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BackgroundThe results of randomized controlled studies on aspirin for the prevention of preeclampsia (PE) are conflicting, and some of the related meta-analyses also have limitations or flaws.Data sourcesA search was conducted on PubMed, Embase, and Cochrane Central Register of Controlled Trials databases, with no time or language restrictions.Study eligibility criteriaRandomized controlled studies comparing aspirin for the prevention of PE were conducted.MethodsSystematic reviews were performed according to the Cochrane Manual guidelines. A fixed-effects model or a random-effects model was chosen to calculate pooled relative risks with 95% confidence intervals based on the heterogeneity of the included studies. The study aimed to investigate the effect of aspirin on the development of PE in high-risk and general populations of women. Publication bias was assessed by funnel plots. All included studies were assessed for bias by the Cochrane Manual of Bias Assessment. Subgroup analyses were conducted on the aspirin dose, time of initial aspirin intervention, and the region in which the research was conducted, to explore the effective dose of aspirin and time of initial aspirin intervention and to try to find sources of heterogeneity and publication bias.ResultsA total of 39 articles were included, including 29 studies involving pregnant women at high risk for PE (20,133 patients) and 10 studies involving a general population of pregnant women (18,911 patients). Aspirin reduced the incidence of PE by 28% (RR 0.72, 95% CI 0.62–0.83) in women at high risk for PE. Aspirin reduced the incidence of PE by 30% in the general population (RR 0.70, 95% CI 0.52–0.95), but sensitivity analyses found that aspirin in the general population was not robust. A subgroup analysis showed that an aspirin dose of 75 mg/day (RR 0.50, 95% CI 0.32–0.78) had a better protective effect than other doses. Starting aspirin at 12–16 weeks (RR 0.62, 95% CI 0.53–0.74) of gestation or 17–28 weeks (RR 0.62, 95% CI 0.44–0.89) reduced the incidence of PE by 38% in women at high risk for PE, but the results were more reliable for use at 12–16 weeks. Heterogeneity and publication bias of the included studies may be mainly due to the studies completed in Asia.ConclusionAspirin is recommended to be started at 12–16 weeks of pregnancy in women at high risk for PE. The optimal dose of aspirin to use is 75 mg/d.Systematic review registration[www.ClinicalTrials.gov], identifier [CRD42022319984].

The mechanisms underlying late-onset preeclampsia (LOPE) remain unknown. Metabolic disturbances have been implicated as a primary factor in LOPE development. Lipids have been shown to have great clinical value in recent years. This study aimed to use lipidomics to provide evidence for the etiology and potential therapeutic approaches for LOPE. Twenty patients with LOPE and 20 healthy controls were enrolled in this study. Placental lipidomic data were acquired using liquid chromatographymass spectrometry (LC-MS/MS), and the data were analyzed by weighted gene correlation network analysis (WGCNA) and statistical methods. Of 1508 identified lipids, 226 were differentially expressed between the LOPE and control groups. In the LOPE group, the abundance of most unsaturated triglycerides (TG) increased, whereas that of other lipids, including phosphatidylcholine (PC), sphingomyelin, and phosphatidylserine (PS) increased. The WGCNA implied that the correlation network module of lipids was highly related to clinical traits. Pathway analysis revealed that these dysregulated lipids are closely related to glycerophospholipid metabolism. Lipidomics may help identify the pathogenesis underlying placental dysfunction in LOPE patients and provide potential therapeutic targets in the future.

Background To investigate the protective effects of the novel peptide antiendothelial dysfunction peptide in preeclampsia (AEDPPE) on tumor necrosis factor α (TNFα)- and lipopolysaccharide (LPS)-induced injury in the vascular endothelium in preeclampsia. Methods The effects of AEDPPE on TNFα-induced vascular endothelial injury were assessed by enzyme-linked immunosorbent assay, quantitative real-time PCR, mitochondrial membrane potential assay, Cell Counting Kit-8 assay, THP-1 monocyte–human umbilical vein endothelial cell (HUVEC) adhesion assay, endothelial tube-forming assay, transcriptomic analysis, preeclamptic symptom analysis, and histological analysis in preeclampsia-like rat models induced by LPS. Results AEDPPE alleviated the upregulation of antiangiogenic factors including soluble fms-like tyrosine kinase-1, endothelin-1, and tissue plasminogen activator and attenuated the reduction in mitochondrial potential induced by TNFα in HUVECs. In addition, AEDPPE treatment counteracted the decrease in tube formation and decreased the numbers of THP-1 monocytes attached to HUVECs caused by TNFα. Mechanistically, cytokine–cytokine receptor interactions enriched many genes and the TNF signaling pathway may be involved in this phenomenon. Moreover, cotreatment with LPS and AEDPPE significantly reversed the preeclampsia-like phenotype including hypertension and proteinuria and improved the functions of the kidney and placenta. Conclusions AEDPPE effectively ameliorated the vascular endothelial injury induced by TNFα and LPS in preeclampsia. We suggest that AEDPPE may be a novel therapeutic candidate for preeclampsia treatment. These findings demonstrate that AEDPPE may play an effective role in ameliorating vascular endothelial dysfunction and be a potential therapeutic agent for preeclampsia.

Aims Gestational diabetes mellitus (GDM)-induced macrosomia is predominantly characterized by fat accumulation, which is closely related to adipocyte differentiation. An unknown long noncoding RNA RP11-290L1.3, referred to as RP11, was identified to be dramatically upregulated in the umbilical cord blood of women with GDM-induced macrosomia in our previous study. We conducted this study to identify the function of RP11 in GDM-induced macrosomia. Methods The effects of RP11 gain- and loss-of-function on HPA-v (human preadipocytes-visceral) adipogenesis were determined with lentivirus mediated cell transduction. The mRNA and protein expression levels of adipogenesis makers were evaluated by qPCR/Western blot. Then, we performed the microarray and pathway analysis to explore the possible mechanisms by which RP11 regulates adipogenesis. Results Overexpression of RP11 significantly enhanced adipocyte differentiation and increased the mRNA and protein expression levels of adipogenesis makers, such as PPARγ, SREBP1c, and FASN by qPCR/Western blot. Knockdown of RP11 showed opposite effects. Microarray and pathway analysis showed, after RP11 knockdown, 1612 genes were upregulated, and 583 genes were down-regulated which were found to be mainly involved in metabolic pathways, insulin signaling pathway and MAPK signaling pathway. Conclusion In conclusion, the unknown lncRNA RP11 serves as a positive factor on preadipocyte differentiation which could shed light on fetal fat accumulation in GDM.

Preeclampsia is a multisystem pregnancy disorder that is characterized by different degrees of placental malperfusion, with release of antiangiogenic factors into the circulation, leading to maternal vascular endothelial injury and high blood pressure. As a major cause of maternal and perinatal mortality and morbidity worldwide, once preeclampsia has been diagnosed, there are no curative treatments except for delivery. Lipids serve as ubiquitous and multifunctional metabolites that are integral and essential to many diverse functions on both a cellular and organismal level. Lipid metabolic abnormalities have emerged as potential risk factors for the development and progression of preeclampsia. This review comprehensively examines decades of discovery to illuminate the roles of lipids and dysregulation in the levels of various lipid classes in preeclampsia. In addition, the roles of lipids are summarized to further understand the pathogenic mechanisms of preeclampsia. Overall, the review highlights the promising potential of pathophysiology and lipid-targeting therapeutic strategies in preeclampsia.

