Lianlian Wang

Patterns and Associated Factors of Caesarean Delivery Intention among Expectant Mothers in China: Implications from the Implementation of China's New National Two-Child Policy.

Objective: This study explores the basic demographic characteristics of expectant mothers in the context of their intentions regarding mode of delivery, in particular, the preference for caesarean delivery, and analyzes the social and psychological factors that influence delivery preference. Method: A cross-sectional survey of pregnant women was conducted during June to August in 2015. This study adopted a stratified sampling method, and 16 representative hospitals in five provinces of China were included. Results: 1755 and 590 of expectant mothers in their first and second pregnancies, respectively, were enrolled in this study. 354 (15.10%) intended to deliver by caesarean section and 585 (24.95%) participants were uncertain prior to delivery. 156 (8.89%) of expectant mothers in their first pregnancy and 198 (33.56%) expectant mothers in their second pregnancy intended to deliver by caesarean section. Ordinal logistic regression analysis found that nationality, parity, trimester of pregnancy, and advanced maternal age were factors associated with intention to deliver by caesarean (ordered logistic regression/three-level caesarean delivery intention criterion; odds ratios p < 0.05). Conclusions: 8.89% of first pregnancy expectant mothers and 33.56% of second pregnancy expectant mothers intended to deliver by caesarean section. Any intervention program to reduce the rate of Caesarean delivery should focus on the Han population, older pregnant women, and expectant mothers in their second pregnancy, at an early gestation.

MicroRNA-764-3p regulates 17β-estradiol synthesis of mouse ovarian granulosa cells by targeting steroidogenic factor-1

Previous studies have reported that microRNA-764-3p (miR-764-3p) is one of the most up-regulated microRNAs (miRNAs) in TGF-β1-stimulated mouse ovarian granulosa cells. However, little is known about the roles and mechanisms of miR-764-3p in granulosa cell function during follicular development. In this study, we found that overexpression of miR-764-3p inhibited 17β-estradiol (E2) synthesis of granulosa cells through directly targeting steroidogenic factor-1 (SF-1). MiR-764-3p inhibited SF-1 by affecting its messenger RNA (mRNA) stability, which subsequently suppressed the expression levels of Cyp19a1 gene (aromatase, a downstream target of SF-1). In addition, SF-1 was involved in regulation of miR-764-3p-mediated Cyp19a1 expression in granulosa cells which contributed, at least partially, to the effects of miR-764-3p on granulosa cell E2 release. These results suggest that miR-764-3p functions to decrease steroidogenesis by targeting SF-1, at least in part, through inactivation of Cyp19a1. Taken together, our data provide mechanistic insights into the roles of miR-764-3p on E2 synthesis. Understanding of potential miRNAs affecting estrogen synthesis will help to diagnose and treat steroid-related diseases.

Intravenous Administration of Lycopene, a Tomato Extract, Protects against Myocardial Ischemia-Reperfusion Injury

Background: Oral uptake of lycopene has been shown to be beneficial for preventing myocardial ischemia-reperfusion (I/R) injury. However, the strong first-pass metabolism of lycopene influences its bioavailability and impedes its clinic application. In this study, we determined an intravenous (IV) administration dose of lycopene protects against myocardial infarction (MI) in a mouse model, and investigated the effects of acute lycopene administration on reactive oxygen species (ROS) production and related signaling pathways during myocardial I/R. Methods: In this study, we established both in vitro hypoxia/reoxygenation (H/R) cell model and in vivo regional myocardial I/R mouse model by ligating left anterior artery descending. TTC dual staining was used to assess I/R induced MI in the absence and presence of acute lycopene administration via tail vein injection. Results: Lycopene treatment (1 μM) before reoxygenation significantly reduced cardiomyocyte death induced by H/R. Intravenous administration of lycopene to achieve 1 μM concentration in circulating blood significantly suppressed MI, ROS production, and JNK phosphorylation in the cardiac tissue of mice during in vivo regional I/R. Conclusion: Elevating circulating lycopene to 1 μM via IV injection protects against myocardial I/R injury through inhibition of ROS accumulation and consequent inflammation in mice.

