Application of Uterine Artery Embolization in Patients With Placenta Accreta Spectrum After Abdominal Aortic Balloon Occlusion.

OBJECTIVE: To evaluate the application of different uterine artery embolization procedures under balloon occlusion of the abdominal aorta in patients with Placenta Accreta Spectrum (PAS) undergoing cesarean section. MATERIALS AND METHODS: A retrospective analysis was performed on clinical data from 72 patients who underwent uterine artery embolization for hemostasis during cesarean section with PAS. The patients were divided into two groups according to the embolization method used during surgery: group A (n = 43) underwent uterine artery embolization by withdrawing the balloon and inserting a Cobra catheter into the uterine artery for embolization, while group B (n = 29) underwent uterine artery embolization with a Cobra catheter inserted via contralateral puncture of the femoral artery and balloon occlusion. General information, surgical data, and postoperative recovery were compared between the 2 groups. RESULTS: The bleeding and transfusion volumes were lower in group B than in group A and the differences between the 2 groups were statistically significant. There were no significant differences in surgical duration, number of embolized vessels, length of hospital stay, postoperative complications, or menstrual recovery between the 2 groups. CONCLUSION: For patients with PAS undergoing cesarean section, uterine artery embolization for hemostasis is preferably performed by inserting a Cobra catheter via contralateral puncture of the femoral artery under abdominal aortic balloon occlusion.

Evaluation of the clinical utility of extended non-invasive prenatal testing in the detection of chromosomal aneuploidy and microdeletion/microduplication.

BACKGROUND: With the development of whole-genome sequencing technology, non-invasive prenatal testing (NIPT) has been applied gradually to screen chromosomal microdeletions and microduplications that cannot be detected by traditional karyotyping. However, in NIPT, some false positives and false negatives occur. This study aimed to investigate the applicability of extended NIPT (NIPT-PLUS) in the detection of chromosomal aneuploidy and microdeletion/microduplication syndrome (MMS). METHODS: A total of 452 pregnancies that underwent prenatal diagnostic testing (amniocentesis or chorionic villus sampling) by chromosomal microarray analysis (CMA), were screened by NIPT-PLUS from the peripheral blood sample of the pregnant women. The results of the two tested items were compared and analysed. RESULTS: Of the 452 cases, 335 (74.12%) had positive CMA results, and 117 (25.88%) had no abnormal results. A total of 86 cases of trisomy 21, 18 and 13 and sex chromosome aneuploidy (SCA) were detected by CMA and NIPT-PLUS, with a detection rate of 96.51% (83/86). Among them, the detection rates of T18, T13; 47, XXY; 47, XXX and 47 XYY were 100%, and the detection rates of T21 and 45 XO were 96.55% and 90%, respectively. The detection sensitivity of rare chromosomal trisomy (RAT) was 80% (4/5). The positive predictive values of NIPT-PLUS for chromosome aneuploidy T21, T18 and T13 and for SCA and RAT were 90.32%, 87.50%, 25.00%, 88.89% and 50%, respectively. A total of 249 cases (74.32%) of chromosomal MMS were detected by CMA. The detection rate of NIPT-PLUS was 63.86% (159/249), and 90 cases (36.14%) were missed. The larger the MMS fragment, the higher the NIPT-PLUS detection sensitivity. In addition, most small fragments were of maternal origin. CONCLUSION: The comparison between the CMA and NIPT-PLUS techniques shows that NIPT-PLUS has high sensitivity for detecting chromosomal aneuploidy and chromosomal copy number variations (CNVs) with fragments > 5 M. However, the sensitivity of CNV for fragments < 5 M is low, and the missed detection rate is high. Additionally, confined placental mosaicism and foetal mosaicism are the key factors causing false negatives in NIPT-PLUS, while maternal chromosomal abnormalities and confined placental mosaicism are key contributors to false positives, so appropriate genetic counselling is especially important for pregnant women before and after NIPT-PLUS testing.

Genetic examination for fetuses with increased nuchal translucency by exome sequencing.

