TIPE2 acts as a tumor suppressor and correlates with tumor microenvironment immunity in epithelial ovarian cancer.

BACKGROUND: Epithelial ovarian cancer (EOC) is one of the deadliest gynecologic cancers. The etiology of EOC has still not been elucidated thoroughly. Tumor necrosis factor-α-induced protein 8-like2 (TNFAIP8L2, TIPE2), an important regulator of inflammation and immune homeostasis, plays a critical role in the progression of various cancers. This study aims to investigate the role of TIPE2 in EOC. METHODS: Expression of TIPE2 protein and mRNA in EOC tissues and cell lines was examined using Western blot and quantitative real-time PCR (qRT-PCR). The functions of TIPE2 in EOC were investigated by cell proliferation assay, colony assay, transwell assay, and apoptosis analysis in vitro. To further investigate the regulatory mechanisms of TIPE2 in EOC, RNA-seq and western blot were performed. Finally, the CIBERSORT algorithm and databases including Tumor Immune Single-cell Hub (TISCH), Tumor Immune Estimation Resource (TIMER), Tumor-Immune System Interaction (TISIDB), and The Gene Expression Profiling Interactive Analysis (GEPIA) were used to elucidate its potential role in regulating tumor immune infiltration in the tumor microenvironment (TME). RESULTS: TIPE2 expression was shown to be considerably lower in both EOC samples and cell lines. Overexpression of TIPE2 suppressed EOC cell proliferation, colony formation, and motility in vitro. Mechanistically, TIPE2 suppressed EOC by blocking the PI3K/Akt signaling pathway, according to bioinformatics analysis and western blot in TIPE2 overexpression EOC cell lines, and the anti-oncogenic potentials of TIPE2 in EOC cells could be partially abrogated by the PI3K agonist, 740Y-P. Finally, TIPE2 expression was positively associated with various immune cells and possibly involved in the regulation of macrophage polarization in ovarian cancer. CONCLUSIONS: We detail the regulatory mechanism of TIPE2 in EOC carcinogenesis, as well as how it correlates with immune infiltration, emphasizing its potential as a therapeutic target in ovarian cancer.

Alterations in the vaginal microbiota of patients with preterm premature rupture of membranes.

Background: Preterm premature rupture of membranes (PPROM) is a common pregnancy complication. Yet, the main cause of PPROM remains poorly understood. In this study, we used 16S rRNA gene sequencing technology to identify the differences in vaginal microbiota between pregnant women with PPROM and those who delivered at term. Methods: Vaginal samples were collected from 48 patients with PPROM and 54 age- and gestational age-matched pregnant women who delivered at term (controls). The vaginal microbiota of the two groups was compared using 16S rRNA gene sequencing of the V3-V4 regions. Results: The vaginal microbial composition of the PPROM group was significantly different from that of the control group. Our results showed that the diversity of vaginal microbiota in patients with PPROM increased compared with controls. The relative abundance of Lactobacillus iners, Gardnerella vaginalis, Prevotella bivia, Ochrobactrum sp., Prevotella timonensis, and Ureaplasma parvum were more abundant in patients with PPROM, while Lactobacillus crispatus and Lactobacillus gasseri were more abundant in controls. Ochrobactrum sp., Prevotella timonensis, and Gardnerella vaginalis, could serve as biomarkers for PPROM. Finally, we proposed several metabolic pathways, including PWY-6339, PWY-6992, and PWY-7295. Conclusion: PPROM is characterized by vaginal microbial dysbiosis. The dysbiotic vaginal microbiota signatures in patients with PPROM include a higher bacterial diversity, decreased autochthonous bacteria, and increased pathogenic bacteria. These results may be beneficial for developing biomarkers for screening and early diagnosis of PPROM and may provide effective preventative treatments.

Fetal Congenital Cardiac and Vascular Disorders Associated with Sertraline Treatment during Pregnancy: Analysis of FAERS Data.

