was added into culture medium to infect HPT-8 cells, and then HCMV pp65 antigen was assayed by immunofluorescence staining. The infection status was determined by virus titration. Real-time quantitative polymerase chain reaction (qRT-PCR) was used to detect virus DNA load in the infected cells. The expression of VIP mRNA and protein in the infected cells was measured by qRT-PCR, immunocytochemistry and Western blotting. Concentration of VIP secreted in supernatants was determined by ELISA. Red-stained HCMV pp65 antigens were found in infected HPT-8 cells 48 h after infection. HCMV replicated in large quantity in infected HPT-8 cells 4 days after infection, reaching a peak at day 6 post-infection. After treatment with baicalein, virus DNA load in infected HPT-8 cells was decreased (P<0.05), and the levels of VIP mRNA and protein, and the concentration were raised to the normal (P>0.05). Our study suggested that baicalein exerts a positive effect on the VIP expression in HCMV-infected EVT at maternal-fetal interface.This paper aimed to study the ability of baicalein to block human cytomegalovirus (HCMV) infection in extravillous cytotrophoblasts (EVT) and its effect on the vasoactive intestinal peptide (VIP) expression in HCMV-infected EVT in vitro. A human trophoblast cell line (HPT-8) was chosen in this study. HCMV with 100 TCID50 was added into culture medium to infect HPT-8 cells, and then HCMV pp65 antigen was assayed by immunofluorescence staining. The infection status was determined by virus titration. Real-time quantitative polymerase chain reaction (qRT-PCR) was used to detect virus DNA load in the infected cells. The expression of VIP mRNA and protein in the infected cells was measured by qRT-PCR, immunocytochemistry and Western blotting. Concentration of VIP secreted in supernatants was determined by ELISA. Red-stained HCMV pp65 antigens were found in infected HPT-8 cells 48 h after infection. HCMV replicated in large quantity in infected HPT-8 cells 4 days after infection, reaching a peak at day 6 post-infection. After treatment with baicalein, virus DNA load in infected HPT-8 cells was decreased (P<0.05), and the levels of VIP mRNA and protein, and the concentration were raised to the normal (P>0.05). Our study suggested that baicalein exerts a positive effect on the VIP expression in HCMV-infected EVT at maternal-fetal interface.

Von Willebrand factor antigen and ADAMTS13 activity assay in pregnant women and severe preeclamptic patients.

The present study examined von Willebrand factor (vWF) levels and ADAMTS13 activity in pregnant and severe preeclamptic women in order to shed light on the prothrombotic state in severe preeclampsia. Thirty healthy women of childbearing age, 22 second trimester pregnant women, 30 third trimester pregnant women and 10 severe preeclamptic patients were recruited in this study. ADAMTS13 activity was determined by the FRETS-vWF73 assay and vWF antigen (vWF:Ag) levels by an enzyme-linked immunosorbent assay. The results showed that there were statistically significant differences in plasma vWF antigen levels between the severe preeclamptic and third trimester pregnant women, between third and second trimester pregnant women (P<0.05). The third trimester pregnant women had significantly lower plasma ADAMTS13 activity than second trimester pregnant women (P<0.05). Nevertheless, no significant differences in plasma ADAMTS13 activity were found between severe preeclamptic patients and the third trimester pregnant women (P>0.05). In conclusion, plasma ADAMTS13 activity is normal in severe preeclampsia despite the increased vWF:Ag levels. Prothrombotic state is involved in the pathogenesis of severe preeclampsia, as a result of endothelial injury.SummaryThe present study examined von Willebrand factor (vWF) levels and ADAMTS13 activity in pregnant and severe preeclamptic women in order to shed light on the prothrombotic state in severe preeclampsia. Thirty healthy women of childbearing age, 22 second trimester pregnant women, 30 third trimester pregnant women and 10 severe preeclamptic patients were recruited in this study. ADAMTS13 activity was determined by the FRETS-vWF73 assay and vWF antigen (vWF:Ag) levels by an enzyme-linked immunosorbent assay. The results showed that there were statistically significant differences in plasma vWF antigen levels between the severe preeclamptic and third trimester pregnant women, between third and second trimester pregnant women (P<0.05). The third trimester pregnant women had significantly lower plasma ADAMTS13 activity than second trimester pregnant women (P<0.05). Nevertheless, no significant differences in plasma ADAMTS13 activity were found between severe preeclamptic patients and the third trimester pregnant women (P>0.05). In conclusion, plasma ADAMTS13 activity is normal in severe preeclampsia despite the increased vWF:Ag levels. Prothrombotic state is involved in the pathogenesis of severe preeclampsia, as a result of endothelial injury.