AIM: This retrospective study aimed to investigate the value of exome sequencing (ES) in fetuses with isolated first-trimester increased nuchal translucency (NT) and normal chromosomes. METHODS: ES was performed on 103 fetuses with isolated first trimester increased NT and normal chromosomes. The detection rate of monogenic conditions was analyzed. RESULTS: Diagnostic variants were detected in nine cases in which phenotypes and genotypes correlated well, two positive cases were Thanatophoric dysplasia type I, and one case was Kabuki syndrome, which had been detected in previous studies. Eight of the nine cases with diagnostic variants developed additional structural malformations later in pregnancy. Among the nine positive cases, six had a NT thickness between 95th percentile (95th-3.4 mm), and three cases with an increased NT of 3.5 mm or greater. Also, there was no statistical difference in the diagnosis of diagnostic variants in cases with or without a thickened nuchal fold (NF). CONCLUSIONS: The diagnostic yield of prenatal ES is low for fetuses with an isolated increased NT. In addition to Noonan syndrome, there are additional genetic syndromes such as Kabuki syndrome and Thanatophoric dysplasia type I that are potentially associated with an increased NT. A cut-off of greater than the 95th percentile may be useful in case selection for ES. Whether it is clinically meaningful to monitor NF values for fetuses with isolated increased NT and normal chromosomes worth considering.

Pathogenic/likely pathogenic copy number variations and regions of homozygosity in fetal central nervous system malformations.

OBJECTIVE: To explore pathogenic/likely pathogenic copy number variations (P/LP CNVs) and regions of homozygosity (ROHs) in fetal central nervous system (CNS) malformations. METHODS: A cohort of 539 fetuses with CNS malformations diagnosed by ultrasound/MRI was retrospectively analyzed between January 2016 and December 2019. All fetuses were analyzed by chromosomal microarray analysis (CMA). Three cases with ROHs detected by CMA were subjected to whole-exome sequencing (WES). The fetuses were divided into two groups according to whether they had other structural abnormalities. The CNS phenotypes of the two groups were further classified as simple (one type) or complicated (≥ 2 types). RESULTS: (1) A total of 35 cases with P/LP CNVs were found. The incidence of P/LP CNVs was higher in the extra-CNS group [18.00% (9/50)] than in the isolated group [5.32% (26/489)] (P < 0.01), while there was no significant difference between the simpletype and complicated-type groups. (2) In the simple-type group, the three most common P/LP CNV phenotypes were holoprosencephaly, Dandy-Walker syndrome, and exencephaly. There were no P/LP CNVs associated with anencephaly, microcephaly, arachnoid cysts, ependymal cysts, or intracranial hemorrhage. (3) Only four cases with ROHs were found, and there were no cases of uniparental disomy or autosomal diseases. CONCLUSION: The P/LP CNV detection rates varied significantly among the different phenotypes of CNS malformations, although simple CNS abnormalities may also be associated with genetic abnormalities.

Downregulation of LINC00221 promotes angiopoiesis in HUVEC and inhibits recruitment of macrophages by augmenting miR-542-3p in trophoblast cells.

PURPOSE: To investigate the effects of long intergenic non-protein coding RNA 221 (LINC00221) on preeclampsia (PE) and its mechanism. METHODS: The expression of LINC00221 was detected in placental tissues from PE patients and normal pregnant women (non-PE). Next, the effects of LINC00221 silencing on trophoblast cells (HTR-8/SVneo and JEG-3) and co-cultured HUVECs or macrophages were evaluated. Afterwards, miR-542-3p was confirmed to bind to LINC00221 directly, and miR-542-3p mimics and inhibitors were transfected into trophoblast cells. Next, a rescue experiment was performed to examine the effect of LINC00221/miR-542-3p axis. Finally, the effect of LINC00221 was also verified in vivo in rat PE models. RESULTS: The expression of LINC00221 was higher in placental tissues of PE patients than those of non-PE. LINC00221 silencing significantly reduced MCP1 level and increased the VEGF level in trophoblast cells. LINC00221 knockdown in trophoblast cells remarkably enhanced VEGFR expression and the angiopoiesis of HUVECs, and decreased the migration and invasion of macrophages and reduced TNF-α level. Besides, LINC00221 knockdown decreased CHOP, p-IREα, p-PERK, and iNOS expression and increased Trx expression. Notably, LINC00221 negatively regulated miR-542-3p expression. MiR-542-3p overexpression had an effect to that of LINC00221 knockdown, while miR-542-3p inhibition had the opposite effect. Treatment with miR-542-3p inhibitors partially reversed the protective effect of LINC00221 silencing. PE rat model results were consistent with those of in vitro experiments. CONCLUSIONS: Downregulation of LINC00221 might reduce dysfunction, inflammatory responses, endoplasmic reticulum stress, and oxidative stress, and thereby protect against PE by augmenting miR-542-3p.

Risk Factors for Macrosomia in Multipara: A Multi-Center Retrospective Study.

