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The aim of the study was to compare the magnetic resonance imaging (MRI) findings of intracranial haemorrhage (ICH) in the middle- and late trimesters and to explore the relationship between the MRI features of foetal ICH and postnatal outcomes. This was a retrospective study which recruited foetal ICH diagnosed by MRI in one tertiary centre from 2015 to 2019. The prenatal and postnatal medical records were reviewed. Of 39 ICH cases, 82.1% (32) had germinal matrix intraventricular haemorrhage (GM-IVH), and 18.9% (7) were diagnosed with non-GM-IVH. The cerebellum, corpus callosum and subdural space were affected in 5, 1 and 1 non-GM-IVH cases, respectively. MRI confirmed possible ICH on sonogram in 10 cases (35.7%) and the remaining 19 added ICH diagnoses that were not obtained on initial ultrasound imaging. Pregnancy outcome data were available in 82.1% of (32) cases, of which 21 were terminated pregnancies, 1 was foetal demise and 10 were delivered. One neonate died after birth and one infant suffered from hearing loss. The remaining eight patients had favourable outcome. In our study, evaluation of the relationship between MRI findings and outcomes remains challenging, depending on the timing of examination and the hematoma itself. MRI was an adjunct to US in diagnosing ICH in utero which helps to assess postnatal development.

Purpose: To clarify the prenatal magnetic resonance (MR) imaging characteristics of foetal cerebellar dysplasia/hypoplasia and developmental malformations and evaluate their diagnostic value. Methods: We retrospectively reviewed MR images of foetuses with suspected intracranial anomalies on screening ultrasound (US) on picture archiving communication system (PACS) servers within a five-year period in our institution. The main abnormal findings and coexistent anomalies were recorded by two experienced radiologists with census reading. The MRI and US results were paired and compared in each case. Results: We recruited 121 cases (average gestational week, 24.5 ± 4.7 weeks) with prenatal MR imaging, including sixty-two cases with simple cerebellar dysplasia or hypoplasia, thirty-one cases with other anomalies and twenty-eight cases with normal MR imaging findings. Cerebellar anomalies included intracranial haemorrhage, arachnoid cysts, Blake’s pouch cysts, Dandy-Walker malformation, cerebellar tonsil hernia and vermis absence. Coexistent cerebral malformations included hydrocephalus, cerebral haemorrhage, holoprosencephaly, brainstem/gyri malformation, ventriculomegaly and agenesis of the corpus callosum. Other detected systemic malformations included tethered cord syndromes (9 cases), club foot (1 case), cardiac malformation (1 case) and lip-palate cleft (1 case). Among 49 cases with both prenatal MR and US, MR imaging confirmed the diagnosis and/or provided more abnormal findings than US in 12 cases. Two dead babies after birth were recorded in cerebellar malformation group. Conclusion: Prenatal MR imaging could better show cerebellar anomalies and coexistent systemic malformations. As a complementary tool of US, MR imaging could help prenatal counselling and treatment selection at term.

OBJECTIVE To investigate the relationship between mild congenital pulmonary airway malformation (CPAM) and its long-term prognosis in childhood and to explore whether surgery is necessary. METHODS We conducted a retrospective cohort of fetuses with mild CPAM diagnosed prenatally with available long-term outcomes in childhood from 2004 to 2016. The patients were divided into two groups according to the fetal CPAM-to-volume ratio (CVR) of less than 1.0 and 1.0-1.6. The primary outcome was a postnatal composite outcome including CPAM-associated respiratory symptoms and surgical resection of the lesion. The secondary outcomes included neonatal asphyxia, perinatal morbidity and mortality. RESULTS Forty-two fetuses were identified as having CVR

ImportanceAlthough certain air pollutants have been associated with adverse obstetric outcomes, evidence regarding the association of ozone (O3) exposure with the risk of hypertensive disorders in pregnancy (HDP) is limited and inconsistent.ObjectivesTo evaluate the association between gestational O3 exposure and HDP (ie, gestational hypertension and preeclampsia) risk, and to explore the window of susceptibility for O3 exposure during pregnancy.Design, Setting, and ParticipantsThis cohort study recruited pregnant patients from the Obstetrics and Gynecology Hospital of Fudan University in Shanghai, China, from March 2017 to December 2018. Participants were older than 18 years, had no infectious diseases or chronic noncommunicable diseases before pregnancy, were Shanghai residents with intent to participate in the study, and had plans to give birth in Shanghai. Gestational hypertension and preeclampsia were diagnosed according to the diagnostic criteria of the Chinese Society of Obstetrics and Gynecology during the study period. Data on residential addresses, demographic characteristics, and household living environments were collected from participants through a questionnaire survey. Data were analyzed from December 10, 2021, to May 10, 2022.ExposuresA high temporospatial resolution model was applied to predict individual levels of daily O3 exposure during pregnancy.Main Outcomes and MeasuresThe outcomes were gestational hypertension and preeclampsia, and data on these diagnoses were extracted from the hospital’s information system. A logistic regression model was used to estimate the associations between O3 exposure and risk of gestational hypertension or preeclampsia. Exposure-response associations were confirmed by restricted cubic spline functions. Distributed lag models were used to identify the O3 exposure window of susceptibility.ResultsAmong the 7841 participants (all females; mean [SD] age, 30.4 [3.8] years), 255 (3.2%) had gestational hypertension and 406 (5.2%) had preeclampsia. Pregnant individuals with HDP had considerably higher prepregnancy body mass indexes and lower educational levels. The mean (SD) O3 exposure levels were 97.66 (25.71) μg/m3 in the first trimester and 106.13 (22.13) μg/m3 in the second trimester. Each 10-μg/m3 increment of O3 exposure during the first trimester was associated with higher gestational hypertension risk (relative risk, 1.28; 95% CI, 1.04-1.57). However, gestational O3 exposure was not associated with the risk of preeclampsia. The restricted cubic spline function analysis revealed an exposure-response association between O3 exposure and risk of gestational hypertension.Conclusions and RelevanceResults of this study showed an association between increased gestational hypertension risk and O3 exposure during the first trimester. Furthermore, gestational weeks 1 to 9 were identified as the window of susceptibility for O3 exposure and elevated gestational hypertension risk. Sustainable O3 control is needed to reduce the disease burden of gestational hypertension.