Background: Preterm birth is one of the main causes of perinatal morbidity and mortality and imposes a heavy burden on families and society. The aim of this study was to identify risk factors and analyze birth conditions and complications of newborns born at Methods: We performed a retrospective cohort study and collected data from 1598 pregnant women and 1660 premature newborns (excluding 229 premature babies who died due to severe illness and abandonment) admitted to the Obstetrics and Gynecology Hospital Affiliated with Nanjing Medical University in China from 2016 to 2020. We compared women’s and newborns’ characteristics by t-tests and Chi-square tests for continuous and categorical variables, respectively. Multivariable logistic regression was performed to estimate the effects of risk factors on EP and VP birth. Results: We identified 3 independent risk factors for EP birth: cervical incompetency (P P P P P P P P P P Conclusion: PPROM, is the most common risk factor for EP and VP birth, and cervical insufficiency, multiple pregnancy, and primipara are independent risk factors for EP birth. Therefore, during pregnancy, attention should be devoted to the risk factors for PPROM, and reproductive tract infection should be actively prevented to reduce the occurrence of PPROM. Identifying the risk factors for cervical insufficiency, actively intervening before pregnancy, and cervical cervix ligation may be considered to reduce the occurrence of EP labor. For iatrogenic preterm birth, the advantages and disadvantages should be carefully weighed, and the gestational period should be extended beyond 28 weeks to enhance the safety of the mother and child and to improve the outcomes of preterm birth.

Early-onset preeclampsia (EOPE) is a serious threat to maternal and foetal health. The present study aimed to identify potential biomarkers and targets for the treatment of EOPE. Expression profiles of placenta from patients with EOPE and healthy controls (GSE103542, GSE74341 and GSE44711) were downloaded from the Gene Expression Omnibus database. Integrated analysis revealed 246 genes and 28 microRNAs (miRNAs) that were differentially expressed between patients with EOPE and healthy controls. Differentially expressed genes (DEGs) were primarily enriched in ‘biological processes’, such as ‘cell adhesion’, ‘female pregnancy’, ‘extracellular matrix organization’ and ‘response to hypoxia’. Significant pathways associated with DEGs primarily included ‘focal adhesion’, ‘ECM-receptor interaction’, ‘PI3K-Akt signaling’ and ‘ovarian steroidogenesis’. A Protein-Protein Interaction network of DEGs was constructed using the Search Tool for the Retrieval of Interacting Genes/Proteins online database, and epidermal growth factor receptor, collagen α-1(I) chain, secreted phosphoprotein 1, leptin (LEP), collagen α-2(I) chain (COL1A2), plasminogen activator inhibitor 1 (SERPINE1), Thy-1 membrane glycoprotein, bone morphogenetic protein 4, vascular cell adhesion protein 1 and matrix metallopeptidase 1 were identified as hub genes. The alterations of hsa-miR-937, hsa-miR-148b*, hsa-miR-3907, hsa-miR-367*, COL1A2, LEP and SERPINE1 in placenta were validated using our local samples. Our research showed that the expression of hsa-miR-937, hsa-miR-1486*, hsa-miR-3907, hsa-miR-367* and hub genes in the placenta were closely associated with the pathophysiology of EOPE. hsa-miR-937, hsa-miR-1486*, hsa-miR-3907, hsa-miR-367* and hub genes could serve as biomarkers for diagnosis and as potential targets for the treatment of EOPE.

Background: Preeclampsia (PE) is a serious risk to the health of pregnant women and fetuses during pregnancy, and there is no effective treatment for this condition. Although many reports have confirmed the therapeutic effects of peptides in diseases, the role of peptides in PE remains poorly understood.Methods: A differentially expressed peptide in PE (AEDPPE) is derived from heat-shock protein beta-1 (HSPB1), amino acids 100 to 109 (DVNHFAPDEL), which we identified in a previous study. We synthesized AEDPPE and investigated its effect on HTR-8/SVneo cell function using a Cell Counting Kit-8, flow cytometric assay, and Transwell and wound-healing assays. Quantitative reverse transcription-PCR and ELISA were used to determine cytokine expression. Pull-down assay, mass spectrometry, Western blot analysis, and immunofluorescence were used to explore the potential targets and signaling pathways regulated by AEDPPE. Finally, we assessed the effect of AEDPPE in the lipopolysaccharide (LPS)-induced PE-like rat model.Results: AEDPPE significantly promoted the migration and invasion of HTR-8/SVneo cells, and it decreased the expression of interleukins 1 beta (IL-1β), interleukin 6 (IL-6), and interleukin 8 (IL-8). These functions performed by AEDPPE remained evident after injury to HTR-8/SVneo cells with tumor necrosis factor-alpha (TNF-α), and AEDPPE reversed the elevated sFlt-1/PlGF ratio induced by TNF-α. AEDPPE may exert these biological effects by binding to heat-shock protein 90β (HSP 90β) and, thus, affect the NF-κB signaling pathway. In an LPS-induced PE-like rat model, AEDPPE significantly improved PE symptoms and fetal rat outcomes.Conclusion: Our study showed that AEDPPE enhanced trophoblast migration and invasion and reduced inflammatory cytokine expression, and we hypothesized that these actions involved the NF-κB signaling pathway. The use of AEDPPE may thus develop into a novel modality in the treatment of PE.

Background: Histological chorioamnionitis (HCA) is a serious threat to fetal health during pregnancy, which is not easily detected due to the lack of clinical symptoms, and there is still a lack of effective predictors and diagnostic indicators. Heparin-binding protein (HBP), an antimicrobial protein secreted by neutrophils, is highly valuable in predicting a variety of infectious diseases and is expected to be an effective predictor of histological chorioamnionitis.Methods: A total of 100 full-term healthy pregnant women delivered by cesarean section (control group) and 51 randomly enrolled pregnant women (pathology group) were included in this study. Amniotic fluid was extracted at delivery for HBP concentration, and postpartum placental pathology was performed in the pathology group to clarify the diagnosis of HCA. The predictive value of HBP in amniotic fluid for HCA was determined by establishing the reference interval for HBP in normal population and the receiver operating characteristic (ROC) curve.Results: The 95% confidence interval (95% CI) for HBP concentration in the amniotic fluid of normal pregnant women was 0- 87.08 ng/ml, with a median of 6.41 ng/ml; HBP concentration in the amniotic fluid of pregnant women with HCA was significantly higher than that of controls (P < 0.001) and non-HCA pregnant women (P < 0.001). The ROC curve showed that when the cut-off value of HBP in amniotic fluid was 82.67 ng/ml, the corresponding sensitivity, specificity, positive predictive value, negative predictive value and area under the curve (AUC) were 84.20%, 96.90%, 94.12%, 91.18% and 0.86 (P < 0.001, 95% CI 0.715-1.000), respectively. Discussion: HBP in amniotic fluid is a potential, good predictor of HCA. We will further to explore its clinical application value.

Objective: This meta-analysis comprehensively evaluated the association between ABO blood group and the risk of preeclampsia (PE).Design: Systematic review and meta-analysis.Data sources: PubMed, Web of Science, and ScienceDirect databases from their inception to September 23, 2020.Methods: Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were obtained through random-effects and fixed-effects models according to heterogeneity. Meta-regression analysis was applied to explore the source of heterogeneity. We conducted a subgroup analysis by the publication year, study design, state, and Newcastle-Ottawa Scale (NOS) score. In addition, we calculated the rate of each ABO blood group in PE by total pooled effects.Results: A total of 12 articles with 714,153 patients were included in our analysis. Compared with people without PE (control group), the O blood group presented a lower risk of PE (OR 0.95, 95% CI 0.93–0.97). The AB (OR 1.46, 95% CI 1.12–1.91) blood group presented a higher risk. However, the total pooled OR and 95% CI for the A (OR 1.02, 95% CI 0.90–1.16) and B (OR 1.02, 95% CI 0.98–1.05) blood groups were not significant. The funnel plot and linear regression equation showed that there was no publication bias for the O, A, or B blood groups (all P > 0.05). However, the funnel plot and linear regression equation for the AB blood group were obviously asymmetric (P < 0.05), and the publication bias persisted even after the trim-and-fill method was applied (P < 0.05). Multivariable meta-regression analysis did not find a specific source of heterogeneity. The A blood group showed an association with early-onset PE (OR 0.53, 95% CI 0.33–0.83), and the other blood groups showed no significant differences. In PE, the rates of the O, A, B, and AB blood groups decreased gradually (0.39, 0.33, 0.19, 0.07).Conclusion: These findings suggest that pregnant women with AB blood group are more likely to develop PE, and more attention should be paid to AB blood group whose blood pressure is high but not sufficient to diagnose PE.Systematic Review Registration: Prospero CRD42021227930.

