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Preeclampsia and intrauterine growth restriction (IUGR) of the fetus are the two most common pregnancy complications worldwide, affecting 5%-10% of pregnant women. Preeclampsia is associated with significantly increased maternal and fetal morbidity and mortality. Hypoxia-induced uteroplacental dysfunction is now recognized as a key pathological factor in preeclampsia and IUGR. Reduced oxygen supply (hypoxia) disrupts mitochondrial and endoplasmic reticulum (ER) function. Hypoxia has been shown to alter mitochondrial reactive oxygen species (ROS) homeostasis and induce ER stress. Hypoxia during pregnancy is associated with excessive production of ROS in the placenta, leading to oxidative stress. Oxidative stress occurs in a number of human diseases, including high blood pressure during pregnancy. Studies have shown that uterine placental tissue/cells in preeclampsia and IUGR show high levels of oxidative stress, which plays an important role in the pathogenesis of both the complications. This review summarizes the role of hypoxia-induced mitochondrial oxidative stress and ER stress in the pathogenesis of preeclampsia/IUGR and discusses the potential therapeutic strategies targeting oxidative stress to treat both the pregnancy complications.

Objective: To investigate the clinical outcomes of different treatment options on singleton short cervix and its influence factors. Methods: Totally 435 cases of singleton pregnancies who were diagnosed with short cervix (≤25 mm) between 12 to 33 +6 gestational weeks in Peking University First Hospital from January 2018 to December 2018 were enrolled, including 21 cases with cervical length <10 mm, 414 cases with cervical length between 10 to 25 mm. The onset time was <24 gestational weeks in 106 cases, while 104 cases were at 24-29 +6 gestational weeks and 225 cases of ≥30 gestational weeks. Gestational outcomes including delivery before 37 weeks, delivery before 34 weeks, neonatal birth weight (NBW) and adverse neonatal outcome (ANO) were compared among three treatment groups: rest group, progesterone group and cerclage group. Influence factors were also investigated. Results: (1) The incidence of short cervix in pregnancy was 7.07% (435/6 155), while 106 cases were at <24 gestational weeks (1.72%, 106/6 155), 104 cases (1.69%, 104/6 155) at 24-29 +6 gestational weeks and 225 cases (3.66%, 225/6 155) at ≥30 gestational weeks. (2) In the group of cervical length <10 mm, rate of delivery before 37 and 34 weeks were 62% (13/21) and 57% (12/21) respectively. One case of progesterone treatment underwent miscarriage. Compared with rest group ( n =8), delivery weeks [28.5 (25.0-40.0) vs 37.0 (28.0-40.0), P =0.020] and NBW [1 245 g (630-3 830 g) vs 2 648 g (1 560-3 830 g), P =0.028] were higher in cerclage group ( n =9), while ANO was not statistically different ( P >0.05). (3) In the group of cervical length ≥10 mm before 24 gestational weeks, the delivery weeks, incidence of delivery before 34 weeks, adjusted incidence of delivery before 37 weeks, NBW and ANO were not statistically different ( P >0.05) among rest group ( n =36), progesterone group ( n =26) and cerclage group ( n =34). In vitro fertilization ( OR =11.97, 95% CI : 1.88-76.44, P =0.009), infection ( OR =46.03, 95% CI : 5.12-413.58, P =0.001), sludge on sonography ( OR =9.87, 95% CI : 1.69-57.60, P =0.011) and history of short cervix ( OR =7.24, 95% CI : 1.04-50.24, P =0.045) were independent risk factors of preterm birth. (4) In the group of cervical length ≥10 mm and gestational weeks between 24-29 +6 , the delivery weeks, incidence of delivery before 37 weeks, incidence of delivery before 34 weeks, NBW and ANO were not statistically different ( P >0.05) among rest group ( n =52), progesterone group ( n =34) and cerclage group ( n =9). Infection was an independent risk factor of preterm birth ( OR =56.40, 95% CI : 4.67-680.61, P =0.002). (5) Outcomes of 223 cases were relatively good in the group of cervical length ≥10 mm beyond 30 gestational weeks. The incidence of delivery before 34 weeks was 6.3% (14/223). The delivery weeks, incidence of delivery before 37 and 34 weeks, NBW and ANO were not statistically different ( P >0.05) among 3 groups. Infection ( OR =10.91, 95% CI : 2.21-53.96, P =0.003) and history of preterm birth ( OR =8.63, 95% CI : 1.25-59.65, P =0.029) were independent risk factors of preterm birth. Conclusions: Short cervix is a common complication of pregnancy. Cervical cerclage is related with better outcome for patients with cervical length <10 mm. Neither progesterone nor cervical cerclage improves pregnancy outcome for >10 mm cervical length patients comparing with rest. Infection, sludge, in vitro fertilization, history of short cervix and history of preterm birth are independent risk factors of preterm birth in short cervix pregnancies.

Objective: MicroRNA-221/222 is involved in the pathogenesis of intrahepatic cholestasis of pregnancy (ICP) to promote the apoptosis of placental bile acids through human trophoblastic cells. This study investigates the effects of miR-221/222 on proliferation, apoptosis and apoptosis-related proteins of human trophoblast HTR-8/SVneo (HTR-8 cells) to understand its role in promoting trophoblastic apoptosis. Methods: The experiment was divided into transfection group and negative control group. Transient transfection method was used in both groups. The transfection efficiency was detected by RT-QPCR after 48 h transfection. CCK-8 was used to detect the proliferation of HTR-8 cells and the apoptosis of HTR-8 cells were analyzed by flow cytometry. Western blot was used to detect the expression of B-cell Lymphoma 2 (Bcl-2) in HTR-8 cells. Data were compared with t-test. Results: The expression of miR-221/222 transfected group (25.43±0.80, 22.70±0.95) was increased significantly in the HTR-8 cells than that to negative control group (1.14±0.14, 1.58±0.14), and P value was < 0.01, the difference was statistically significant. The expression of Bcl-2 protein in mir-221/222 transfection group was (0.56 ± 0.03, 0.53 ± 0.03), and the protein expression was decreased compared with negative control group (0.72 ± 0.003, 0.76 ± 0.04). P value was < 0.05, the difference was statistically significant, and compared with the mir-221/222 negative control group (8.827 ± 0.48, 11.80 ± 0.45), cell apoptosis of mir-221/222 transfection group (42.53 ± 4.47, 24.09 ± 2.53) increased significantly, P value was < 0.01, and the difference was statistically significant. Proliferation rate in mir-221/222 transfection group was (0.82 ± 0.02, 0.74±0.01), and proliferation was inhibited, when compared with control group (1.15 ± 0.08, 1.06 ± 0.08), P value was < 0.05, and the difference was statistically significant. Conclusion: miR-221/222 may promote the apoptosis of human trophoblastic cells by down regulating the expression of apoptosis inhibitory protein bcl-2, leading to placental dysfunction and impairing the normal bile acid transport function of placenta. This mechanism may be involved in the occurrence and development of ICP.

Objective: To investigate the role of endoplasmic reticulum stress (ERS)-induced trophoblast apoptosis in the development of intrahepatic cholestasis during pregnancy (ICP)., Methods: Twenty pregnant women with ICP and 20 normal pregnant women undergoing cesarean section were enrolled in this study. The number of placenta syncytial knots in these women was determined using HE staining. The mRNA expressions of GRP78, CHOP, caspase-3, and caspase-7 were detected using RT-PCR in the placental tissues of the women and also in HTR-8/SVneo cells treated with different doses of deoxycholic acid (DCA). Caspase-3 and caspase-7 activities were also detected in DCA-treated HTR-8/SVneo cells using commercial assay kits, and the presence of apoptotic bodies in the cells were detected with electron microscopy., Results: Compared with normal placental tissues, the placenta from women with ICP showed significantly increased syncytial knots (P<0.01) and obviously enhanced mRNA expressions of GRP78, CHOP, caspase-3, and caspase-7 (P<0.05). In HTR-8/SVneo cells treated with different doses of DCA (0, 10, 50, and 100 µmol/L), the mRNA expressions of GRP78, CHOP, caspase-3 and caspase-7 were significantly increased in a dose-dependent manner (P<0.05) and the protein levels of GRP78 and CHOP were also increased dose-dependently. Treatment with DCA at 50 µmol/L for 24 h significantly upregulated caspase-3 and caspase-7 activity in the cells (P<0.05), and the cells treated with 50 µmol/L DCA for 12 h showed the presence of apoptotic bodies., Conclusion: The activation of ERS and enhanced apoptosis of the trophoblasts occur in the placenta of women with ICP. DCA can significantly increase the expressions of ERS markers and thus lead to trophoblast apoptosis, suggesting that ERS-induced trophoblasts apoptosis may play a key role in the development of ICP.