Preeclampsia is regarded as an evolution-related disease that has only been observed in humans and our closest relatives, and the important factor contributing to its pathogenesis is endothelial dysregulation secondary to a stressed placenta. Hypoxia-inducible factor 1 subunit alpha (HIF1α), a highly conserved molecule in virtually all mammals, is regarded as a crucial regulator of the hypoxia adaptation and evolution. Persistent high expression of HIF1α in the placenta is one of the pathogenic mechanisms of preeclampsia. Therefore, human-specific molecules should link increased HIF1α to preeclampsia. We reported that urothelial cancer associated 1 (UCA1) is a potential mediator because it is a human-specific long noncoding RNA (lncRNA) that is upregulated in placental tissues and maternal serum from women with preeclampsia and is regulated by HIF1α. The cellular HIF1α-UCA1 pathway promoted the adaptation of trophoblasts to hypoxia by inducing vascular endothelial growth factor (VEGF) secretion and changes in the levels of key enzymes in glycolysis. On the other hand, circulating exosomal UCA1 secreted from stressed trophoblasts induced vascular endothelial dysfunction, especially excess ROS production, as measured by exosome extraction and a coculture system. At the molecular level, UCA1 physically bound to ubiquitin-specific peptidase 14 (USP14), which is a deubiquitinating enzyme, and UCA1 functioned as a scaffold to recruit USP14 to profilin 1 (PFN1), an actin-binding protein contributing to endothelial abnormalities and vascular diseases. This ternary complex inhibited the ubiquitination-dependent degradation of PFN1 and prolonged its half-life, further activating the RhoA/Rho-kinase (ROCK) pathway to induce ROS production in endothelial cells. Taken together, these observations suggest a role for the evolution-related UCA1 in the HIF1α-induced adaptive pathogenic mechanism of preeclampsia, promoting the survival of hypoxic trophoblasts and injuring maternal endothelial cells.

Catechyl lignin (C-lignin) is a linear homopolymer of caffeyl alcohol found in the seed coats of diverse plant species. Its properties make it a natural source of carbon fibers and high-value chemicals, but the mechanism of in planta polymerization of caffeyl alcohol remains unclear. In the ornamental plant Cleome hassleriana, lignin biosynthesis in the seed coat switches from guaiacyl lignin to C-lignin at ∼12 d after pollination. Here we found that the transcript profile of the laccase gene ChLAC8 parallels the accumulation of C-lignin during seed coat development. Recombinant ChLAC8 oxidizes caffeyl and sinapyl alcohols, generating their corresponding dimers or trimers in vitro, but cannot oxidize coniferyl alcohol. We propose a basis for this substrate preference based on molecular modeling/docking experiments. Suppression of ChLAC8 expression led to significantly reduced C-lignin content in the seed coats of transgenic Cleome plants. Feeding of 13C-caffeyl alcohol to the Arabidopsis (Arabidopsis thaliana) caffeic acido-methyltransferase mutant resulted in no incorporation of 13C into C-lignin, but expressing ChLAC8 in this genetic background led to appearance of C-lignin with >40% label incorporation. These results indicate that ChLAC8 is required for C-lignin polymerization and determines lignin composition when caffeyl alcohol is available.

Associations between individual exposure to ozone (OWe aimed to explore the associations of gestational OA total of 7834 pregnant women were included. Individual ONearly 13.29 % of participants developed GDM. After controlling for covariates, we observed increased GDM risks per IQR increment of OIn summary, we found that gestational O

Context Universal early-pregnancy screening for overt diabetes reveals intermediate hyperglycemia (fasting plasma glucose [FPG] [5.1-6.9 mM]). Objective We evaluated the association between early-pregnancy intermediate hyperglycemia and adverse pregnancy outcomes among women without gestational diabetes. Methods This retrospective cohort study was conducted at the Obstetrics and Gynecology Hospital, Shanghai, China, from 2013 to 2017. All singleton pregnancies with FPG less than or equal to 6.9 mM in early pregnancy and receiving a 75-g oral glucose tolerance test (OGTT) were included. Women with prepregnancy diabetes were excluded. Individuals with normal OGTT were analyzed. Pregnancy outcomes for FPG less than 5.1 mM and intermediate hyperglycemia were evaluated. The primary outcomes were large for gestational age (LGA) and primary cesarean delivery. Multivariate logistic regressions were conducted. Statistical significance was defined as P less than .05. Results In total, 24 479 deliveries were included, of which 23 450 (95.8%) had normal OGTTs later in pregnancy (NGT). There were 807 (3.4%) women who had an FPG of 5.1 to 6.9 mM in early pregnancy. Compared to the NGT group with an FPG of less than 5.1 mM in early pregnancy (N = 20692), the intermediate hyperglycemia NGT group (N = 693) had a higher age and body mass index (BMI), and significantly higher rates of LGA, primary cesarean delivery, preterm birth, preeclampsia, and neonatal distress. The rates of primary cesarean delivery (adjusted odds ratio [AOR] 1.24; 95% CI, 1.05-1.45), preterm birth (AOR 1.75; 95% CI, 1.29-2.36), and neonatal distress (AOR 3.29; 95% CI, 1.57-6.89) remained statistically significantly higher after adjustments for maternal age, BMI, and other potential confounding factors. Conclusion Women with intermediate hyperglycemia in early pregnancy are at an increased risk for adverse maternal-fetal outcomes, even with normal future OGTTs.

