Hypobaric hypoxia causes low fecundity in zebrafish parents and impairment of skeletal development in zebrafish embryos and rat offspring.

Hypobaric Hypoxia (HH) negatively affects the cardiovascular and respiratory systems as well as gonadal development and the therefore next generation. This study investigated the effects of HH on zebrafish and SD rats, by exposing them to a low-pressure environment at 6000 m elevation for 30 days to simulate high-altitude conditions. It was indicated that parental zebrafish reared amh under HH had increased embryo mortality, reduced hatchability, and abnormal cartilage development in the offspring. Furthermore, the HH-exposed SD rats had fewer reproductive cells and smaller litters. Moreover, the transcriptome analysis revealed the down-regulation of steroid hormone biosynthesis pathways. The expression of the gonad-associated genes (amh, pde8a, man2a2 and lhcgr), as well as the gonad and cartilage-related gene bmpr1a, were also down-regulated. In addition, Western blot analysis validated reduced bmpr1a protein expression in the ovaries of HH-treated rats. In summary, these data indicate the negative impact of HH on reproductive organs and offspring development, emphasizing the need for further research and precautions to protect future generations' health.

Relationship of Placental and Serum Lipoprotein-Associated Phospholipase A2 Levels with Hypertensive Disorders of Pregnancy.

Background: A series of studies has shown that lipoprotein-associated phospholipase A2 (Lp-PLA2) is closely associated with abnormal lipid metabolism and vascular endothelial cell injury, but its role in hypertensive disorders of pregnancy (HDP) remains unclear. This study aims to determine the relationship between placental and serum LP-PLA2 levels and HDP, and to provide a feasible method for predicting HDP. Methods: The placental and serum Lp-PLA2 levels of 63 patients with HDP (20, 25, and 18 cases with gestational hypertension, mild preeclampsia, and severe preeclampsia, respectively) and 20 women with normal pregnancies (control group) were measured via a combination of tissue microarray and immunohistochemistry, real-time quantitative RT-PCR and enzyme-linked immunosorbent assay (ELISA). Results: 1) The gene and protein expression levels of placental LP-PLA2: the HDP group had significantly higher levels than those of the control group (P < 0.05). The mild preeclampsia group had significantly higher levels than those of the control group (P < 0.05); the severe preeclampsia group had significantly higher levels than those of the mild preeclampsia group (P < 0.05). 2) Serum levels of Lp-PLA2: the HDP group had significantly higher levels than those of the control group (P < 0.05). The Lp-PLA2 levels increased gradually with the progression of the HDP; there were significant differences in the four groups using pair-wise comparisons (P < 0.05). 3) Serum levels of LP-PLA2 were positively correlated with placental LP-PLA2 levels in the HDP group (r = 0.435, P < 0.05). Conclusion: Elevated Lp-PLA2 levels may be associated with the occurrence of HDP, and changes of Lp-PLA2 levels in the maternal blood may be regarded as a monitoring indicator for this disease.

Gene expression in rat placenta after exposure to di(2-ethylhexyl) phthalate.

The organic compound di(2-ethylhexyl) phthalate (DEHP) is widely used as a plasticizer in many products. Exposure to DEHP has been reported to lead to adverse pregnancy outcomes by suppressing placenta growth and development. The aim of this study was to determine the gene expression profiles of rat placenta exposed to (DEHP) and identify genes crucial for the DEHP response. Three groups of Wistar rats were administered an intragastric dose of 1,000 mg/kg DEHP, 500 mg/kg DEHP, or corn oil, RNA was isolated from placenta tissue, and hybridization was performed. Gene expression profiles were analyzed by identifying functional enrichment, differentially expressed genes (DEGs), protein-protein interaction (PPI) networks and modules, and transcription factor (TF)-miRNA-target regulatory networks. We obtained 2,032 DEGs, including cytochrome P450, family 2, subfamily R, polypeptide 1 (CYP2R1), sterol O-acyltransferase 2 (SOAT2), and 24-dehydrocholesterol reductase (DHCR24) from the steroid biosynthesis pathway and somatostatin receptor 4 (SSTR4) and somatostatin receptor 2 (SSTR2) in the neuroactive ligand-receptor interaction pathway. The PPI network included 476 nodes, 2,682 interaction pairs, and three sub-network modules. Moreover, eight miRNAs, three TFs, and 176 regulatory pairs were obtained from the TF-miRNA-target regulatory network. CYP2R1, SOAT2, DHCR24, SSTR4, and SSTR2 may affect DEHP influence on rat placenta development.