Objective: To retrospectively analyze the clinical characteristics of patients with acute fatty liver of pregnancy (AFLP), and to discuss perioperative and anesthetic management. Methods: A retrospective review was conducted on the records of pregnant patients with a diagnosis of acute fatty liver of pregnancy in Peking University Third Hospital from January 2007 to December 2015. 12 cases were identified. The clinical features, preoperative laboratory findings, types of delivery, anesthetic techniques for cesarean section, and the outcomes of parturients and fetus were collected and analyzed. Results: Among the 12 cases, 91.7% were primigravid, 50% had twin pregnancies, and one was diagnosed with concomitant preeclampsia. The common clinical features included nausea (6 cases, 54.5%), vomiting (5 cases, 45.5%), jaundice (5 cases, 45.5%), malaise (3 cases, 27.3%), epigastric discomfort (2 cases, 18.2%), anorexia (2 cases, 18.2%) and regurgitation (1 case, 9.1%). Laboratory tests mainly showed impaired hepatic function and hypoglycemia. Cesarean deliveries were performed in 10 of the 11 patients diagnosed antepartum. Cesarean section was performed under neuraxial anesthesia (1 case) or general anesthesia (9 cases). The patient transferred to our center after delivery and diagnosed postpartum died. All the patients diagnosed antepartum survived. 6 out of the 18 fetuses were transferred to the pediatric department due to preterm, low birth weight, intrauterine restriction or asphyxiation, and were all survived. Conclusions: AFLP is one of the most severe complications in parturients. Prognosis can be improved with early diagnosis and prompt termination of pregnancy. Hepatic function, coagulation status and urgency of delivery should be well considered to choose the appropriate anesthetic method, and anesthetic management should be individualized.

Objective: To evaluate the effect of endoplasmic reticulum stress in trophocytes, in patients with intrahepatic cholestasis of pregnancy (ICP). Methods: Sixty-one pregnant women who were hospitalized in Women's Hospital, School of Medicine, Zhejiang University from January to December 2015 were recruited. Thirty-one women who were diagnosed as ICP were defined as the ICP group and 30 healthy pregnant women were defined as the control group. The localization and expression intensity of glucose regulated protein 78 (GRP-78) in placental tissues were detected by immunohistochemistry technique. Electronic microscope was used to observe ultra-microstructure change of the endoplasmic reticulum in trophocytes and cell line Swan71. Reverse transcription (RT)-PCR and western blot were used to investigate the expression of GRP-78 mRNA and protein in Swan 71 cell. Results: (1) GRP-78 protein was mainly expressed in the cytoplasm of cytotrophoblasts and syncytiotrophoblasts. The protein expression of GRP-78 in placentas of the ICP group (13.2±2.4) was significantly higher than that in the control group (7.8±1.3, P< 0.01). (2) The volume of endoplasmie reticulum did not increase and the microvilli developed well, with no swelling and no expansion of endoplasmic reticulum in the control group.In the ICP group, microvilli injury, endoplasmic reticulum edema were found; the volume of endoplasmic reticulum increased, with dilation, vacuolation and significant degranulation. After treated with 100 μmol/L cholyglycine for 24 hours, universal dilatation of the endoplasmic reticulum were seen in the Swan71 cells. (3) In Swan71 cells, cholylglycine displayed a concentration-dependent up-regulation on the expression of GRP-78. The expressions of GRP-78 mRNA in 0, 25, 50, 100 μmol/L cholylglycine experimental group were 1.01±0.17, 2.17±0.16, 5.47±0.36, 5.65±0.82, respectively. The expression of GRP-78 protein in 0, 25, 50, 100 μmol/L cholylglycine experimental group were 1.01±0.04, 1.17±0.15, 1.33±0.13, 1.73±0.13, respectively. The expression of GRP-78 mRNA and protein in 100 and 50 μmol/L cholylglycine experimental group were significantly higher than 0 μmol/L (all P< 0.01). Conclusion: The obvious expansion of endoplasmic reticulum and the increased expression of GRP-78 in trophocytes indicated that endoplasmic reticulum stress of trophocytes may be involved in the pathogenesis of ICP.

Objective: To establish a prediction model of fetal meconium-stained amniotic fluid in re-pregnant women with intrahepatic cholestasis of pregnancy (ICP)., Methods: Clinical data of 180 re-pregnant women with ICP delivering in Women's Hospital, Zhejiang University School of Medicine between January 2009 to August 2014 were collected. An artificial neural network model (ANN) for risk evaluation of fetal meconium-stained fluid was established and assessed., Results: The sensitivity, specificity and accuracy of ANN for predicting fetal meconium-stained fluid were 68.0%, 85.0% and 80.3%, respectively. The risk factors with effect weight >10% were pregnancy complications, serum cholyglycine level,maternal age., Conclusion: The established ANN model can be used for predicting fetal meconium-stained amniotic fluid in re-pregnant women with ICP.

Pregnancy-related pelvic ring disease brings great suffering to pregnant women, including the separation of the pubic symphysis and sacroiliac joint pain. Hormonal changes leading to ligamentous laxity is the main reason for Pregnancy-related pelvic ring disease. In normal pregnant cases, and the physiologic widening at the symphysis is about 3-7 mm. When the widening of the symphysis is more than 10 mm, it may lead to symptoms and need active treatment. Currently the diagnosis of the pubic symphysis separation is based on the clinical symptoms and signs. The treatment of acute pubic symphysis separation bases on conservative therapy, includes bed rest and physical therapy. But when the widening of the symphysis is more than 4 cm, the surgery intervention may be a good treatment. If the conservative treatment is not obviously effective, the surgery consists of plate fixation in the pubic symphysis and sacroiliac screw fixation. Other indications for the surgical intervention include inadequate reduction, recurrent diastasis, intractable symptoms, and open rupture.