Fetal growth restriction (FGR) is one of the major complications of pregnancy, which can lead to serious short-term and long-term diseases. High-mobility group box 3 (HMGB3) has been found to contribute to the development of many cancers. However, the role of HMGB3 in the pathogenesis of FGR is blank. Here, we measured the expression level of HMGB3 in the placenta tissues of six normal pregnancies and five FGR patients by western blotting and quantitative real-time polymerase chain reaction (qRT-PCR). CCK8 assay, transwell assay and flow cytometry were used to detect the functional effects of overexpression and silencing of HMGB3 on the HTR8/SVneo trophoblast cell line. The results showed that the protein levels of HMGB3 were significantly decreased in FGR placentas compared to normal controls, while mRNA levels of HMGB3 were not significantly altered. Furthermore, when overexpressed of protein HMGB3 of the trophoblast cells, the proliferation and migration abilities were significantly promoted, and the apoptosis abilities of these cells were statistically inhibited. Cell functional experiments showed the opposite results when the expression of HMGB3 was silent. And the expression of cell function-related genes PCNA, Ki67, Tp53, Bax, MMP-2 and E-cadherin was observed to show corresponding changes by qRT-PCR. The results of mass spectrometry showed that HMGB3 may directly or indirectly interact with 71 proteins. In summary, our results indicated that HMGB3 might be of very great significance to the pathogenesis of FGR and might play the role by leading the dysfunction of placental villous trophoblast cells and through the interaction with some other proteins.

Recently, a large number of long noncoding RNAs (lncRNAs) have been reported in human diseases that are evolutionarily conserved and are likely to play a role in many biological events including pre-eclampsia. In our previous research, we selected thousands of lncRNAs for their relationship with early-onset pre-eclampsia. Among these lncRNAs, a lncRNA named uc.294 attracted our attention, was once reported to specifically be expressed at a high level in the early-onset of pre-eclampsia. This study aims to investigate the function of uc.294 in early-onset pre-eclampsia and the possible mechanism. The uc.294 expression level in early-onset pre-eclampsia or in normal placenta tissues was evaluated by quantitative real-time polymerase chain reaction. To detect the proliferation, invasion, and apoptosis capacity of the trophoblast cells, we performed the Cell Counting Kit-8 assay, transwell assay, and flow cytometry, respectively. Here we report, for the first time, that uc.294 inhibits proliferation, invasion, and promotes apoptosis of trophoblast cells HTR-8/SVneo by working in key aspects of biological behaviors. However, how uc.294 acts to regulate gene functions in early-onset pre-eclampsia needs further exploration.

Background: Increased fetal umbilical artery resistance can cause fetal hypoxia, redistribute fetal blood flow, dilate the middle cerebral artery, and reduce the cerebroplacental rate (CPR). CPRMethods: A total of 114 pregnant women with CPR < 1 who gave birth at Obstetrics and Gynecology Hospital Affiliated to Nanjing Medical University from January 2015 to December 2019 were analyzed retrospectively. The age, height, and weight of the aforementioned pregnant women, as well as the gestational age when CPRResults: ① the pregnant women in the continued pregnancy group waited for an average period of 3 weeks prior to the termination of pregnancy beyond 32 weeks. The average weight of the newborn was 1429 g, which was significantly lower than that of the average newborn at the corresponding gestational age. In the continued pregnancy group, intrauterine death was reported in 18 cases (40.9%) and intrauterine death of one fetus in a twin pregnancy was reported in 2 cases. Intrauterine death occurred 2–33 day after CPRConclusion: Intrauterine hypoxia is considered severe when CPR

This study sought to identify potential bioactive peptides from the placenta that are involved in preeclampsia (PE) to obtain information about the prediction, diagnosis and treatment of PE. The liquid chromatography/mass spectrometry was used to perform a comparative analysis of placental peptides in normal and PE pregnancies. Gene ontology (GO), pathway analysis and ingenuity pathway analysis (IPA) were used to evaluate the underlying biological function of the differential peptides based on their protein precursors. Transwell assays and qPCR were used to study the effect of the identified bioactive peptides on the function of HTR-8/SVneo cells. A total of 392 upregulated peptides and 420 downregulated peptides were identified (absolute fold change ≥ 2 and adjusted P value

Background and Objective: Fetal growth restriction (FGR) is a pathological condition in which the fetus cannot reach its expected growth potential. When it is diagnosed as a suspected FGR, it remains an unsolved problem whether to direct induction or continue expectant management. To effectively reduce the incidence of neonatal adverse outcomes, we aimed to evaluate whether either method was associated with a lower incidence of neonatal adverse outcomes.Methods: We searched the relevant literature through the PubMed, Web of Science, and Cochrane Library from inception to January 10, 2020. We defined induction as the experimental group and expectant management as the control group. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using random-effects models owing to heterogeneity. Furthermore, we conducted a sensitivity analysis to explore the robustness of the included literature. We used the Newcastle-Ottawa scale (NOS) to evaluate the quality of the available studies. We applied the funnel plot to describe the publication bias. Additionally, subgroup analysis based on the study method, sample size, area, NOS score, Apgar score 0.05).Conclusion: Regardless of induction or expectant management of a suspected FGR, the neonatal adverse outcomes showed no obvious differences. More studies should be conducted and confounding factors should be taken into consideration to elucidate the differential outcomes of the two approaches for suspected FGR.

To compare conservative management and cesarean hysterectomy in patients with placenta increta or percreta.In this multicenter retrospective study, we recorded data on 2219 patients with placenta increta or percreta from 20 tertiary care centers in China from 1 January 2011 to 31 December 2015. Propensity score analysis was used to control for baseline characteristics. We divided patients into conservative management (C) and hysterectomy (H) groups. The primary outcome was operative/postoperative maternal morbidity; secondary outcomes were maternal-neonatal outcomes.In total, 17.9% (398/2219) of patients had placenta increta and percreta; 82.1% (1821/2219) of the patients were in group C. After propensity score matching, 140 pairs of patients from the two groups underwent one-to-one matching. Group C showed less average blood loss within 24 h of surgery (1518 ± 1275 vs. 4309 ± 2550 ml in group H,Either conservative management or hysterectomy should be considered after thorough evaluation and detailed discussion of risks and benefits. A balance between bleeding control and fertility can be achieved.

Preeclampsia (PE) is a pregnancy-specific complication characterized by hypertension and proteinuria, and it is one of the primary global causes of maternal and perinatal mortality. Poor remodeling of placental arteries and endothelial dysfunction serve important roles in the pathogenesis of PE. Peptide derived from complement C4 A chain (PDCC4) was identified in our previous peptidome analysis of serum from patients with PE. The present study aimed to investigate the effect of PDCC4 on endothelial dysfunction in PE. TNF-α stimulated HUVECs were employed to mimic endothelial dysfunction in PE, and Cell Counting Kit 8 assay, wound healing assay, tube formation assay, RNA-sequencing (seq) and western blot analysis were performed using HUVECs. Moreover, an in vivo model of PE was established using pregnant rats treated with lipopolysaccharide (LPS), and blood pressure monitoring, histopathological examination, ELISA and immunohistochemistry were performed on rats. It was found that TNF-α impaired proliferation, migration and tube formation of HUVECs, but pretreatment with PDCC4 moderated these effects. RNA-seq and western blotting demonstrated that the PI3K/mTOR/HIF1α signaling pathway was activated by PDCC4, and a selective PI3K inhibitor reversed the protective function of PDCC4 on TNF-α stimulated HUVECs. Additionally, PDCC4 alleviated hypertension, histopathological changes of placenta and kidney and the expression levels of endothelial injury markers and inflammatory cytokines induced by LPS in rats. These results suggested that PDCC4 relieved endothelial dysfunction in PE via PI3K/mTOR/HIF1α signaling pathway and may be a potential therapy for PE.