Objective: Sertraline is one of the most commonly used antidepressants worldwide and is one of the first-choice treatments for depression during pregnancy. This study is aimed at testing the possible association between sertraline intrauterine exposure and congenital cardiac and vascular disorder occurrences by assessing the publicly available US Food and Drug Administration Adverse Event Reporting System (FAERS). Methods: Disproportionality analysis and Bayesian analysis were used to mine FAERS for suspected congenital cardiac and vascular disorder data for sertraline intrauterine exposure from the first quarter of 2004 to the second quarter of 2021. Results: Among the 914 cases of sertraline used with congenital cardiovascular disease in the FAERS database, the reporting areas were mainly in the United States and Europe. The number of adverse events reported every year since 2004 has no many differences. Congenital anomalies are the most frequently reported serious clinical outcome. Among the 69 positive signals detected from 914 cases, 31 were invalid signals, and 38 were valid signals according to criteria. The most common ones are heart disease congenital, atrial septal defect, ventricular septal defect, patent ductus arteriosus, and persistent fetal circulation. Conclusions: Mining FAERS data can analyze and study the adverse reactions of sertraline in a more comprehensive and in-depth manner, thereby effectively reducing the risk of clinical medication.

A risk prediction model of perinatal blood transfusion for patients who underwent cesarean section: a case control study.

BACKGROUND: Severe obstetric hemorrhage is a leading cause of severe maternal morbidity. A perinatal blood transfusion is the key factor in the treatment of severe obstetric hemorrhage. Our aim is to identify patients with a high risk of perinatal blood transfusions before Cesarean Section, which can promote the effectiveness of the treatment of severe obstetric hemorrhage, as well as improve obstetric preparations. METHODS: This study retrospectively analyzed the data of 71 perinatal blood transfusion patients and 170 controls, who were both underwent Cesarean Section from July 2018 to September 2019. These data were included in the training set to build the risk prediction model of needing blood transfusion. Additionally, the data of 148 patients with the same protocol from October 2019 to May 2020 were included in the validation set for model validation. A multivariable logistic regression model was used. A risk prediction nomogram was formulated per the results of the multivariate analysis. RESULTS: The strongest risk factors for perinatal blood transfusions included preeclampsia (OR = 6.876, 95% CI: 2.226-23.964), abnormal placentation (OR = 5.480, 95% CI: 2.478-12.591), maternal age (OR = 1.087, 95% CI: 1.016-1.166), predelivery hemoglobin (OR = 0.973, 95% CI: 0.948-0.998) and predelivery fibrinogen (OR = 0.479, 95% CI: 0.290-0.759). A risk prediction model of perinatal blood transfusions for cesarean sections was developed (AUC = 0.819; sensitivity: 0.735; specificity: 0.848; critical value: 0.287). CONCLUSIONS: The risk prediction model can identify the perinatal blood transfusions before Cesarean Section. With the nomogram, the model can be further quantified and visualized, and clinical decision-making can subsequently be further simplified and promoted.

Analysis of Maternal and Neonatal Outcome of Patients with Preterm Prelabor Rupture of Membranes.

Background: Preterm prelabor rupture of membranes (PPROM) increases risk of maternal and neonatal diseases. Expectant treatment is one major treatment for PPROM patients, but it raises concerns on infection. Currently, the optimal delivery time for PPROM patients is still unclear, and there are various outcomes for the patients with PPROM. Previous studies conducted to analyze the pregnancy outcome showed inconsistent results. The purpose of this study is to retrospectively analyze the maternal and neonatal outcomes for comparison among different latency periods of patients with PPROM at a university hospital in China. Method: This was a retrospective study. We divided all patients with PPROM into four groups according to gestational weeks, namely, group A (GA 24-27+6), group B (GA 28-31+6), group C (GA 32-33+6), and group D (GA34-36+6). The maternal and neonatal outcomes of each group were observed, respectively. Groups B and C were separately divided into two subgroups according to the median latency period of each group, namely, B1, B2, C1, and C2. Then, the differences of pregnancy outcomes between B1 and B2, C1 and C2, were compared, respectively. A p value < 0.05 was considered statistically significant. Result: Group A: the common maternal and neonatal complications were the increased infection index before labour, neonatal hyperbilirubinemia and neonatal respiratory distress syndrome. Groups B, C, and D: the common maternal and neonatal complications were the increased infection index before labour, fetal distress, neonatal pneumonia, neonatal hyperbilirubinemia, and patent foramen ovale. Comparison of pregnancy outcome between group B1 and group B2 showed higher incidence rate of increased infection index before labour, lower incidence rate of respiratory distress syndrome, electrolyte disturbance, and premature brain in group B2 than those in group B1. Comparison of pregnancy outcome between group C1 and group C2 showed the higher incidence of increased infection index before labour, bigger birth weight, and shorter hospital stay in group C2 than those in group C1. Conclusion: Increased infection index before labour was common maternal complication in four groups. Neonatal hyperbilirubinemia and neonatal pneumonia were top neonatal complications in four groups. The prolongation of latency period was beneficial to newborns of patients with gestational week at 28-31+6 weeks, while it did not benefit those with gestational week beyond 32 weeks.

