Energy metabolism as therapeutic target for aged wound repair by engineered extracellular vesicle.

Aging skin, vulnerable to age-related defects, is poor in wound repair. Metabolic regulation in accumulated senescent cells (SnCs) with aging is essential for tissue homeostasis, and adequate ATP is important in cell activation for aged tissue repair. Strategies for ATP metabolism intervention hold prospects for therapeutic advances. Here, we found energy metabolic changes in aging skin from patients and mice. Our data show that metformin engineered EV (Met-EV) can enhance aged mouse skin repair, as well as ameliorate cellular senescence and restore cell dysfunctions. Notably, ATP metabolism was remodeled as reduced glycolysis and enhanced OXPHOS after Met-EV treatment. We show Met-EV rescue senescence-induced mitochondria dysfunctions and mitophagy suppressions, indicating the role of Met-EV in remodeling mitochondrial functions via mitophagy for adequate ATP production in aged tissue repair. Our results reveal the mechanism for SnCs rejuvenation by EV and suggest the disturbed energy metabolism, essential in age-related defects, to be a potential therapeutic target for facilitating aged tissue repair.

Prediction of preeclampsia from retinal fundus images via deep learning in singleton pregnancies: a prospective cohort study.

INTRODUCTION: Early prediction of preeclampsia (PE) is of universal importance in controlling the disease process. Our study aimed to assess the feasibility of using retinal fundus images to predict preeclampsia via deep learning in singleton pregnancies. METHODS: This prospective cohort study was conducted at Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine. Eligible participants included singleton pregnancies who presented for prenatal visits before 14 weeks of gestation from September 1, 2020, to February 1, 2022. Retinal fundus images were obtained using a nonmydriatic digital retinal camera during their initial prenatal visit upon admission before 20 weeks of gestation. In addition, we generated fundus scores, which indicated the predictive value of hypertension, using a hypertension detection model. To evaluate the predictive value of the retinal fundus image-based deep learning algorithm for preeclampsia, we conducted stratified analyses and measured the area under the curve (AUC), sensitivity, and specificity. We then conducted sensitivity analyses for validation. RESULTS: Our study analyzed a total of 1138 women, 92 pregnancies developed into hypertension disorders of pregnancy (HDP), including 26 cases of gestational hypertension and 66 cases of preeclampsia. The adjusted odds ratio (aOR) of the fundus scores was 2.582 (95% CI, 1.883-3.616; P  < 0.001). Otherwise, in the categories of prepregnancy BMI less than 28.0 and at least 28.0, the aORs were 3.073 (95%CI, 2.265-4.244; P  < 0.001) and 5.866 (95% CI, 3.292-11.531; P  < 0.001). In the categories of maternal age less than 35.0 and at least 35.0, the aORs were 2.845 (95% CI, 1.854-4.463; P  < 0.001) and 2.884 (95% CI, 1.794-4.942; P  < 0.001). The AUC of the fundus score combined with risk factors was 0.883 (sensitivity, 0.722; specificity, 0.934; 95% CI, 0.834-0.932) for predicting preeclampsia. CONCLUSION: Our study demonstrates that the use of deep learning algorithm-based retinal fundus images offers promising predictive value for the early detection of preeclampsia.

E2-Loaded Microcapsules and Bone Marrow-Derived Mesenchymal Stem Cells with Injectable Scaffolds for Endometrial Regeneration Application.

Bone marrow-derived mesenchymal stem cells (BMSCs) have been recognized as new candidates for the treatment of serious endometrial injuries. However, owing to the local microenvironment of damaged endometrium, transplantation of BMSCs yielded disappointing results. In this study, Pectin-Pluronic® F-127 hydrogel as scaffolds were fabricated to provide three-dimensional architecture for the attachment, growth, and migration of BMSCs. E2 was encapsulated into the W/O/W microspheres to construct pectin-based E2-loaded microcapsules (E2 MPs), which has the potential to serve as a long-term reliable source of E2 for endometrial regeneration. Then, the BMSCs/E2 MPs/scaffolds system was injected into the uterine cavity of mouse endometrial injury model for treatment. At 4 weeks after transplantation, the system increased proliferative abilities of uterine endometrial cells, facilitated microvasculature regeneration, and restored the ability of endometrium to receive an embryo, suggesting that the BMSCs/E2 MPs/scaffolds system is a promising treatment option for endometrial regeneration. Furthermore, the mechanism of E2 in promoting the repair of endometrial injury was also investigated. Exosomes are critical paracrine mediators that act as biochemical cues to direct stem cell differentiation. In this study, it was found that the expression of endometrial epithelial cell (EEC) markers was upregulated in BMSCs treated by exosomes secreted from endometrial stromal cells (ESCs-Exos). Exosomes derived from E2-stimulated ESCs further promoted the expression level of EECs markers in BMSCs, suggesting exosomes released from ESCs by E2 stimulation could enhance the differentiation efficiency of BMSCs. Therefore, exosomes derived from ESCs play paracrine roles in endometrial regeneration stimulated by E2 and provide optimal estrogenic response.