Prevalence and Sociodemographic and Lifestyle Determinants of Anemia during Pregnancy: A Cross-Sectional Study of Pregnant Women in China

Objective: This study aimed to assess the differences regarding anemia among pregnant women with diverse characteristics and lifestyle factors. Methods: A cross-sectional study of pregnant women was conducted between June and August 2015 in 16 hospitals in five provinces of Mainland China. Self-reported doctor-diagnosed anemia was used in the study. Results: We included 2345 pregnant women. Of the participants, 1755 (74.8%) were pregnant women of first pregnancy (PWFP) and 590 (25.2%) were second pregnancy (PWSP). The mean age of the participants was 28.1 years (SD 4.1). Overall, the prevalence of anemia was 12.7% (13.4% and 10.7% among PWFP and PWSP, respectively). The prevalence for not eating breakfast was 11.0%. Compared with PWFP, PWSP was inversely associated with the risk of anemia (odds ratio (OR) 0.66, 95% CI 0.48–0.91). Compared with those being registered in a low ranking hospital, pregnant women who were admitted to a high (OR 0.40, 95% CI 0.28–0.57) or a medium ranking hospital (OR 0.58, 95% CI 0.37–0.92) were inversely associated with the risk of anemia. Compared with women of low income (<¥4,500), those with high income were less likely to have anemia (OR 0.68, 95% CI 0.50–0.94). Compared with women with non-manual jobs, women with manual jobs (OR 1.70, 95% CI 1.17–2.45) and unemployed women (OR 1.42, 95% CI 1.04–1.93) were associated with a greater likelihood of suffering from anemia. Conclusions: Pregnant women not eating breakfast are of concern. Anemia is highly prevalent among pregnant women in China. Lower socio-economic status, manual jobs, PWFP, and those who attend a lower quality hospital have a greater likelihood of suffering from anemia. Tailored interventions are needed to address these issues.

Triethylenetetramine Synergizes with Pharmacologic Ascorbic Acid in Hydrogen Peroxide Mediated Selective Toxicity to Breast Cancer Cell

Breast cancer is characterized by overexpression of superoxide dismutase (SOD) and downregulation of catalase and more resistance to hydrogen peroxide (H2O2) than normal cells. Thus, relatively high H2O2 promotes breast cancer cell growth and proliferation. However, excessive intracellular H2O2 leads to death of breast cancer cells. In cancer cells, high level ascorbic acid (Asc) is able to be autoxidized and thus provides an electron to oxygen to generate H2O2. In the present study, we demonstrated that triethylenetetramine (TETA) enhances Asc autoxidation and thus elevates H2O2 production in MCF-7 cells. Furthermore, Asc/TETA combination significantly impaired cancer cell viability, while having much milder effects on normal cells, indicating Asc/TETA could be a promising therapy for breast cancer. Moreover, SOD1 and N-acetyl-L-cysteine failed to improve MCF-7 cells viability in the presence of Asc/TETA, while catalase significantly inhibited the cytotoxicity of Asc/TETA to breast cancer cells, strongly suggesting that the selective cytotoxicity of Asc/TETA to cancer cells is H2O2-dependent. In addition, Asc/TETA induces RAS/ERK downregulation in breast cancer cells. Animal studies confirmed that Asc/TETA effectively suppressed tumor growth in vivo. In conclusion, TETA synergizes pharmacologic Asc autoxidation and H2O2 overproduction in breast cancer cells, which suppresses RAS/ERK pathway and results in apoptosis.

Determinants of second pregnancy among pregnant women: A hospital-based cross-sectional survey in China

Objectives This study aimed to explore determinants of second pregnancy and underlying reasons among pregnant Chinese women. Design The study was a population-based cross-sectional survey. Setting 16 hospitals in 5 provinces of Mainland China were included. Participants A total of 2345 pregnant women aged 18 years or above were surveyed face to face by investigators between June and August 2015. Main outcome measures The pregnancy statuses (first or second pregnancy) and reasons for entering second pregnancy. Results A total of 1755 (74.8%) and 590 (25.2%) women in their respective first and second pregnancies were enrolled in this study. The most common self-reported reasons for entering second pregnancy among participants included the benefits to the first child (26.1%), love of children (25.8%), adoption of the 2-child policy (11.5%), concerns about losing the first child (7.5%) and suggestions from parents (7.5%). Pregnant women with low (prevalence ratio (PR) 1.96; 95% CI 1.62 to 2.36) and moderate education level (PR 1.97; 95% CI 1.65 to 2.36) were more likely to have a second pregnancy than their higher educated counterparts. Income was inversely associated with second pregnancy. However, unemployed participants (PR 0.79; 95% CI 0.66 to 0.95) were less likely to enter a second pregnancy than those employed. Women with moderate education were 3 times more likely to have a second child following the ‘2-child policy’ than the low education level subgroup. Conclusions 1 in every 4 pregnant women is undergoing a second pregnancy. The benefits of the firstborn or the love of children were the key drivers of a second pregnancy. Low socioeconomic status was positively associated with a second pregnancy as well. The new 2-child policy will have an influence on Chinas demographics.