Objective: To study the clinical effect of fetoscopic laser occlusion of chorioangiopagous vessels (FLOC) in treating twin to twin transfusion syndrome., Methods: The clinical data of 44 consecutive cases of twin to twin transfusion syndrome (TTTS)who had FLOC in the Department of Obstetrics and Gynaecology of Peking University Third Hospital were reviewed and analyzed for perioperative complications, perinatal outcomes and fetal survival rate., Results: (1) PATIENT CHARACTERISTICS: the mean maternal age was (29±4) years, the median gestational age at TTTS being primarily diagnosed was 20.4 weeks, the median gestational age at FLOC was 21.2 weeks. According to the Quintero staging system, there were 9 cases had stages progressed before the operation. (2) FLOC parameter and intraoperative complications: 44 cases all could tolerate the operation; there was 1 case of placenta vascular rupture in the operation, no fetal body injury by laser or placental abruption. 3 cases underwent cervical cerclage following FLOC. The average operation time of 41 cases alone with FLOC was (60.1±15.1) minutes. (3) Postoperative complications: the rate of intrauterine fetal death was 15% (13/88), the rate of intrauterine growth restriction after FLOC was 5% (4/88), the rate of membranes rupture less than 28 weeks was 16% (7/44), the rate of TAPS after FLOC was 5% (2/44), the rate of membrane sepration after FLOC was 5% (2/44). (4) Perinatal outcome and survival rate: there were 25 patients after FLOC had delivered in the perinatal period. The average gestational age of delivery was (33.5±2.7) weeks. The donor fetuses survival rate was 88% (22/25), the recipient fetuses survival rate was 100% (25/25). The birth weight of donor fetuses was significantly less than that of recipient fetuses (1 631g vs 2 071 g, P = 0.016). From Quintero staging I to IV, the rate that 44 cases of TTTS had entered the perinatal period was 4/7, 11/14, 7/19, 3/4; both twins survival rates were 4/7, 10/14, 5/19, 3/4; all the fetal survival rate was 8/14, 75% (21/28), 32% (12/38), 6/8, respectively. (5) Compared the early stage (I+II) with the advanced stage (III+IV), the rates that 44 cases of TTTS had entered the perinatal period (71% vs 44%) and that both twins survived (67% vs 35%) had no statistically significance. The rate that all the fetus survived in the early stage was significantly (69% vs 39%) more than that in the advanced stage. (6) All the cases of neoborn were followed up till 1 month postpartum, the donor fetuses and the recipient fetuses had 12 and 5 cases of cardiac abnormalities respectively, each had 1 case of neonatal death and 2 cases of neonatal white matter damage., Conclusions: FLOC for TTTS is associated with a better survival rate. Quintero staging probably does not effectively predict the fetal diagnosis of TTTS after FLOC. When TTTS diagnosed, the sooner FLOC given, the better fetal prognosis had.

Intrahepatic cholestasis of pregnancy (ICP) is an unique complication in pregnancy, which usually manifests in the second or third trimester, and mainly harms the fetus. Its pathogenesis is not yet clear, and placental pathological changes are insufficient to explain the clinical phenomenon.Recent studies had shown that the important cause of perinatal deaths may be the damage to the placental structure and function caused by the high bile acid level. In addition, the change of placental structure and function, umbilical cord factors, and endocrine changes can also cause the fetal development and intrauterine hypoxia. In recent years related researches focus on the toxic effect of bile acid on fetus heart, lungs, brain, liver, and other important organs, the placental vascular pathology, hemodynamic changes, umbilical cord blood vessel factors and the endocrine changes.

Objective: To analyze the clinical characteristics and perinatal outcome of early-onset intrahepatic cholestasis of pregnancy (ICP)., Methods: A total of 305 ICP cases were collected in the First Affiliated Hospital of Chongqing Medical University between June 2006 and May 2012. According to the onset time of ICP, patients were divided into early-onset ICP group (onset time < 28 gestational weeks) and late-onset ICP group (onset time ≥ 28 gestational weeks). The late-onset ICP group was further divided into 28 - 31(+6) gestational weeks and ≥ 32 gestational weeks according to the onset time. The biochemical indices and perinatal outcome of each group were assessed., Results: (1) When the diagnosis was made for the first time, the maternal serum concentrations of total bile acid (TBA) and total bilirubin (TBIL) in early-onset ICP group were (41 ± 9) and (32 ± 9) µmol/L, respectively; while TBA and TBIL in late-onset ICP group were (32 ± 6) and (22 ± 9) µmol/L, and the difference between the two groups was statistically significant (P < 0.05). (2) There was no significant difference in alanine aminotransferase (ALT) and aspartate aminotransferase (AST) between early-onset ICP group and late-onset ICP group (P > 0.05). The ALT of early-onset ICP group and late-onset ICP group were (159 ± 50) and (145 ± 52) U/L, respectively; and AST were (151 ± 49) and (138 ± 44) U/L, respectively. (3) The early-onset ICP group had significant higher (P < 0.05) incidence of meconium staining (18.8% vs. 7.4%), fetal distress (22.9% vs. 8.9%), newborn asphyxia (14.6% vs. 5.4%), premature delivery (33.3% vs. 15.6%), developing into severe ICP (41.7% vs. 25.3%) and cesarean section (91.7% vs. 78.6%) when compared to the late-onset ICP group. No significant difference in the incidence of premature delivery, developing into severe ICP and cesarean section was found between the two types of late-onset ICP. (4) There was significant differences in average birth weight and gestational weeks at delivery between the two groups [early-onset ICP group: (3113 ± 443) g and (36.3 ± 2.6) weeks]; late-onset ICP group: [(3513 ± 450) g and (37.7 ± 1.6) weeks]., Conclusion: The early-onset ICP patients presented worse clinical manifestations than late-onset ICP patients, and early-onset ICP is more likely to lead to premature delivery and fetal distress.

Objective: To detect the expression profiles of suppressor of cytokine signaling 3 (SOCS3), interleukin (IL)-10, and tumor necrosis factor-alpha (TNF-a) in the placenta of women with intrahepatic cholestasis of pregnancy (ICP) and determine the clinical significance of the differential expressions., Methods: Placentas were collected from 37 ICP gravidas who delivered through cesarean section at the First Teaching Hospital of Xingjiang Medical University from October 2010 to May 2011 and from 35 healthy pregnant women (controls). SOCS3, TNF-a, and IL-10 protein levels were detected by immunoblotting and the Envision immunohistochemical method., Results: TNF-a and IL-10 expression was detected in placentas of both groups, and was present mainly in the cytoplasm of trophoeytes. IL-10 expression was obviously lower in the ICP placentas than in the control placentas; meanwhile, TNF-a expression was obviously higher than in the control placentas (Z=-2.63, P less than 0.01). SOCS3 protein was significantly more abundant in the control placentas than in the ICP placentas. Furthermore, SOCS3 and IL-10 placental expressions were positively correlated (r=0.494, P less than 0.01), but there was a negative correlation between SOCS3 and TNF-a placental expressions (r=-0.472, P less than 0.01)., Conclusion: In ICP, an increase of the type 1 cytokine, TNF-a, is associated with decreases of the type 2 cytokine, IL-10, and of SOCS3, which may reduce the secretion of IL-10. Furthermore, SOCS3 may contribute to ICP pathogenesis by modulating the Th1/Th2 cytokine balance.

Objective: To evaluate the clinical effect of fetoscopic laser occlusion of chorioangiopagous vessels (FLOC) for monochorionic diamniotic twins (MCDA) pregnancies complicated with twin-to-twin transfusion syndrome(TTTS)., Methods: The clinical data of 33 consecutive cases of TTTS from Mainland China, who had FLOC in the Department of Obstetrics and Gynaecology of Prince of Wales Hospital (The Chinese University of Hong Kong) from November 2003 to December 2010, were reviewed and analyzed for peri-operative complications, perinatal outcomes and fetal survival rate. Clinical stage of TTTS was according to the Quintero staging system., Results: (1) Pregnancy characteristics: the mean maternal age was 30; the median gestational age at FLOC was 23(+4) weeks; according to the Quintero staging system, 3 cases were Quintero staging I, 14 cases were Quintero staging II, 7 cases were Quintero staging III and 9 cases were Quintero staging IV. For the 3 stage I cases, FLOC was performed for severe maternal symptoms of polyhyramnios or severe fetal cardiac dysfunction. (2) COMPLICATIONS: intraoperative complications occurred in 5 patients including four uterine bleedings at the puncture site, one placental vascular anastomosis bleeding. Postoperative complications occurred in 6 patients including 2 abortions and 1 intrauterine death within one week after operation, 2 abortions and 1 amniotic band syndrome occurred from two to four weeks after operation. (3) Perinatal outcome and fetal survival rate: the median interval of 33 patients between FLOC and delivery was 9(+4) weeks; the median gestational age at delivery was 31(+6) weeks; the gestation at delivery was less than 24 weeks in 6% (2/33), 24 to 28 weeks in 21% (7/33), 28 to 32 weeks in 18% (6/33), 32 to 37 weeks in 55% (18/33). The mean birth weight of the donor was 1600 g (350 - 2520 g); the mean birth weight of the recipiert was 1930 g (400 - 3040 g). The overall survival rate, the double infant survival rate, the single survival rate and survival rate for at least one twin was 59% (39/66), 52% (17/33), 15% (5/33) and 67% (22/33), respectively. The overall survival rate dropped from 61% (17/28) in Quintero staging II to 9/18 in Quintero staging IV., Conclusions: FLOC for MCDA complicated with TTTS is associated with an overall survival of about 60%. Major complications are rare. The outcome is not only related to Quintero staging but also the close monitoring and timely termination of pregnancy.