Extracellular Vesicles Derived from Human Umbilical Cord Mesenchymal Stem Cells Promote Trophoblast Cell Proliferation and Migration by Targeting TFPI2 in Preeclampsia.

Preeclampsia is a pregnancy disorder characterized by systemic organ damage and high blood pressure. It has been reported that microRNA-195 (miR-195) is associated with preeclampsia. In this study, we discovered the target of miR-195 in regulating human extravillous cytotrophoblast-derived transformed cell proliferation and migration. We analyzed the clinicopathological factors of preeclampsia and normal pregnancies. The messenger ribonucleic acid (mRNA) levels of miR-195 and tissue factor pathway inhibitor 2 (TFPI2) were measured in placental tissues derived from normal and preeclampsia patients by real-time polymerase chain reaction (PCR). Human umbilical cord mesenchymal stem cell (hUC-MSC)-derived extracellular vesicles were verified by western blot. HTR8-S/Vneo cell proliferation was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, and cell migration rate was assessed by the transwell assay. Relative luciferase activities were measured in TFPI2 wild-type (WT) and mutant cells. miR-195 expression was negatively correlated with TFPI2 mRNA levels in preeclampsia patients. Extracellular vesicles derived from hUC-MSCs enhanced HTR8-S/Vneo cell proliferation and migration. In addition, miR-195 isolated from hUC-MSCs enhanced HTR8-S/Vneo cell proliferation and migration by targeting TFPI2. Our findings demonstrate that the upregulation of miR-195 in extracellular vesicles derived from hUC-MSCs promotes HTR8-S/Vneo cell proliferation and migration by targeting TFPI2.

Successful pregnancy in the blind hemicavity of Robert's uterus: a rare case report and brief literature review.

BACKGROUND: Robert's uterus is a rare congenital anomaly, characterized as an asymmetric septate uterus that has a blind hemicavity with unilateral menstrual fluid retention and a unicornuate hemicavity connecting to the cervix unimpededly. Patients with Robert's uterus generally present with menstrual disorders and dysmenorrhea, and some may have reproductive problems as well, including infertility, recurrent miscarriage, preterm labor and obstetric complications. In this case, we describe a successful pregnancy implanted on the obstructed hemicavity and delivered a liveborn girl. Meanwhile, we highlight diagnostic and therapeutic difficulties in patients with atypical symptoms of Robert's uterus. CASE PRESENTATION: A 30-year-old Chinese primigravida sought for emergency treatment at 26 weeks and 2 days of gestation because of preterm premature rupture of membranes (PPROM). At the age of 19, the patient was misdiagnosed with hyperprolactinemia and pituitary microadenoma for showing symptom of hypomenorrhea and was suspected to have a uterine septum in the first trimester. She was diagnosed with Robert's uterus at 22 weeks of gestation by repetitious prenatal transvaginal ultrasonography, which was subsequently confirmed by magnetic resonance imaging. At 26 weeks and 3 days of gestation, the patient was suspected to have oligohydramnion, irregular uterine contraction, and umbilical cord prolapse, and she expressed a strong will of saving the baby. Emergency cesarean delivery was performed and a small hole, together with several weak spots, was found at the lower and back wall of the septum of the patient. The treatment was effective and both the mother and the infant, who had an extremely low birth weight, were discharged in good health conditions. CONCLUSIONS: Pregnancy in the blind cavity of Robert's uterus with living neonates is incredibly rare. In our case, the favorable outcome may result from the unusual hole found at the septum, which may play a role in communicating amniotic fluid between the two hemicavities so to keep the neonate alive. we highlight the importance of early diagnosis and pre-pregnancy treatment of this uterine malformation, and the timely termination of pregnancy, for improving birth quality and reducing mortality.