Prenatal fine particulate matter (PMWe included 267 mother-child pairs in this analysis. Prenatal PMThe PMPrenatal exposure to PM

Maternal emotional symptoms during pregnancy increase the risk of neurodevelopmental problems in offspring, and microbiota have been shown to be a potential mechanism underlying the link. However, the associations among maternal prenatal emotional symptoms, the meconium microbiota, and offspring neurodevelopment have yet to be fully elucidated. The aim of this prospective cohort study was to assess the relationship between maternal prenatal emotional symptoms and neurodevelopment of the child at 24 months of age, and to investigate the potential role of the neonatal meconium microbiota in the relationship.A total of 410 mother-child pairs (152 women in the Symptoms group vs. 258 women in the No-symptoms group) were recruited from the ongoing Shanghai Maternal-Child Pairs Cohort. This study included a subgroup of women who were assessed for maternal anxiety and depressive symptoms at 32-36 weeks of gestation. Neonatal meconium samples were collected after birth for 16 S sequencing. Children's neurodevelopment was measured using the Ages and Stages Questionnaire, Third Edition (ASQ-3) and Strengths and Difficulties Questionnaire (SDQ) at 24 months postnatally (n = 287).Compared with the No-symptoms group, children in the Symptoms group had a higher degree of hyperactivity and total difficulties at 24 months of age. Increases in alpha diversity, distinct overall composition, enriched relative abundance of Proteobacteria, and different predicted microbial functions were observed in the meconium of neonates exposed to maternal prenatal emotional symptoms. The neonatal gut microbiota alpha diversity and relative abundance of genera from the Proteobacteria phylum and Lactobacillus were negatively correlated with children's degree of prosocial behavior, tendency toward hyperactivity, and poor fine motor development. In addition, mediating effects of neonatal meconium microbial richness and the relative abundance of Lactobacillus were observed between maternal emotional symptoms and children's prosocial behavior.Maternal prenatal emotional symptoms are associated with alterations in the offspring meconium microbiota and children's neurodevelopment at 24 months of age, and the microbial richness indices and Lactobacillus may play a mediating role. Future research is needed to identify and understand the biological pathways and metabolisms linking the relationships among maternal emotional symptoms, meconium microbiota, and neurodevelopment of children.

Gestational diabetes mellitus (GDM) has become a new global epidemic with a rapidly increasing prevalence. Previous studies have suggested that air pollution is associated with GDM risk, but the results are inconsistent, and mechanistic studies are limited. Based on a hospital-based cohort, a total of 6374 participants were included in this study. Individual daily PM

Increasing evidence supports that maternal exposure to vanadium (V) is associated with adverse birth outcomes including preterm birth and low birth weight. However, the effect of V exposure on intrauterine fetal growth and the underlying biological mechanism are still unclear. The present study includes 227 mother-infant pairs from the Shanghai Maternal-Child Pairs Cohort to assess the gender-specific effect of intrauterine V exposure on fetal growth and related cytokines. Maternal blood samples were collected to measure V concentration and biomarkers of growth. We used multiple linear regression to evaluate the gender-specific effect of prenatal V exposure on birth parameter and growth-related cytokines. Mixed-effect models were applied to assess the non-linear association between gestational V exposure and intrauterine fetal growth. Covariates adjusted in the regression models as potential confounders including maternal age, pre-pregnancy body mass index, gestational weeks, parity, socio-demographic status, etc. Results showed that prenatal V exposure was negatively associated with birth weight (β = −64.73) in female newborns and body length (β = −0.10) in male. During the fetal period, maternal V exposure was associated with decreased biparietal diameter (β = −0.91), head circumference (β = −2.96), femur length (β = −0.72) and humerus length (β = −0.64) in male. Trimester-specific analyses showed that serum V concentration in the second trimester was associated with significant reductions in intrauterine growth parameters. Besides, prenatal V exposure could down-regulate the expression of growth hormone (GH) in both maternal blood (β = −0.23) and umbilical cord blood (β = −1.66) in male fetuses, and the expression of brain derived neurotrophic factor (BDNF) in cord blood in females (β = −0.52). Our results suggest that prenatal V exposure has a gender-specific effect on fetal growth and the second trimester may be a sensitive window. The disruption of grow-related cytokines may potentially be the biological mechanism of these effects.

C-lignin is a linear polymer of caffeyl alcohol, found in the seed coats of several exotic plant species, with promising properties for generation of carbon fibers and high value chemicals. In the ornamental plant Cleome hassleriana, guaiacyl (G) lignin is deposited in the seed coat for the first 6-12 days after pollination, after which G-lignin deposition ceases and C-lignin accumulates, providing an excellent model system to study C-lignin biosynthesis. We performed RNA sequencing of seed coats harvested at 2-day intervals throughout development. Bioinformatic analysis identified a complete set of lignin biosynthesis genes for Cleome. Transcript analysis coupled with kinetic analysis of recombinant enzymes in Escherichia coli revealed that the switch to C-lignin formation was accompanied by down-regulation of transcripts encoding functional caffeoyl CoA- and caffeic acid 3-O-methyltransferases (CCoAOMT and COMT) and a form of cinnamyl alcohol dehydrogenase (ChCAD4) with preference for coniferaldehyde as substrate, and up-regulation of a form of CAD (ChCAD5) with preference for caffealdehyde. Based on these analyses, blockage of lignin monomer methylation by down-regulation of both O-methyltransferases (OMTs) and methionine synthase (for provision of C1 units) appears to be the major factor in diversion of flux to C-lignin in the Cleome seed coat, although the change in CAD specificity also contributes based on the reduction of C-lignin levels in transgenic Cleome with down-regulation of ChCAD5. Structure modeling and mutational analysis identified amino acid residues important for the preference of ChCAD5 for caffealdehyde.