The increased incidence of macrosomia has caused an enormous burden after the transition from the almost 40-year one-child policy to the universal two-child policy in 2015 and further to the three-child policy in 2021 in China. However, studies on risk factors of macrosomia in multipara under the new fertility policy in China are limited. We aim to explore the incidence and risk factors for macrosomia in multipara to provide the scientific basis for preventing macrosomia in multipara. A multi-center retrospective study was conducted among 6200 women who had two consecutive deliveries in the same hospital and their second newborn was delivered from January to October 2018 at one of 18 hospitals in 12 provinces in China. Macrosomia was defined as birth weight ≥ 4000 g. Logistic regression models were performed to analyze risk factors for macrosomia in multipara. The incidence of macrosomia in multipara was 7.6% (470/6200) and the recurrence rate of macrosomia in multipara was 27.2% (121/445). After adjusting for potential confounders, a higher prepregnancy BMI, higher gestational weight gain, history of macrosomia, a longer gestation in the subsequent pregnancy were independent risk factors of macrosomia in multipara (p < 0.05). Healthcare education and preconception consultation should be conducted for multipara patients with a history of macrosomia to promote maintaining optimal prepregnancy BMI and avoid excessive gestational weight gain to prevent macrosomia.

Methylation Mediated Silencing of miR-155 Suppresses the Development of Preeclampsia In Vitro and In Vivo by Targeting FOXO3.

Preeclampsia (PE) is a common pregnancy-related syndrome characterized by chronic immune activation. This study is aimed at exploring the role of miR-155 in the inflammatory pathogenesis of PE. Placental tissues and peripheral blood were collected from all subjects. BSP detection analysis was performed to evaluate miR-155 methylation levels. ELISA was performed to measure the levels of inflammatory cytokines and MMP2 in serum samples and cellular supernatants. HTR-8/SVneo and JEG-3 cells were transfected with miR-155 mimic and the inhibitor to establish the overexpressed miR-155 and silenced miR-155 cell models, respectively. Treatment with 5-Aza was performed to alter the DNA methylation level of miR-155. The PE rat model was established after subcutaneous injection of NG-nitro-L-arginine methyl ester. The CCK-8 assay, TUNEL staining, and Transwell assay were performed. Reverse transcription-quantitative PCR, Western blot analysis, and immunohistochemical assay were used to analyze related gene expression levels. The luciferase reporter assay was used to investigate the direct interaction between FOXO3 and miR-155. Results showed that miR-155 was remarkably upregulated and inversely correlated with the promoter methylation level in the placental tissue from PE patients. The in vitro experiments indicated that miR-155 decreased viability, migration, and invasion, but increased apoptosis in trophoblast cells. FOXO3 was confirmed as the target of miR-155. Transfection of the miR-155 inhibitor suppressed inflammation and oxidative stress, but elevated proliferation, migration, and invasion of trophoblast cells, which were abolished by 5-Aza treatment or cotransfection with si-FOXO3. In summary, our data suggested that methylation-mediated silencing of miR-155 can inhibit the apoptosis, inflammation, and oxidative stress of trophoblast cells by upregulating FOXO3.

Expression and role of miR-146a and SMAD4 in placental tissue of pregnant women with preeclampsia.

INTRODUCTION: To investigate the expression of miR-146a in severe preeclampsia (PE) and its effect on trophoblast cell proliferation, invasion and apoptosis, as well as its relationship with SMAD4. MATERIAL AND METHODS: Participants were divided into the severe PE group (n = 30) and the normal group (n = 30). The expression of miR-146a and SMAD4 in placenta tissue was detected by immunohistochemistry, qRT-PCR, and western blot. Trophoblast cell lines HTR-8/SVneo were cultured to detect the expression of miR-146a under the Cobalt chloride (CoCl2 )-simulated hypoxia. The effects of miR-146a transfection on cell proliferation, invasion, apoptosis, and SMAD4 expression were analyzed. RESULTS: Compared with the normal group, miR-146a expression was decreased and the protein and mRNA levels of SMAD4 were increased in placenta tissues of the severe PE group. Our in vitro experiments showed that the expression of miR-146a decreased after CoCl2 treatment. Silencing miR-146a caused increased expression of SMAD4 and decreased expression of VEGF. After transfection with miR-146a inhibitor, compared with the NC group, the invasion and proliferation of HTR-8/Svneo cells were decreased, while the apoptosis was enhanced. CONCLUSION: The expression of miR-146a decreased in severe PE and was negatively correlated with SMAD4 expression. The expression of miR-146a was inhibited under hypoxia, and the low expression of miR-146a affected the proliferation, invasion, and apoptosis of trophoblast cells.

