The improvement of inflammatory infiltration and pregnancy outcome in mice with recurrent spontaneous abortion by human amniotic mesenchymal stem cells.

Recurrent spontaneous abortion is thought to be mostly triggered by immune-related causes. Mesenchymal stem cells, which exhibit the traits of multi-directional differentiation capacity and low immunogenicity, have recently been recommended as a viable treatment for spontaneous abortion-prone mice to increase the success of pregnancy. Amniotic membrane tissue is a byproduct of pregnancy and delivery that has a wide range of potential uses due to its easy access to raw materials and little ethical constraints. To construct an abortion-prone mouse model for this investigation, CBA/J female mice were coupled with male DBA/2 mice, while CBA/J female mice were paired with male BALB/c mice as a control. The identical volume of human amniotic mesenchymal stem cells or phosphate buffer was injected intraperitoneally on the 4.5th day of pregnancy. CBA/J female mice were sacrificed by cervical dislocation on the 13.5th day of pregnancy, the embryo absorption rate was calculated, and the uterus, decidua tissues and placenta were gathered for examination. Through detection, it was discovered that human amniotic mesenchymal stem cells significantly increased the expression of interleukin 10 and transforming growth factor beta, while they significantly decreased the expression of interleukin 1 beta and interleukin 6, improved vascular formation and angiogenesis, and minimized the embryo absorption rate and inflammatory cell infiltration in the recurrent spontaneous abortion + human amniotic mesenchymal stem cells group. In any case, human amniotic mesenchymal stem cells regulate inflammatory factors and cell balance at the maternal-fetal interface, which result in a reduction in the rate of embryo absorption and inflammatory infiltration and provide an innovative perspective to the clinical therapy of recurrent spontaneous abortion.

Identification of differentially expressed miRNAs in serum extracellular vesicles (EVs) of Kazakh sheep at early pregnancy.

MiRNAs-containing extracellular vesicles (EVs) possess the unique function of mediating intercellular communication and participating in many biological processes such as post-transcriptional gene regulation of embryo implantation and placental development. In the present study, Illumina small-RNA sequencing was used to identify differentially expressed (DE) miRNAs in serum EVs of pregnant (P) and non-pregnant (NP) Kazakh sheep at Day 17 from mating. The specifically and differentially expressed miRNAs at early pregnancy in sheep were verified by using RT-PCR. The target genes of DE miRNAs were predicted by bioinformatics software, and the functional and pathway enrichment analysis was performed on Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) terms. A total of 562 miRNAs (210 novel miRNAs) were identified by sequencing, of which 57 miRNAs were differentially expressed, 49 were up-regulated, 8 were down-regulated and 22 novel miRNAs were specifically expressed in the pregnant sheep. Eight highly expressed known miRNA (miR-378-3p, miR-320-3p, miR-22-3p, let-7b, miR-423-3p, miR-221, miR-296-3p, miR-147-3p) in pregnant group were down-regulated in the control group. miRNAs-containing pregnancy-related terms and regulatory pathways regulation were enriched using both GO and KEGG analyses. Moreover, we also envisioned a miRNA-mRNA interaction network to understand the function of miRNAs involved in the early pregnancy serum regulatory network. The results of RT-PCR verification confirmed the reliability of small-RNA sequencing. Among them, miR-22-3p and miR-378-3p were significantly differentially expressed (DE) between pregnant sheep and non-pregnant group (p <  0.01). The site at which oar-miR-22-3p binds MAPK3 was determined with a dual-luciferase system. This is the first integrated analysis of the expression profiles of EV-miRNAs and their targets during early pregnancy in ewes. These data identify key miRNAs that influence the implantation of sheep in the early stage of pregnancy, and provide theoretical basis for further molecular regulatory mechanisms research.

Knockdown of differentiation antagonizing non-protein coding RNA exerts anti-tumor effect by up-regulating miR-214 in endometrial carcinoma.