Abdominal circumference profiles of macrosomic infants born to mothers with or without hyperglycemia in China.

Objectives: Serial measurements of sonographic fetal abdominal circumference (AC) are useful for monitoring fetal growth during pregnancy and are essential for predicting macrosomia. The study was aiming to compare the AC profiles of infants born to mothers with or without hyperglycemia in Chinese population.Subjects and methods: The "GDM Prevalence Study (GPS)" was a large study conducted in 22 hospitals in three large cities in China, which included 34,085 NGT (normal glucose tolerant) women, 8272 GDM (gestational diabetes mellitus) women and 729 DM (diabetes mellitus) women. A total of 116,740 scans and 103,377 valid AC measurements were performed for the NGT, GDM and DM groups at different gestational age. AC profiles and fetal growth rates at different stages of pregnancy were compared between different groups.Results: The overall AC growth rate (ß) was higher in the macrosomia group than in the no macrosomia group in NGT (ß =10.250 versus 9.541, p < .001), GDM (ß = 10.572 versus 9.705, p < .001) and DM (ß = 11.363 versus 9.924, p < .001) pregnancies. Significant differences were observed between NGT-macrosomia, GDM-macrosomia and DM-macrosomia. Significant differences were also noted between NGT-no macrosomia, GDM-no macrosomia and DM-no macrosomia women. Participants in NGT-macrosomia group exhibited larger AC values than NGT-no macrosomia group beginning at 21 gestational weeks, and GDM-macrosomia group exhibited larger AC values than GDM-no macrosomia group beginning at 22 gestational weeks. AC growth rate was higher in NGT-macrosomia and GDM-macrosomia groups than in the corresponding no macrosomia groups between 22 and 30 gestational weeks.Conclusions: The overall AC growth rates are higher in macrosomia group compared to the no macrosomia group in NGT, GDM as well as DM participants. The significant difference of AC growth rates in NGT-macrosomia and GDM-macrosomia indicate the possible differential underlying mechanisms in developing macrosomia with or without hyperglycemia exposure. Our study demonstrate that larger fetal AC measurements around 21-22 weeks are associated with subsequent diagnosis of macrosomia, suggesting that macrosomia management should be initiated much earlier than we thought.

High glucose and bupivacaine­induced cytotoxicity is mediated by enhanced apoptosis and impaired autophagy via the PERK­ATF4­CHOP and IRE1­TRAF2 signaling pathways.

Bupivacaine has previously been reported to induce neurotoxicity, which is further enhanced by high glucose levels. In the present study, the underlying molecular mechanisms via which bupivacaine induces cytotoxicity under high glucose conditions were investigated in cultured human SH­SY5Y cells. In order to identify the optimal concentrations of glucose and bupivacaine that induced cytotoxicity, SH­SY5Y cells were treated with 30­100 mM glucose and 0.5­1.0 mM bupivacaine. Based on the dose response experiments, 50 mM glucose and 0.5 mM bupivacaine was used in the present study. The effects that 3­MA (autophagy inhibitor) and rapamycin (RAPA; autophagy inducer) exerted on cell apoptosis, autophagy and the expression of protein kinase R­like endoplasmic reticulum kinase (PERK)­activating transcription factor 4 (ATF4)­C/EBP­homologous protein (CHOP) and inositol­requiring enzyme 1 (IRE1)­tumor necrosis factor receptor associated factor 2 (TRAF2) signaling proteins were measured in high glucose and bupivacaine­treated cells. Cell viability was measured using a Cell Counting Kit­8 assay, cell apoptosis was assessed using flow cytometry, and protein expression was determined using western blot analyses. Compared with the control group, high glucose and bupivacaine significantly increased ATF4, CHOP and caspase­12 expression, increased apoptosis, and decreased p­IRE1, TRAF2, LC3­II/LC3­I and Beclin1 expression. Promoting autophagy with RAPA partly reversed the high glucose and bupivacaine­induced changes in p­PERK, CHOP, TRAF2, Beclin1, caspase­12 and apoptosis, while inhibiting autophagy with 3­MA further enhanced the changes in ATF4, CHOP, p­IRE1, TRAF2 and apoptosis. High glucose and bupivacaine induced cytotoxicity in SH­SY5Y cells, at least in part, through enhancing cell apoptosis and inhibiting autophagy via the PERK­ATF4­CHOP and IRE1­TRAF2 signaling pathways.

Value of fasting plasma glucose to screen gestational diabetes mellitus before the 24th gestational week in women with different pre-pregnancy body mass index.