IntroductionThe purpose of this study was to explore the effects and mechanisms of the long noncoding RNA (lncRNA) MIR210HG in preeclampsia development.Material and methodsWe collected placental tissue from 25 patients with preeclampsia (PE) and 25 healthy pregnant women and analysed the differences in lncRNAs between the placental tissues. HTR8/SVneo cells were transfected with the MIR210HG from the samples, and we observed the effects on the biological activities of HTR8/SVneo cells in conditions of hypoxia and reoxygenation (H/R) by transwell and wound-healing assays. To clarify the mechanisms of action, we used the Western blot assay to measure the expression levels of relative proteins (MUC1-C, SMAD2, Snail, E-cadherin and N-cadherin) and cellular immunofluorescence to measure Erk protein nuclear volume. We also evaluated the correlations between expression of MIR210HG and that of miR-1226-3p, miR-1226-3p and MUC1-C by luciferase reporter assay.ResultsChip hybridisation and scans revealed that MIR210HG expression was significantly more depressed in patients with PE than in healthy pregnant women (p < 0.001). With MIR210HG overexpression, HTR8/SVneo cell invasion and migration were significantly increased in an environment of H/R plus pcDNA3.1, microRNA negative control (miR-NC) or hsa-miR-1226-3p in comparison with an environment of H/R alone (p < 0.001, respectively). Levels of miR-1226-3p were significantly suppressed in lncRNA samples subjected to H/R (p < 0.001, respectively). In addition, miR-1226-3p depressed MIR210HG activity, thereby ameliorating PE.ConclusionsBy regulating miR-1226-3p/MUC1-C activity, MIR210HG can help ameliorate preeclampsia.

Preeclampsia (PE) is a complex disorder that is characterized by hypertension and proteinuria after the 20th week of pregnancy, and it causes most neonatal morbidity and perinatal mortality. Most studies suggest that placental dysfunction is the main cause of PE. However, genetic factors, immune factors, and systemic inflammation are also related to the pathophysiology of this syndrome. Thus far, the exact pathogenesis of PE is not yet fully understood, and intense research efforts are focused on PE to elucidate the pathophysiological mechanisms. MicroRNAs (miRNAs) refer to small single-stranded and noncoding molecules that can negatively regulate gene expression, and miRNA regulatory networks play an important role in diverse pathological processes. Many studies have confirmed deregulated miRNA in pregnant patients with PE, and the function and mechanism of these differentially expressed miRNA are gradually being revealed. In this review, we summarize the current research about miRNA involved in PE, including placenta-specific miRNA, their predictive value, and their function in the development of PE. This review will provide fundamental evidence of miRNA in PE, and further studies are necessary to explore the roles of miRNA in the early diagnosis and treatment of PE.

Objective The present study was designed to investigate whether the novel peptide cysteine-based peptide (Cys-peptide) had protective effects on preeclamptic animal and cell models. Methods We investigated effects of Cys-peptide on (1) preeclamptic symptoms (e.g. hypertension, proteinuria, fetal growth restriction (FGR)) in preeclampia-like rat models induced by lipopolysaccharides (LPS), (2) TNFα-induced cytotoxicity of human umbilical vascular endothelial cells (HUVECs) and HTR-8 cells (an immortalised human trophoblast cell line), (3) endothelial dysfunction and injured angiogenesis, (4) migration and invasion of trophoblast cells induced by TNFα. Results Cys-peptide ameliorated LPS-induced hypertension, proteinuria and FGR and other PE symptoms in preeclampia-like rat models. In addition, Cys-peptide attenuated TNFα-induced cytotoxicity by decreasing soluble fms-like tyrosine kinase-1 (sFlt-1), endothelin-1 (ET-1) and tissue plasminogen activator (tPA) mRNA expression in both cells. Furthermore, Cys-peptide restored endothelial dysfunction and rescued angiogenesis caused by TNFα in vitro. Importantly, Cys-peptide could reverse insufficient ability to invade and migrate of trophoblast cells. Conclusions These results suggest Cys-peptide can play beneficial roles in preeclampsia-like rat and cell models. Therefore, we propose that Cys-peptide is probably a novel therapeutic candidate for PE.

Objective We aimed to explore the expression level and biological function of lncRNA PVT1 in human trophoblast cells. Methods The expression levels of PVT1 in cancer cell lines, HTR8/SVneo cell, HUVEC cell, the maternal placenta of GDM patients, PE patients and normal pregnancy were detected by qRT-PCR. The cell culture, cell transfection, CCK-8 assay, flow cytometry, wound scratch assay and transwell were carried out to determine the effects of silencing and overexpression of PVT1 on the HTR8/SVneo trophoblast cell line. Nuclear and chromatin RNA fraction assay, RNA-sequencing, western blot and qRT-PCR were conducted to preliminarily explore possible mechanisms. Results The relative PVT1 expression level in HTR-8/Svneo cells was higher compared to other cancer cells and HUVEC, and was lower in the GDM and PE placentas than in the normal placentas. The results showed that PVT1 knockdown notably inhibited the proliferation, migration and invasiveness abilities of trophoblast cells, and significantly promoted the apoptosis. Furthermore, overexpression of PVT1 showed the opposite results. We identified 105 differentially expressed genes after PVT1 knockdown, 23 were up-regulated and 82 were down-regulated. GO enrichment analysis and pathway enrichment analysis showed that the DEGs were closely related to the functional changes of trophoblast cells. Because of the enrichment of 7 DEGs and less Q value, PI3K/AKT pathway was prominent and attracted our attention. More importantly, we confirmed that knockdown of PVT1 obviously decreased AKT phosphorylation and decreased the expression of DEGs (GDPD3, ITGAV and ITGB8) while overexpression of PVT1 promoted the AKT phosphorylation and increased the expression of DEGs (GDPD3, ITGAV and ITGB8). PVT1 was primarily distributed in the nuclear compartment and also distributed in the cytoplasmic of HTR-8/Svneo cells. Conclusions This study provided the evidence that PVT1 played a vital role in trophoblast cells, and it is important for maintaining the normal physiological function of trophoblast cells. The PVT1 expression was lower in the GDM and PE placentas than the normal placentas, which might disrupt the function of trophoblast cells through PI3K/AKT pathway.