Differentiation antagonizing non-protein coding RNA (DANCR) is a valuable long noncoding RNA (lncRNA) that involves in the progress of various cancers. However, the functions of DANCR in endometrial carcinoma (EC) have not been validated. In the present study, we aimed to evaluate the roles of DANCR in EC and explore the underlying mechanism. Expression patterns of DANCR in EC specimens and normal control specimens were determined using qRT-PCR. DANCR was knocked down in EC cell lines (AN3CA and HEC-1B) through transfection with small interfering RNA (siRNA) targeting DANCR (si-DANCR). Cell proliferation was examined using the cell counting kit-8 (CCK-8) assay. Cell apoptosis was measured by flow cytometry. Online software starBase was used to predict the target gene of DANCR. Luciferase reporter assay was carried out to confirm the association between DANCR and the predicted target microRNA (miRNA). DANCR expression was up-regulated in EC tissues as compared to the normal control tissues. Knockdown of DANCR in AN3CA and HEC-1B cells markedly suppressed cell proliferation and induced cell apoptosis. miR-214 was found to be a target miRNA of DANCR and its expression was significantly decreased in EC tissues. Suppression of miR-214 abolished the effects of si-DANCR on cell proliferation and apoptosis in AN3CA and HEC-1B cells. DANCR played an important role in promoting tumorigenesis of EC via sponging miR-214. DANCR might serve as a therapeutic target for the treatment of EC.

Identification and Genetic Analysis of a Factor IX Gene Intron 3 Mutation in a Hemophilia B Pedigree in China.

OBJECTIVE: Hemophilia B is caused by coagulation defects in the factor IX gene located in Xq27.1 on the X chromosome. A wide range of mutations, showing extensive molecular heterogeneity, have been described in hemophilia B patients. Our study was aimed at genetic analysis and prenatal diagnosis of hemophilia B in order to further elucidate the pathogenesis of the hemophilia B pedigree in China. MATERIALS AND METHODS: Polymerase chain reaction amplification and direct sequencing of all the coding regions was conducted in hemophilia B patients and carriers. Prenatal diagnosis of the proband was conducted at 20 weeks. RESULTS: We identified the novel point mutation 10.389 A>G, located upstream of the intron 3 acceptor site in hemophilia B patients. The fetus of the proband's cousin was identified as a carrier. CONCLUSION: Our identification of a novel mutation in the F9 gene associated with hemophilia B provides novel insight into the pathogenesis of this genetically inherited disorder and also represents the basis of prenatal diagnosis.

The Moderating Effect of Self-Efficacy on Pregnancy Stress and Smartphone Addiction of Pregnant Women in Late Pregnancy: A Longitudinal Study.

Purpose: We aimed to understand the current situation of smartphone addiction in pregnant women, and explored the moderating effect of self-efficacy between pregnancy stress and smartphone addiction. Patients and Methods: This study adopted a longitudinal design to collect pregnant women from the obstetrics and gynecology department of a tertiary hospital in Shenyang in 2020 from early pregnancy (T1) to their late pregnancy (T2). A total of 342 questionnaires were collected, including the Smartphone Addiction Scale-Short Version (SAS-SV), the Pregnancy Pressure Scale (PPS), and the Chinese version of the General Self-Efficacy Scale (GSES). Multiple hierarchical regression and simple slope test were used to test the moderating effect of self-efficacy. Results: Smartphone addiction in T2 (44.74) was more sever than in T1 (33.11). The interaction item of T1 pregnancy stress and T2 self-efficacy was positively correlated with smartphone addiction (ß=0.205, P<0.01) and explained an additional 3.2% variance (ΔR2=0.032, P<0.01). The influence of pregnancy stress on smartphone addiction was gradually decreased in the low, mean, and high groups of self-efficacy. Conclusion: Smartphone addiction in late pregnancy was more severe than that in early pregnancy, possibly due to increased pregnancy stress. The self-efficacy of pregnant women could reduce the impact of pregnancy stress on smartphone addiction. Medical staff can alleviate the bad behavior by improving their self-efficacy.

Status and development of research on clear cell carcinoma of the ovary-a visualization-based bibliometric analysis.