Metabolic Biomarkers of Monochorionic Twins Complicated With Selective Intrauterine Growth Restriction in Cord Plasma and Placental Tissue

The selective intrauterine growth restriction (sIUGR) of monochorionic diamniotic (MCDC) twins causes phenotypic growth discordance, which is correlated with metabolomic pertubations. A global, untargeted identification of the metabolic fingerprint may help elucidate the etiology of sIUGR. Umbilical cord blood and placentas collected from 15 pairs of sIUGR monochorionic twins, 24 pairs of uncomplicated twins, and 14 singletons diagnosed with intrauterine growth restriction (IUGR) were subjected to gas chromatography-mass spectrometry based metabolomic analyses. Supervised multivariate regression analysis and pathway analysis were performed to compare control twins with sIUGR twins. A generalized estimating equation (GEE) model was utilized to explore metabolic differences within sIUGR co-twins. Linear logistic regression was applied to screen metabolites that significantly differed in concentration between control twins and sIUGR twins or IUGR singletons. Umbilical cord blood demonstrated better global metabolomic separation of sIUGR and control twins compared to the placenta. Disrupted amino acid and fatty acid metabolism as well as high levels of exposure to environmental xenobiotics were associated with sIUGR. The metabolic abnormalities in MCDA twins suggested that in utero growth discordance is caused by intrauterine and extrauterine environmental factors, rather than genetics. Thus, this study provides new therapeutic targets and strategies for sIUGR management and prevention.

QSOX1 regulates trophoblastic apoptosis in preeclampsia through hydrogen peroxide production.

Abstract Objective: Oxidative stress plays a significant role in the pathogenesis of preeclampsia (PE), by inducing trophoblast cell death and consequent placental dysfunction. Quiescin sulfhydryl oxidase 1 (QSOX1) is upregulated in many types of cancer cells; it promotes disulfide bond formation as well as hydrogen peroxide (H2O2) production. The aims of present study are to investigate the expression pattern of QSOX1 in placentae of pregnancies complicated by PE and the role of QSOX1 in the regulation of trophoblastic function, thus providing in-depth understanding of the putative involvement of QSOX1 in the development of PE. Methods: Human term placenta from normal pregnancies and from pregnancies complicated by PE was collected to measure QSOX1 expression and H2O2 levels. Down-regulation of QSOX1 in HTR-8/SVneo cells was achieved by siRNA interference. An in vitro cellular PE model was generated by hypoxic incubation. Protein expression levels were assessed by Western blotting, and H2O2 levels were determined in the cell culture medium as well as in the cell lysate. Trophoblast apoptosis was evaluated by TUNEL staining. Results: QSOX1 was overexpressed in the PE placenta. Inhibition of QSOX1 expression in HTR-8/SVneo cells attenuated cell apoptosis and intracellular H2O2 levels. Hypoxia-induced QSOX1 expression in HTR-8/SVneo cells and led to apoptosis of HTR-8/SVneo cells, and knock-down of QSOX1 rescued hypoxia-induced trophoblast apoptosis. Conclusions: Hypoxia-induced upregulation of QSOX1 and a consequent elevation in intracellular H2O2 increased apoptosis in placentae of pregnancies complicated by PE.

AMPK Hyper-Activation Alters Fatty Acids Metabolism and Impairs Invasiveness of Trophoblasts in Preeclampsia

Background/Aims: Preeclampsia (PE) has long been assumed to be an ischemic disease of the placenta, although there is limited evidence as to how the ischemia impacts on the placenta. AMP-activated protein kinase (AMPK) is a key regulator of cellular energy metabolism and plays an important role in a variety of ischemic diseases by enhancing energy production. The present study investigated placental metabolism in PE, and the role of AMPK in regulating trophoblast function. Methods: placentas from normal and PE complicated pregnancies were subjected to GC-MS to identify fatty acids (FA) metabolic fingerprints, and total FA oxidation was assessed by malondialdehyde (MDA) measurement. The AMPK-ACC signaling pathway was assessed by q-PCR and Western Blotting. HTR8/SVneo trophoblast cultures were exposed to different oxygenation conditions to establish an in vitro PE cell model; further analysis by GC-MS for metabolite profiling was then undertaken. Trophoblasts invasion was assessed by a matrigel transwell assay in the presence/absence of AMPK expression and after manipulations of AMPK activity, and then further validated by human villi outgrowth experiments. Results: AMPK phosphorylation and MDA production were significantly elevated in placentas from pregnancies complicated by PE. Metabolism of cis double bond FA was inhibited while trans double bond FA metabolism was promoted in PE placentas. HTR8/SVneo cell culture conditions of persistent low oxygenation mimicked the hyper-activation of AMPK and enhanced the FA oxidation that was observed in PE. AMPK activation impaired trophoblast invasion, while AMPK inhibition promoted trophoblast invasion. Conclusion: PE complicated placentas are associated with AMPK hyper-activation and consequent alterations in FA oxidation, which inhibit trophoblast invasion.