BACKGROUND: Gestational diabetes mellitus (GDM) is usually diagnosed between 24th and 28th gestational week using the 75-g oral glucose tolerance test (OGTT). It is difficult to predict GDM before 24th gestational week because fast plasma glucose (FPG) decreases as the gestational age increases. It is controversial that if FPG ≥5.1 mmol/L before 24th gestational week should be intervened or not. The aim of this study was to evaluate the value of FPG to screen GDM before 24th gestational week in women with different pre-pregnancy body mass index (BMI). METHODS: This was a multi-region retrospective cohort study in China. Women who had a singleton live birth between June 20, 2013 and November 30, 2014, resided in Beijing, Guangzhou and Chengdu, and received prenatal care in 21 selected hospitals, were included in this study. Pre-pregnancy BMI, FPG before the 24th gestational week, and one-step GDM screening with 75 g-OGTT at the 24th to 28th gestational weeks were extracted from medical charts and analyzed. The pregnant women were classified into four groups based on pre-pregnancy BMI: Group A (underweight, BMI < 18.5 kg/m), Group B (normal, BMI 18.5-23.9 kg/m), Group C (overweight, BMI 24.0-27.9 kg/m) and Group D (obesity, BMI ≥28.0 kg/m). The trend of FPG before 24th week of gestation was described, and the sensitivity and specificity of using FPG before the 24th gestational week to diagnose GDM among different pre-pregnancy BMI groups were reported. Differences in the means between groups were evaluated using independent sample t-test and analysis of variance. Pearson Chi-square test was used for categorical variables. RESULTS: The prevalence of GDM was 20.0% (6806/34,087) in the study population. FPG decreased gradually as the gestational age increased in all pre-pregnancy BMI groups until the 19th gestational week. FPG was higher in women with higher pre-pregnancy BMI. FPG before the 24th gestational week and pre-pregnancy BMI could be used to predict GDM. The incidence of GDM in women with FPG ≥5.10 mmol/L in the 19th to 24th gestational weeks and pre-pregnancy overweight or obesity was significantly higher than that in women with FPG ≥5.10 mmol/L and pre-pregnancy BMI <24.0 kg/m (78.5% [62/79] vs. 52.9% [64/121], χ = 13.425, P < 0.001). CONCLUSIONS: FPG decreased gradually as the gestational age increased in all pre-pregnancy BMI groups until the 19th gestational week. Pre-pregnancy overweight or obesity was associated with an increased FPG value before the 24th gestational week. FPG ≥5.10 mmol/L between 19 and 24 gestational weeks should be treated as GDM in women with pre-pregnancy overweight and obesity.

Moderate prenatal alcohol exposure suppresses the TLR4-mediated innate immune response in the hippocampus of young rats.

Prenatal alcohol exposure (PAE) could lead to developmental disorders of the central nervous system (CNS) and mental retardation. Toll-like receptor (TLR) 4 plays an important role in PAE-induced neurodevelopmental defects. However, how PAE affects TLR4 response in the brain remains controversial. Using a moderate PAE model by feeding pregnant rats with liquid ethanol diet, we investigated the TLR4-mediated response to intraventricular injection of lipopolysaccharide (LPS) in the hippocampus of PEA rats at postnatal day (PND) 30. The results showed that PAE significantly up-regulated the expression of Toll-Interleukin-1 Receptor (TIR)-domain-containing adaptor protein inducing interferon (IFN)-ß (TRIF), TNF-α, and IL-1ß in the rat hippocampus in the absence of LPS, indicated by western blot assay. LPS treatment dramatically up-regulated the expressions of TLR4 and its downstream molecules in the hippocampus of paired-food and control groups. But no such significant changes of those molecules were found in the hippocampus of PAE animals. Moreover, the LPS stimulation even down-regulated the levels of TLR4 and TRIF in the PAE group. These data suggest that the relatively moderate level of PAE may lead to a mild neuroinflammation and a suppression of TLR4-mediated response to LPS in the hippocampus of young rats. As innate immunity plays crucial roles in CNS development, moderate PAE-induced suppression of TLR4-mediated response may serve as a new candidate mechanism of CNS developmental defects.

Identification of novel candidate indicators for assessing zinc status during pregnancy in mice from microarray data.