Background: Clear cell carcinoma of the ovary (CCCO) is a relatively rare type of epithelial ovarian cancer (EOC) that has unique biological characteristics and clinical features. Researchers have paid less attention to this disease than to other types of EOCs. However, in recent years, research in this area has still progressed. In this paper, a bibliometric analysis is used to integrate and analyse the literature in the field of CCCO in the past 20 years to determine research development, better understand the current status of research, and provide a reference for future study directions in this field. Methods: With CCCO as the research subject, relevant publications indexed in the Web of Science (WOS) core dataset from September 2003 to September 2023 were retrieved. After screening the publications, we used EXCEL, VOSviewer, CiteSpace, Charticulator, Gephi, OriginPro and other tools to perform in-depth analyses of and to visualize the data. Results: Through a comprehensive analysis of the literature in this field, we found that research on CCCO experienced a relatively rapid increase in 2006 and is now in a period of relatively high fluctuation. The quality of the literature in this field is generally high. In this field, countries in East Asia and North America play core roles, with Japan accounting for the most studies. A stable research group has been formed in this field, and extensive collaboration has occurred among the various research groups. In the past 20 years, basic research and clinical research in the field of CCCO have developed together, and a healthy development model in which basic and clinical research promote each other has formed. Research in this field has been continuously developed from a preliminary understanding of clinical features to in-depth explorations of the pathogenesis and the continuous optimization of treatment methods. The key molecular events in the pathogenesis and development of this disease and the application of novel antitumour drugs for this disease are the current research focuses and the future development direction in this field. Conclusions: Research on CCCO has progressed significantly in the past 20 years, but there are still many important issues regarding its pathogenesis and treatment that need to be addressed, and therefore, more research in this area should be conducted in the future. The study of key molecular events and the use of novel antitumour drugs are future development directions in this field.

Independent factors associated with birth defects during the whole of pregnancy in Shenyang City, China: a case-control study.

Background: Birth defects, as a kind of diseases that seriously affect human life, have always attracted much attention. In the past, perinatal data have been studied for birth defects. This study analyzed the surveillance data of birth defects during the perinatal period and the whole of pregnancy, as well as the independent influencing factors, to help to minimize their risk of birth defects. Methods: A total of 23,649 fetuses delivered in the hospital from January 2017 to December 2020, were enrolled in this study. There were 485 cases of birth defects, including live births and stillbirths by detailed inclusion and exclusion criteria. Maternal and neonatal clinical data were collated to analyze the influencing factors associated with birth defects. Pregnancy complications and comorbidities were diagnosed according to the criteria of the Chinese Medical Association. Univariate and multivariate logistic regression models were used to investigate the association between independent variables and birth defect events. Results: The incidence of birth defects during the whole of pregnancy was 175.46/10,000, while the incidence of perinatal birth defects was 96.22/10,000. The birth defect group had significantly higher maternal age, gravidity, parity, rate of preterm birth, cesarean section (CS) rate, scarred uterus, stillborn, and male newborns compared to the control group. Multivariate logistic regression model analysis showed that preterm birth [odds ratio (OR): 1.69, 95% confidence interval (CI): 1.01 to 2.86], CS (OR: 1.46, 95% CI: 1.08 to 1.98), scarred uterus (OR: 1.70, 95% CI: 1.01 to 2.85), and low birth weight (OR >4 compared to the other two classes) were significantly associated with birth defects during the whole of pregnancy (all P<0.05). The independent influencing factors associated with perinatal birth defects included CS (OR: 1.43, 95% CI: 1.05 to 1.93), gestational hypertension (OR: 1.70, 95%: 1.04 to 2.78), and low birth weight (OR >3.70 compared to the other two classes). Conclusions: The discovery and monitoring of known influencing factors associated with birth defects, such as, preterm birth, gestational hypertension, low birth weight, should be enhanced. For the controllable influencing factors, obstetrics providers should work with patients to minimize their risk of birth defects.

The effect of maternal age and duration of labor on perinatal and neonatal outcomes: a retrospective cohort study.