Accumulating evidence revealed that the leading risk factor of endometrial cancer is exposure to endogenous and exogenous estrogens, while the exact mechanism underlying estrogen contribution to endometrial cancer progression has not been elucidated clearly. Interleukin (IL)-6 has been verified to be critical for tumor progression in several human cancers. In this study, we provided evidence that 17β-estradiol (E2) could significantly promote endometrial cancer cells viability, migration and invasion through activation of IL-6 pathway, which involved in its downstream pathway and target genes (p-Stat3, Bcl-2, Mcl-1, cyclin D1 and MMP2). Meanwhile, utilization of IL-6-neutralizing antibody could partially attenuate the increased cancer growth and invasion abilities in Ishikawa and RL95-2 endometrial cancer cell lines and an orthotopic endometrial cancer model. We established a causative link between estrogen and IL-6 signaling activation in the development of endometrial cancer. The molecular mechanism defined in this study provided the evidence that E2 promotes endometrial carcinoma progression via activating the IL-6 pathway, indicating that interruption of IL-6 might be an essential therapeutic strategy in estrogen-dependent endometrial cancer.

Additional file 1. The modified thioacidolysis protocol for rapid biomass lignin and tricin analysis.

BackgroundBiomass composition varies from plant to plant and greatly affects biomass utilization. Lignin is a heterogeneous phenolic polymer derived mainly fromp-coumaryl, coniferyl, and sinapyl alcohols and makes up to 10–25% of lignocellulosic biomass. Recently, tricin, anO-methylated flavone, was identified as a lignin monomer in many grass species. Tricin may function as a nucleation site for lignification and is advocated as a novel target for lignin engineering to reduce lignin content and improve biomass digestibility in grasses. Thioacidolysis is an analytical method that can be adapted to analyze both lignin monomeric composition and tricin content in the lignin polymer. However, the original thioacidolysis procedure is complex, laborious, and time consuming, making it difficult to be adopted for large-scale screening in biomass research. In this study, a modified, rapid higher throughput thioacidolysis method was developed.ResultsIn combination with gas chromatography–mass spectrometry (GC–MS) and liquid chromatography–mass spectrometry (LC–MS), the modified thioacidolysis method can be used to simultaneously characterize the lignin composition and tricin content using 2–5 mg of dry samples. The modified method eliminates the solvent extraction and drastically improves the throughput; 80 samples can be processed in one day per person. Our results indicate that there is no significant difference in the determination of lignin S/G ratio and tricin content between the original and modified methods.ConclusionsA modified thioacidolysis protocol was established. The results demonstrate that the modified method can be used for rapid, high-throughput, and reliable lignin composition and tricin content analyses for screening transgenic plants for cell wall modifications or in large-scale genome-wide association studies (GWAS).

This study was designed to examine the impact of prenatal fine particulate matter (PM2.5) exposure on fetal growth and the underlying placental epigenetic mechanism in a cohort of Chinese women. Within the prospective Shanghai Mother-Child Pairs cohort (Shanghai MCPC), 329 women carrying singleton pregnancy with a due date in 2018 were recruited between 2017 and 2018. Maternal PM2.5 exposure levels were estimated using gestational exposure prediction model combining satellite-driven ambient concentrations and personal air sampling. Fetal growth characteristics were evaluated by prenatal ultrasound examinations and anthropometric measurements at birth. In a discovery phase, whole-genome DNA methylation analysis was performed using the Infinium 850 K array. In a validation phase, placental DNA methylation was measured using bisulfite pyrosequencing for five candidate genes that showed the most significant alterations and function relevance in our methylation array screen, including BID (BH3 interacting domain death agonist), FOXN3 (Forkhead box N3), FOXP1 (Forkhead box P1), IGF2 (Insulin-like growth factor 2) and HSD11B2 (Hydroxysteroid 11-beta dehydrogenase 2). Multivariate linear regression models were applied to examine the associations among PM2.5 exposure, fetal growth characteristics and DNA methylation on placental candidate genes. Sobel tests were used to evaluate the mediating role of DNA methylation in multivariable models. After excluding women who withdrew or failed to provide placenta, a total of 287 pregnant women with an average age of 30 entered the final analysis. Increased PM2.5 exposure was significantly associated with reduced biparietal diameter (BPD) (β: −0.136 mm, 95% CI: −0.228 to −0.043), head circumference (HC) (β: −0.462 mm, 95% CI: −0.782 to −0.142), femur length (FL) (β: −0.113 mm, 95% CI: −0.185 to −0.041) and abdominal circumference (AC) (β: −0.371 mm, 95% CI: −0.672 to −0.071) in the second trimester and birth length (β: −0.013 cm, 95% CI: −0.025 to −0.001). Prenatal PM2.5 exposure could lead to aberrant changes in DNA methylation profile of placenta genome, which were mainly enriched in reproductive development, energy metabolism and immune response. DNA methylation of IGF2 and BID showed significant associations with PM2.5 exposures during all exposure windows. In addition, BID methylation was negatively correlated with HC (β: −1.396 mm, 95% CI: −2.582 to −0.209) and BPD (β: −0.330 mm, 95% CI: −0.635 to −0.026) in the second trimester. Further mediation analysis indicated that BID methylation mediated about 30% of the effects of PM2.5 exposure on HC. These findings collectively suggested that prenatal PM2.5 exposure may cause adverse effects on fetal growth by modifying placental DNA methylation.

Introduction Circular RNAs (circRNAs) are non-coding RNAs that are implicated in preeclampsia (PE) pathogenesis; however, their expression and functions in PE remain unclear. In this study, we aimed to investigate the expression of circRNAs in PE and construct a competing endogenous RNA (ceRNA) network, and analyze the associated pathways in PE pathogenesis. Methods We performed circRNA sequencing to identify the differential expression profile of circRNAs in PE as compared to normal pregnancy. The circRNA candidates were validated using quantitative reverse transcription polymerase chain reaction (qRT-PCR). Subsequently, we used datasets from the GEO database to generate the interaction network between circRNAs, microRNAs (miRNAs), and mRNAs. GO and KEGG enrichment analyses were performed to understand the functional significance of the differentially expressed circRNAs in PE. Results We identified 361 differentially expressed circRNAs (252 upregulated and 109 downregulated) in preeclamptic placentas. Within the selected 31 circRNAs, 6 of them were verified by qRT-PCR. GO and KEGG analyses revealed the potential pathways affected by these circRNAs, e.g., T cell receptor signaling and MAP kinase pathways. A total of 134 miRNAs and 199 mRNAs were revealed to be differentially expressed in PE by analyzing datasets from the GEO database. The circRNA-miRNA-mRNA network comprised 206 circRNAs, 50 miRNAs, and 38 mRNAs. KEGG analysis of the 38 mRNAs included pathways involved in AMPK and PI3K-Akt signaling. Discussion Our results reported the differential expression profile of circRNAs and the circRNA-miRNA-mRNA network in PE, which provides potential therapeutic targets for this disease.