BACKGROUND: This study aimed to identify potential zinc status indicators and to clarify the mechanisms underlying zinc deficiency-induced organ damage and mortality in mice. METHODS: The dataset GSE97112, including placental tissues of mice fed diets containing normal and low concentrations of zinc, was downloaded and preprocessed. Differentially expressed genes (DEGs) were calculated and identified for zinc deficiency-related gene clusters by using the weighed gene co-expression network analysis (WGCNA) algorithm. The Gene Ontology (GO)-Biological Process (BP) and KEGG pathway of genes in the zinc deficiency-related WGCNA modules were analyzed, and the protein-protein interaction (PPI) network was constructed. In addition, modules of the PPI network were identified, and transcription factors (TFs) and miRNAs regulating DEGs were predicted. Finally, drug-gene interactions were selected. RESULTS: A total of 1055 DEGs containing 586 up- and 469 down-regulated genes were obtained. Three modules based on WGCNA had high correlation with degree of zinc deficiency. Annexin A1 (ANXA1), C-C motif chemokine receptor 3 (CCR3), C-X-C motif chemokine receptor 2 (CXCR2), and interleukin 2 (IL-2) were hub nodes in the PPI network. Three modules in the PPI network were identified, including module 1 associated with olfactory conduction and module 2 associated with inflammatory response. ANXA1, CCR3, and IL-2 were regulated by TFs. In addition, CXCR2, ANXA, and IL-2 were drug targets. CONCLUSION: CXCR2, ANXA1, and CCR3 as well as olfactory receptor-related genes (proteins) may be used as biomarkers to assess zinc status in mice.

Analysis of correlation factors and pregnancy outcomes of hypertensive disorders of pregnancy - a secondary analysis of a random sampling in Beijing, China.

OBJECTIVE: We aimed to assess the prevalence and risk factors for hypertensive disorders and to study the main pregnancy outcomes in the Beijing area of China. STUDY DESIGN: This study randomly sampled 15 hospitals in Beijing from Jun 2013 to Nov 2013 and evaluated 15 194 deliveries. Logistic regression analysis was used to study the association between risk factors and hypertensive disorders. Pregnancy outcomes included preterm birth, cesarean delivery and small for gestational age (SGA). RESULTS: The prevalence of hypertensive disorders, preeclampsia (PE) and severe PE was 4.4, 2.7 and 1.8%, respectively. The risk factors for hypertensive disorders and severe PE were maternal body mass index before pregnancy, gestational weight gain (GWG), gestational diabetes and pre-gestational diabetes, and third trimester cholesterol (CHOL) levels. First trimester high-density lipoprotein was a protective factor for severe PE. The incidence of hypertensive disorders increased with maternal age. Preterm delivery, cesarean delivery and small infant size for gestational age were more prevalent in the severe PE group compared with the non-hypertensive group. CONCLUSIONS: In the Beijing area of China, maternal body mass index before pregnancy, GWG, maternal complications of gestational diabetes and pre-gestational diabetes, and third trimester CHOL levels are risk factors for both hypertensive disorders of pregnancy and severe PE. First trimester high-density lipoprotein is a protective factor for severe PE. Severe preeclampsia leads to a higher incidence of preterm delivery, cesarean delivery and SGA infants.

Association between X-Ray Repair Cross-Complementing Group 1 Arg399Gln Polymorphism and Cervical Cancer Risk: A Meta-Analysis in the Chinese Population.

BACKGROUND: Many studies have examined the association of X-ray repair cross-complementing group 1 (XRCC1) Arg399Gln polymorphism with cervical cancer susceptibility. However, the results of these studies are inconsistent. To further assess the effects of XRCC1 Arg399Gln polymorphism on the risk of cervical cancer in the Chinese population, a meta-analysis was performed. METHODS: Relevant studies were identified using PubMed, Springer Link, Ovid, Chinese Wanfang Data Knowledge Service Platform, Chinese National Knowledge Infrastructure, and Chinese Biology Medicine through December 2015. Pooled ORs and 95% CIs were used to assess the strength of the associations. RESULTS: This meta-analysis identified 7 studies, including 1,589 cases and 2,235 controls. In the total analyses, a significantly elevated risk of cervical cancer was associated with variants of XRCC1 Arg399Gln (GA vs. GG: OR 1.30, 95% CI 1.13-1.49; AA + GA vs. GG: OR 1.27, 95% CI 1.02-1.58). In the subgroup analyses stratified by geographic areas and histopathology type, it revealed the significant result in South China. CONCLUSIONS: This meta-analysis showed that the XRCC1 Arg399Gln GA variant might be risk alleles for cervical cancer susceptibility in the Chinese population, and further studies in other ethnic groups are required to arrive at definite conclusions.

Relationship of Liver X Receptors α and Endoglin Levels in Serum and Placenta with Preeclampsia.