An intractable epilepsy phenotype of ASNS novel mutation in two patients with asparagine synthetase deficiency.

BACKGROUND AND OBJECTIVE: Asparagine synthetase deficiency (ASNSD) is a rare neurometabolic disease caused by variations of the ASNS gene. It manifests as microcephaly, severe developmental delay, and spastic quadriplegia. 71% of ASNSD patients died during early infancy. We aim to investigate mutations related to intractable epilepsy in one Chinese genealogy. MATERIAL AND METHODS: Head Magnetic Resonance Imaging (MRI), whole exome sequencing (WES), and Liquid Chromatography-Mass Spectrometry (LC-MS) to help 2 patients with intractable epilepsy find the underlying mechanisms of disease. RESULTS: These two patients had a compound heterozygous mutation (c.224A > G, p.N75S and c.1612A > G, p.M538V) in the ASNS gene, of which c.1612A > G was a novel mutation. The asparagine levels in patients' plasmas were normal. In addition, they had a later onset, longer survival, and were milder than previously reported ASNSD patients. CONCLUSIONS: Two patients were diagnosed with a milder form of ASNSD. Clinically, the asparagine level in the patient's plasma cannot be used as the only basis to diagnose this disease. This study has expanded the disease phenotype spectrum of ASNSD and broadened the variation profile of the ASNS gene, which can assist in the clinical diagnosis and treatment of ASNSD patients.

Genetic diagnosis of common fetal renal abnormalities detected on prenatal ultrasound.

OBJECTIVES: This retrospective study aimed to investigate the correlations between phenotypes of fetal renal abnormalities on prenatal ultrasound and genetic aetiologies detected using chromosomal microarray analysis (CMA) and whole-exome sequencing (WES). METHODS: Fetuses with renal abnormalities were subjected to CMA and were further analysed by WES when CMA-negative. The detection rates for chromosomal abnormalities and monogenic variants among different types of isolated renal abnormalities and those with extrarenal abnormalities (non-isolated cases) were determined and compared. RESULTS: CMA detected chromosomal abnormalities in 78 of 577 fetuses (13.52%). WES detected monogenic variants in 31 of 160 fetuses (19.38%) that had non-diagnostic CMA results. In cases of isolated hyperechogenic kidney, polycystic kidney disease, and multicystic dysplastic kidney, the detection rates of copy number variants (CNVs) by CMA and monogenic variants by WES were not significantly different (p > 0.05). However, monogenic variants were more frequently detected than CNVs when kidney abnormalities were accompanied by reduced amniotic fluid (p < 0.05). Other renal abnormalities identified on prenatal ultrasound had different detection rates. CONCLUSIONS: Our findings contribute to the overall knowledge of genetic variants associated with prenatally identified renal anomalies and may aid in decision making regarding prenatal genetic testing options for affected pregnancies.

Risk of gestational diabetes recurrence and the development of type 2 diabetes among women with a history of gestational diabetes and risk factors: a study among 18 clinical centers in China.