Risk Factors and Pregnancy Outcomes: Complete versus Incomplete Placenta Previa in Mid-pregnancy

SummaryThis prospective study was conducted to compare risk factors and pregnancy outcomes between women with complete placenta previa and those with incomplete placenta previa diagnosed in mid-pregnancy. The study was carried out from April 2014 to December 2015, during which 70 patients with complete previa and 113 with incomplete previa between 20+0 weeks and 25+6 weeks of gestation were included. Maternal demographics and pregnancy outcomes were compared between the two groups. Comparisons between categorical variables were tested by chi-squared test and those between continuous variables by Student t test. Resolution of previa occurred in 87.43% of the studied women. The mean gestational age at resolution was 32.1±4.4 weeks. Incidence of maternal age ≥35 years and incidence of prior uterine operation ≥3 were high in women with complete previa (28.6% vs 8.8%, P=0.003; 28.6% vs. 8.8%, P=0.003). Resolution of previa occurred less often in complete previa group (74.3% vs. 95.6%, P=0.001). Women with complete previa admitted earlier (37.3±2.0 weeks 38.1±1.4 weeks, P=0.011) and delivered earlier (37.7±1.2 weeks vs. 38.3±1.4 weeks, P=0.025). Maternal age ≥35 years and prior uterine operation ≥3 increase the risk of complete previa in mid-pregnancy. Placenta previa is more likely to persist in women with complete previa than those with incomplete previa diagnosed in midpregnancy. What is more, women with complete previa in mid-pregnancy delivers earlier.

Relationship between placenta location and resolution of second trimester placenta previa

This prospective study was conducted to assess the rate of resolution of second trimester placenta previa in women with anterior placenta and posterior placenta, and that in women with and without previous cesarean section. In this study, placenta previa was defined as a placenta lying within 20 mm of the internal cervical os or overlapping it. We recruited 183 women diagnosed with previa between 20+0 weeks and 25+6 weeks. They were grouped according to their placenta location (anterior or posterior) and history of cesarean section. Comparative analysis was performed on demographic data, resolution rate of previa and pregnancy outcomes between anterior group and posterior group, and on those between cesarean section group and non-cesarean section group. Women with an anterior placenta tended to be advanced in parity (P=0.040) and have increased number of dilatation and curettage (P=0.044). The women in cesarean section group were significantly older (P=0.000) and had more parity (P=0.000), gravidity (P=0.000), and dilatation and curettage (P=0.048) than in non-cesarean section group. Resolution of previa at delivery occurred in 87.43% women in this study. Women with a posterior placenta had a higher rate of resolution (P=0.030), while history of cesarean section made no difference. Gestational age at resolution was earlier in posterior group (P=0.002) and non-cesarean section group (P=0.008) than in anterior group and cesarean section group correspondingly. Placenta location and prior cesarean section did not influence obstetric outcomes and neonatal outcomes. This study indicates that it is more likely to have subsequent resolution of the previa when the placenta is posteriorly located for women who are diagnosed with placenta previa in the second trimester.SummaryThis prospective study was conducted to assess the rate of resolution of second trimester placenta previa in women with anterior placenta and posterior placenta, and that in women with and without previous cesarean section. In this study, placenta previa was defined as a placenta lying within 20 mm of the internal cervical os or overlapping it. We recruited 183 women diagnosed with previa between 20+0 weeks and 25+6 weeks. They were grouped according to their placenta location (anterior or posterior) and history of cesarean section. Comparative analysis was performed on demographic data, resolution rate of previa and pregnancy outcomes between anterior group and posterior group, and on those between cesarean section group and non-cesarean section group. Women with an anterior placenta tended to be advanced in parity (P=0.040) and have increased number of dilatation and curettage (P=0.044). The women in cesarean section group were significantly older (P=0.000) and had more parity (P=0.000), gravidity (P=0.000), and dilatation and curettage (P=0.048) than in non-cesarean section group. Resolution of previa at delivery occurred in 87.43% women in this study. Women with a posterior placenta had a higher rate of resolution (P=0.030), while history of cesarean section made no difference. Gestational age at resolution was earlier in posterior group (P=0.002) and non-cesarean section group (P=0.008) than in anterior group and cesarean section group correspondingly. Placenta location and prior cesarean section did not influence obstetric outcomes and neonatal outcomes. This study indicates that it is more likely to have subsequent resolution of the previa when the placenta is posteriorly located for women who are diagnosed with placenta previa in the second trimester.