BACKGROUND: Liver X receptor alpha (LXRα) and endoglin have been postulated to play roles in trophoblast invasion and lipid metabolic disturbances. However, the relationship between LXRα and endoglin levels in serum and placenta of patients with preeclampsia remains poorly understood. The objective of this study was to identify correlations between LXRα, endoglin and preeclampsia and provide new feasible methods of clinical prediction and treatment for preeclampsia. METHODS: We enrolled 45 patients with preeclampsia (24 with moderate preeclampsia and 21 with severe preeclampsia) and 15 normal pregnant women (control group) who were admitted to the Department of Obstetrics of the General Hospital of Beijing Command between October 2012 and July 2013 in this study. Serum and placental LXRα and endoglin levels were analyzed by enzyme-linked immunosorbent assay, real-time quantitative PCR, tissue microarray and immunohistochemistry. RESULTS: Serum and placental LXRα and endoglin levels were significantly higher in patients with preeclampsia than those in control group (P<0.05, each). Moreover, patients with severe preeclampsia displayed significantly higher LXRα and endoglin levels than those with moderate preeclampsia (P<0.05, each). The LXRα sensitivity, specificity and positive and negative predictive values were 66.00%, 80.00%, 89.19% and 48.48%, respectively, while those of endoglin levels were 62.00%, 85.00%, 91.18% and 47.22%, respectively. LXRα and endoglin levels in serum and placenta from patients with preeclampsia were positively correlated (serum: r = 0.486, P<0.01; placenta: r = 0.569, P<0.01). CONCLUSIONS: Elevated LXRα and endoglin levels may be associated with preeclampsia pathogenesis and development and could be used as potential predictors for this disorder.

Is It Time to Change Our Reference Curve for Femur Length? Using the Z-Score to Select the Best Chart in a Chinese Population.

OBJECTIVE: To use Z-scores to compare different charts of femur length (FL) applied to our population with the aim of identifying the most appropriate chart. METHODS: A retrospective study was conducted in Beijing. Fifteen hospitals in Beijing were chosen as clusters using a systemic cluster sampling method, in which 15,194 pregnant women delivered from June 20th to November 30th, 2013. The measurements of FL in the second and third trimester were recorded, as well as the last measurement obtained before delivery. Based on the inclusion and exclusion criteria, we identified FL measurements from 19996 ultrasounds from 7194 patients between 11 and 42 weeks gestation. The FL data were then transformed into Z-scores that were calculated using three series of reference equations obtained from three reports: Leung TN, Pang MW et al (2008); Chitty LS, Altman DG et al (1994); and Papageorghiou AT et al (2014). Each Z-score distribution was presented as the mean and standard deviation (SD). Skewness and kurtosis and were compared with the standard normal distribution using the Kolmogorov-Smirnov test. The histogram of their distributions was superimposed on the non-skewed standard normal curve (mean = 0, SD = 1) to provide a direct visual impression. Finally, the sensitivity and specificity of each reference chart for identifying fetuses <5th or >95th percentile (based on the observed distribution of Z-scores) were calculated. The Youden index was also listed. A scatter diagram with the 5th, 50th, and 95th percentile curves calculated from and superimposed on each reference chart was presented to provide a visual impression. RESULTS: The three Z-score distribution curves appeared to be normal, but none of them matched the expected standard normal distribution. In our study, the Papageorghiou reference curve provided the best results, with a sensitivity of 100% for identifying fetuses with measurements < 5th and > 95th percentile, and specificities of 99.9% and 81.5%, respectively. CONCLUSIONS: It is important to choose an appropriate reference curve when defining what is normal. The Papageorghiou reference curve for FL seems to be the best fit for our population. Perhaps it is time to change our reference curve for femur length.

Subchronic Exposure to Arsenic Represses the TH/TRß1-CaMK IV Signaling Pathway in Mouse Cerebellum.