Objective: Ultrasound determination of chorionicity is poor in early pregnancy in China. In an effort to increase the accuracy rate of prompt chorionicity determination, clinical training was provided to primary care physicians. This study assesses the effects of implementing clinical guidelines on chorionicity determination. Methods: A multi‑centered cohort study was conducted between January 2014 and June 2017 in 12 hospitals without fetal medicine centers. In 2014, the obstetricians and ultrasound physicians were trained in clinical practice and ultrasound examination relating to chorionicity determination. Linear and binary regression analyses were conducted to identify the effects of introducing the new protocols, including the diagnosis rate of chorionicty and perinatal outcomes, taking the data from 2014 as a baseline. Pregnancy outcomes were additionally adjusted for maternal age. Results: During the period of this study, 3,599 twin pregnancies from 12 centers were enrolled, and a total of 2,998 twin pregnancies were extracted. The rate of overall chorionicity determination, including antenatal and postpartum diagnosis, increased successively from 49.5% in 2014 to 93.5% in 2017 (P < 0.0001). The rate of ultrasonic chorionicity diagnosis before 14 weeks increased from 25.2% in 2014 to 65.0% in 2017 (P < 0.0001). These changes were associated with decreasing incidence of preterm birth, a lower risk of stillbirth, whether for one (P = 0.0456 in 2016) or two fetuses (P = 0.0470 in 2016; P = 0.0042 in 2017) and a decreased rate of admission to neonatal intensive care unit (43.0% in 2014, 37.4% in 2017; P = 0.0032). Conclusions: The implementation of a clinical practice guideline improved both overall and early chorionicity determinations. Regular training workshops of antenatal care are recommended to further promote capability in clinical diagnosis and treatment.

Background. Gestational diabetes mellitus (GDM) contributes to adverse pregnancy and birth outcomes. In recent decades, extensive research has been devoted to the early prediction of GDM by various methods. Machine learning methods are flexible prediction algorithms with potential advantages over conventional regression. Objective. The purpose of this study was to use machine learning methods to predict GDM and compare their performance with that of logistic regressions. Methods. We performed a retrospective, observational study including women who attended their routine first hospital visits during early pregnancy and had Down’s syndrome screening at 16-20 gestational weeks in a tertiary maternity hospital in China from 2013.1.1 to 2017.12.31. A total of 22,242 singleton pregnancies were included, and 3182 (14.31%) women developed GDM. Candidate predictors included maternal demographic characteristics and medical history (maternal factors) and laboratory values at early pregnancy. The models were derived from the first 70% of the data and then validated with the next 30%. Variables were trained in different machine learning models and traditional logistic regression models. Eight common machine learning methods (GDBT, AdaBoost, LGB, Logistic, Vote, XGB, Decision Tree, and Random Forest) and two common regressions (stepwise logistic regression and logistic regression with RCS) were implemented to predict the occurrence of GDM. Models were compared on discrimination and calibration metrics. Results. In the validation dataset, the machine learning and logistic regression models performed moderately (AUC 0.59-0.74). Overall, the GBDT model performed best (AUC 0.74, 95% CI 0.71-0.76) among the machine learning methods, with negligible differences between them. Fasting blood glucose, HbA1c, triglycerides, and BMI strongly contributed to GDM. A cutoff point for the predictive value at 0.3 in the GBDT model had a negative predictive value of 74.1% (95% CI 69.5%-78.2%) and a sensitivity of 90% (95% CI 88.0%-91.7%), and the cutoff point at 0.7 had a positive predictive value of 93.2% (95% CI 88.2%-96.1%) and a specificity of 99% (95% CI 98.2%-99.4%). Conclusion. In this study, we found that several machine learning methods did not outperform logistic regression in predicting GDM. We developed a model with cutoff points for risk stratification of GDM.

Background: Preeclampsia is a devastating hypertensive disorder of pregnancy with unknown mechanism. Recent studies have considered abnormal autophagy as a new cellular mechanism for this disorder, while little is known about how autophagy is involved and what initial factors are related. Here, we report a previously unrecognized preeclampsia-associated autophagic regulator, PKCβ, that is involved in placental angiogenesis. Methods: PKCβ levels were evaluated by quantitative real-time PCR (qRT-PCR), Western blotting, immunofluorescence, and analysis of public data. The autophagy-regulating role of PKCβ inhibition in the pathogenesis of preeclampsia was studied in a mouse model, and in human umbilical vein endothelial cells (HUVECs) and human choriocarcinoma cells (JEG-3). Findings: PKCβ was found to be significantly downregulated in human preeclamptic placentas. In a mouse model, the selective inhibition of PKCβ by Ruboxistaurin (RBX) was sufficient to induce preeclampsia-like symptoms, accompanied by excessive autophagic flux and a disruption in the balance of pro- and anti-angiogenic factors in mouse placentas. By contrast, autophagic inhibition by 3-methyladenine (3-MA) partially normalized hypertension, proteinuria and placental angiogenic imbalance in PKCβ inhibited mice, suggesting that autophagy acts as a mediator for the pathogenic effect of PKCβ inhibition. Our in vitro experiments demonstrated that the inhibition of PKCβ activated autophagy, thus blocking VEGFA-induced HUVEC tube formation and resulting in the significant upregulation of sFLT1 and downregulation of VEGFA in JEG-3 cells. Interpretation: These data support a novel model in which autophagic activation due to PKCβ inhibition leads to the impairment of angiogenesis and eventually results in preeclampsia. The restoration of PKCβ may provide a new paradigm for the treatment of preeclampsia. Funding Statement: This work was supported by the Shanghai Key Program of Clinical Science and Technology Innovation (17411950500, 17411950501 and 18511105602), National Natural Science Foundation of China (81741047, 81971411 and 81801468), Shanghai Medical Center of Key Programs for Female Reproductive Diseases (2017ZZ01016), National Key Basic Research Plan of China (973 Plan) (2015CB943300), and The Major Program of the National 13th Five‐ Year Plan of China (2016YFC1000400). Declaration of Interests: The authors stated that they have nothing to disclose. Ethics Approval Statement: All participants provided written informed consent for the use of their placenta tissues. The study was approved by the Ethics Committee of Obstetrics and Gynecology Hospital of Fudan University. All animal protocols were performed in accordance with the guidelines issued by Fudan University for the care and use of laboratory animals.