Research trends of pregnancy with scarred uterus after cesarean: a bibliometric analysis from 1999 to 2018.

BACKGROUND: In recent years, the number of women who are pregnant again with the history of cesarean section, has increased year by year in China. Scarred uterine attracts much attention due to its particularity. This study aimed to understand the knowledge domain and development trends of scarred uterus after cesarean section. METHODS: Data were obtained from the Web of Science Core Collection databases (WoSCCd) including SSCI and SCI-Expanded. We carried out a comprehensive literature retrieval using index words as follows: "TI=((((prior) OR (previous) OR (after) OR (post)) AND ((cesarean) OR (caesarean))) OR (scarred uterus) OR ((uterine) AND ((scar) OR (scarring) OR (wound))))". The time interval for the search was from 1999 to 2018, totally 20 years. A document type was only article and the language of article was English. All electronic searches were performed on 15 May 2019. CiteSpace, HistCite, and VOSviewer software were used to facilitate the analysis. RESULTS: The analysis included 1938 bibliographic records. The annual number of publications exhibited the solid increase. A total of 84 countries contributed to the overall published output during the study period. USA published the highest number of publications (n = 508, 26.2%), which also had the highest total global citation score (10,826). American Journal of Obstetrics and Gynecology, Obstetrics and Gynecology, and Journal of Maternal-fetal & Neonatal Medicine were the top three journals that published the articles. The top 10 productive institutions, such as Northwestern University, Tel Aviv University, and Karolinska Institute were located mainly in USA, Israel, and Sweden, and top 10 authors originated totally from USA. Vaginal birth after cesarean, uterine rupture, painless labor, and scar pregnancy were research hotspots and may be promising in the next few years. CONCLUSIONS: This bibliometrics provides a comprehensive analysis that delineates the scientific productivity, collaboration, and research hotspots about scarred uterus after cesarean section, which is very helpful to focus on the future research direction.

Association study of hypertension susceptibility genes ITGA9, MOV10, and CACNB2 with preeclampsia in Chinese Han population.

OBJECTIVE: Preeclampsia (PE) is a disorder that occurs during the pregnancy and could affect the maternal and perinatal mortality as well as morbidity. The aim of our study is to investigate the associations between the hypertension susceptibility genes ITGA9, MOV10 and CACNB2 with PE in Chinese Han population. METHODS: A case-control study including 178 PE patients and 202 healthy controls was conducted to assess the associations between three loci (ITGA9 rs155524, MOV10 rs2932538 and CACNB2 rs4373814) and PE. The TaqMan probe assay was applied for genotyping in our study. Quantitative real-time PCR was performed to detect the mRNA expression levels of ITGA9, MOV10 and CACNB2. ELISA was carried out to detect the concentration of serum sFlt-1 or PLGF. RESULTS: Our study detected no significant differences in allelic frequencies of three SNPs between PE patients and healthy controls. In the genetic model, the results showed that the patients with ITGA9 rs155524 GA or AA genotypes had a higher risk of PE development compared to those with GG genotype in codominant model. And PE patients had a higher frequency of GA + AA genotypes based on the dominant model. Subgroup analysis showed ITGA9 rs155524 was associated with early-onset PE but not with late-onset PE. No association was observed between MOV10 and CACNB2 with PE in any genetic model and subgroup analysis. Quantitative real-time PCR results showed that ITGA9 mRNA expression level was apparently increased in the placental tissues of PE patients. In addition, ITGA9 expression levels of GA + AA subjects were apparently higher than that in the genotype GG of placental tissues. sFlt-1/PLGF ratio was higher in GA + AA subjects than that in GG subjects. Regression analysis revealed that ratio of sFlt-1/PLGF was positively correlated with ITGA9 mRNA expression level. CONCLUSION: This study has identified ITGA9 is a promising candidate susceptibility gene for early-onset PE. Our findings demonstrated that the high expression of ITGA9 might be associated with an increased risk of PE.

Risk factors for massive hemorrhage during the treatment of cesarean scar pregnancy: a systematic review and meta-analysis.