We previously reported that arsenic (As) impaired learning and memory by down-regulating calmodulin-dependent protein kinase IV (CaMK IV) in mouse cerebellum. It has been documented that the thyroid hormone receptor (TR)/retinoid X receptor (RXR) heterodimer and thyroid hormone (TH) may be involved in the regulation of CaMK IV. To investigate whether As affects the TR/RXR heterodimer and TH, we determined As concentration in serum and cerebellum, 3,5,3'-triiodothyronine (T3) and thyroxin (T4) levels in serum, and expression of CaMK IV, TR and RXR in cerebellum of mice exposed to As. Cognition function was examined by the step-down passive avoidance task and Morris water maze (MWM) tests. Morphology of the cerebellum was observed by Hematoxylin-Eosin staining under light microscope. Our results showed that the concentrations of As in the serum and cerebellum of mice both increased with increasing As-exposure level. A significant positive correlation was found between the two processes. Adeficit in learning and memory was found in the exposed mice. Abnormal morphologic changes of Purkinje cells were observed in cerebellum of the exposed mice. Moreover, the cerebellar expressions of CaMK IV protein and the TRß gene, and TRß1 protein were significantly lower in As-exposed mice than those in controls. Subchronic exposure to As appears to increase its level in serum and cerebella of mice, impairing learning and memory and down-regulating expression of TRß1 as well as down-stream CaMK IV. It is also suggested that the increased As may be responsible for down-regulation of TRß1 and CaMK IV in cerebellum and that the down-regulated TRß1 may be involved in As-induced impairment of learning and memory via inhibiting CaMK IV and its down-stream pathway.

Risk of adverse pregnancy outcomes stratified for pre-pregnancy body mass index.

OBJECTIVE: To estimate the risk of adverse maternal and perinatal outcomes in women with different pre-pregnancy body mass index (BMI). METHODS: We conducted a cohort study with 14 451 singleton pregnancies in 15 medical centers in Beijing between 20 June 2013 and 30 November 2013 using cluster random sampling. We divided participants into four groups based on pre-pregnancy BMI: Group A (underweight): BMI < 18.5 kg/m(2), Group B (normal): 18.5-23.9 kg/m(2), Group C (overweight): 24-27.9 kg/m(2), Group D (obesity): ≥28 kg/m(2). We used multivariate analysis to evaluate the association of the risk of adverse pregnancy outcomes and pre-pregnancy BMI. RESULTS: The prevalence of maternal overweight and obesity was 14.82% (2142/14 451) and 4.71% (680/14 451) in the study population, respectively. Higher pre-pregnancy BMI is associated with higher prevalence of gestational diabetes (GDM), macrosomia, Cesarean section (C-section), preeclampsia and postpartum hemorrhage. Pre-pregnancy overweight or obesity increases the risk of adverse pregnancy outcomes, regardless of GDM status. CONCLUSIONS: Pre-pregnancy overweight or obesity is associated with increased risk of adverse pregnancy outcomes. Nutrition counseling is recommended before pregnancy in women who have overweight or obesity.

TP53 codon 72 polymorphism and susceptibility to cervical cancer in the Chinese population: an update meta-analysis.

BACKGROUND: Although many epidemiologic studies investigated the TP53 codon 72 polymorphism and its association with cervical cancer (CC), definite conclusions cannot be drawn. AIM OF THE STUDY: To evaluate the association between TP53 codon 72 polymorphism and risk of cervical cancer in the Chinese population. METHODS: A computerized literature search was carried out in PubMed, Springer Link, Ovid, Chinese Biomedical Database (CBM), Chinese National Knowledge Infrastructure (CNKI), and Chinese Wanfang Database to collect relevant articles. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to calculate the strength of association. RESULTS: A total of 16 studies including 1684 CC cases and 1178 controls were involved in this meta-analysis. Overall, significant increased association was found between the Pro/Pro carriers and CC risk when all studies in Chinese population pooled into the meta-analysis (heterozygous model: OR = 1.22, 95% CI: 1.01-1.46). In subgroup analyses stratified by ethnicity and source of controls, the same results were observed in Han and in hospital-based studies. CONCLUSION: Our results suggest that the TP53 codon 72 polymorphism may be potential biomarkers for CC risk in the Chinese population, especially for Han Chinese, and studies with wider spectrum of population are required for definite conclusions.

Deregulation of miR-128 in ovarian cancer promotes cisplatin resistance.

OBJECTIVE: Platinum-based chemotherapy is the standard treatment in advanced ovarian cancer, but most patients will relapse with drug-resistant disease. MicroRNAs have been demonstrated to function in chemoresistance in cancers. In this study, we focused on the role of miR-128 in cisplatin-resistant ovarian cancer. MATERIALS AND METHODS: The expression of miR-128 RNA and its targeted genes, the polycomb ring finger oncogene Bmi-1 and ATP-binding cassette subfamily C member 5 (ABCC5), were investigated in the epithelial ovarian cancer cells and ovarian carcinomas. RESULTS: miR-128 expression was significantly reduced in the cisplatin-resistant human epithelial ovarian cancer cell line SKOV3/CP compared with parental SKOV3 cells and decreased upon treatment with cisplatin in a concentration-dependent manner in SKOV3, OVCAR3, and PEO14 cells. Overexpression of miR-128 resensitized SKOV3/CP cells to cisplatin and reduced the expression of cisplatin-resistant-related proteins ABCC5 and Bmi-1, whereas miR-128 inhibitors increased cisplatin resistance in SKOV3 cells. Cisplatin combined with miR-128 agomirs inhibited the growth of SKOV3/CP xenograft tumors more effectively than cisplatin alone. Diminished expression of ABCC5 and Bmi-1 and higher cisplatin concentrations were observed in tumor tissue of mice treated with miR-128 agomirs in addition to cisplatin. CONCLUSIONS: Taken together, our findings suggest that miR-128 may act as a promising therapeutic target for improvement of tumor sensitivity to cisplatin.