Predictors for histological chorioamnionitis among women with preterm prelabour rupture of membranes after dexamethasone treatment: a retrospective study.

OBJECTIVE: To investigate reliable biomarkers for predicting histological chorioamnionitis (HCA) in women with preterm prelabour rupture of membranes (PPROM). DESIGN: A retrospective study. SETTING: A maternity care hospital in Shanghai. POPULATION: Women with PPROM before 34+0/7  weeks of gestation. METHODS: Mean values of biomarkers were compared by two-way analysis of variance (ANOVA). Log-binomial regression models were used to assess the association between biomarkers and risk of HCA. A stepwise logistic regression model was used to develop a multi-biomarker prediction model and identify the independent predictors. The area under the receiver operating characteristic curve (AUC) was used to assess prediction performance. MAIN OUTCOME MEASURES: The ability of the individual biomarker and the combination of multiple biomarkers to predict HCA. RESULTS: In 157 mothers with PPROM, 98 (62.42%) women had HCA and 59 (37.58%) women did not have HCA. No significant differences were observed between the two groups in white blood cell, neutrophil or lymphocyte counts, whereas both high-sensitivity C-reactive protein (hsCRP) and procalcitonin (PCT) were significantly higher in the HCA group. HsCRP and PCT were found to be independently associated with the risk of HCA, and PCT had a larger AUC value than hsCRP (p < 0.05). The optimal multi-biomarker prediction model for HCA (AUC = 93.61%) included hsCRP at 72 hours and PCT at 48 and 72 hours, and PCT had a stronger prediction capacity than hsCRP. CONCLUSIONS: PCT could be a reliable biomarker for the early prediction of HCA in women with PPROM within 72 hours of dexamethasone treatment.

Prediction model for successful induction of labor by cervical strain elastography diagnosed at late-term pregnancy in nulliparous women: a prospective cohort study.

BACKGROUND: The use of cervical strain elastography for nulliparous women during late-term pregnancy remains unclear. This study assesses the predictive value of late-term cervical strain elastography for successful induction of labor (IOL) in nulliparous women. METHODS: This single-centered, prospective study included 86 patients undergoing IOL between January 2020 and March 2022. Univariate and multivariate analyses were conducted to identify predictive factors for successful IOL. The predictive values were assessed using the area under receiver operating characteristic (ROC) curves. RESULTS: IOL was successful in 58 patients. The hardness ratio and cervical length were significantly associated with successful late-term IOL in nulliparous women. The predictive value of the combination of hardness ratio and cervical length was higher than that of cervical length alone. CONCLUSIONS: The hardness ratio and cervical length assessed by cervical strain elastography during late-term pregnancy are predictors of the success of IOL in nulliparous women. The predictive value of the combination of hardness ratio and cervical length was higher than that of cervical length alone.

CT-based machine learning radiomics predicts CCR5 expression level and survival in ovarian cancer.

OBJECTIVE: We aimed to evaluate the prognostic value of C-C motif chemokine receptor type 5 (CCR5) expression level for patients with ovarian cancer and to establish a radiomics model that can predict CCR5 expression level using The Cancer Imaging Archive (TCIA) and The Cancer Genome Atlas (TCGA) database. METHODS: A total of 343 cases of ovarian cancer from the TCGA were used for the gene-based prognostic analysis. Fifty seven cases had preoperative computed tomography (CT) images stored in TCIA with genomic data in TCGA were used for radiomics feature extraction and model construction. 89 cases with both TCGA and TCIA clinical data were used for radiomics model evaluation. After feature extraction, a radiomics signature was constructed using the least absolute shrinkage and selection operator (LASSO) regression analysis. A prognostic scoring system incorporating radiomics signature based on CCR5 expression level and clinicopathologic risk factors was proposed for survival prediction. RESULTS: CCR5 was identified as a differentially expressed prognosis-related gene in tumor and normal sample, which were involved in the regulation of immune response and tumor invasion and metastasis. Four optimal radiomics features were selected to predict overall survival. The performance of the radiomics model for predicting the CCR5 expression level with 10-fold cross- validation achieved Area Under Curve (AUCs) of 0.770 and of 0.726, respectively, in the training and validation sets. A predictive nomogram was generated based on the total risk score of each patient, the AUCs of the time-dependent receiver operating characteristic (ROC) curve of the model was 0.8, 0.673 and 0.792 for 1-year, 3-year and 5-year, respectively. Along with clinical features, important imaging biomarkers could improve the overall survival accuracy of the prediction model. CONCLUSION: The expression levels of CCR5 can affect the prognosis of patients with ovarian cancer. CT-based radiomics could serve as a new tool for prognosis prediction.