PURPOSE: Cesarean scar pregnancy (CSP) is one of the serious complications associated with cesarean delivery (CD). This meta-analysis aims to identify risk factors associated with massive hemorrhage during the CSP treatment. METHODS: Eight electronic databases were searched for case-control studies published before December 31th, 2018, which compared the possible factors causing massive bleeding during the CSP treatment. Quantitative synthesis was performed by RevMan 5.3. Sensitivity analysis and publication bias were performed by Stata 12.0. RESULTS: Total 20 case - control studies including 3101 CSP patients with previous CD met the inclusion criteria. Bleeding group had 573 patients and the control group had 2528 patients. The risk factors for massive bleeding during CSP treatment included multiple gravidities (MD = 0.15, 95% CI 0.03-0.28, P = 0.73), big maximum diameter of gestation sac (MD = 18.49 mm, 95%CI 15.34-21.65, P < 0.01), high gestational days (MD = 8.98 days, 95% CI 4.12-13.84, P < 0.01), high ß-HCG level (MD = 21.39 IU/ml, 95% CI 7.36-35.41, P = 0.03; MD = 3.02 U/ml, 95% CI 0.21-5.84, P < 0.01) and rich blood flow around the lesion (OR = 6.73, 95% CI 3.93-11.51, P = 0.59). While, thick myometrium (MD = - 4.94 mm, 95% CI - 6.12 to - 3.75, P < 0.01) may be protective factor. CONCLUSIONS: Multiple gravidities, big gestation sac, large gestational days, high serum ß-HCG level, abundant blood supply to pregnancy sac and thin myometrium maybe the risk factors for massive bleeding during the CSP treatment.

Prediction of adverse maternal and perinatal outcomes in preeclampsia based on B-type natriuretic peptide: a retrospective study.

BACKGROUND: Elevated B-type natriuretic peptide (BNP) is closely related to preeclampsia. Whether it is a predictor of adverse outcomes in preeclampsia is unclear. This study aimed to investigate the relationship between BNP and adverse outcomes of preeclampsia, and to establish the prediction models and nomograms based on BNP. METHODS: A retrospective analysis was conducted involving 284 women with preeclampsia admitted to a tertiary hospital from January 2017 to July 2019. Logistic regression and receiver operating characteristic (ROC) curve were used to analyze the relationship between BNP and adverse outcomes. Multivariate logistic regression was used to establish the models for predicting adverse outcomes. Then the nomogram and ROC curve of the models were generated. RESULTS: In preeclampsia, BNP is a risk factor for adverse outcomes, and as the level of BNP increases, the incidence of adverse outcomes increases. Preeclampsia with BNP >118 pg/mL was associated with a significantly increased risk of adverse outcomes. The results showed that BNP has a predictive value for adverse maternal outcomes, and the area under the ROC curve (AUC) was 0.739 [P<0.001, 95% confidence interval (CI): 0.684-0.789]. Then, the prediction models for adverse maternal and perinatal outcomes based on BNP combined with other multi-factors were established. The discriminative ability of the 2 models was found to be good, the AUC was 0.844 (95% CI: 0.796-0.884) and 0.792 (95% CI: 0.740-0.838), respectively. Therefore, BNP was shown to significantly improve the discriminative ability of the prediction models. CONCLUSIONS: The BNP is an important risk factor for evaluating the adverse outcomes of preeclampsia. Combined with multi-factors, BNP can be used to predict the adverse outcomes.

Promoting TTC4 and HSP70 interaction and translocation of annexin A7 to lysosome inhibits apoptosis in vascular endothelial cells.

We previously demonstrated that Tetraticopeptide 4 (TTC4) inhibited apoptosis in vascular endothelial cells (VEC) deprived of serum and fibroblast growth factor 2 (FGF-2). In this study, we aimed to resolve the mechanism of TTC4 inhibiting VEC apoptosis. TTC4, predicted as a HSP70 co-chaperone protein, may regulate the fate of cells by affecting the activity of HSP70, however, there is no experimental evidence showing the interaction of TTC4 and HSP70. Using Co-immunoprecipitation (Co-IP), we demonstrated that TTC4 interacted with HSP70. If HSP70 was knockdown, TTC4 no longer suppressed apoptosis. Furthermore, we found ABO, an inhibitor of annexin A7 (ANXA7) GTPase, could promote the interaction of TTC4 and HSP70 and the translocation of ANXA7 to lysosome. At the same time, ABO inhibited the interaction of HSP70 and ANXA7. Moreover, Akt, as a downstream effector of HSP70 was upregulated, and ANXA7 translocating to lysosome protected the stability of lysosomal membrane. Here, we discovered a special mechanism by which TTC4 inhibited apoptosis via HSP70 in VECs. On the one hand, increasing TTC4 and HSP70 interaction upregulated Akt that inhibited apoptosis. On the other hand, decreasing HSP70 and ANXA7 interaction promoted the translocation of ANXA7 to lysosome, which inhibited apoptosis through protecting the lysosomal membrane stability.