Systemic injection of low-dose lipopolysaccharide fails to break down the blood-brain barrier or activate the TLR4-MyD88 pathway in neonatal rat brain.

We aimed to investigate whether peripheral low-dose lipopolysaccharide (LPS) induces the breakdown of the blood-brain barrier (BBB) and/or the activation of toll-like receptor 4 (TLR4) in the neonatal rat brain. Neonatal rats received intraperitoneal injections of low-dose LPS (0.3 mg/kg∙bw), and the BBB compromise was detected by Evans Blue extravasation and electron microscopy. Meanwhile, TLR4, adaptin myeloid differentiation factor 88 (MyD88), nuclear transcription factor kappa-B (NF-κB) p50 and tumor necrosis factor alpha (TNFα) in the neonatal rat brain were determined by quantitative real-time polymerase chain reaction (PCR) and Western Blot. Immunohistochemistry was used to determine the distribution and activation of microglia in the brain after LPS administration. It was demonstrated that Evans Blue extravasation was not observed in the brain parenchyma, and that tight junctions of cerebral endothelial cells remained intact after systemic injections of LPS in neonatal rats. Although intracerebroventricular injections of LPS activated microglia and up-regulated the expression of TLR4, MyD88, NF-κB p50 and TNFα in the neonatal rat brain, systemic LPS did not induce these responses. These findings indicate that while the neonatal rat brain responds to the direct intra-cerebral administration of LPS through robust TLR4 activation, systemic low-dose LPS does not induce the innate immune reaction or compromise the BBB in neonatal rats.

[Study on the effect of di-(2-ethylhexyl) phthalate on pregnant rats and the protection of zinc against it in pregnancy].

OBJECTIVE: To investigate the effect of di-(2-ethylhexyl) phthalate (DEHP) on pregnant rat and the protection of zinc. METHODS: Fifty rats were randomized equally into 5 groups consisting of blank (given 1 ml 0.9% sodium chloride), corn oil (given 1 ml corn oil), zinc (given 1 ml zinc gluconate including 1.2 mg zinc), DEHP (given 50 mg×kg(-1)×d(-1) DEHP) and DEHP + zinc (given 50 mg×kg(-1)×d(-1) DEHP + zinc gluconate). At the beginning of the experiment (about 7 d before pregnancy), the female rats were administered with corresponding drugs everyday. The pregnant rats were killed and the fetal rats were removed on 19th day. The following results in each group were recorded: the body weight and the organic weight of the female rats, the number and the weight of fetus rats and the placental weight. RESULTS: The weight and the coefficient of female rats' kidney/body, spleen/body, brain/body, and heart/body in DEHP group compared with other groups were not statistical significance (all P > 0.05). The coefficient of female rats' liver/body, uterus/body, and ovary/body of blank group were (4.4 ± 0.7)%, (1.26 ± 0.09)%, (0.083 ± 0.009)% respectively, corn oil group were (4.5 ± 0.6)%, (1.29 ± 0.10)%, (0.084 ± 0.008)%, zinc group were (4.4 ± 0.4)%, (1.26 ± 0.08)%, (0.084 ± 0.009)%, DEHP group were (5.4 ± 1.0)%, (1.11 ± 0.08)%, (0.074 ± 0.012)%, and DEHP + zinc group were (4.4 ± 1.0)%, (1.28 ± 0.10)%, (0.082 ± 0.007)%; in DEHP group the coefficient of female rats' liver/body, uterus/body, and ovary/body compared with other groups was statistical significance (P < 0.05). The fetal quantity, fetal weight and placental weight of female rats of blank group were 12.8 ± 2.7, (6.03 ± 0.16) g, (1.00 ± 0.03) g respectively, corn oil group were 13.6 ± 3.1, (6.07 ± 0.20) g, (1.00 ± 0.04) g, zinc group were 13.3 ± 3.1, (6.16 ± 0.18) g, (1.00 ± 0.05) g, DEHP group were 9.2 ± 4.1, (4.03 ± 0.09) g, (0.95 ± 0.03) g, and zinc + DEHP group were 12.1 ± 2.9, (6.09 ± 0.17) g, (0.99 ± 0.03) g. In DEHP group the fetal quantity, fetal weight and placental weight of female rats compared with other groups were statistical significance (P < 0.05). CONCLUSION: DEHP can damage female rats and fetal rats in gestation period. Zinc supplied before pregnancy can relieve the influence by DEHP.