Objective: To investigate the stereological changes of placental lobular villi vessels in patients with intrahepatic cholestasis of pregnancy (ICP)., Methods: Stereological analysis on vessels volume and cross-areas of placental samples taken from 10 normal and 10 ICP patients at 37-40 week pregnancy were performed., Results: Compared with normal pregnancy, the ICP patients had 29% reduction in the volume of placental lobular villi vessels [(287.81 +/- 69.81) mL vs. (203.63 +/- 41.29) mL]; 21% reduction in the cross-areas [(617119.5 +/- 158422.65) microm2 vs. (485087.6 +/- 104707.63) microm]2; but no change in the numbers [(313.40 +/- 137.51) vs. (365.20 +/- 96.73)] of lobular villi vessels (P>0.05). Similarly, significant decreases in the volume [(131.98 +/- 84.68) mL vs. (55.98 +/- 21.08) mL] and cross-areas [(271809.6 +/- 162354.35) microm2 vs. (127576.2 +/- 54897.44) microm2] of placental lobular villi vessels with smooth muscles in the ICP patients were also found (P<0.05). But the volume [(161.48 +/- 75.80) mL vs. (155.91 +/- 30.52) mL] and cross-areas [(342639.6 +/- 145717.51) microm2 vs. (341849.3 +/- 57043.88) microm2] of placental lobular villi vessels without smooth muscle in the ICP patients remained unchanged (P>0.05). The placental lobular villi vascular volume was negatively correlated (r = -0.413) with the maternal plasma level of total bile acid (TBA) (P>0.05), and positively correlated (r=0.302) with the onset week of ICP (P>0.05). But the correlations were not statistically significant., Conclusion: Patients with ICP have 29% reduction in placental lobular villi vascular volume, which is mainly a result of reduction of lobular villi vessels with smooth muscles. The placental lobular villi vascular volume is possibly negatively correled with maternal plasma level of TBA, and positively correled with the onset week of ICP.

Objective: To explore the expression and clinical significance of constitutive androstane receptor (CAR) in placenta syntrophoblast from patients with intrahepatic cholestasis of pregnancy (ICP)., Methods: Placenta were collected from women with ICP who delivered from April 2009 to March 2010 in First Affiliated Hospital of Chongqing Medical University. According to the severity of ICP, patients were classified into mild ICP group (n = 10) and severe ICP group (n = 10). Ten healthy pregnant women who delivered in the same period were chosen as control group. The location of CAR protein in placenta was studied by immunohistochemical streptavidin-biotin complex (SABC) method. CAR mRNA level was determined by reverse transcription (RT)-PCR technique and CAR protein expression level was determined by western blot., Results: (1) CAR was located in the placenta syncytiotrophoblastic cells in control group and mild ICP group, showed light tan when stained, and was mainly in the cytoplasm. In severe ICP group, CAR was also located in placenta syncytiotrophoblastic cells but mainly in the nucleolus, showed dark tan when stained. (2) The mRNA expressions of CAR in control group, mild ICP group, severe ICP group were 0.06 ± 0.03, 0.07 ± 0.03 and 0.56 ± 0.03, respectively. CAR in severe ICP group was significantly higher than those in control group and mild ICP group (P < 0.05). The difference of mRNA between control group and mild ICP group was not statistically significant (P > 0.05). (3) The CAR protein levels in control group, mild ICP group, severe ICP group were 0.74 ± 0.03, 0.79 ± 0.03 and 1.02 ± 0.04, respectively. CAR protein expression in the severe ICP group was significantly higher than the other two groups (P < 0.05). And there was no statistical significance between mild group and control group (P > 0.05)., Conclusion: In ICP women, especially severe ICP patients, the CAR expression in placenta syncytiotrophoblastic cells increased appreciably, which may be involved in the maintenance of placenta barrier function and protection in ICP pathogenesis.

Objective: To investigate the effect of Interleukin (IL)-18, IL-12 and tumor necrosis factor-α (TNF-α) in hepatic injury in intrahepatic cholestasis of pregnancy (ICP)., Methods: Sixty-two cases of ICP patients (ICP group), 30 cases of normal pregnant women (control group) and 30 cases of hepatitis B (HBV) women (hepatitis group) were recruited. Serum IL-18, IL-12 and TNF-α were examined by ELISA. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were examined by automatic biochemical analysis instrument., Results: (1) In hepatitis group, serum concentrations of IL-18, IL-12 and TNF-α were (256 ± 51) ng/L, (122 ± 96) ng/L and (207 ± 3) ng/L; serum levels of ALT and AST were (363 ± 174) U/L and (359 ± 237) U/L, respectively. In ICP group, serum concentrations of IL-18, IL-12 and TNF-α were (72 ± 32) ng/L, (42 ± 28) ng/L and (48 ± 14) ng/L; serum levels of ALT and AST were (201 ± 128) U/L and (132 ± 87) U/L, respectively.While in control group, serum concentrations of IL-18, IL-12 and TNF-α were (43 ± 13) ng/L, (10 ± 3) ng/L and (33 ± 9) ng/L; serum levels of ALT and AST were (13 ± 4) U/L and (15 ± 3) U/L, respectively. Serum IL-18, IL-12, TNF-α, ALT and AST levels in hepatitis group were significantly higher than those in ICP group and control group (P < 0.05). Serum IL-18, IL-12, TNF-α, ALT and AST levels in ICP group were significantly higher than those in control group(P < 0.05). (2) In severe ICP subgroup, serum concentrations of IL-18, IL-12 and TNF-α were (81 ± 32) ng/L, (50 ± 25) ng/L and (50 ± 14) ng/L; serum levels of ALT and AST were (269 ± 111) U/L and (181 ± 73) U/L. In mild ICP subgroup, serum concentrations of IL-18, IL-12 and TNF-α were (48 ± 18) ng/L, (17 ± 4) ng/L and (40 ± 10) ng/L; serum levels of ALT and AST were (87 ± 46) U/L and (50 ± 21) U/L, respectively. Serum IL-18, IL-12, TNF-α, ALT and AST levels in severe ICP subgroup were significantly higher than those in mild ICP subgroup and control group (P < 0.05). And serum ALT and AST levels in mild ICP subgroup were significantly higher than those in control group (P < 0.05). (3) There were 16 cases with preterm birth (50%, 16/32) and 10 cases with meconium-stained amniotic fluid (31%, 10/32) in severe ICP subgroup, significantly higher than those in mild ICP subgroup (P < 0.05), which contained 2 preterm births (7%, 2/30) and 1 meconium-stained amniotic fluid (3%, 1/30). While in control group, the numbers were 1 (3%, 1/30) and 1 (3%, 1/30), respectively. As for the cases of neonates whose 1 minute Apgar score were not more than 7, there were 2 cases, 1 case and 1 case in severe ICP subgroup, mild ICP subgroup and control group, respectively, which showed no significant difference (P > 0.05)., Conclusion: Serum IL-18, IL-12 and TNF-α may be involved in the process of hepatic injury of ICP.