Prognosis of pregnancy-associated breast cancer: a meta-analysis.

BACKGROUND: Pregnancy-associated breast cancer (PABC) is defined as breast cancer that is diagnosed during pregnancy and/or the postpartum period. Definitions of the duration of the postpartum period have been controversial, and this variability may lead to diverse results regarding prognosis. Moreover, evidence on the dose-response association between the time from the last pregnancy to breast cancer diagnosis and overall mortality has not been synthesized. METHODS: We systematically searched PubMed, Embase, and the Cochrane Library for observational studies on the prognosis of PABC published up to June 1, 2019. We estimated summary-adjusted hazard ratios (HRs) and the corresponding 95% confidence intervals (CIs). Subgroup analyses based on diagnosis time, PABC definition, geographic region, year of publication and estimation procedure for HR were performed. Additionally, dose-response analysis was conducted by using the variance weighted least-squares regression (VWLS) trend estimation. RESULTS: A total of 54 articles (76 studies) were included in our study. PABC was associated with poor prognosis for overall survival (OS), disease-free survival (DFS) and cause-specific survival (CSS), and the pooled HRs with 95% CIs were 1.45 (1.30-1.63), 1.39 (1.25-1.54) and 1.40 (1.17-1.68), respectively. The corresponding reference category was non-PABC patients. According to subgroup analyses, the varied definition of PABC led to diverse results. The dose-response analysis indicated a nonlinear association between the time from the last delivery to breast cancer diagnosis and the HR of overall mortality (P < 0.001). Compared to nulliparous women, the mortality was almost 60% higher in women with PABC diagnosed at 12 months after the last delivery (HR = 1.59, 95% CI 1.30-1.82), and the mortality was not significantly different at 70 months after the last delivery (HR = 1.14, 95% CI 0.99-1.25). This finding suggests that the definition of PABC should be extended to include patients diagnosed up to approximately 6 years postpartum (70 months after the last delivery) to capture the increased risk. CONCLUSION: This meta-analysis suggests that PABC is associated with poor prognosis, and the definition of PABC should be extended to include patients diagnosed up to approximately 6 years postpartum.

Association between polymorphism in Cyclophilin A gene and its serum and placental expression in Han Chinese women with severe preeclampsia.

OBJECTIVES: Cyclophilin A (CypA) plays important roles in inflammation and oxidative stress and is significantly increased in serum of preeclampsia (PE) patients. We aimed to investigate CypA genetic polymorphism and its serum and placenta expressions in severe PE of Han Chinese women. METHODS: A case-control study of 82 severe PE patients and 179 healthy pregnancies was conducted. Single-nucleotide polymorphism (SNP) sites of rs3735481, rs9638978 and rs11984372 were analyzed by TaqMan assay. CypA serum levels were determined by enzyme-linked immunosorbent assay (ELISA). CypA mRNA levels and protein expressions in placentas were assessed by quantitative real-time polymerase chain reaction (PCR), western blot, and immunofluorescence assay, respectively. RESULTS: There were significantly lower frequency of rs3735481 allele C (odds ratio (OR): 0.60, 95% confidence interval (CI): 0.36-0.98; p = .04), and significantly higher frequency of rs9638978 allele A in severe PE especially in early onset PE patients (OR: 2.23, 95% CI: 1.35-3.71, p = .002). Frequency of rs9638978 AA genotype was significantly higher in early onset PE (p < .001). CypA serum levels were significantly higher in severe PE especially in early onset PE (p < .001). Meanwhile, CypA serum levels were significantly lower in carriers with the AC genotype of rs3735481 (p = .019) and significantly higher in carriers with the AA genotype of rs9638978 (p = .017). CypA mRNA levels and protein expressions were found to be significantly increased in PE placentas (both p < .01). CONCLUSIONS: The CypA genetic polymorphisms of rs3735481 and rs9638978 may be associated with severe PE, and rs9638978 AA genotype may be associated with an increasing risk of early onset severe PE in Han Chinese women. High CypA levels in serum and placenta may contribute to the pathogenesis of severe PE. Our results may provide a new clue for the etiology of severe PE.

Endothelial SIRT6 Is Vital to Prevent Hypertension and Associated Cardiorenal Injury Through Targeting Nkx3.2-GATA5 Signaling.