Association Between Maternal Weight Gain in Different Periods of Pregnancy and the Risk of Venous Thromboembolism: A Retrospective Case-Control Study.

Background: Venous thromboembolism (VTE) remains an important cause of maternal deaths. Little is known about the associations of specific periods of gestational weight gain (GWG) with the category of VTE, pulmonary embolism (PE), or deep venous thrombosis (DVT) with or without PE. Methods: In a retrospective case-control study conducted in Shanghai First Maternity and Infant Hospital from January 1, 2017 to September 30, 2021, cases of VTE within pregnancy or the first 6 postnatal weeks were identified. Controls without VTE were randomly selected from women giving birth on the same day as the cases, with 10 controls matched to each case. Total GWG and rates of early, mid, and late GWG values were standardized into z-scores, stratified by pre-pregnant body mass index (BMI). The adjusted odds ratios (aORs) and 95% confidence intervals (CIs) were estimated through multivariate logistic regression models. Results: There were 196 cases (14.4 per 10,000) of VTE within pregnancy or the first 6 postnatal weeks were identified. Higher total weight gain was associated with increased risks of PE (aOR, 13.22; 95% CI, 2.03-85.99) and VTE (OR, 10.49; 95% CI, 1.82-60.45) among women with underweight. In addition, higher total weight gain was associated with increased risk of PE (aOR, 2.06; 95% CI, 1.14-3.72) among women with healthy weight. Similarly, rate of higher early weight gain was associated with significantly increased risk for PE (aOR, 2.15; 95% CI, 1.05-4.42) among women with healthy BMI. The lower rate of late weight gain was associated with increased risks of PE (aOR, 7.30; 95% CI, 1.14-46.55) and VTE (OR, 7.54; 95% CI, 1.20-47.57) among women with underweight. No significant associations between maternal rate of mid GWG and increased risk for any category of VTE, PE, or DVT with or without PE were present, regardless of maternal pre-pregnant BMI. Conclusion: The GWG associations with the category of VTE, PE, or DVT with or without PE differ at different periods of pregnancy. In order to effectively improve maternal and child outcomes, intensive weight management that continues through pregnancy may be indispensable.

Exosomal miR-195 in hUC-MSCs alleviates hypoxia-induced damage of trophoblast cells through tissue factor pathway inhibitor 2.

MicroRNA-195 (miR-195) was decreased in the patients with pre-eclampsia (PE), which was implicated to modulate PE. Moreover, tissue factor pathway inhibitor 2 (TFPI2), which was highly expressed in the placenta of PE patients, was negatively correlated with miR-195 levels. This study aimed to explore the role of miR-195 in the cell therapy for the treatment of PE and the underlying mechanisms. Human umbilical cord mesenchymal stem cells (hUC-MSCs) were transfected with miR-195 mimic or mimic negative control to extract exosomes. HTR8/SVneo was incubated under hypoxia condition to induce cell damage, and co-co-cultured with exosomes derived from hUC-MSCs to evaluate its effect. Hypoxia time-dependently caused a decrease on miR-195 level with an increase on TFPI2 expression in HTR8/SVneo. MiR-195 directly bind to TFPI2 and inhibited TFPI2 expression in hUC-MSCs. Moreover, hypoxia-induced cell damage in HTR8/SVneo was significantly attenuated by co-culture with hUC-MSC-derived exosomes. Exosomes extracted from miR-195-overexpressed hUC-MSCs, could further ameliorate hypoxia-induced cell damage, due to the excessive amount of miR-195 delivered by exosomes. Exosomal miR-195 in hUC-MSCs alleviated hypoxia-induced cell damage through TFPI2, which might provide a potential therapeutic approach for pre-eclampsia.