Relationship of adiponectin and resistin levels in umbilical serum, maternal serum and placenta with neonatal birth weight.

OBJECTIVE: Adiponectin and resistin have been postulated to play a role in the regulation of energy metabolism during pregnancy. However, relationship of adiponectin and resistin levels in umbilical serum, maternal serum and placenta with neonatal birth weight remains to be poorly understood. The purpose of the study was to clarify the correlations between adiponectin and resistin levels and neonatal birth weight. METHODS: Enzyme immunoassay was used to measure the adiponectin and resistin levels in maternal and umbilical serum from 40 normal pregnant women (control group), 30 women with macrosomia (macrosomia group) and 30 women with fetal growth restriction (FGR group). Immunohistochemistry was used to measure adiponectin and resistin levels in placenta. RESULTS: Serum adiponectin and resistin levels were significantly increased in control women compared with that in macrosomia mothers, but significantly decreased compared with that in FGR mothers. The levels of adiponectin and resistin in control babies were significantly higher than that in macrosomic babies, whereas significantly lower than that in FGR babies. The placental expressions of adiponectin and resistin in macrosomia, control and FGR group were gradually elevated, and there was a significant difference between them. Umbilical serum adiponectin levels and placental adiponectin expression were inversely correlated with birth weight. Umbilical serum levels and placental expression of resistin had positive correlation with maternal serum resistin and negative correlation with birth weight. In addition, maternal serum resistin levels were inversely correlated with birth weight. CONCLUSION: It is suggested that adiponectin and resistin play an important role in controlling body weight and may be related to the occurrence of fetal macrosomia and FGR.

[Effects of di-(2-ethylexyl) phthalate on apoptosis of cytotrophoblasts in early pregnancy].

OBJECTIVE: To investigate the influence of di-(2-ethylexyl) phthalate (DEHP) on cell apoptosis and expression of Bcl-2 and bax in cultured human first trimester cytotrophoblasts. METHODS: Human first trimester cytotrophoblasts were cultured with DEHP at concentration of 0, 25, 50, 100 µmol/L for 24 hours. Cell apoptosis was detected by the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL) and flow cytometer method. The expression of apoptosis-associated genes, including Bcl-2 and bax, were detected by reverse transcription (RT)-PCR in cultured cytotrophoblast cells. The protein expression of Bcl-2 and bax in cytotrophoblast cells was measured by western blot. RESULTS: (1) The expression of Bcl-2: when incubated with DEHP at concentration of 0, 25, 50 and 100 µmol/L, the expression of Bcl-2 were 1.00 ± 0.05, 1.03 ± 0.04, 1.04 ± 0.03, 1.04 ± 0.04, which did not show statistical difference (P > 0.05). The expression of Bcl-2 protein were 0.11 ± 0.02, 0.11 ± 0.04, 0.12 ± 0.02, 0.12 ± 0.03, which also didn't reach statistical difference (P > 0.05). (2) The expression of bax: when incubated with DEHP at concentration of 50 and 100 µmol/L, the expression of bax protein were 0.63 ± 0.04 and 0.81 ± 0.04, which were significantly higher than 0.23 ± 0.05 with DEHP at 0 µmol/L (P < 0.05). The expression of bax mRNA were 0.96 ± 0.04 and 1.02 ± 0.04, which was significantly higher than 0.81 ± 0.05 with DEHP at 0 µmol/L (P < 0.05). (3) Apoptosis: when incubated with DEHP at concentration of 50 and 100 µmol/L for 24 hours, the apoptotic cell ratio were (18.8 ± 2.6) % and (20.3 ± 2.0) % by annexin V-FITC/PI staining, which were significantly higher than (10.6 ± 1.4) % at 0 µmol/L and (18.1 ± 4.6) % and (19.5 ± 1.2) % by TUNEL staining, which were significantly higher than (11.2 ± 3.1) % at 0 µmol/L of DEHP (P < 0.05). CONCLUSION: DEHP could induce apoptosis of cytotrophoblast cells by increasing bax gene expression, but had no effect on Bcl-2 expression.