RATIONALE: Endothelial dysfunction is an important determinant risk factor for the development of hypertension and its complications. Thus, identification of potential therapeutic targets for preventing endothelial dysfunction has major clinical importance. Emerging evidence indicates that epigenetic modifications are closely associated with the regulation of endothelial function. Among them, HDAC (histone deacetylase)-mediated epigenetic processes in vascular homeostasis and cardiovascular disease have attracted much attention. SIRT6 (sirtuin 6) is one member of SIRTs (class III HDAC) that are highly conserved NAD+-dependent deacetylases. OBJECTIVE: This study was designed to elucidate the role of SIRT6 in the pathogenesis of hypertension, discover the new targets of SIRT6, and explore related mechanisms on the regulation of endothelial function. METHODS AND RESULTS: The levels of endothelial SIRT6 were significantly reduced in 2 independent hypertension models: desoxycorticosterone acetate/salt-induced and Ang II (angiotensin II)-induced hypertensive mice. Utilizing genetically engineered endothelial-specific SIRT6 knockout (Cre+/SIRT6fl/fl) mice, we found that endothelial-specific deletion of SIRT6 significantly enhanced blood pressure, exacerbated endothelial dysfunction and cardiorenal injury in experimental hypertension. Functionally, SIRT6 has pleiotropic protective actions in endothelial cells, which include promoting endothelium-dependent vasodilatation and vascular NO bioavailability, reducing cellular permeability, ameliorating endothelial senescence and apoptosis, and facilitating autophagy. Mechanistically, SIRT6 induced the expression of GATA5 (GATA-binding protein 5), a novel regulator of blood pressure, through inhibiting Nkx3.2 (NK3 homeobox 2) transcription by deacetylating histone H3K9 (histone H3 lysine 9), thereby regulating GATA5-mediated signaling pathways to prevent endothelial injury. Finally, we provide direct evidence for the therapeutic potential of SIRT6 in desoxycorticosterone acetate/salt-induced hypertensive mice by overexpression of SIRT6 in vivo. CONCLUSIONS: This study for the first time demonstrates that SIRT6 prevents hypertension and its complications by maintaining endothelial function. Pharmacological targeting of SIRT6 may be an innovative therapeutic strategy for treating patients with hypertension.

Safety and efficacy of preoperative abdominal Aortic balloon occlusion in placenta increta and/or percreta.

BACKGROUND: With the increase of cesarean deliveries globally, the incidence of placenta adhesive disorder has been on the rise greatly which is associated closely with maternal and infant morbidity and mortality. We sought to investigate the safety and efficacy of preoperative transfemoral balloon occlusion of abdominal aorta in cesarean section of women with placenta increta or percreta. METHODS: We conducted a retrospective study of 31 patients with placenta increta or percreta diagnosed by ultrasound and/or magnetic resonance imaging. The observation group included 19 patients who received transfemoral abdominal aorta balloon occlusion for preoperative prophylaxis, while the other 12 patients in the control group did not receive any preoperative interventional managements. Clinical outcomes were compared between the two groups. RESULTS: Patients in observation group had significantly less estimated blood loss during surgery than those in control group (1.2 L versus 3.15 L, P = 0.006). The average transfusion volume of the observation group was significantly lower than the control group (0.8 L versus 1.95 L, P = 0.017). Seventy-nine percent (15 of 19) patients in the observation group and 50% (6 of 12) in the control group had their uterus successfully retained (P = 0.093). No peripheral tissues including bladder, ureter, and bowel were injured in all patients. Neonatal weight and Apgar scores of 1 min and 5 min had no statistical difference (P = 0.513 and P = 1, respectively) between the two groups. The mean radiation exposure time of fetus in the observation group was 22.68 ± 8.07 s and mean radiation exposure dose was 4.20 ± 1.49 mGy. Both operation time and postoperative hospital stay had no statistical difference between the two groups (2 versus 2.75 h, P = 0.063; 7.0 versus 6.5 d, P = 0.846). No patients had long-term complications after 6-8 wk follow-up. CONCLUSIONS: Application of preoperative transfemoral abdominal aorta balloon occlusion during cesarean section is a safe and effective strategy for patients with placenta increta and/or percreta. It could reduce intraoperative blood loss and enhance the possibility of uterus preservation and ensure the safety of life from severe complications.

Establishment of ApoE-knockout mouse model of preeclampsia and relevant mechanisms.