Background/objectives Gestational weight gain (GWG) recommendations for pregnant women with gestational diabetes mellitus (GDM) in China are lacking. The present study aims to examine whether specific GWG targets for women with GDM can improve pregnancy outcomes in comparison with GWG according to the Institute of Medicine (IOM) targets. Subjects/methods Pregnant women diagnosed with GDM were selected from a retrospective cohort study of 8299 singleton pregnant women aged 18–45 years in 2012 (n = 1820). GWG ranges were calculated using a receiver operating characteristic (ROC) curve analysis (ROC targets) and the interquartile range (IR) method (the range from the 25th to 75th percentiles of the GWG among GDM women without adverse pregnancy outcomes, IR targets). Results The incidences of small for gestational age (SGA) births and pregnancy hypertension among women with GDM who gained weight within the ROC targets were lower than the incidences in women who gained weight within the IOM targets (SGA, 7.5% vs. 8.6%; pregnancy hypertension, 12.6% vs. 14.1%; both P

AIM Previous studies have shown serum human epididymis protein 4 (HE4) and cancer antigen 125 (CA125) levels could serve as predictive markers in the diagnosis of ovarian cancer. However, HE4 levels have been less well studied during pregnancy, especially in threatened abortion, while CA125 levels were fluctuated. Our study aimed to assess the stability of HE4 and CA125 levels through trimesters and in cases of threatened abortion. METHODS Forty-six nonpregnant women (control), 167 healthy pregnant women and 46 pregnant threatened abortion (TA; 8-12 weeks pregnancy) women who visited the Obstetrics and Gynecology Hospital of Fudan University from September to December 2017 were recruited. The healthy pregnant women group included 57 women in the first trimester (T1), 55 in the second (T2) and 55 in the third (T3). Serum levels of HE4 and CA125 were measured by electrochemiluminescent immunoassay. RESULTS Both HE4 and CA125 levels in the T3 group were significantly higher than in the control group (P

Adnexal torsion is one of the most common gynecologic surgical emergencies. All age groups can be affected, but torsion of normal-sized ovary that happens during late pregnancy is rare and challenging to be diagnosed. The objective of this article is to present a case of adnexal torsion in a normal-sized ovary suspected by magnetic resonance imaging (MRI) in the third trimester of pregnancy. A 36-year-old woman at 32 + 5 weeks gestational age was admitted to hospital due to recurrent severe left lower abdominal pain. Doppler ultrasound failed to demonstrate the ovarian diseases, while MRI scan suspected the diagnosis of adnexal torsion. The patient received emergent exploratory laparotomy, and the left adnexa with a necrotic ovary was removed. Tocolytic therapy was used before and after surgery. Finally, she delivered a healthy full-term infant via cesarean section. Adnexal torsion occurring in a normal-sized ovary was quite rare in the third trimester pregnancy. MRI might be better than ultrasound in the early diagnosis of ovarian torsion.

Gestational diabetes mellitus (GDM) has become a new global epidemic with a rapidly increasing prevalence. Previous studies have suggested that air pollution is associated with GDM risk, but the results are inconsistent, and mechanistic studies are limited. Based on a hospital-based cohort, a total of 6374 participants were included in this study. Individual daily PM2.5 exposure at a 1-km resolution was predicted using a full-spatiotemporal-coverage model. The results of multiple linear regression showed that glycated hemoglobin (HbA1c) was significantly associated with PM2.5 both in the 1-month preconception and in the first trimester of pregnancy. Additionally, HbA1c decreased 0.437% (95% CI: − 0.629, − 0.244) as the serum 25-hydroxyvitamin D (25(OH)D) increased by one interquartile range (IQR) (9.2 ng/ml). An IQR increase in PM2.5 exposure was also negatively associated with serum 25(OH)D (estimated change% and 95% CI: − 7.249 (− 9.054, − 5.408) in the 1-month preconception and − 13.069 (− 15.111, − 10.979) in the first trimester of pregnancy). Mediation analysis showed that serum 25(OH)D status mediated the association between HbA1c and PM2.5 exposure both in the preconception and in the first trimester (mediated percent: 2.00% and 4.05% (Sobel p ＜ 0.001), respectively). The result suggested a vicious cycle among PM2.5 exposure, lower serum VD status and a higher HbA1c. More studies are warranted since the protective effect of 25(OH)D against glucose disorders associated with air pollution in this study was limited.