Objective: To study the expressions of FXR, PPARa and Bile acid metabolism related genes in intrahepatic cholestasis of pregnant rats., Methods: 60 clean SD pregnant rats were selected and divided randomly into three groups. Since the 13th day of pregnancy rats in control group were injected subcutaneously with refined vegetable oil 2.0 mg/kg/d Rats in no-treated group were injected subcutaneously with the 17-a-ethynylestradiol (EE) 1.25 mg/kg/d until the 17th day. Those rat ih treated group were injected subcutaneously with the 17-a-ethynylestradiol (EE) 1.25 mg/kg/d until the 17th day and then were treated with fenofibrate for another four days until the 21th day. All rats were killed at the 21th day and livers were collected for study. The levels of serum TBA were examined by ELISA. The mRNA expressions of PPARa, FXR, CYP7A1, CYP27A1 and CYP8B1 were examined by real-time PCR. (1), Results: The levels of TBA were significantly higher in no-treated group (68.7+/-4.2)mumol/L and treated group (69.5+/-3.8)mumol/L compared with that of control group (26.6+/-2.3)mumol/L at the 17th day (P value is less than 0.05) and no difference found between treated and no-treated groups (P value is more than 0.05). The levels of TBA were higher in no-treated group (69.4+/-3.7)mumol/L and treated group (48.5+/-4.8)mumol/L as compared to control group (27.1+/-3.2)mumol/L at the 21th day (P value is less than 0.05). The lever of TBA was significantly lower in Treated group compared with No-treated group (P value is less than 0.05). (2) The mRNA expressions of CYP7A1, FXR, CYP27A1 and CYP8B1 increased in No-treated group (1.55+/-0.03, 1.75+/-0.02, 2.45+/-0.01, 2.15+/-0.01, respectively) and were all higher as compared to control group (0.75+/-0.02, 1.25+/-0.03, 0.65+/-0.03, 1.50+/-0.02, respectively) (P value is less than 0.05). However, the mRNA expression of PPARa decreased in No-treated group (0.85+/-0.02) compared with control group (1.45+/-0.02) (P value is less than 0.05). The mRNA expressions of CYP27A1, PPARa and CYP8B1 increased in treated group (1.25+/-0.01, 1.65+/-0.05, 1.65+/-0.02, respectively) and were all higher than that of control group (P value is less than 0.05)., Conclusion: Abnormal expressions of CYP7A1, FXR, CYP27A1, CYP8B1 and PPARa may play a role in pathogenesis of estrogen-induced intrahepatic cholestasis. Activator of PPARa may be used as therapeutical drug for ICP.

Objective: To detect the expression and significance of suppressor of cytokine signaling 3(SOCS3) in the placentas of pregnant women with intrahepatic cholestasis of pregnancy (ICP)., Methods: Totally, 44 ICP gravidas, including 21 severe ICP and 23 mild ICP who delivered through cesarean section at the Second Xiangya Hospital of Central South University from April 2008 to January 2009, were selected as the ICP group, and another 25 healthy pregnant women were chosen as control. Placentas of the above gravidas were collected and the expression and localization of SOCS3 were determined by immunohistochemical peroxidase streptomyces-avidin link (SP) method (indicated by the percentage of positive cells and average gray scale) and the levels of interleukin-10 (IL-10) and interferon-γ (IFN-γ) from placenta homogenation were measured by enzyme linked immunoadsorbent assay (ELISA)., Results: (1) SOCS3 were expressed in placentas of both groups mainly in the intracytoplasma of trophocyte. However, weakly positive, positive, and strongly positive expressions were found in the severe ICP, mild ICP and the control group, respectively. Almost no expression was detected in membrane and nucleus of the trophoblasts. (2) The percentage of SOCS3 positive cells in the severe ICP group was significantly lower than in the control and the mild ICP group, respectively [(0.15 ± 0.08) % vs (0.69 ± 0.12) % and (0.42 ± 0.09) %, P < 0.01]. The average gay SOCS3 in placental tissue in the severe ICP group was significantly higher than that in control and mild ICP group, respectively (204 ± 7 vs 81 ± 7 and 147 ± 7, P < 0.01). (3) Significant lower level of IL-10 in placenta homogenation was found in the severe ICP group than in the control and mild ICP group [(1.16 ± 0.68) µg/L, vs (1.39 ± 0.08) µg/L and (1.22 ± 0.75) µg/L, P < 0.01]. (4) The opposite results were found in the level of IFN-γ in trophoblasts and the ratio of IFN-γ/IL-10 [severe ICP group: (16.8 ± 0.7) µg/L and 16.02 ± 2.79; control group: (10.5 ± 0.3) µg/L and 8.56 ± 0.14; mild ICP group: (13.4 ± 0.5) µg/L and 8.56 ± 0.14, P < 0.01]. (5) Negative correlation was shown between the percentage of SOCS3 positive cells in trophoblasts and the ratio of IFN-γ/IL-10 (r = -0.685 and -0.702, P < 0.01), and the average gay SOCS3 was positively correlated with the ratio of IFN-γ/IL-10 (r = 0.621 and 0.891, P < 0.01) in both mild and severe ICP group., Conclusions: SOCS3 may participate in the pathogenesis of ICP and its expression may affected by the severity of ICP, and SOCS3 may also play a role in the immunological regulation in ICP patients.

Objective: To explore the clinical features and outcomes of patients with cerebral venous sinus thrombosis (CVT) during pregnancy and puerperium., Methods: A retrospective study was performed in 24 cases of pregnant women with CVT among 15 625 deliveries in Xuanwu Hospital from January 2002 to October 2009, including 7 cases happened during pregnancy and 17 during puerperium. The etiology, clinical presentations, imaging examination results, other relevant examinations, and pregnant outcomes of these patients were analyzed., Results: (1) Incidence and etiology: the incidence of CVT during pregnancy and puerperium was 0.15% (24/15 652) and 29% (7/24) of the patients fell ill during pregnancy and 71% (17/24) during puerperium. Five were complicated with severe preeclampsia, while another 5 complicated with hyperemesis. One woman was complicated with anemia. CVT was identified after spontaneous delivery in 9 cases and 8 after cesarean section. (2) CLINICAL PRESENTATIONS: Among the 24 CVT cases, 22 (92%) suffered from headache, 16 (67%) reported nausea and vomiting, 15(63%) experienced hyperspasmia and 6 (25%) complained of blurred vision. On admission, 8 (33%) patients were unconscious, 3 (13%) with hemiplegia, and 8 (33%) were febrile. (3) Imaging and laboratory examinations: twelve patients underwent digital subtraction arteriography (DSA) and were diagnosed. Fifteen women showed superior sagittal sinus thrombosis in MRI and magnetic resonance intravenous angiograph (MRV). Examination of the fundus found papilledema in 4 cases. Normal cerebral sinus fluid and laboratory routine tests were reported in 13 cases, but 6 cases of hyperlipidemia, 7 cases of abnormal activated partial thromboplastin time (APTT), 5 cases of abnormal international normalized ratio (INR), 3 cases elevated platelet count, 4 cases of positive D-dipolymer, 1 cases of low hemoglobulin level (<10 g/L), 4 cases with abnormal hematocrit, and 10 cases of elevated fibrinogen (>4 g/L) were identified. (4) Management and pregnancy outcomes: among the 7 cases happened during pregnancy, 2 were complicated with severe preeclampsia and delivered through cesarean section immediately and discharged after proper management including depressurization, spasmolysis, dehydration and anticoagulant therapy. Five of the 7 cases presented with CVT during early pregnancy, among which 1 was discharged after dilation and curettage followed by anticoagulant therapy, 2 received endovascular thrombolysis after which one was discharged and the other one left with right hemiparesis and 2 patients died. Among the 17 patients presented with CVT during puerperium, 10 received anticoagulant therapy after which 4 were fully recovered, 5 left with functional disturbance (3 with hemiplegia, 1 with incomplete motor aphasia and hemiparesis and 1 with blurred vision) and one died. Among the rest 7 cases who underwent endovascular thrombolysis, 3 were fully recovered, 3 left with functional impairment (1 with blind and headache and 2 with hemiplegia), and one died. Altogether, there were 14 patients underwent systemic anticoagulant therapy after which 7 were fully recovered, 5 left with dysfunction and 2 died. Among the 10 cases received endovascular thrombolysis, 4 were fully recovered, 4 remained some dysfunction and 2 died., Conclusions: CVT, mostly presented as superior sagittal sinus thrombosis, are more common in puerperium than during pregnancy and DSA is the golden standard for the diagnosis of CVT. Anticoagulant therapy and endovascular thrombolysis are effective in the treatment of CVT, but may left the patients with functional disturbance or even death. Prompt diagnosis and treatment ensure a better outcome for pregnant women complicated with CVT.