In the present study, we established an ApoE-knockout mouse model of preeclampsia to examine the role of vascular endothelial injury associated with abnormal lipid metabolism in the pathogenesis of preeclampsia. To establish the ApoE-knockout homozygous (ApoE-/-) and heterozygous (ApoE+/-) mouse model, mice were mated with the same genotype and orbital blood on day 19 of conception was collected. The progeny mice were assigned into 3 groups: ApoE-/, ApoE+/- and wild-type (WT) groups. Total cholesterol, triglyceride, low-density and high-density lipoprotein were measured in the serum at the end of conception. During conception, the systolic blood pressure of caudal artery was measured every 4 days. Using bicinchoninic acid protein assay, urinary protein and creatinine ratio was measured with a creatinine kit. We observed the pathological changes of glomerular filtration membrane and macroscopic/microscopic morphological changes of placenta by hematoxylin and eosin (H&E) staining and transmission electron microscope. Take fetal mouse through cesarean section on 19th day, measure the birth weight and placental weight of fetal mouse. Using ELISA we measured the expression levels of toll-like receptor 4 (TLR4) and soluble fms-like tyrosine kinase-1 (sFlt-1). Our results showed that the differences in serum lipid levels were not statistically significant (P>0.05). The mean systolic blood pressure, urinary protein and creatinine in ApoE-/- group were significantly higher than ApoE+/- group and WT group (P<0.05). Thickening and edema of glomerular filtration membrane, capillary thrombosis, significant edema and necrosis of placental villous stroma were observed in ApoE-/- group. No significant change was detected in the ApoE+/- or WT group. The TLR4 and sFlt-1 expression levels in ApoE-/- group were significantly higher than ApoE+/- and WT group (P<0.05). We concluded that ApoE-knockout mouse could simulate the pathologic process of preeclampsia, while the changes in serum lipids were not noteworthy, thus the pathogenesis of preeclampsia may be mediated by TLF4 and sFlt-1.

Rac1/ß-Catenin Signalling Pathway Contributes to Trophoblast Cell Invasion by Targeting Snail and MMP9.

BACKGROUND/AIMS: Preeclampsia is an idiopathic and serious complication during gestation in which placental trophoblast cells differentiate into several functional subtypes, including highly invasive extravillous trophoblasts (EVTs). Although the cause and pathogenesis of preeclampsia have remained unclear, numerous studies have suggested that the inadequacy of EVT invasion leads to imperfect uterine spiral artery remodelling, which plays a crucial role in the development of preeclampsia. Rac1, or Ras-related C3 botulinum toxin substrate 1, was found to be a key regulator of the migration, invasion uand apoptosis of various tumour cells. Because EVTs share similar invasive and migratory biological behaviours with malignant cells, this study aimed to determine whether the Rac1 signalling pathway affects trophoblast invasion and is thus involved in the pathogenesis of preeclampsia. METHODS: We measured the activity of Rac1 and its downstream targets, ß-catenin, Snail and MMP9 in placental tissues from patients experiencing a normal pregnancy and those with preeclampsia. Furthermore, we treated HTR-8/SVneo cells with a shRNA Rac1 vector and the ß-catenin inhibitor IWP-2 and explored Rac1 signalling pathway activation as well as the effects of Snail and ß-catenin on trophoblast invasion. RESULTS: In placental samples from patients experiencing a normal pregnancy and those with preeclampsia, active Rac1 levels and MMP9 protein and mRNA levels were significantly decreased in term pregnancy samples compared to early pregnancy samples. Lower levels were found in preeclampsia samples than in normal term pregnancy samples, and these levels significantly declined in severe preeclampsia samples compared with mild preeclampsia samples. Further analyses demonstrated that both Rac1 shRNA and the ß-catenin inhibitor significantly suppressed MMP9 and Snail activation in trophoblasts, thus impairing trophoblast invasion. Notably, silencing Rac1 down-regulated the expression of ß-catenin in HTR-8/SVneo cells, demonstrating that ß-catenin is a downstream effector of Rac1 in trophoblast invasion. CONCLUSION: Our data suggest that Rac1-mediated activation of ß-catenin might regulate Snail and MMP9 expression subsequently promoting trophoblast invasion in pregnancy.

Antibiotic prophylaxis to prevent postoperative infectious morbidity in low-risk elective cesarean deliveries: a prospective randomized clinical trial.