Selective versus routine use of episiotomy for vaginal births in Shanghai hospitals, China: a comparison of policies.

BACKGROUND: To assess the effects of policy of selective versus routine episiotomy on mother and baby for women delivering vaginally in Shanghai and whether the hospital type has any effect on the outcomes. METHOD: This was a multi-center retrospective cohort study in Shanghai between March 2015 and May 2017. The study population were vaginal births with selective or routine episiotomy (n = 5478) in 20 secondary or tertiary hospitals. Main Outcome Measure was the incidence of severe perineal lacerations. The adjusted odds ratios (aOR) and 95% confidence intervals (CI) were estimated by logistic regression and presented as the effect sizes. All models were stratified by the utilization of level (secondary and tertiary) and type (general and Obstetric) of hospital. RESULTS: The primary outcome was not significantly different between vaginal births with routine and selective episiotomy. Patients with selective episiotomy had a lower risk of postpartum hemorrhage, and newborns in the selective episiotomy group had a lower risk of shoulder dystocia and Neonatal Ward compared to those with routine episiotomy. Newborns in selective episiotomy group had a lower risk of birth injury in tertiary hospital. However, newborns in selective episiotomy group had a higher risk of birth injury in general hospitals. CONCLUSION: Selective episiotomy is safe and can be recommended over routine episiotomy in obstetric and tertiary hospital settings in China.

Influence of ambient air pollution on successful pregnancy with frozen embryo transfer: A machine learning prediction model.

Numerous air pollutants have been reported to influence the outcomes of in vitro fertilization (IVF). However, whether air pollution affects implantation in frozen embryo transfer (FET) process is under debate. We aimed to find the association between ambient air pollution and implantation potential of FET and test the value of adding air pollution data to a random forest model (RFM) predicting intrauterine pregnancy. Using a retrospective study of a 4-year single-center design，we analyzed 3698 cycles of women living in Shanghai who underwent FET between 2015 and 2018. To estimate patients' individual exposure to air pollution, we computed averages of daily concentrations of six air pollutants including PM2.5, PM10, SO2, CO, NO2, and O3 measured at 9 monitoring stations in Shanghai for the exposure period (one month before FET). Moreover, A predictive model of 15 variables was established using RFM. Air pollutants levels of patients with or without intrauterine pregnancy were compared. Our results indicated that for exposure periods before FET, NO2 were negatively associated with intrauterine pregnancy (OR: 0.906, CI: 0.816-0.989). AUROC increased from 0.712 to 0.771 as air pollutants features were added. Overall, our findings demonstrate that exposure to NO2 before transfer has an adverse effect on clinical pregnancy. The performance to predict intrauterine pregnancy will improve with the use of air pollution data in RFM.

Ultrasound-Indicated Cervical Cerclage Efficacy Between 16 and 28 Weeks of Gestation in Twin Pregnancy: Retrospective Cohort Study.

Objective: The aim of this study is to determine if cervical cerclage administration reduces the preterm birth (PTB) rate at a gestational age (GA) of 16-28 weeks in women with twin pregnancy. Methods: This is a retrospective cohort study on asymptomatic twin pregnancy with an ultrasound-identified cervix length (CL) of ≦25 mm. The patients were divided into two groups: ultrasound-indicated cerclage (UIC) group and control (expectant management) group. The primary outcome was a PTB rate at <34 weeks. A logistic regression was also performed, and a subgroup analysis stratified by CL and GA at first short cervix diagnosis was planned. Results: In all 320 women, there were no differences in the overall <34-week PTB rates and neonatal outcomes between the UIC group and control group. After performing a multivariate logistic regression analysis, the subgroup analyses were planned. In patients with a CL of ≦15 mm, the <34-week PTB rate was significantly decreased in the UIC subgroup compared with the control subgroup (60.78% vs 78.26%; odds ratio (OR) = 0.43, confidence interval (CI) = 95% [0.22-0.86]; and p = 0.020). In patients with a first short cervix diagnosis GA of ≦24 weeks, the <34-week PTB rate was significantly decreased in the UIC subgroup when compared with the control subgroup (61.54% vs 84.75%; OR = 0.29; CI = 95% [0.13-0.63]; and p = 0.001). Furthermore, compared with the control groups, the UIC groups had higher mean birth weight, lower perinatal mortality, and lower NICU admission, and the differences were statistically significant. Conclusion: UIC could significantly reduce the <34-week PTB rate and improve perinatal outcomes in patients with a CL of ≦15mm or first short cervix diagnosis GA of ≦24 weeks with asymptomatic twin pregnancy during the second trimester.