Study question What is the role of insulin-like growth factor 2 (IGF2)-derived miR-483-3p in macrosomia? Summary answer IGF2-derived intronic miR-483-3p is overexpressed in macrosomia placentas, and miR-483-3p prompts HTR-8/SVneo extravillous trophoblast cell line proliferation through down-regulation of its target RB1 inducible coiled-coil 1 (RB1CC1). What is known already Macrosomia is a common pregnancy-associated disease and causes a number of adverse maternal and perinatal outcomes. The development of macrosomia is reportedly attributable to over proliferation of the placental cells. MicroRNAs (miRNAs) play an important role in the development of fetal and placenta by regulating their target genes. Here, we investigated the role of IGF2-derived intronic miR-483-3p in macrosomia. Study design, size, duration The expression of IGF2, miR-483-3p and its target gene in placental tissues from 30 pregnant women who had macrosomia was compared to those of 30 gestation-matched healthy pregnant controls. For in vitro studies, the human first trimester extravillous trophoblast cell line, HTR-8/SVneo cell was used. Participants/materials, setting, methods Placenta tissues were collected from pregnant women who had macrosomia without diabetes or other complications (n = 30) and healthy pregnant controls (n = 30). HTR-8/SVneo cells were transfected with specific miRNA mimics or inhibitors. MiRNA and mRNA isolated from placenta tissues or cells were measured by quantitative real-time PCR. Protein was measured by western blot. Cell proliferation was assayed using a colorimetric proliferation assay method. Cell cycle and apoptosis were analyzed by flow cytometry. The putative targets of miR-483-3p were predicted using the TargetScan, miRanda, miRDB and DIANA algorithms. Dual luciferase reporter assay was used to measure the relationship of miR-483-3p and RB1CC1. Main results and the role of chance IGF2-derived miR-483-3p was overexpressed in macrosomia placentas. miR-483-3p promoted proliferation in HTR-8/SVneo cells and had a positive relationship with its host gene IGF2. Subsequently, RB1CC1 was confirmed as a direct target of miR-483-3p, which may be an important mediator of cell growth regulation for miR-483-3p. Large scale data N/A. Limitations, reasons for caution The level of IGF2 and its intronic miR-483-3p in the serum of these participants was not investigated. Further studies are required to understand the mechanisms underlying the cause of the increase of IGF2 and miR-483-3p in macrosomia. Wider implications of the findings These findings give a new insight into the role of intronic miRNA and its host gene in the development of macrosomia. Furthermore, it may offer a new target for prognostic and therapeutic intervention for macrosomia. Study funding/competing interest(s) This work was supported by awards from National Natural Science Foundation of China (Nos. 81401213, 81673217, 81703260), Jiangsu Provincial Medical Youth Talent (No. QNRC2016110), Jiangsu Overseas Visiting Scholar Program for University Prominent Young & Middle-aged Teachers and Presidents, the Priority Academic Program for the Development of Jiangsu Higher Education Institutions (Public Health and Preventive Medicine), the Education Department of Jiangsu Province (No. 16KJB330010), the Science and Technology Department of Jiangsu Province (No. BK20160227), the China Postdoctoral Science Foundation funded project (No. 2016M601892). The authors declare no competing financial interests.

The objective of this study is to identify the maternal and neonatal outcomes in women with placenta increta or placenta percreta in China.We retrospectively analyzed 2219 cases from 20 tertiary care centers in China between January 2011 and December 2015. All cases were diagnosed of placenta increta or placenta percreta, based on either intraoperative findings or histopathological findings.The incidence of placenta increta and placenta percreta progressively increased from 0.18% in 2011 to 0.78% in 2015. Compared with the placenta increta, placenta percreta was strongly related to serious adverse outcomes: postpartum hemorrhage (65.9% versus 38.6%, p = .003), blood transfusion (86.2% versus 46.5%, p .001), hysterectomy (43.3% versus 11.2%, p .001), preterm birth (65.7% versus 49.9%, p .001), and the need for neonatal intensive care unit (NICU) admission (54.5% versus 36.7%, p .001).The incidence of placenta increta and placenta percreta is likely to increase in China. The depth of placenta implantation is associated with the severity of outcomes. Placenta percreta tends to have worse maternal and neonatal outcomes.

There is an urgent need in China to better predict vaginal birth after cesarean (VBAC) to face the challenge of the second child policy. We aimed to validate a widely used VBAC prediction model (Grobman’s model) and a modified version of this model in a Chinese population. In this retrospective cohort study, 444 women with one cesarean delivery and at least one subsequent attempt for a trial of labor in Nanjing, China were included. The considered potential VBAC predictors included Grobman’s background variables and five new variables. Overall, a total of 370 women had VBAC, with a success rate of 83.3%. The new background variables “maternal height” and “estimated fetal weight” were considered as two additional predictors for VBAC. The AUC of Grobman’s model was 0.831 (95%CI = 0.775–0.886) while the AUC of our modified model with two new variables added was 0.857 (sensitivity = 72.2%, specificity = 83.8%). However, the difference between the AUC of the two models was not significant (Z = −1.69, P = 0.091). We confirmed that Grobman’s model was accepted in the Chinese population. A modified model that is supplemented with maternal height and estimated fetal weight needs to be further studied in the Chinese population.

Background/Aims: Early screening and diagnosis is important for minimizing gestational adverse outcomes. Routine screening of gestational diabetes mellitus (GDM) at 24–28 weeks with 75 g oral glucose challenge test (OGCT) leaves limited time for intervention and prevention. This study aims to analyze maternal serum peptides in the early second-trimester for prediction of gestational diabetes mellitus (GDM). Methods: Serum samples were collected from 16-18-week pregnant women that visited Nanjing Maternity and Child Health Care Hospital from April to August 2015. According to gestational outcome with or without GDM in late pregnancy, 200 of serum samples from GDM mothers and controls were randomly divided into two subgroups. Peptidomic identification of serum peptides was performed by combining ultrafiltration and liquid chromatography-tandem mass spectrometry (LC-MS/MS) to investigate the differentially-expressed peptides between two groups. Results: A total of 297 identified peptides, originating from 228 proteins, were significantly differentially expressed in the GDM group compared with control. These precursor proteins may play critical roles in cell death of cortical neurons, elongation of cellular protrusions, and stabilization of microtubules. Major networks identified included those involving lipid metabolism, molecular transport and small molecule biochemistry. Conclusion: We provide for the first time a validated peptidome profile of early second-trimester serum in normal and GDM mothers, and we investigated the potential serum biomarkers for GDM. We concluded that 297 peptides could serve as potential biomarkers for GDM.

Preeclampsia is a kind of disease that severely harms the health of pregnant women and infants. To better understand the molecular mechanisms involved in preeclampsia, we used liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS) to construct a comparative peptidomic profiling of human serum between normal and preeclamptic pregnancies. A total of 201 peptides were confidently identified, with 21 up-regulated and three down-regulated. Further analysis indicated that these differentially expressed peptides correlate with enzyme regulator activity, biological regulation, and coagulation cascades occurring during pathological changes of preeclampsia. The identification of key peptides in serum may serve not only as a basis for better understanding and further exploring the etiology and pathogenesis of PE, but also as potential biomarkers and in providing targets for future therapy in PE, especially in early onset severe PE (sPE). J. Cell. Biochem. 118: 4341-4348, 2017. © 2017 Wiley Periodicals, Inc.

Preeclampsia (PE), a life-threatening, complicated pregnancy-associated disease, has recently become a research focus in obstetrics. However, the peptidome of the amniotic fluid in PE patients has rarely been investigated. The present study used peptidomic profiling to perform a comparative analysis of human amniotic fluid between normal and PE pregnancies. Centrifugal ultrafiltration and liquid chromatography-tandem mass spectrometry (LC-MS/MS) was combined with isotopomeric dimethyl labels to gain a deeper understanding of the role of proteins and the peptidome in the onset of PE. Following ultrafiltration and LC-MS/MS, 352 peptides were identified. Of these, 23 peptides were observed to be significantly differentially expressed (6 downregulated and 17 upregulated; P