OBJECTIVE: To determine the effectiveness and cost of antibiotic chemoprophylaxis in reducing infectious morbidity in low-risk women undergoing elective cesarean delivery. METHODS: A prospective randomized clinical trial was performed at a single tertiary care center in Jinan, China between November 2012 and December 2013. Women were randomized to receive either antibiotic prophylaxis or no antibiotics prior to elective cesarean delivery at term. The infectious morbidity (fever, surgical site infection - SSI, endometritis and urinary tract infection), routine blood tests and hospital costs were measured. RESULTS: Total of 414 women were enrolled into the study; and 202 women received antibiotic chemoprophylaxis and 212 women received no antibiotics. Demographic and clinical characteristics were similar between the two groups. Total of one case in the treatment group and four case in the non-treatment group developed endometritis, giving the postoperative infection rate of 1.2%, which was not statistically significant between the two groups (χ(2) = 1.679, p = 0.195). The secondary outcomes were also not different between the two groups, except the costs of hospitalization, which was significantly higher in the treatment group (p < 0.001). CONCLUSIONS: In low-risk women undergoing elective cesarean delivery at term, prophylactic antibiotics did not reduce the risk of postoperative infection, but significantly increased the cost of hospitalization.

Decreased placental miR-126 expression and vascular endothelial growth factor levels in patients with pre-eclampsia.

OBJECTIVES: To detect microRNA (miR)-126 expression and its correlation with vascular endothelial growth factor (VEGF) levels in placentas from patients with pre-eclampsia compared with those from normotensive pregnancies. METHODS: miR-126 expression, and VEGF mRNA and protein levels, in placentas collected sequentially from patients with pre-eclampsia and normotensive pregnancies were measured using real-time reverse transcription-polymerase chain reaction and Western blot, respectively. The relationship between miR-126 and VEGF expression was analysed statistically. The regulatory effect of miR-126 on VEGF expression in human placental choriocarcinoma (BeWo) cells in vitro was also investigated. RESULTS: miR-126 expression was decreased, and VEGF mRNA and protein levels were significantly lower, in placentas from patients with pre-eclampsia (n = 115) compared with placentas from normotensive pregnancies (n = 115). A positive correlation was found between VEGF mRNA and miR-126 expression (r = 0.79). In addition, miR-126 overexpression significantly upregulated VEGF expression in BeWo cells, whereas miR-126 downregulation decreased VEGF expression. CONCLUSIONS: miR-126 was downregulated in placentas from patients with pre-eclampsia and this correlated with decreased VEGF expression. These findings indicate that miRNA-126 may be involved in pre-eclampsia pathogenesis and could be a potential biomarker for this disease.

Decreased expression of microRNA-206 in breast cancer and its association with disease characteristics and patient survival.

OBJECTIVES: MicroRNA-206 (miR-206) is downregulated in many human malignancies, which correlates with tumour progression. This study characterized the contribution of miR-206 to the initiation and progression of human breast cancer. METHODS: Consecutive primary breast cancer patients who received radical resection were enrolled. Breast cancer tissue samples were obtained during surgery. MiR-206 levels in matched pairs of cancer tissue and normal adjacent tissue (NAT) samples were examined using quantitative reverse transcription-polymerase chain reaction. The relationship between miR-206 levels and clinicopathological characteristics and overall survival was also investigated. RESULTS: In 128 patients with breast cancer, miR-206 was downregulated in 119 (93%) tumour tissue compared with their matched NAT samples. Decreased miR-206 was significantly associated with advanced clinical stage and lymph node metastasis. Univariate and multivariate Cox proportional hazard regression analysis revealed that a low miR-206 level was an unfavourable prognostic factor for overall survival, in patients with breast cancer. CONCLUSIONS: This study indicated that miR-206 may be a good candidate as a novel prognostic indicator in breast cancer patients.

Prognostic significance of serum microRNA-221 expression in human epithelial ovarian cancer.

OBJECTIVE: To evaluate the feasibility of using serum microRNA (miR)-221 as a noninvasive diagnostic and prognostic biomarker in epithelial ovarian cancer (EOC). METHODS: In this retrospective study, real-time reverse transcription-polymerase chain reaction was used to measure miR-221 expression in serum samples from patients with EOC and healthy age-matched controls. Correlations between serum miR-221 levels and clinicopathological factors and prognosis were explored. RESULTS: Serum miR-221 was upregulated in patients with EOC (n = 96) compared with healthy controls (n = 35). The level of serum miR-221 expression was significantly associated with International Federation of Gynecology and Obstetrics stage, and tumour grade. Furthermore, multivariate analysis of overall survival showed that high serum miR-221 expression was an independent unfavourable prognostic factor in EOC. CONCLUSIONS: These findings indicate that serum miR-221 may have a role as a novel diagnostic and prognostic marker, and may have potential as a therapeutic target in EOC.