Association of age at benign hysterectomy with leukocyte telomere length in a nationally representative population.

OBJECTIVES: Hysterectomy is one of the most common gynecological surgical procedures, and most hysterectomies are performed for benign indications. Despite the frequency and known benefits of the procedure, it remains unclear whether it has potential adverse effects on long-term health and longevity. The aim of this study was to evaluate the association of age at benign hysterectomy with leukocyte telomere length, in data from the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2002. STUDY DESIGN: In total, 811 women who had a hysterectomy were included in this cross-sectional study. MAIN OUTCOME MEASURES: To estimate the association of age at benign hysterectomy with telomere length, multivariate regression analyses adjusted for age, race/ ethnicity, education, marital status, income poverty ratio, body mass index (BMI), physical activity, smoking behavior, alcohol consumption, history of chronic disease and history of oophorectomy were conducted. Fitted smoothing curves were also evaluated. RESULTS: We found leukocyte telomere length was positively correlated with age at benign hysterectomy after adjusting for other confounders in both a minimally adjusted model [ß = 4.18, 95%CI: (0.17,8.20)] and a fully adjusted model [ß = 4.63, 95% CI:(0.56,8.70)]. CONCLUSIONS: Earlier age at benign hysterectomy was associated with shorter telomere length in a nationally representative population of women. These data provide new information in pre-surgical counseling and decision-making.

Pregnancy outcomes and associated factors for uterine rupture: an 8 years population-based retrospective study.

BACKGROUND: Uterine rupture is an obstetrical emergency with serious undesired complications for laboring mothers resulting in fatal maternal and neonatal outcomes. The aim of this study was to assess the incidence of uterine rupture, its association with previous uterine surgery and vaginal birth after caesarean section (VBAC), and the maternal and perinatal implications. METHODS: This is a population-based retrospective study. All pregnant women treated for ruptured uterus in one center between 2013 and 2020 were included. Their information retrieved from the medical records department were reviewed retrospectively. RESULTS: A total of 209,112 deliveries were included and 41 cases of uterine rupture were identified. The incidence of uterine rupture was 1.96/10000 births. Among the 41 cases, 16 (39.0%) had maternal and fetal complications. There were no maternal deaths secondary to uterine rupture, while perinatal fatality related to uterine rupture was 7.3%. Among all cases, 38 (92.7%) were scarred uterus and 3 (7.3%) were unscarred uterus. The most common cause of uterine rupture was previous cesarean section, while cases with a history of laparoscopic myomectomy were more likely to have serious adverse outcomes, such as fetal death. 24 (59.0%) of the ruptures occurred in anterior lower uterine segment. Changes in Fetal heart rate monitoring were the most reliable signs for rupture. CONCLUSIONS: Incidence of uterine rupture in the study area, Shanghai, China was consistent with developed countries. Further improvements in obstetric care and enhanced collaboration with referring health facilities were needed to ensure maternal and perinatal safety.

Esomeprazole inhibits hypoxia/endothelial dysfunction-induced autophagy in preeclampsia.

Preeclampsia (PE) affects 3 to 5% of pregnant women worldwide and is associated with fetal and maternal morbidity and mortality. Although a complete understanding of PE remains elusive, it has been widely accepted that a dysfunction of the placenta plays a key role in the pathogenesis of PE. In this study, we investigated the role of excessive placental autophagy during PE pathogenesis and explored whether esomeprazole ameliorates PE by inhibiting the autophagy in the placenta. The PE cellular model was established by treating the cells' L-NAME and hypoxia. The PE mice model was established by L-NAME administration and was confirmed by the increased systolic blood pressure (SBP) and urinary protein detected. The autophagy and key proteins were detected in human placental tissue, in cells, and in the mice model by Western blot and immunofluorescence staining. Results showed that excessive autophagy could be detected in human PE placental tissue, in the PE cellular model, and in the PE mice model. Hypoxia induces autophagy by activating AMPKα and inhibiting mTOR in vivo and in vitro. Esomeprazole inhibits L-NAME-induced autophagy in mice by inhibiting AMPKα and activating mTOR. In conclusion, this study demonstrates that the excessive autophagy induced by the SIRT1/AMPKα-mTOR pathway plays a significant role in the pathogenesis of PE. However, esomeprazole treatment inhibits AMPKα but activates mTOR, resulting in the inhibition of autophagy in the placenta and, therefore, mitigates PE symptoms.