Background The mission of the BioEnergy Science Center (BESC) was to enable efficient lignocellulosic-based biofuel production. One BESC goal was to decrease poplar and switchgrass biomass recalcitrance to biofuel conversion while not affecting plant growth. A transformation pipeline (TP), to express transgenes or transgene fragments (constructs) in these feedstocks with the goal of understanding and decreasing recalcitrance, was considered essential for this goal. Centralized data storage for access by BESC members and later the public also was essential. Results A BESC committee was established to codify procedures to evaluate and accept genes into the TP. A laboratory information management system (LIMS) was organized to catalog constructs, plant lines and results from their analyses. One hundred twenty-eight constructs were accepted into the TP for expression in switchgrass in the first 5 years of BESC. Here we provide information on 53 of these constructs and the BESC TP process. Eleven of the constructs could not be cloned into an expression vector for transformation. Of the remaining constructs, 22 modified expression of the gene target. Transgenic lines representing some constructs displayed decreased recalcitrance in the field and publications describing these results are tabulated here. Transcript levels of target genes and detailed wall analyses from transgenic lines expressing six additional tabulated constructs aimed toward modifying expression of genes associated with wall structure (xyloglucan and lignin components) are provided. Altered expression of xyloglucan endotransglucosylase/hydrolases did not modify lignin content in transgenic plants. Simultaneous silencing of two hydroxycinnamoyl CoA:shikimate hydroxycinnamoyl transferases was necessary to decrease G and S lignin monomer and total lignin contents, but this reduced plant growth. Conclusions A TP to produce plants with decreased recalcitrance and a LIMS for data compilation from these plants were created. While many genes accepted into the TP resulted in transgenic switchgrass without modified lignin or biomass content, a group of genes with potential to improve lignocellulosic biofuel yields was identified. Results from transgenic lines targeting xyloglucan and lignin structure provide examples of the types of information available on switchgrass lines produced within BESC. This report supplies useful information when developing coordinated, large-scale, multi-institutional reverse genetic pipelines to improve crop traits. Electronic supplementary material The online version of this article (10.1186/s13068-017-0991-x) contains supplementary material, which is available to authorized users.

To investigate the expression, DNA methylation status and its regulatory mechanism of tissue factor pathway inhibitor 2 (TFPI-2) in human placenta tissues of preeclampsia (PE).We studied the mRNA and protein expression and the promoter methylation levels of TFPI-2 in the PE placentas compared with those in the normal pregnant (NP) women. Quantitative real-time polymerase chain reaction, immunohistochemistry, western blot, and Sequenom MassARRAY were used for placenta tissue detection.The expressions of TFPI-2 mRNA and protein were significantly elevated in the PE placentas when compared with those in the NP ones (P0.05). Hypomethylation of the TFPI-2 promoter was detected both in PE patients and NP women, with a significant decrease in PE placentas (P=0.005). The methylation level was significantly decreased at CpG_6 (-168 to -167), CpG_15 (-98 to -97) and CpG_18.19 (-68 to -65) in PE patients than that in normal placentas (P0.05). However, the expression of DNMT-1 didn't show significant difference between the two groups (P0.05).Over-expression of TFPI-2 and aberrant promoter mythylation status presented in the PE placentas, suggesting that epigenetic mechanism might contribute to the pathogenesis of PE.

Background It has been reported that during the culture of human placental explants, the syncytiotrophoblast dies between 3 and 24 h and is then replaced within 48 h by a new syncytiotrophoblast layer formed by the fusion of underlying cytotrophoblasts. Most frequently the death of the syncytiotrophoblast is indicated by the uptake of nuclear stains such as propidium iodide (PI). This process is reportedly similar in both early and late gestation placental explants. Methods We cultured first trimester placental explants for up to 48 h and tested membrane intactness by exposure to PI. Connexin and pannexin mRNAs were quantified by RT-PCR and protein levels determined by immunofluorescence. The syncytiotrophoblast membrane leak was determined by culturing explants in the presence of hemichannel blockers. Extrusion of extracellular vesicles from the syncytiotrophoblast was quantified. Results Nuclei of the syncytiotrophoblast were stained with PI following approximately 4 h of culture and this was prevented by culturing the explants with pannexin-1 blockers. Expression of pannexin-1 hemichannels increased during explant culture (p = 0.0027). Extracellular vesicles were most abundantly extruded from the explants during the first 3 h of culture and the temporal pattern of extrusion was unaltered by blocking hemichannels. Discussion We show the mechanism of uptake of nuclear non-viability stains into the syncytiotrophoblast during explant culture is via upregulation of pannexin 1 hemichannels. Contrary to suggestions by some, the production of extracellular vesicles from cultured placental explants is not an in vitro artefact resulting from the apparent death of the syncytiotrophoblast in explant cultures.

Background: Polybrominated diphenyl ethers (PBDEs) are environmental chemicals with harmful effects on pregnancy, but their effects on adverse developmental outcomes are not fully understood. The placental DNA methylation is strongly influenced by prenatal environmental factors and has been linked to fetal growth. Objective: To evaluate the association between in utero PBDEs exposure, placental DNA methylation changes (growth regulatory genes), and pathophysiology of fetal growth (birth outcomes, fetal growth retardation) in a population-based pregnancy cohort study. Methods: This was a nested case-control study within the prospective Wenzhou Birth Cohort including 130 fetal growth retardation (FGR) cases and 130 healthy controls and their mothers recruited from June 2016 to June 2017. FGR was diagnosed based on the comprehensive evaluation of ultrasound results at 24, 28, and 32 weeks of gestation. Neonatal birth measurements were obtained from medical records. Gestational exposure to 19 PBDEs, including 13 lower BDE congeners (BDE-17–190) and 6 higher brominated BDE congeners (BDE-196–209), were determined by gas chromatography tandem mass spectrometry in the umbilical cord blood. Placental DNA methylation changes of one repetitive element (LINE1) and two candidate genes (HSD11B2, IGF2) were characterized by quantitative polymerase chain reaction-pyrosequencing. Multiple linear regression and logistic regression models were used to examine the associations among PBDEs exposure, fetal growth indicators, and DMR (differential methylation region) methylation fractions. Sobel tests were conducted to assess DNA methylation as a mediator in multivariate models. Results: After excluding women who withdrew from the study or were lost to follow-up or failed to provide placenta or umbilical cord blood, 249 mother-newborn pairs (124 FGR cases, 125 controls) were included in the final analysis. Elevated BDE-206 (OR: 1.569, 95% CIs: 1.053–2.338), BDE-17–190 (OR: 2.860, 95% CIs: 1.233–6.634), BDE-196–209 (OR: 1.688, 95% CIs: 1.024–2.783) and ∑19PBDEs (OR: 2.387, 95% CIs: 1.220–4.668) concentrations were associated with increased risk of FGR in newborns. FGR birth was also associated with increased DNA methylation of HSD11B2 (OR: 1.145, 95% CIs: 1.032–1.270) and decreased DNA methylation of IGF2 (OR: 0.892, 95% CIs: 0.845–0.941). In addition, BDE-17–190 showed significant associations with DNA methylation of HSD11B2 and IGF2 (β: 1.127, 95% CIs: 0.069–2.186; β: −3.452, 95% CIs: −5.512–1.392), indicating placental DNA methylation changes of HSD11B2 and IGF2 were related to both lower BDE congeners exposure and fetal growth. Further mediation analyses showed that IGF2 methylation mediated about 40% of the effects of BDE-17–190 in umbilical cord blood on neonatal FGR. Conclusion: We report an inverse association between in utero exposures to PBDEs and fetal growth and provide evidence supporting epigenetic gene plasticity in these associations. Changes in placental DNA methylation might be part of the underlying biological pathway between prenatal PBDEs exposure and adverse fetal growth. Keywords: PBDEs, DNA methylation, Fetal growth, Fetal growth restriction, Placenta