BACKGROUND: Gestational diabetes mellitus (GDM) brings health issues for both mothers and offspring, and GDM prevention is as important as GDM management. It was shown that a history of GDM was significantly associated with a higher maternal risk for GDM recurrence. The incidence of GDM recurrence was unclear because of the incidence of second-child was low before 2016 in China. We aim to investigate the prevalence of GDM recurrence and its associated high-risk factors which may be useful for the prediction of GDM recurrence in China. METHODS: A retrospective study was conducted which enrolled participants who underwent regular prenatal examination and delivered twice in the same hospital of 18 research centers. All participants were enrolled from January 2018 to October 2018, where they delivered the second baby during this period. A total of 6204 women were enrolled in this study, and 1002 women with a history of GDM were analyzed further. All participants enrolled in the study had an oral glucose tolerance test (OGTT) result at 24 to 28 weeks and were diagnosed as GDM in the first pregnancy according to the OGTT value (when any one of the following values is met or exceeded to the 75-g OGTT: 0 h [fasting], ≥5.10 mmol/L; 1 h, ≥10.00 mmol/L; and 2 h, ≥8.50 mmol/L). The prevalence of GDM recurrence and development of type 2 diabetes mellitus were calculated, and its related risk factors were analyzed. RESULTS: In 6204 participants, there are 1002 women (1002/6204,16.15%) with a history of GDM and 5202 women (5202/6204, 83.85%) without a history of GDM. There are significant differences in age (32.43 ±â€Š4.03 years vs. 33.00 ±â€Š3.34 years vs. 32.19 ±â€Š3.37 years, P  < 0.001), pregnancy interval (4.06 ±â€Š1.44 years vs. 3.52 ±â€Š1.43 years vs. 3.38 ±â€Š1.35 years, P  = 0.004), prepregnancy body mass index (BMI) (27.40 ±â€Š4.62 kg/m2vs. 23.50 ±â€Š3.52 kg/m2vs. 22.55 ±â€Š3.47 kg/m2, P < 0.001), history of delivered macrosomia (22.7% vs. 11.0% vs. 6.2%, P < 0.001) among the development of diabetes mellitus (DM), recurrence of GDM, and normal women. Moreover, it seems so important in the degree of abnormal glucose metabolism in the first pregnancy to the recurrence of GDM and the development of DM. There are significant differences in OGTT levels of the first pregnancy such as area under the curve of OGTT value (18.31 ±â€Š1.90 mmol/L vs. 16.27 ±â€Š1.93 mmol/L vs. 15.55 ±â€Š1.92 mmol/L, P < 0.001), OGTT fasting value (5.43 ±â€Š0.48 mmol/L vs. 5.16 ±â€Š0.49 mmol/L vs. 5.02 ±â€Š0.47 mmol/L, P < 0.001), OGTT 1-hour value (10.93 ±â€Š1.34 mmol/L vs. 9.69 ±â€Š1.53 mmol/L vs. 9.15 ±â€Š1.58 mmol/L, P < 0.001), OGTT 2-hour value (9.30 ±â€Š1.66 mmol/L vs. 8.01 ±â€Š1.32 mmol/L vs. 7.79 ±â€Š1.38 mmol/L, P < 0.001), incidence of impaired fasting glucose (IFG) (fasting plasma glucose ≥5.6 mmol/L) (31.3% vs. 14.6% vs. 8.8%, P < 0.001), and incidence of two or more abnormal OGTT values (68.8% vs. 39.7% vs. 23.9%, P < 0.001) among the three groups. Using multivariate analysis, the factors, such as age (1.07 [1.02-1.12], P = 0.006), prepregnancy BMI (1.07 [1.02, 1.12], P  = 0.003), and area under the curve of OGTT in the first pregnancy (1.14 [1.02, 1.26], P  = 0.02), have an effect on maternal GDM recurrence; the factors, such as age (1.28 [1.01-1.61], P  = 0.04), pre-pregnancy BMI (1.26 [1.04, 1.53], P = 0.02), and area under the curve of OGTT in the first pregnancy (1.65 [1.04, 2.62], P = 0.03), have an effect on maternal DM developed further. CONCLUSIONS: The history of GDM was significantly associated with a higher maternal risk for GDM recurrence during follow-up after the first pregnancy. The associated risk factors for GDM recurrence or development of DM include age, high pre-pregnancy BMI, history of delivered macrosomia, the OGTT level in the first pregnancy, such as the high area under the curve of OGTT, IFG, and two or more abnormal OGTT values. To prevent GDM recurrence, women with a history of GDM should do the preconception counseling before preparing next pregnancy.

Changes in the live birth profile in Henan, China: A hospital registry-based study.

BACKGROUND: Preterm complications and neonatal asphyxia are the leading causes of death in those under 5 years of age. However, little information exists for the province of Henan, China. The purpose of this study was to explore changes in the live birth profile in a provincial hospital over the past 32 years in Henan, China. METHODS: A retrospective analysis was conducted to reveal the characteristics of live neonates from 1987 to 2018. RESULTS: There were 118 253 live births during the period, including 19 798 (16.74%) preterm births. The neonatal death rate was 6.45‰, and the top risk factor was preterm birth complications and birth asphyxia. Before 1998, neonatal death occurred primarily among term infants. Between 1999 and 2018, preterm infants, especially extreme and very preterm infants with very low birthweight, constituted more than half of all mortalities, and the preterm birth rate increased from 5.94% in 1999 to 16.69% in 2018. The risk factors associated with preterm birth were being male (aOR = 1.18, P < 0.001), advanced maternal age (>35 years old; aOR = 1.08, P = 0.008), gravidity ≥2 (aOR = 1.15, P < 0.001), parity ≥2 (aOR = 1.50, P < 0.001), placenta previa (aOR = 7.41, P < 0.001), twin or multiple births (aOR = 10.63, P < 0.001), hypertension (aOR = 2.08, P < 0.001), and rupture of membrane (aOR = 5.03, P < 0.001). CONCLUSIONS: The preterm birth rate has increased over the past 32 years from 4.98% to 16.69% in a provincial hospital in China. Preterm birth was the leading reason for neonatal death, and birth asphyxia was the major risk factor for death in term infants.