// Xuejing Song 1, 2, * , Can Rui 1, * , Li Meng 3 , Rui Zhang 1 , Rong Shen 3 , Hongjuan Ding 1 , Jun Li 4 , Jingyun Li 4 , Wei Long 1 1 Department of Obstetrics, Obstetrics and Gynecology Hospital Affiliated to Nanjing Medical University, Nanjing, China 2 Fourth Clinical Medicine College, Nanjing Medical University, Nanjing, China 3 Nanjing Maternity and Child Health Medical Institute, Obstetrics and Gynecology Hospital Affiliated to Nanjing Medical University, Nanjing, China 4 State key Laboratory of Reproductive Medicine, Department of Plastic and Cosmetic Surgery, Maternal and Child Health Medical Institute, Obstetrics and Gynecology Hospital Affiliated to Nanjing Medical University, Nanjing, China * These authors contributed equally to this work Correspondence to: Wei Long, email: wlong@njmu.edu.cn Jingyun Li, email: dagumahao@163.com Keywords: lncRNA, RPAIN, early onset preeclampsia, complement protein C1q Received: October 09, 2016 Accepted: December 01, 2016 Published: December 09, 2016 ABSTRACT Long non-coding RNAs (lncRNAs) are key regulatory molecules that are involved in a variety of biological processes and human diseases. Their impact on early onset preeclampsia remains unclear. In this study, we tested the expression of RPAIN (transcript variant 12 of RPA interacting protein, a non-coding RNA, NR_027683.1) in placenta tissues derived from 25 pregnant women with PE and 15 healthy pregnant women using quantitative real-time PCR. The effect of RPAIN on trophoblast proliferation, invasion, and apoptosis and the underlying mechanisms were examined in trophoblast cell lines (HTR-8/SVneo). The results showed that RPAIN expression levels were significantly increased in early onset preeclamptic placentas compared to normal controls. The proliferation and invasive abilities of the trophoblast cells were significantly inhibited, and the apoptosis abilities of the trophoblast cells were significantly promoted when RPAIN was overexpressed. In addition, the overexpression of RPAIN inhibited the expression of complement protein C1q. Furthermore, C1q overexpression rescued the decreased cell invasion and enhanced cell apoptosis in RPAIN-overexpressing trophoblast cells. Our results suggest that increased RPAIN levels may contribute to the development of preeclampsia through regulating trophoblast invasion and apoptosis via C1q. Therefore, we proposed RPAIN as a novel lncRNA molecule, which might contribute to the development of PE (preeclampsia) and might compose a potential diagnostic and therapeutic target for this disease.

Early-onset preeclampsia (EOPE), which is the most severe form of the syndrome, confers a high risk of neonatal morbidity and perinatal death. We aim to study the roles of long non-coding RNAs (lncRNAs) in the pathogenesis of early-onset preeclampsia (EOPE). Therefore, we examined the expression profiles of lncRNAs between early-onset preeclampsia and preterm controls using microarray analysis. Quantitative real-time PCR (qRT-PCR) was performed to verify the selected differentially expressed lncRNAs. In total, we identified 15,646 upregulated and 13,178 downregulated lncRNAs in the placenta of EOPE patients compared to the preterm controls. Gene ontology and pathway analysis revealed that compared to the preterm controls, many of the processes over-represented in the EOPE patients were related to cell migration and cell motility. A selection of the differentially expressed lncRNA transcripts was confirmed using qRT-PCR, particularly RP11-465L10.10, which is associated with the MMP9 gene. These data may offer a background/reference resource for future functional studies of lncRNAs related to EOPE.

Background As a serious pregnancy-specific condition, preeclampsia (PE) is a serious pregnancy-specific condition characterized by insufficient trophoblastic invasion and shallow placental implantation. Long noncoding RNA uc.187, which is transcribed from an ultra-conserved region is highly expressed in the placental tissue of patients with PE, is associated with abnormal trophoblast invasion. Therefore, we aimed to further characterize the relationship between uc.187 and PE through in vitro experimental studies to find new targets to treat PE. Methods In this study, we constructed PE rat models induced by lipopolysaccharide, experimented with overexpressing uc.187 and performed experiments using HTR-8/SVneo cells. Results We found uc.187 was elevated in the placenta of PE rats. By injecting pregnant rats with a lentivirus containing the lncRNA uc.187, we successfully triggered maternal hypertension along with a series of symptoms similar to PE in humans. In vitro experiments demonstrated that high levels of uc.187 lead to decreased trophoblast invasion. In addition, our results revealed that uc.187 had high expression in PE and fetal growth restricted cells, but low expression in placental site trophoblastic tumors compared with the control groups. Results of western blot and cell immunofluorescence indicated that the aberrant biological behavior of HTR-8/SVneo cells were related to the distribution of β-catenin in the cytoplasm and nucleus. Conclusions Taken together, our study revealed that uc.187 was negatively correlated to trophoblastic cell invasion, and overexpression of uc.187 could induce PE-like symptoms in a pregnant rat model by affecting the distribution of β-catenin in the cytoplasm and nucleus.

Purpose : Offspring obesity is one of long-term complications of Gestational diabetes mellitus (GDM). The aim of this study is to identify proteins differentially expressed in the umbilical vein blood plasma, which could become markers for early diagnosis of childhood obesity. Experimental design : Umbilical vein plasma samples were collected from 30 control and 30 GDM patients in 2007–8 whose offspring were suffering from obesity at 6–7 years old. Multiplexed isobaric tandem mass tag (TMT) labeling combined with liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used to identify differentially expressed proteins. Ingenuity Pathway Analysis (IPA) was performed to identify canonical pathways, biological functions and networks of interacting proteins. Western blotting was used to verify the expression of three selected proteins. Results : A total of 318 proteins were identified, of which 12 proteins were up-regulated in GDM group while 24 down-regulated. Lipid metabolism was the top category identified by IPA. Three randomly chosen proteins were validated by Western blotting, which were consistent with LC-MS. Conclusion : There are significant differences of protein profile in the umbilical vein blood plasma between normal and GDM patients with obese offspring. The results indicate that a variety of proteins and biological mechanisms may contribute to childhood obesity. This article is protected by copyright. All rights reserved

Background/Aims: Forkhead Box Protein C2 (FOXC2) has been reported to be overexpressed in a variety of human cancers. However, it is unclear whether FOXC2 regulates epithelial-mesenchymal transition (EMT) in CDDP-resistant ovarian cancer cells. The aim of this study is to investigate the effects of FOXC2 on EMT and invasive characteristics of CDDP-resistant ovarian cancer cells and the underlying molecular mechanism. Methods: MTT, Western blot, scratch wound healing, matrigel transwell invasion, attachment and detachment assays were performed to detect half maximal inhibitory concentration (IC50) of CDDP, expression of EMT-related proteins and invasive characteristics in CDDP-resistant ovarian cancer cell line (SKOV3/CDDP) and its parental cell line (SKOV3). Small hairpin RNA (shRNA) was used to knockdown FOXC2 and analyze the effect of FOXC2 knockdown on EMT and invasive characteristics of SKOV3/CDDP cells. Also, the effect of FOXC2 upregulation on EMT and invasive characteristics of SKOV3 cells was analyzed. Furthermore, the molecular mechanism underlying FOXC2-regulating EMT in ovarian cancer cells was determined. Results: Compared with parental SKOV3 cell line, SKOV3/CDDP showed higher IC50 of CDDP (43.26μM) (P

Background/Aims: FOXC2 has been reported to play a role in tumor progression, but the correlations of FOXC2 with the cisplatin (CDDP) resistance of ovarian cancer cells are still unclear. The purpose of the present study is to investigate the roles of FOXC2 in the CDDP resistance of ovarian cancer cells and its possible mechanisms. Methods: Quantitative real-time PCR (qRT-PCR) was performed to detect the expression of FOXC2 mRNA in CDDP-resistant or sensitive ovarian cancer tissues and cell lines (SKOV3/CDDP and SKOV3). Gain- and loss-of-function assays were performed to analyze the effects of FOXC2 knockdown or overexpression on the in vitro and in vivo sensitivity of ovarian cancer cells to CDDP and its possible molecular mechanisms. Results: The relative expression level of FOXC2 mRNA in CDDP-resistant ovarian cancer tissues was higher than that in CDDP-sensitive tissues. Also, the expression of FOXC2 mRNA and protein in CDDP-resistant ovarian cancer cell line (SKOV3/CDDP) cell line was higher than that in its parental cell line (SOKV3). Small hairpin RNA (shRNA)-mediated FOXC2 knockdown significantly increased the in vitro and in vive sensitivity of SKOV3/CDDP cells to CDDP by enhancing apoptosis, while upregulation of FOXC2 significantly decreased the in vitro and in vivo sensitivity of SKOV3 cells to CDDP by reducing apoptosis. Furthermore, FOXC2 activates the Akt and MAPK signaling pathways, and then induced the decreased expression of Bcl-2 protein and the increased expression of Bax and cleaved caspase-3 proteins. Conclusions: FOXC2 mediates the CDDP resistance of ovarian cancer cells by activation of the Akt and MAPK signaling pathways, and may be a potential novel therapeutic target for overcoming CDDP resistance in human ovarian cancer.