Defining intertwin birth weight discordance and optimal delivery time in dichorionic twins: a retrospective cohort study.

BACKGROUND: A high birth weight discordance (BWD) places twins at high risks of adverse perinatal outcomes; however, there is no commonly accepted definition of intertwin BWD. Given that gestational age (GA) is closely associated with both BWD and adverse neonatal outcomes, the aim of our study is to develop a measure that takes both BWD and GA into account to define BWD and explore the potentially optimal delivery time in dichorionic twins, with the balance against the risk of intrauterine demise and adverse neonatal outcomes. METHODS: About 99,000 mixed gender twin pairs from the US matched multiple birth file from 1995 to 2000 were enrolled in our study. We set up a two-dimensional matrix model to select the BWD cutoff point related to outcomes. The optimal delivery time was identified based on the risks of adverse neonatal outcomes and fetal death by GA. RESULTS: The combination of BWD and GA had a higher predictive performance for adverse neonatal outcomes than BWD alone (area under ROC curve (AUC): 0.816 vs. 0.523, p < .001). When GA was controlled for, the growth discordant cutoff point was BWD at the 40% level. The optimal delivery time suggested in dichorionic twins with BWD higher than 40% was identified at 33-34 gestational weeks. CONCLUSIONS: The combination of BWD and GA was a better predictor for adverse neonatal outcomes than BWD alone. In dichorionic twins with BWD >40%, pregnancy may be continued till 33-34 gestation weeks if there is no indication for immediate delivery.

MiR-590-3p and its targets VEGF, PIGF, and MMP9 in early, middle, and late pregnancy: their longitudinal changes and correlations with risk of fetal growth restriction.

AIMS: The term "fetal growth restriction (FGR)" is commonly used to describe fetuses with an estimated fetal weight that is less than 10th percentile for gestational age. This study aimed to investigate the longitudinal change of microRNA-590-3p (miR-590-3p), vascular endothelial growth factor (VEGF), placental growth factor (PIGF), and matrix metalloproteinase (MMP)9 expressions in early, middle, and late pregnancy, and their correlations with the fetal growth restriction (FGR) risk. METHODS: Totally, 970 pregnant women in early pregnancy were enrolled, and their plasma samples were, respectively, acquired in early pregnancy (at 10th or 11th week of gestational age), middle pregnancy (at 20th or 21st week of gestational age), and late pregnancy (at 33th or 34th week of gestational age) for miR-590-3p, VEGF, PIGF, and MMP9 determinations. RESULTS: MiR-590-3p underwent a growing trend, but VEGF, PIGF, and MMP9 experienced declined trend along with pregnancy (all P < 0.001). Furthermore, the negative association of miR-590-3p with VEGF, PIGF, and MMP9 became stronger along with the pregnancy. Besides, miR-590-3p expression in middle and late pregnancy was higher, but VEGF, PIGF, and MMP9 expressions in middle and late pregnancy were lower in women affected by FGR compared to normal pregnant women (all P < 0.001). In addition, miR-590-3p, VEGF, PIGF, and MMP9 expression in middle and late pregnancy were of good value in predicting FGR risk. CONCLUSIONS: miR-590-3p exhibits a growing trend during pregnancy, and its expression in middle and late pregnancy is associated with increased FGR risk via interaction with VEGF, PIGF, and MMP9.

The influence of hypertensive disorders during pregnancy on the perinatal outcome of different chorionic twins.