Conservative management versus cesarean hysterectomy in patients with placenta increta or percreta.

OBJECTIVE: To compare conservative management and cesarean hysterectomy in patients with placenta increta or percreta. MATERIALS AND METHODS: In this multicenter retrospective study, we recorded data on 2219 patients with placenta increta or percreta from 20 tertiary care centers in China from 1 January 2011 to 31 December 2015. Propensity score analysis was used to control for baseline characteristics. We divided patients into conservative management (C) and hysterectomy (H) groups. The primary outcome was operative/postoperative maternal morbidity; secondary outcomes were maternal-neonatal outcomes. RESULTS: In total, 17.9% (398/2219) of patients had placenta increta and percreta; 82.1% (1821/2219) of the patients were in group C. After propensity score matching, 140 pairs of patients from the two groups underwent one-to-one matching. Group C showed less average blood loss within 24 h of surgery (1518 ± 1275 vs. 4309 ± 2550 ml in group H, p<.001). There were more patients with blood loss >1000 ml in group H than in group C (93.6% [131/140] vs. 61.4% [86/140], p<.001). More patients received blood transfusions in group H than in group C (p=.014). There was no significant difference between the groups in terms of bladder injury, postoperative anemia, fever, and disseminated intravascular coagulation. Neonatal outcomes in the two groups were similar. CONCLUSION: Either conservative management or hysterectomy should be considered after thorough evaluation and detailed discussion of risks and benefits. A balance between bleeding control and fertility can be achieved.

Long non-coding RNA SOS1-IT1 promotes endometrial cancer progression by regulating hypoxia signaling pathway.

Endometrial cancer (EC) is one of the most common types of gynecological cancer. Hypoxia is an important clinical feature and regulates various tumor processes. However, the prognostic value of hypoxia-related lncRNA in EC remains to be further elucidated. Here, we aimed to characterize the molecular features of EC by the development of a classification system based on the expression profile of hypoxia-related lncRNA. Based on univariate Cox regression analysis, we identified 17 hypoxia-related lncRNAs significantly associated with overall survival. Next, the least absolute shrinkage and selection operator Cox regression model was utilized to construct a multigene signature in the TCGA EC cohort. The risk score was confirmed as an independent predictor for overall survival in multivariate Cox regression analysis and receiver operating characteristic (ROC) curve analysis. Besides, the survival time of EC patients in different risk group was significantly correlated to clinicopathologic factors, such as age, stage and grade. Furthermore, hypoxia-related lncRNA associated with the high-risk group were involved in various aspects of the malignant progression of EC via Gene Ontology, Kyoto Encyclopedia of Genes and Genomes pathway, and Gene Set Enrichment Analysis. Moreover, the risk score was closely correlated to immunotherapy response, microsatellite instability and tumor mutation burden. Finally, we select one hypoxia-related lncRNA SOS1-IT1 to validate its role in hypoxia and EC progression. Interestingly, we found SOS1-IT1 was overexpressed in tumor tissues, and closely correlated with clinicopathological parameters of EC. The expression level of SOS1-IT1 was significantly increased under hypoxia condition. Additionally, the important hypoxia regulatory factor HIF-1α can directly bind SOS1-IT1 promoter region, and affect its expression level. In summary, this study established a new EC classification based on the hypoxia-related lncRNA signature, thereby provide a novel sight to understand the potential mechanism of human EC development.

A randomized controlled trial of low-dose aspirin for the prevention of preeclampsia in women at high risk in China.