Objective: To investigate the clinical feature, treatment and prognosis of both the mother and the fetus with gestational diabetes insipidus., Methods: A total of 7 cases of gestational diabetes insipidus collected in the First Affiliated Hospital of Wenzhou Medical College, Wenzhou Combination of Traditional Chinese Medicine with Western Medicine Hospital, and Zhejiang Taizhou Hospital from June 1993 to June 2006 were analyzed retrospectively., Results: Seven cases symptoms all characterized by excessive thirst polydipsia and polyuria. The average 24 h urinary output was between 11 L to 13 L and manifested of hypobaricuria. After effective treatment (three cases were treated with 1-deamino-8-D-arginine vasopressin, another three patients were managed with hydrochlorothiazide, and the last one was cured with antisterone), seven patients with gestational diabetes insipidus did not have any severe consequences. Their symptoms of excessive thirst, polyuria, and polydypsia disappeared from 7 days to 3 months after parturition. Urinary volume returned to normal standard of 1000-2000 ml during 24 hours. Specific gravity of urine recovered normally between a range 1.015-1.025 and serum sodium recovered between 135-147 mmol/L. The average duration of illness was 52 days. Eight newborn infants survived. Two of them were sent to neonatal intensive care unit for treatment. One was because of premature delivery caused by antepartum eclampsia, and the other case was one of the twins who had hydronephrosis. The baby of the first case left hospital after 3 weeks' treatment. The latter one's symptom disappeared 2 weeks after delivery. No obvious symptom was discovered among all the babies through follow-up telephone calls 42 days after childbirth., Conclusion: Gestational diabetes insipidus is a rare endocrinopathy complicating pregnancy. This disorder is characterized by excessive thirst, polydypsia, polyuria, hypobaric urine and electrolyte disturbances usually manifesting in the third trimester of pregnancy or puerperium. This is a transient syndrome. The first treatment of choice in patients with gestational diabetes insipidus is 1-deamino-8-D-arginine vasopressin and the second-choice is hydrochlorothiazide. Early diagnosis and appropriate management of the disease may reduce the hazard for both the mother and the fetus during perinatal period.

Objective: To investigate the changes of umbilical cord and the vasoactive substance in umbilical vein in intrahepatic cholestasis of pregnancy., Methods: By HE staining method we analyzed the pathologic change of umbilical cord of 25 women with intrahepatic cholestasis of pregnancy (ICP) and fetal distress (ICP fetal distress group), 25 ICP women without fetal distress group (ICP control group) and 27 normal pregnancies (control group). The nitric oxide synthase (NOS) and endothelin-1 (ET-1) were detected in human umbilical vein endothelial cells (HUVEC) by immunohistochemistry method. Umbilical vein total bile acid (TBA) and NOS and ET-1 were measured., Results: (1) A remarkable high TBA level was found in umbilical vein in ICP, and it was higher in ICP fetal distress group (19.0 +/- 2.3) micromol/L than in ICP control group (9.0 +/- 1.7) micromol/L (P < 0.05); it was higher in ICP control group than the control group (4.4 +/- 1.5) micromol/L (P < 0.05). (2) A significant difference was found in the endotheliocytes of umbilical vein in ICP fetal distress group compared with ICP control group. The ratio of cells with pathological changes in ICP fetal distress group (92%, 23/25) was higher than ICP control group (68%, 17/25; P < 0.05). The occurrence of the pathological changes was associated with TBA. (3) The expression of eNOS in ICP fetal distress group 0.09 +/- 0.06 was lower than in ICP control group 0.21 +/- 0.08 (P < 0.05), and it was lower in ICP control group than in control group 0.47 +/- 0.07 (P < 0.05). In contrast, the expression of ET-1 in ICP fetal distress group 0.49 +/- 0.08 was higher than in ICP control group 0.32 +/- 0.07 (P < 0.05), and it was higher in ICP control group than control group 0.14 +/- 0.06 (P < 0.05). The expression of inducible nitric oxide synthase (iNOS) in ICP fetal distress group 0.20 +/- 0.04 and ICP control group 0.21 +/- 0.05 was lower than in control group 0.26 +/- 0.04 (P < 0.05), but no significant difference was found in ICP fetal distress group and ICP control group (P > 0.05). (4) The expression of eNOS, iNOS and ET-1 was correlated with umbilical vein TBA in ICP (r1 = -0.88, r2 = -0.45, r3 = 0.9; P < 0.01), respectively., Conclusions: High level of TBA in ICP is harmful to the umbilical vein endothelium, which is correlated with the raised expression of ET-1, and the decreased expression of eNOS,and iNOS in human umbilical cord endothelium cells. All these changes of umbilical vein may be associated with the occurrence of fetal distress in ICP.

Objective: To investigate the alteration on the expression levels of protein and messenger RNA (mRNA) of aquaporin-8 (AQP8) in the hepatocytes of pregnant rats with intrahepatic cholestasis induced by ethinylestradiol., Methods: A total number of 20 15-day pregnant rats were randomly divided into two groups: control group, intrahepatic cholestasis of pregnancy (ICP) group. In ICP group, rats were subcutaneously injected with ethinylestradiol (2.5 mg x kg(-1) x d(-1)) for 5 days to make the model of ICP. In control group, rats received subcutaneous injection of appropriate volume of propylene glycol for 5 days. The protein expression and subcellular localization of AQP8 in the hepatocytes of pregnant rats were detected using immunohistochemical methods. The mRNA expression of AQP8 in the hepatocytes was assayed by RT-PCR method., Results: The model of ICP of pregnant rats was made successfully. Expressions of AQP8 protein and mRNA were detected in two groups. AQP8 protein level in ICP group was 10.8 +/- 2.4, significantly decreased than in control group 17.1 +/- 2.2 (P < 0.05). AQP8 mRNA level in ICP group was 1.07 +/- 0.11, significantly higher than in control group 0.80 +/- 0.11 (P < 0.05)., Conclusion: Down-regulated AQP8 protein expression and up-regulated AQP8 mRNA expression in the hepatocytes of pregnant rats with intrahepatic cholestasis may contribute to the pathogenesis of ICP.

Objective: To investigate the expression of HIF-1alpha mRNA and HIF-2alpha mRNA in placentas of pregnant women with intrahepatic cholestasis of pregnancy(ICP)., Methods: Twenty samples of placentas from pregnant women with ICP and 20 samples of normal term placentas were selected. The expression levels of HIF-1alpha mRNA and HIF-2alpha mRNA were measured by RT-PCR., Results: There was no statistically significant difference in respect to the expression levels of HIF-1alpha mRNA and HIF-2alpha mRNA between the two groups of samples (P > 0.05)., Conclusion: Under hypoxic conditions, HIF-1alpha and HIF-2alpha proteins are not transcriptionally regulated at the mRNA level but are probably regulated at the post-mRNA level.

