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.

Use of the RCOG risk assessment model and biomarkers to evaluate the risk of postpartum venous thromboembolism.

BACKGROUND: Venous thromboembolism (VTE) is a leading cause of morbidity and mortality during pregnancy and the puerperium. The vast majority of VTE occurs after childbirth. China has not yet established standard risk assessment model for postpartum venous thromboembolism (VTE), the Royal College of Obstetricians and Gynecologists (RCOG) risk assessment model (RAM) is commonly used in clinic at present. Herein, we aimed to evaluate the validity of the RCOG RAM in the Chinese population and try to formulate a local risk assessment model by combining with other biomarkers for VTE prophylaxis. METHODS: The retrospective study was conducted from January 2019 to December 2021at Shanghai First Maternity and Infant Hospital which has approximately 30,000 births annually, and the incidence of VTE, differences between RCOG-recommended risk factors, and other biological indicators from medical records were evaluated. RESULTS: The study included VTE (n = 146) and non-VTE(n = 413) women who examined by imaging for suspicion of postpartum VTE. There was no statistical difference in the incidence rate of postpartum VTE between the low-score group (23.8%) and the high-score group (28%) after stratification by RCOG RAM. However, we found that cesarean section (in the low-score group), white blood cell (WBC) ≥ 8.64*10^9/L (in the high-score group), low-density lipoprotein(LDL) ≥ 2.70 mmol/L, and D-dimer ≥ 3.04 mg/L (in both groups) were highly associated with postpartum VTE. Subsequently, the validity of the RCOG RAM combined with biomarkers as a model for the risk assessment of VTE was estimated and the results showed that this model has good accuracy, sensitivity, and specificity. CONCLUSIONS: Our study indicated that the RCOG RAM was not the best strategy for predicting postpartum VTE. Combined with some biomarkers (including the value of LDL and D-Dimer, and WBC count), the RCOG RAM is more efficient when identifying high-risk groups of postpartum VTE in the Chinese population. TRIAL REGISTRATION: This purely observational study does not require registration based on ICMJE guidelines.

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.

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.

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.

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.

Tubal ectopic pregnancy: a retrospective cohort study on clinical characteristics, treatment options and reproductive outcomes within 5 years.

PURPOSE: To investigate the association between different treatments of tubal ectopic pregnancy (EP) -expectant management, methotrexate (MTX), selected or recommended laparoscopic surgery-and the subsequent reproductive outcomes. METHODS: We conducted a retrospective cohort study including 228 EPs. The patients were divided into four treatment groups: 28 (12.3%) with expectant management successfully, 60 (26.3%) with MTX successfully, 140 patients with laparoscopic salpingectomy, of which 47 (20.6%) were assigned to selected surgery group because they opted for surgical treatment versus MTX, 93 (40.8%) were assigned to recommended surgery group as recommended by the attending physician. RESULTS: The recommended surgery group had the lowest rate of intrauterine pregnancy (IUP) (77.42%) and live birth (LB) (72.04%), while the incidence of recurrent EP (REP) (20.43%) was the highest, but the statistical differences were not significant. We did not observe significant differences of the EP-IUP time interval, rates of LB and miscarriage (MIS) between the four groups. Compared to the MTX group, recommended surgery was negatively associated with IUP (adjusted OR, 95%CI: 0.34, 0.11-1.03) and LB (0.35, 0.14-0.92), while it had higher risk for REP (3.48, 1.03-11.74) in the subsequent pregnancy. Further, compared to selective surgery group, recommended surgery was negatively associated with IUP (0.15, 0.03-0.68) and LB (0.23, 0.07-0.74), while it had higher risk for REP (6.83, 1.43-32.67) in the subsequent pregnancy. Expectant treatment was negatively associated with assisted reproductive technology (ART) (0.08, 0.02-0.40) compared with MTX. Of the185 patients who had LBs, all adverse outcomes were not statistically different between the four groups. CONCLUSION: Patients with recommended laparoscopic salpingectomy had worse reproductive outcomes than the other treatment groups. The disease status of EP may play an important role in the association rather than the surgery alone.

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.

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.