BACKGROUND: Low-dose aspirin has been the most widely studied preventive drug for preeclampsia. However, guidelines differ considerably from country to country regarding the prophylactic use of aspirin for preeclampsia. There is limited evidence from large trials to determine the effect of 100 mg of aspirin for preeclampsia screening in women with high-risk pregnancies, based on maternal risk factors, and to guide the use of low-dose aspirin in preeclampsia prevention in China. OBJECTIVE: The Low-Dose Aspirin in the Prevention of Preeclampsia in China study was designed to evaluate the effect of 100 mg of aspirin in preventing preeclampsia among high-risk pregnant women screened with maternal risk factors in China, where preeclampsia is highly prevalent, and the status of low-dose aspirin supply is commonly suboptimal. STUDY DESIGN: We conducted a multicenter randomized controlled trial at 13 tertiary hospitals from 11 provinces in China between 2016 and 2019. We assumed that the relative reduction in the incidence of preeclampsia was at least 20%, from 20% in the control group to 16% in the aspirin group. Therefore, the targeted recruitment number was 1000 participants. Women were randomly assigned to the aspirin or control group in a 1:1 allocation ratio. Statistical analyses were performed according to an intention-to-treat basis. The primary outcome was the incidence of preeclampsia, diagnosed along with a systolic blood pressure of ≥140 mm Hg or a diastolic blood pressure of ≥90 mm Hg after 20 weeks of gestation, with a previously normal blood pressure (systolic blood pressure of <140 mm Hg and diastolic blood pressure of <90 mm Hg), and complicated by proteinuria. The secondary outcomes included maternal and neonatal outcomes. Logistic regression analysis was used to determine the significance of difference of preeclampsia incidence between the groups for both the primary and secondary outcomes. Interaction analysis was also performed. RESULTS: A total of 1000 eligible women were recruited between December 2016 and March 2019, of which the final 898 patients were analyzed (464 participants in the aspirin group, 434 participants in the control group) on an intention-to-treat basis. No significant difference was found in preeclampsia incidence between the aspirin group (16.8% [78/464]) and the control group (17.1% [74/434]; relative risk, 0.986; 95% confidence interval, 0.738-1.317; P=.924). Likewise, adverse maternal and neonatal outcomes did not differ significantly between the 2 groups. Meanwhile, the incidence of postpartum hemorrhage between the 2 groups was similar (6.5% [30/464] in the aspirin group and 5.3% [23/434] in the control group; relative risk, 1.220; 95% confidence interval, 0.720-2.066; P=.459). We did not find any significant differences in preeclampsia incidence between the 2 groups in the subgroup analysis of the different risk factors. CONCLUSION: A dosage of 100 mg of aspirin per day, initiated from 12 to 20 gestational weeks until 34 weeks of gestation, did not reduce the incidence of preeclampsia in pregnant women with high-risk factors in China.

Morbidity and maternal and infant outcomes of hypertensive disorder in pregnancy in China in 2018.

Hypertensive disorder in pregnancy is a disease that occurs during pregnancy. We aimed to analyze the morbidity and maternal and infant outcomes with respect to the hypertensive disorder in pregnancy in China in 2018. Clinical data of 38 590 cases from 161 hospitals were retrospectively collected. The differences in morbidity and maternal and infant mortality among the major regions and provinces were compared. The overall national average morbidity was 4.74%, and the ratios of gestational hypertension, preeclampsia, eclampsia, chronic hypertension, and chronic hypertension with superimposed preeclampsia were 29.17%, 55.02%, 0.66%, 6.53%, and 8.62%, respectively. The overall maternal mortality was 0.61/100 000, and the case fatality was 0.13%. Morbidity associated with hypertensive disorder in pregnancy was 7.74% in North China, 6.62% in Northwest China, 6.40% in Central China, 5.83% in Northeast China, 4.28% in East China, 3.85% in South China, and 2.88% in Southwest China. The morbidity in each province was 1.62-11.28%. The overall perinatal mortality was 3.59% (81.09% for stillbirths; 18.91% for neonatal deaths). Perinatal mortality decreased with increasing gestational weeks from 24 to 37 + 6 weeks. Perinatal mortality for delivery at 32 weeks of gestation in all regions of the country was <10%. Morbidity varied across regions in China, with the lowest in Southwest and the highest in North China. The low maternal mortality is related to the large-scale development of standardized maternal health care in China. For severe hypertensive disorder patients, gestation should be prolonged to 32 weeks as often as possible for better neonatal survival rates.

Expression and significance of microRNA-126 and VCAM-1 in placental tissues of women with early-onset preeclampsia.

OBJECTIVE: To investigate the expression of microRNA-126 (miR-126) and vascular endothelial cell adhesion molecule-1 (VCAM-1) in the placental tissues of women with early-onset preeclampsia (EOPE) and their effects on trophoblast invasion. MATERIALS AND METHODS: The placental tissues of 30 pregnant women with EOPE who delivered in the Third Affiliated Hospital of Zhengzhou University from November 2019 to May 2020 were selected as the preeclampsia (PE) group, and the placental tissues of 30 healthy pregnant women with normal prenatal examination were selected as the normal group. Immunohistochemistry was used to localize VCAM-1 in placental tissues，the expression of miR-126 and VCAM-1 in placenta tissues of two groups and HTR-8/SVneo cells transfected with miR-126 were detected by real-time polymerase chain reaction (RT-PCR) and Western blot, and the correlation between them was analyzed. The invasion ability of cells transfected with miR-126 was observed by Transwell invasion test. RESULTS: Compared with the normal group, the expression of miR-126 was higher and VCAM-1 was lower in the placental tissues of the PE group, and the difference were statistically significant (p < 0.01). Moreover, VCAM-1 was negatively correlated with the expression of miR-126 (r = -0.391, p < 0.05). In vitro experiment, the expression level of VCAM-1 in miR-126 mimics transfection group was decreased, and the expression level of VCAM-1 in miR-126 inhibitor transfection group was increased; the invasion ability of HTR-8/SVneo cells transfected with miR-126 mimics was decreased, and the invasion ability of HTR-8/SVneo cells transfected with miR-126 inhibitor was enhanced. CONCLUSION: There was a negative correlation between the expression of miR-126 and VCAM-1 in EOPE.MiR-126 and VCAM-1 may participate in the occurrence and development of EOPE by affecting the invasion ability of trophoblast cells.