OBJECTIVE: To investigate the influence of hypertensive disorders of pregnancy (HDP) on the perinatal outcomes in twin pregnancies. METHODS: This was a retrospective single-center study in which, 2160 twin pregnancies delivered between January 2016 and December 2019 were analyzed, 1661 of which were dichorionic (DC) and 499 monochorionic (MC). The perinatal outcomes were compared in 404 twin pregnancies with HDP, including 157 gestational hypertension (GH), 107 mild pre-eclampsia (MPE), 140 severe pre-eclampsia (SPE), and 1756 twins without hypertensive disorders of pregnancy (no-HDP). Multiple linear regression was performed to analyze the association between perinatal outcome and HDP. Stratified sampling by twin chorionicity (DC and MC) was also conducted. RESULTS: There were 330 (19.9%) DC cases complicated with HDP and 74 (14.8%) MC with HDP, and the difference between the two groups was statistically significant (p=.011). After stratification by chorionicity, in the DC twin, there were significantly more deliveries in the GH group, MPE group, and SPE group before 37 weeks than in the no-HDP group (p=.000). Statistically significant differences were found among the four groups in the average small fetus birthweight, the intertwin weight difference, the relative weight discordance, the growth discordance, the incidence of very low birth weight (VLBW), low birth weight (LBW), and the Apgar scores of the small fetus (p<.05). In MC twins, By comparison only on the average gestational age at delivery, the average small fetus birthweight, Apgar scores of large and small fetuses among the four groups, the difference was statistically significant (p<.05). According to multiple linear regression analysis, after controlling for multiple confounding factors, it was found when the degree of HDP in DC twins increased by one grade, the small fetus birthweight decreased by an average of 19.044 g (p=.007), the intertwin weight difference increased by an average of 14.311 g (p=.034), the relative weight discordance increased by an average of 0.6% (p=.013), and the gestational age at delivery decreased by an average of 0.160 weeks (p=.001). CONCLUSIONS: The perinatal outcomes of different chorionic twins with HDP are different. HDP has a greater impact on the perinatal outcomes of DC twins. The risk of adverse perinatal outcomes in DC twin pregnancy will increase accordingly with each increase in the grade of HDP, but HDP has little or no relevance on the perinatal outcomes of MC twins.

Epidemiology of uterine rupture among pregnant women in China and development of a risk prediction model: analysis of data from a multicentre, cross-sectional study.

OBJECTIVES: To describe the epidemiology of uterine rupture in China from 2015 to 2016 and to build a prediction model for uterine rupture in women with a scarred uterus. SETTING: A multicentre cross-sectional survey conducted in 96 hospitals across China in 2015-2016. PARTICIPANTS: Our survey initially included 77 789 birth records from hospitals with 1000 or more deliveries per year. We excluded 2567 births less than 24 gestational weeks or unknown and 1042 births with unknown status of uterine rupture, leaving 74 180 births for the final analysis. PRIMARY AND SECONDARY OUTCOME MEASURES: Complete and incomplete uterine rupture and the risk factors, and a prediction model for uterine rupture in women with scarred uterus (assigned each birth a weight based on the sampling frame). RESULTS: The weighted incidence of uterine rupture was 0.18% (95% CI 0.05% to 0.23%) in our study population during 2015 and 2016. The weighted incidence of uterine rupture in women with scarred and intact uterus was 0.79% (95% CI 0.63% to 0.91%) and 0.05% (95% CI 0.02% to 0.13%), respectively. Younger or older maternal age, prepregnancy diabetes, overweight or obesity, complications during pregnancy (hypertensive disorders in pregnancy and gestational diabetes), low education, repeat caesarean section (≥2), multiple abortions (≥2), assisted reproductive technology, placenta previa, induce labour, fetal malpresentation, multiple pregnancy, anaemia, high parity and antepartum stillbirth were associated with an increased risk of uterine rupture. The prediction model including eight variables (OR >1.5) yielded an area under the curve (AUC) of 0.812 (95% CI 0.793 to 0.836) in predicting uterine rupture in women with scarred uterus with sensitivity and specificity of 77.2% and 69.8%, respectively. CONCLUSIONS: The incidence of uterine rupture was 0.18% in this population in 2015-2016. The predictive model based on eight easily available variables had a moderate predictive value in predicting uterine rupture in women with scarred uterus. Strategies based on predictions may be considered to further reduce the burden of uterine rupture in China.