Antibiotics have long been used to combat human and animal diseases and promote the growth of livestock. Due to the low metabolic rate of antibiotics, they cannot be fully absorbed by human and animal bodies. Most antibiotics are discharged into the environment in the form of active ingredients or metabolites, resulting in residues in the environmental medium. More and more attention has been paid to the environmental pollution caused by unreasonable and irregular use of antibiotics. Antibiotics in the environment could cause different degrees of toxic effects on various environmental media such as water and soil, and even induce the production of resistance genes, which will bring serious threats to human life and health. This chapter introduces the exposure of antibiotics and their effects on ecological environment and human health. Moreover, we focus on the state-of-art researches on antibiotic resistance gene and initiate several prospects of future research.

AIM The study aimed to describe the features of magnetic resonance imaging (MRI) in fetuses with tethered-cord syndrome (TCS) or lower spinal cord (LSC) and to analyse the clinical outcomes and complications during follow-up. MATERIALS AND METHODS This is a retrospective study of fetuses diagnosed with TCS or LSC using MRI from January 2015 to August 2019. The average gestational week (GW) at MRI examination was 25.46 ± 4.73 GW (range: 21–39 GW). MRI was used 1 to identify the anatomical landmarks of the spine 2 ; to measure the width of the conus medullaris and record the ending position of the LSC 3 ; and to analyse other neurological deformities. The diagnostic results between MRI and ultrasonography (US) were compared. RESULTS A total of 38 fetuses with suspected intracranial or spinal lesions on US or MRI were included. Among all fetuses, 17 fetuses were diagnosed with LSC or TCS without associated anomalies. Twenty-one fetuses had complications of central nervous system (CNS) anomalies, one fetus also had a diagram hernia, and one fetus had an inverse foot. MRI provided more diagnoses than US in nine fetuses. Two cases of diastematomyelia detected on MRI were missed on US. The capability of MRI was comparable with that of US in terms of displaying spina bifida. CONCLUSION In the present study, fetal MRI showed better performance than US for depicting TCS and related CNS abnormalities. MRI provided clinicians with additional information in terms of prenatal counselling and management.

This study was designed to assess the effect of lactational polybrominated diphenyl ether (PBDE) exposure on early physical development of both healthy and fetal growth restriction (FGR) infants. Z scores of head circumference-for-age (ZHC), length-for-age (ZLEN), weight-for-age (ZWEI) and weight-for-length (ZWFL) were calculated according to the WHO Child Growth Standards. FGR infants had a higher PBDE exposure level and faster growth speed from 42 days to 6 months compared with healthy infants. Exposure of lower brominated BDEs (BDE28∼154) and the sum of 18 BDE congeners (BDE28∼209) negatively associated with ZHC [mean difference estimate (95 % CI): -0.71 (-1.22, -0.22) and -0.81 (-1.31, -0.33)] in FGR boys. Both BDE153 and BDE196 exposure had a significant correlation with ZLEN of boys in FGR group [mean difference estimate (95 % CI): -0.28 (-0.48, -0.07) and -0.52 (-0.91, -0.14)]. Each 10 ng/g lipid increase in the concentrations of BDE154 were respectively associated with 0.16 increase in ZWEI among boys in healthy group. No significant association was found in girls. Lactational PBDE exposure had effects on the early growth of both FGR and healthy infants. The encouragement of breastfeeding should therefore be considered in conjunction with PBDE contamination levels.

Proanthocyanidins (PAs) are primarily composed of the flavan-3-ol subunits (-)-epicatechin and/or (+)-catechin, but the basis for their different starter and extension unit compositions remains unclear. Genetic and biochemical analyses show that, in the model legume Medicago truncatula, two 2-oxoglutarate-dependent dioxygenases, anthocyanidin synthase (ANS) and its homologue leucoanthocyanidin dioxygenase (LDOX), are involved in parallel pathways to generate, respectively, the (-)-epicatechin extension and starter units of PAs, with (+) catechin being an intermediate in the formation of the (-)-epicatechin starter unit. The presence/absence of the LDOX pathway accounts for natural differences in PA compositions across species, and engineering loss of function of ANS or LDOX provides a means to obtain PAs with different compositions and degrees of polymerization for use in food and feed. Proanthocyanidins (PAs) are a class of plant natural products that are involved in plant defence and are also beneficial to human health. Now a new mechanism is discovered to elucidate the origin of PA units and explain the diversity of PA production in different plant species and tissues.