Preterm birth is the most important cause of neonatal mortality and morbidity worldwide. The aim of this study was to identify factors associated with preterm birth and examine the heterogeneity and interactions between these factors. We collected data from 1607 pregnant women treated at Nanjing Maternity and Child Health Care Hospital in China. The women included in the study were divided into the full-term group and the preterm-birth group. We used t-tests to compare the characteristics of age and body mass index, Chi-square tests for the other variables, and we used the Wald test to calculate the interaction between factors that may affect preterm birth. The heterogeneity test was used to study the relationship between subgroups. Multivariable logistic regression analysis was used to explore the associations between risk factors and preterm birth, which included all risk factors. All tests were 2-tailed, P < 0.05 was considered significant, and 95% confidence intervals were estimated for percentages. There was no statistical difference in basic characteristics such as age between the full-term and preterm groups. We found 6 independent risk factors that were associated with preterm birth (P

Objective We aimed to explore the expression level and biological function of miR-145–5p in preeclampsia (PE). Methods The differentially expressed miRNA/mRNA between normal placentas and PE placentas were screened using the GSE84260 and GSE73374 datasets from the Gene Expression Omnibus Database. The expression of miR-145–5p in PE placentas was detected by qRT-PCR. The CCK-8 assay, wound healing and transwell were carried out to determine the cell growth, migration and invasion when miR-145–5p was overexpressed or inhibited. The real-time quantitative PCR (qRT-PCR), Western Blot and dual-luciferase reporter assays were conducted to preliminarily explore possible mechanisms. Results A total of 33 miRNAs were found significantly differentially expressed in PE patients, 19 were significantly upregulated and 14 were significantly downregulated. The relative miR-145–5p expression was lower in PE placentas than normal placentas. The viability and invasion were suppressed when miR-145–5p was inhibited in trophoblasts cells, while miR-145–5p overexpression promoted the effectiveness. In addition, mRNA and protein expression of FLT1 in HTR-8/SVneo cell was also downregulated with miR-145–5p overexpression, suggesting that FLT1 is the target gene of miR-145–5p. Consistent with miR-145–5p overexpression, the mRNA and protein expression of FLT1 also were upregulated with miR-145–5p interference. Furthermore, the expression of miR-145–5p was regulated by the Hypoxic conditions. Conclusions In conclusion, the results showed miR-145–5p may participate in PE development by affecting the proliferation and invasion of trophoblast cells. This is a new perspective to understand the etiology and pathogenesis of PE, which may provide a new breakthrough for the early prediction and diagnosis of PE.

To identify the 24-h proteinuria value with quantitative analysis and how it correlates with the severity of preeclampsia and subsequent adverse maternal outcomes in the Chinese population.Eleven hospitals in 10 provinces across China were chosen, in which 1,738 pregnant women complicated by hypertensive disorders of pregnancy (HDP) with the records of 24 h proteinuria were enrolled. They were allocated into four groups: patients with maximal quantified proteinuria 0.3 g/24 h (Group 1, n = 328); patients with maximal quantified proteinuria ≥ 0.3 g/24 h and 2.0 g/24 h (Group 2, n = 638); patients with maximal quantified proteinuria ≥ 2.0 g/24 h and 5.0 g/24 h (Group 3, n = 353); and patients with maximal quantified proteinuria ≥ 5.0 g/24 h (Group 4, n = 419). Logistic regression analysis were conducted to assess the differences in maternal outcomes between different subgroups of 24-h proteinuria and to identify independent risk factors of adverse maternal outcomes in preeclampsia. The multivariable risk prediction model of adverse maternal outcome for HDP was established with receiver operating characteristic curve (ROC) curve and its predicted value was assessed.Thrombocytopenia and cerebral or visual symptoms were more frequent in Groups 3 and 4 than Groups 1 and 2 but no differences were found between Groups 3 and 4 or Groups 1 and 2. Maternal complications were more frequent in Groups 3 and 4 than in Groups 1 and 2 [Group 3 vs. Group 1, odds ratios (ORs) = 3.359 (1.067-10.571); Group 4 vs. Group 1, OR = 3.628 (1.189-11.086); Group 3 vs. Group 2, OR = 2.845 (1.155-7.003); Group 4 vs. Group 2, OR = 3.082 (1.304-7.288)]. However, no significant difference was found between Groups 4 and 3 or between Groups 2 and 1. The proteinuria ≥ 2 g/24 h had an area under the receiver operating characteristic curve (AUC ROC) of 0.668 (95% confidence interval (CI) 0.632-0.705) for predicting adverse maternal outcome. After adjusting for the effects of other symptoms, signs, and laboratory tests, it was the independent risk factor and predictor factor of the adverse maternal outcome (OR = 3.683, 95% CI 2.439-5.562, P0.001). The final risk prediction model had an AUC ROC of 0.800 (95% CI 0.769-0.830, P0.001).The proteinuria ≥ 2 g/24 h is an independent predictive factor of adverse maternal outcomes in preeclampsia, but its individual predictive value is limited. The risk prediction model is effective in assessing the risk of adverse maternal outcomes in patients with HDP.

Gestational diabetes mellitus (GDM) is associated with an increased risk of serious complications for mother and child during pregnancy. The main option for diagnosis of GDM is 75 g oral glucose tolerance test (OGTT) at 24–28 gestation weeks, when harms to both mother and child have already potentially occurred. The aim of this study was to investigate new biomarkers for earlier detection and assessment of GDM at early second trimester (16–18 gestation weeks). We systematically used multiplexed isobaric tandem mass tag labeling combined with liquid chromatography mass spectrometry (LC-MS/MS) to screen differentially expressed proteins in plasma collected at 16–18 gestational weeks between pregnant women with and without GDM outcome. A total of 828 proteins were identified, of which 36 proteins implicated in immune response, inflammation, transport, platelet aggregation, catalyze and defense response were identified as differentially regulated proteins in GDM. To assess the validity of the results, four selected proteins including C-reactive protein, sex hormone-binding globulin, Ficolin 3 and pregnancy-specific beta-1-glycoprotein 4 were selected for subsequent Western blot analysis. This is the first comprehensive study that integrates multiple state-of-the-art proteomic technologies to discover the earlier potential plasma biomarkers for GDM.

Background/Aims: Exosomes are extracellular vesicles that are involved in several biological processes. The roles of proteins from human umbilical cord blood exosomes in the pathogenesis of preeclampsia remains poorly understood. Methods: In this study, we used high-resolution LC-MS/MS technologies to construct a comparative proteomic profiling of human umbilical cord blood exosomes between normal and preeclamptic pregnancies. Results: A total of 221 proteins were detected in human umbilical cord blood exosomes, with 14 upregulated and 15 downregulated proteins were definitively identified between preeclamptic and control pregnancies. Further bioinformatics analysis (Gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis) indicated that these differentially expressed proteins correlate with enzyme regulator activity, binding, extracellular region, cell part, biological regulation, cellular process and complement and coagulation cascades occurring during pathological changes of preeclampsia. Conclusion: Our results show significantly altered expression profiles of proteins in human umbilical cord blood exosomes between normal and preeclampsia pregnancies. These proteins may be involved in the etiology of preeclampsia.