Correlation Analysis between GDM and Gut Microbial Composition in Late Pregnancy.

The prevalence of GDM is very high worldwide. The specific pathogenesis of GDM is currently not very clear. Recent research suggests that changes in the intestinal flora during pregnancy play a key role in it. Therefore, this study is aimed at exploring the characteristics of the intestinal flora of patients with gestational diabetes in the third trimester of pregnancy and at finding the intestinal flora with significant differences in healthy pregnant women to provide a basis for future clinical attempts of using intestinal microecological agents to treat gestational diabetes mellitus (GDM). We sequenced the V3-V4 regions of the 16S ribosomal ribonucleic acid (rRNA) gene from stool samples of 52 singleton pregnant women at >28 weeks of gestation. Our results showed that there were significant differences between the NOR group vs. GDM group and the G group vs. LG group among Bacteroides, Firmicutes, and Firmicutes/Bacteroides. At the species level, there were significant differences in the abundance of eight species in the NOR and GDM groups. Among them, the relative abundance of Clostridium_spiroforme, Eubacterium_dolichum, and Ruminococcus_gnavus was positively correlated with FBG, and Pyramidobacter_piscolens was negatively correlated with FBG, whereas there were significant differences in the abundance of five species in the G and LG groups. Functional analysis showed that there were differences in the biosynthesis and metabolism of polysaccharides, digestive system, classification, and degradation of the intestinal microbes between the NOR and GDM groups and between the G and LG groups. These results indicated that the gut microbes between GDM patients in the third trimester of pregnancy and healthy controls had essential characteristic changes and might be involved in the regulation of patients' blood glucose levels.

Association between morphologic grading and implantation rate of Euploid blastocyst.

BACKGROUND: Standard morphologic evaluation has been the most widely adopted approach to embryo selection, and remains the most common strategy.The objective of the study to determine the association between the morphologic grading and implantation rate of euploid blastocysts in single frozen-thawed embryo transfer (SET) cycles. METHODS: A total of 271 patients aged 20-40 years undergoing euploid SET from January 2017 to December 2019 were included in retrospective cohort study.The cycles were divided into three groups based on their morphologic grading before cryopreservation: good-quality (n = 58), average-quality (n = 88) and poor-quality blastocysts (n = 125). The pregnancy outcome of the three morphologic groups were analyzed and a logistic regression of implantation rate was conducted. RESULTS: Good-quality blastocysts yielded statistically significantly higher implantation rates than poor-quality (79.31% vs. 48%; P<0.001). Planned subgroup analyses by age and the day of TE biopsy were conducted. Logistic regression analyses that adjusted for these variables identified higher implantation rates (adjusted odds ratio(aOR) = 4.083, 95% confidence interval (CI):1.836-9.082, P<0.001) for the good-quality blastocysts than for those that underwent poor-quality cycles in women aged < 35 years, but not in women aged ≥35 years (aOR = 6.074, 95% CI: 0.456-80.919, P = 0.172). The implantation rates were higher among women with good-quality blastocysts on both Day 5 and Day 6 of TE biopsy than among those with poor-quality blastocysts (Day 5, aOR = 3.294, 95% CI:1.260-8.616, P = 0.015; Day 6, aOR = 4.179, 95% CI:1.004 ~ 17.399, P = 0.049). Day 5 euploid blastocysts had no significant difference in implantation potential and early spontaneous abortion rate compared with similarly graded Day 6 euploid blastocysts. CONCLUSIONS: Blastocyst morphologic grading was associated with implantation rate for euploid embryo transfers after adjustment for potential confounders. These findings suggest that evaluating blastocyst morphology is critical when selecting the best euploid blastocyst.