Objective: Owing to the molecular mechanisms unexplored yet to fetal hypoxia signaling in the intrahepatic cholestasis of pregnancy (ICP), and therefore we intend to investigate the significant expression of the hypoxia-inducible transcription factor-1alpha (HIF-1alpha) in placenta of pregnant women with ICP during hypoxia., Methods: The villous placenta tissues were in vitro cultured under hypoxia condition. The immuno-histochemistry technique was applied to probe the HIF-1alpha and P53 expressions in placentas of pregnant women and patient with ICP., Results: Under the condition of normal concentration oxygen, P53 was highly expressed in the placenta of pregnant women with ICP (P < 0.01), however the HIF-1alpha expression was not up to higher than in normal control. Under the condition of lower concentration oxygen (2% O2), the HIF-1alpha and P53 expressions were detected from the placental villous tissues cultured for 4 h of normal control and patient with ICP, and with HIF-1alpha and P53 proteins increased in the placenta of pregnant women with ICP (P < 0.05 and P < 0.001 respectively). Whatever was hypoxia condition, P53 protein got always a high expression, and had a positive correlation with HIF-1alpha expression in ICP (P < 0.01)., Conclusion: Under hypoxic conditions, high increase of HIF-1alpha may influence the increase of P53 directly, which may be one of the hypoxia pathogenesis factors in ICP. The fetal hypoxia and stillbirth may be the results of unbalance of HIF-1alpha and P53 which induced apoptosis under hypoxia condition.

Objective: To study the levels of inhibin (INH) and epidermal growth factor (EGF) in maternal plasma and umbilical cord plasma of patients with hypertensive disorder complicating pregnancy, and to explore their influence on the disease and fetal growth., Methods: Enzyme linked immunosorbent assay (ELISA) was used to detect maternal and umbilical cord plasma INH and EGF levels in 65 patients with hypertensive disorder complicating pregnancy (test groups) and 21 normal pregnant women (control group)., Results: Plasma level of INH in test groups (499 +/- 52) ng/L was significantly higher than that (421 +/- 36) ng/L in control group (P < 0.01); however, the umbilical cord plasma level of INH had no significant difference (P > 0.05). Plasma level of EGF in test groups (408 +/- 60) ng/L was significantly lower than that (463 +/- 87) ng/L in control group (P < 0.05), also there was significant difference in umbilical cord plasma level of two groups (232 +/- 99) ng/L vs (380 +/- 97) ng/L (P < 0.01). The level of EGF in umbilical cord blood was positively correlated with newborn's body weight and placental weight., Conclusions: Plasma levels of INH and EGF in pregnancy women are related with hypertensive disorder complicating pregnancy. EGF level of umbilical cord blood affects the growth of fetus and placenta.

Objective: To investigate the relation of changes of fetal bile acid and morphologic ultrastructure of human placental syncytial cells in intrahepatic cholestasis of pregnancy (ICP)., Methods: Total bile acid of cord venous blood was measured by cycle enzyme method between intrahepatic cholestasis of pregnancy and control groups after birth. The ultrastructure of human placental syncytial cell was analyzed by morphologic study in two groups., Results: (1) The total bile acid of cord venous blood in ICP group was significantly higher than in control group [(8.6 +/- 3.2) micromol/L vs (4.6 +/- 1.5) micromol/L] (P < 0.05). (2) The amount and number density of syncytial microvilli ultrastructure reduced significantly in ICP group [respectively (21 +/- 12) e/Es, (1.9 +/- 1.3) microm(-3)], compared with control group [respectively (35 +/- 11) e/Es, (4.1 +/- 3.2) microm(-3)] (P < 0.05). The average volume and surface area density of placental syncytial cell in ICP group [respectively (0.1200 +/- 0.0050) microm(3), (2.500 +/- 0.600) microm(2)/microm(3)] were statistically increased compared with that in control group [respectively (0.0500 +/- 0.0010) microm(3), (1.300 +/- 0.400) microm(2)/microm(3)] (P < 0.05). But no significant difference in the volume density of placental syncytial microvilli was observed between two groups (P > 0.05). The average volume, surface area density and volume density of mitochondrion in ICP group [respectively (0.0200 +/- 0.0020) microm(3), (0.600 +/- 0.010) microm(2)/microm(3), (0.0800 +/- 0.0090) microm(3)/microm(3)] were significantly enlarged than in control group [respectively (0.0100 +/- 0.0050) microm(3), (0.500 +/- 0.030) microm(2)/microm(3), (0.0500 +/- 0.0020) microm(3)/microm(3)] (P < 0.05). The average volume, surface area density and volume density of endoplasmic reticulum in ICP group [respectively (0.0200 +/- 0.0010) microm(3), (0.900 +/- 0.010) microm(2)/microm(3), (0.0900 +/- 0.0050) microm(3)/microm(3)] were significantly larger than in control group [respectively (0.0100 +/- 0.0030) microm(3), (0.500 +/- 0.030) microm(2)/microm(3), (0.0500 +/- 0.0010) microm(3)/microm(3)] (P < 0.05). No significant difference in number density of mitochondrion and endoplasmic reticulum between two groups was found (P > 0.05)., Conclusion: In ICP, high levels of bile acids may impair cellular organelle, resulting in abnormality of physiological function of syncytial cells, and affecting the synthesis and transportation functions of placenta.

Objective: To investigate the mechanism for the apoptosis of hippocampus neuron induced by hypothyroidism in perinatal rats., Methods: Hypothyroidism was induced by administration of propylthiouracil (PTU, 50 mg/d) solution to the dams from gestational day 15 by gavage. Pups from both hypothyroid and control groups were harvested at 1, 5, 10 and 15d, respectively. Blood samples were collected at the time of death for the determination of thyroid hormone. Serum free triiodothyronine (FT(3)) and free thyroxine (FT(4)) were measured by chemoluminescence. Hippocampus specimens were collected from the control and hypothyroid pups.Mitochondia was examined under transmission electron microscopy. Translocation of apoptogenic molecules (Bax, cytochrome C and AIF) and activation of caspase-3 were analyzed by Western Blotting., Result: Significantly low circulating FT(3) and FT(4) levels confirmed the hypothyroid status of the experimental pups. Electron microscopy showed that altered morphology of mitochondria significantly increased under hypothyroid conditions. The expression of Bax in the cytosol of hypothyroid pups was higher than that of control pups at all stages of development (P<0.05),and significantly higher in mitochondria (P<0.001). The expression of cytochrome c in the cytosol of hypothyroid pups was significantly higher than that of control pups at all stages of development (1,10 and 15 d:P<0.05, 5d: P<0.001), and lower in mitochondria (P<0.05). The expression of AIF in the cytosol of hypothyroid pups was higher than that of control pups at all stages of development (P<0.001), and significantly lower in mitochondria (1, 5d: P<0.001, 10, 15 d: P<0.01). he expression of caspase-3 P20 in the cytosol of hypothyroid pups was significantly higher as compared with that of the age-matched controls (1, 15d: P<0.01, 5,1 0 d: P<0.001)., Conclusion: The intrinsic death pathway in mitochondria may be one of the mechanisms with which hypothyroid induces apoptosis of hippocampus neuron in developing rats.

Objective: To explore the possible mechanism of placental dysfunction in patients with intrahepatic cholestasis of pregnancy (ICP)., Methods: Serum level of cholylglycine (CG) in 30 cases with ICP (ICP group) and 27 normal pregnant women (control group) was examined by radio-immunoassay before delivery. bax and bcl-2 level in placenta was detected by immunohistochemistry method., Results: (1) Serum CG level in ICP group was (51.8 +/- 5.9) micro mol/L, and in control group it was (9.4 +/- 5.6) micro mol/L. The difference between the two groups was significant (P < 0.05). (2) bax expression level in syncytiotrophoblast of ICP group was: 2(-), 9(+), 11 (++), 8(+++), and bcl-2 expression level was: 12(+), 12(++), 6(+++); bax expression level in control group was: 9 (-), 13(+), 4(++), 1(+++) and bcl-2 expression level was: 3(+), 4(++), 20(+++). bax expression level in syncytiotrophoblast of ICP group was higher than that of the control (P < 0.0005), and bcl-2 expression level was lower than in the control (P < 0.0005), both significantly. A significant positive correlation between CG level and bax expression level and a negative correlation between CG and bcl-2 were found in ICP group (P < 0.005, P < 0.005)., Conclusion: One of the possible mechanisms involved in placental dysfunction of ICP is overexpression of bax in syncytiotrophoblast caused by high concentrations of bile acid, leading to increased apoptosis.