Background: Fetal macrosomia and its associated complications are the most frequent and serious morbidities for infants associated with gestational diabetes mellitus (GDM). The associations between long non-coding RNAs (lncRNAs) and macrosomia have been rarely reported; therefore, we investigated the umbilical cord lncRNA profiles in GDM macrosomia. Method: Thirty pairs of GDM macrosomia and normal controls were divided into three subgroups randomly, and the umbilical cord vein blood from each subgroup was mixed, and hybridized to a microarray containing probes representing 33,000 lncRNA genes. Quantitative real-time polymerase chain reaction (qPCR) was used to validate selected differentially expressed lncRNAs. The gene ontology (GO), pathway and network analysis were performed. Result: The microarray identified 8814 lncRNAs that were expressed in the umbilical cord blood, of which 349 were significantly upregulated and 892 were significantly downregulated (fold-change ≥ 2.0) in GDM group. The highest enriched GOs targeted by downregulated transcripts were biological regulation. Pathway analysis indicated that nine pathways corresponded to downregulated transcripts. Conclusions: Certain lncRNAs that were aberrantly expressed in the umbilical cord blood from GDM macrosomia might play a partial or key role in GDM macrosomia development. This study provided potential targets for treatment of macrosomia and novel insights into macrosomia biology.

The purpose of this study was to investigate the association between male infertility and single-nucleotide polymorphisms (SNPs) of DNA methyltransferases (DNMT) genes (DNMT3B: rs2424909, DNMT1: rs4804490, DNMT3A: rs1550117 and DNMT3L: rs7354779). Eight hundred and thirty three idiopathic infertile males and four hundred and ten fertile controls from the hospitals affiliated to Nanjing Medical University between 2010 and 2012 were recruited in the study. We demonstrated a significantly increased risk of idiopathic infertility with abnormal semen parameters in association with the heterozygous genotype of variant rs4804490. Moreover, the AA genotype of variant rs4804490 was associated with significantly decreased risk for male infertility with abnormal semen parameters. A decreased risk of idiopathic infertility with abnormal semen parameters was associated with the homozygous genotype of variant rs2424909. These results suggested that variants in different DNMT genes have different relationships with idiopathic male infertility, and Chinese men carrying these variants have an increased or decreased risk of abnormal semen parameters.

Omental adipose tissue plays a central role in insulin resistance in gestational diabetes mellitus (GDM), and the molecular mechanisms leading to GDM remains vague. Evidence demonstrates that maternal hormones, such as estradiol, contribute to insulin resistance in GDM. In this study we determined the differential expression patterns of microRNAs (miRNAs) in omental adipose tissues from GDM patients and pregnant women with normal glucose tolerance using AFFX miRNA expression chips. MiR-222, 1 of 17 identified differentially expressed miRNAs, was found to be significantly up-regulated in GDM by quantitative real-time PCR (P < .01), and its expression was closely related with serum estradiol level (P < .05). Furthermore, miR-222 expression was significantly increased in 3T3-L1 adipocytes with a high concentration of 17β-estradiol stimulation (P < .01), whereas the expressions of estrogen receptor (ER)-α protein and insulin-sensitive membrane transporter glucose transporter 4 (GLUT4) protein (P < .01) were markedly reduced. In addition, ERα was shown to be a direct target of miR-222 in 3T3-L1 adipocytes by using the luciferase assay. Finally, antisense oligonucleotides of miR-222 transfection was used to silence miR-222 in 3T3-L1 adipocytes. The results showed that the expressions of ERα and GLUT4, the insulin-stimulated translocation of GLUT4 from the cytoplasm to the cell membrane and glucose uptake in mature adipocytes were dramatically increased (P < .01). In conclusion, miR-222 is a potential regulator of ERα expression in estrogen-induced insulin resistance in GDM and might be a candidate biomarker and therapeutic target for GDM.

Two novel Nickel(II) complexes ( NiL 2 1 and NiL 2 2 ) with remarkable two-photon absorption (TPA) and optical power limiting (OPL) properties were synthesized and fully characterized. Single crystals were obtained and solved by X-ray diffraction analysis. Their photophysical properties had been further investigated both experimentally and theoretically. The third-order nonlinear optical (NLO) properties (TPA and OPL) were investigated by open/closed aperture Z-scan measurements using femtosecond pulse laser in the range from 680 to 1080 nm. The results revealed that the two Nickel(II) complexes exhibited strong two-photon absorption and superior optical power limiting properties, which are much better than that of the free ligands.

Background: Fetal growth restriction (FGR) is the main cause of intrauterine fetal death and the second leading cause of death in the neonatal period. A large body of evidence suggests that FGR may be associated with the placenta, although its etiology and pathogenesis remain to be fully elucidated. Methods and Results: To better understand the molecular mechanisms underlying the pathological development of the placenta in FGR, we used tandem mass tags (TMTs) to construct a large-scale comparative proteomic profile of human placentas from normal and FGR pregnancies. A total of 1,198 kinds of proteins were identified in the control and FGR placentas, of which 95 were differentially expressed between two groups. Ingenuity Pathway Analysis (IPA) was used to organize these differentially expressed proteins into networks of interacting proteins and to identify the modules of functionally related proteins. Western blotting was used to verify the expression patterns of several randomly selected proteins. Conclusion: The placentas of women with FGR displayed significant proteome differences compared with normal pregnancy. The results indicate that a variety of mechanisms and proteins may contribute to the development of FGR. Further studies and validations are required to elucidate the exact roles of these proteins in FGR pathogenesis.

The crystal structures and two-photon absorbing properties of trans-/cis-oligo(phenylene vinylene) derivatives were reported for the first time. Both experimental and theoretical results revealed that the two-photon absorption cross sections of them largely depend on their conformations.

Two novel terpyridine-based chromophores with D-A (D = donor, A = acceptor) structural model containing modified triphenylamine moiety (L 1 and L 2 ) have been conveniently synthesized via formylation and reduction in satisfactory yields, and fully characterized. The single crystals of them were obtained and determined by X-ray diffraction analysis. The relationships between structure and photophysical properties of the two chromophores were investigated both experimentally and theoretically. The measured maximum TPA cross-sections per molecular weight (δ max/MW) of the chromophores are 0.63 GM/(g mol) (L 1 ) and 0.72 GM/(g mol) (L 2 ), respectively, in DMF as a high polar solvent. The results indicate that the value of δ max/MW could be well tuned by the intramolecular charge transfer (ICT), which could be realized by introducing additional electron-donor/acceptor groups.

A novel chromophore (Z)-ethyl-3-(4-((4-([2,2′:6′,2″-terpyridin]-4′-yl)phenyl) (phenyl) amino)phenyl)-2-cyanoacrylate( 3 ), constructed with triphenylamine moiety as the electron donor (D), 2, 2: 6, 2-terpyridine moiety as an electron acceptor (A), and ethyl cyanocaetate group as an auxiliary electron acceptor (A′), has been designed and synthesized. The crystal structures of 3 and its mediator 2 (4″-(4′-(4-(Diphenylamino) phenyl) aldehyde)-2,2′:6′,2″-Terpyridine), have been determined by single crystal X-ray diffraction analysis. The linear and nonlinear spectra of these chromophores were investigated on the basis of experimental and calculation methods. The two-photon absorption (TPA) cross-sections of 1 – 3 were determined by a femtosecond open-aperture Z-scan technique. The maximum value of the TPA cross-section ( σ ) for 3 is 7938.3 GM in DMF solution. However, much weaker two-photon absorption responses were observed at the same condition for chromophore 1 and 2 , respectively. The results of the work indicate that, the photophysical properties of the D–A configuration group are influenced largely by the auxiliary moiety (A′) attached.

To evaluate the maternal serum 25(OH)D concentrations and its association with gestational diabetes and other pregnancy outcomes.zMethods:In our nested case-control study, 4718 pregnancy women were included, who were attending second- and third-trimester screening in Nanjing, China. Serum 25(OH)D concentrations were tested by enzyme-linked immunoassay, and the pregnancy and birth outcomes were obtained via electronic medical record collection and information extraction. The associations of 25(OH)D concentrations with gestational diabetes and other pregnancy outcomes were assessed by logistic regression analysis. And receiver-operator characteristic curve analysis was also conducted.For the total population, the median (IQR) concentrations of 25(OH)D was 43.7 (35.5-57.9) nmol lLow 25(OH)D concentrations (50.0 nmol l