Objective: To investigate the changes of gene p53, bax and bcl-2 expression and to study the role on cell apoptosis in placenta through apoptosis in placenta with intrahepatic cholestasis of pregnancy (ICP)., Methods: TdT-mediated dUTP nick end labeling (TUNEL) and immuno-histochemistry methods were used for 31 placental samples with ICP and 31 normal placental samples to detect apoptosis index and the expression of p53, bax and bcl-2 in placenta tissues., Results: The apoptosis index in placental cytotrophoblast, syncytiotrophoblast, decidual cells and mediate cell on ICP group was significantly higher than that in control group (P < 0.01). The expression of p53 was higher than those of control. Bax expression in syncytoitrophoblast, decidual cell and mediate cell in ICP group was higher (P < 0.01), but the expression of bax in placental cytotrophoblast cell was not significantly higher (P > 0.05). The expression of bcl-2 of these positions in ICP group was lower than that in control group (P < 0.01) p53, bax and bcl-2 expressions in (chi +/- s)% in the syncytoitrophoblast cells of placenta with ICP is 75.9 +/- 8.2, 65.8 +/- 13.8, 45.3 +/- 11.3., Conclusion: The placental dysfunction may closely relate to the apoptosis. Abnormal overexpression of p53, bax and the low expression of bcl-2 on placental tissue of ICP was the main reason of placental apoptosis.

Objective: To study the relationship of the pathological changes with the expression of vascular cell adhesion molecule-1(VCAM-1) in the placenta of patients with pregnancy-induced hypertension (PIH) that is complicated by intrauterine growth retardation (IUGR)., Methods: Tissue specimens of the placenta were respectively collected from 30 patients with PIH complicated by IUGR, 28 patients with IUGR, 25 patients with PIH and 30 normal women after delivery. After HE and PAS staining, the tissue sections were observed microscopically to detect morphological changes in the placenta. Immunohistochemical examination was employed to detect the expression of the VCAM-1 in the decidual vascular endothelium, syncytiotrophoblast and villous capillary vessel of the placenta in these tissue specimens., Results: Significant pathological changes were observed in 22 placentas of the patients with PIH complicated by IUGR, with the incidence of 73.33 %. The pathological changes exemplified by stromal fibrosis, fibrinoid necrosis and leucocyte infiltration of the villi, increase in villous syncytial nodules, decrease in villous vascular tissues, hyperplasia of cytotrophoblasts and basal lamina thickening were more prevalent in the placentas of patients with PIH complicated by IUGR than in normal women (P<0.05). The expression of VCAM-1 in the decidual vascular endothelium and placental villous capillary vessels was observed to be significantly higher in the placentas with pathological changes than in those without (P<0.05), which was the opposite to the changes in the expression in the syncytiotrophoblast (P<0.05)., Conclusion: Significant pathological changes can be present in the placenta of patients with PIH complicated by IUGR, and may be intimately related to abnormal expressions of VCAM-1 in the placenta.

Objective: To investigate the role of tumor necrosis factor-alpha (TNFalpha) in the pathogenesis of pregnancy induced hypertension (PIH) by damaging endothelial cells., Methods: 41 patients with PIH and 17 healthy pregnant women were studied. The concentration of TNFalpha in maternal plasma was measured by sensitive radioimmunoassay. The morphology of endothelial cells of placental blood vessels was observed. Endothelial cells were incubated in the presence of TNFalpha (400 U/ml) and sera (30% vol/vol) from PIH women and normal pregnant women to observe their growth and shape., Results: Maternal plasma TNFalpha level in PIH was 2.29 microgram/L +/- 0.51 microgram/L, higher than that in normal pregnancy (the latter was 1.73 microgram/L +/- 0.25 microgram/L, t = 5.60, P < 0.01). The endothelial cells of placental blood vessels in PIH revealed morphologic damages. Both sera of PIH women and TNFalpha were cytotoxic to endothelial cells in culture, including inhibition of the proliferation and morphologic changes of the cells., Conclusion: Damage of the endothelial cells of placental blood vessels is associated with the abnormal increase in the maternal blood TNFalpha. Sera of PIH women can damage the endothelial cells in culture and this effect is also associated with TNFalpha.

Objective: To investigate the early recognition and management of milder cases of acute fatty liver in pregnancy (AFLP)., Methods: Twelve cases of AFLP treated in our hospital during the past two and half years were retrospectively studied with emphasis on symptoms, laboratory findings, liver biopsy and maternal complications. The 12 cases were classified into 2 groups. Group 1, 6 cases of advanced AFLP diagnosed clinically, were treated in the first year of the study. Group 2, 6 cases of milder AFLP diagnosed by postpartum liver biopsy, were treated during the last one and half years of the study., Results: The mean gestational age at onset was 34 +/- 3 weeks. In the early stage, all cases had malaise, nausea, loss of appetite and epigastric distress followed by jaundice in the third trimester of pregnancy. Laboratory findings included raised transaminases (< or = 300 IU/L) and total serum bilirubin (32.5-510.8 micro mol/L) levels, hypoalbuminemia (18-30 g/L), hypofibrogenemia (< 2.4 g/L), prolonged prothrombin time and prolonged partial thromboplastin time. Maternal complications were frequent including hepatic encephalopathy (9), ascites (9), hypoglycemia (7), renal failure (3), hematemesis (4), preeclampsia (6), and postpartum hemorrhage (5). Cesarean sections were performed in 7 cases. In group 2, both mother and fetuses had 100% survival. However, the mortality of the mothers and fetuses in group 1 were both 50%., Conclusions: With increasing awareness, especially in the early recognition of AFLP cases and prompt progressive management, including early termination of pregnancy and large dose infusion of fresh frozen plasma, the prognosis of AFLP is obviously improved. Percutaneous liver biopsy should be done when the coagulation tests became normal and the amounts of ascites decreased after delivery.

Pathological study on the placenta of 18 cases of pregnancy complicated with systemic lupus erythematosus (SLE) and 23 cases of normal pregnancy was done. The average weight and placenta-villi area ratio of the placenta from pregnancy with SLE were significantly lower than those of the normal (P < 0.05). Scanning under electron microscope showed the placental villi of the SLE group slender and branching little, with their ends bean-sprout looking and the surface covered with pin-point holes, even slitted masses. Immunohistologic examination indicated deposition of IgG, IgA, IgM, C3 on the villi capillary wall surface, which suggested damage of the placental function of the SLE gravidae by the immunologic compounds.

Ninety-seven cases of liver disease in pregnancy confirmed by pathological examination were studied. The results showed that in addition to virus hepatitis (58.8%), which was the leading cause, there were quite a proportion of other liver diseases. Among these acute fatty liver of pregnancy accounted for 18.6%, intrahepatic cholestasis of pregnancy were 16.5%. The causes of misdiagnosis and the bases for differential diagnosis were discussed. It was considered that early pathological examination of liver and other morphological study were important in diagnosis of liver diseases in pregnancy.

Twenty four cases of intrauterine death occurred in 3,834 deliveries from Jan. 1985 to Dec. 1987 in our hospital. The causes of fetal deaths were analysed on the basis of maternal complications and pathologic findings. Maternal complications, such as pregnancy induced hypertension, abnormal glucose tolerance test, anemia, infection ............ were observed in 18 cases (75.0%). At delivery, 4 babies (16.6%) were found to have cord around neck and 1 with short umbilical cord. Marked abnormalities of placenta were demonstrated in 12 cases (50.0%) and fetal abnormalities in 4 cases (16.6%). Clinically, intrauterine deaths were often preceded by signs of growth retardation, reduced fetal movements and abnormal NST test. Gravidography, fetal movement counting, non-stress test, and ultrasonic scanning may be helpful in predicting this catastrophe.