Background: This study aimed to investigate the effect of maternal age and duration of labor on perinatal and neonatal outcomes. The results of this study are expected to provide a basis to aid maternal and child health care personnel to implement health education for late childbearing women. Methods: This was a retrospective observational study, wherein 9,241 parturients were included from 2016 to 2018. Parturients were divided into three groups based on age: <28 (n=2,911), 28-30 (n=3,631), and >30 (n=2,699) years. According to the total duration of labor, those who did not undergo cesarean section (CS) were subgrouped into <420 minutes (n=4,065) and ≥420 minutes (n=4,094) groups. A multivariate logistic regression model was used to investigate associations between age/total duration of labor group factors to different postpartum outcomes, including a switch to emergency CS, puerperal morbidity, abnormal fetal heart rate, and meconium-stained amniotic fluid (MSAF). Results: The rates of postpartum outcomes significantly differed in maternal age groups, including switch to emergency CS (9.07% vs. 13.03% vs. 11.23%; P<0.001), puerperal morbidity (6.32% vs. 6.46% vs. 5.00%; P=0.035), and abnormal fetal heart rate (25.34% vs. 28.21% vs. 25.67%; P=0.017). Of the comparisons between labor time groups, it was found that participants with longer labor time were also significantly higher in the use of episiotomy/forceps (46.61% vs. 69.77%; P<0.001), bleeding amount (381.35±108.02 vs. 389.60±146.40 mL; P=0.004), oxytocin use (25.03% vs. 39.56%; P<0.001), puerperal morbidity (1.98% vs. 6.86%; P<0.001), abnormal fetal heart rate (20.07% vs. 25.15%; P<0.001), and MSAF (26.53% vs. 31.91%; P<0.001). Multivariate logistic regression analysis showed that as age increased, the ORs of switching to emergency CS (1.58 and 1.87, both P<0.001) and having abnormal fetal heart rate (1.20 and 1.38; both P<0.01) also increased. Participants with longer labor time groups the ORs of puerperal morbidity (2.33; P<0.001) and MSAF (1.13; P=0.023) also increased. Conclusions: With the adjustment of covariates. Higher maternal age seems associated to the risk of switching to emergency CS and having abnormal fetal heart rate; longer total duration of labor seems associated to the risk of puerperal morbidity and MSAF.

Comprehensive Analysis of the Expression and Prognosis for MCM4 in Uterine Corpus Endometrial Carcinoma.

Background: Mini chromosome maintenance protein 4 (MCM4) belongs to the family of mini chromosome maintenance proteins (MCMs) that plays a crucial role in DNA replication and cell cycle regulation. Given that MCM4 has been reported to be aberrantly expressed in a variety of tumor tissues, and is strongly associated with poor patient prognosis, it has rarely been reported in uterine corpus endometrial carcinoma (UCEC). Methods: We explored the role of MCM4 in UCEC through multi-omics analysis, including gene expression levels, survival prognosis, the biological function of interacting proteins, immune infiltration, and diagnostic value. Finally, these results were confirmed by biological experiments. Results: MCM4 was highly expressed in various malignancies including UCEC compared to normal samples and was associated with poor prognosis in patients with UCEC [including OS (HR = 1.74, p = 0.009), PFI (HR = 1.73, p = 0.002), PFI (HR = 2.23, p = 0.003)]. In the Cox regression analysis, MCM4 was an independent prognostic biomarker. Further studies showed those interacting proteins of MCM4 were enriched in DNA repair and cell cycle. Moreover, high expression of MCM4 was accompanied by lower infiltration of immune cells such as Treg cells and B cells. The distribution of MCM4 expression in molecular and immune subtypes was significantly different (p < 0.05), with high expression in the copynumber high (CN_HIGH) molecular subtype and the IFN-gamma dominant (C2) immune subtype. RT-qPCR and immunohistochemistry results also showed that MCM4 expression was significantly upregulated in endometrial cancer tissues and negatively correlated with patient prognosis (p < 0.05). Subsequent biological experiments confirmed that MCM4 promoted cell growth and invasion and inhibited apoptosis in vitro. Conclusion: Therefore, MCM4 could be a new potential biomarker for UCEC.

MicroRNA miR-106a-5p targets forkhead box transcription factor FOXC1 to suppress the cell proliferation, migration, and invasion of ectopic endometrial stromal cells via the PI3K/Akt/mTOR signaling pathway.

Emerging evidence has exhibited an obvious decreased expression of miR-106a-5p in the ectopic endometrial tissue of endometriosis (EMS) patients. Thus far, the pathophysiological function of miR-106a-5p in EMS is unknown. A previous study showed an increased FOXC1 expression in the ectopic endometrial tissue of patients with EMS. Moreover, we found that there was a binding site of miR-106a-5p on the 3'UTR of FOXC1 through bioinformatics predictions. Hence, we speculated that miR-106a-5p might affect the development of EMS via targeting FOXC1. We first showed a decreased level of miR-106a-5p and an increased level of FOXC1 mRNA in ectopic endometrial tissues compared with normal tissues. Functionally, we transfected ectopic endometrial stromal cells (ESCs) with miR-106a-5p mimics or NC mimics and indicated an inhibitory role of miR-106a-5p on ESC proliferation, invasion, and migration. Mechanistically, FOXC1 was found to be a target gene of miR-106a-5p. To confirm whether miR-106a-5p exerted an inhibitory activity in ESCs via targeting FOXC1, miR-106a-5p mimic was co-transfected into ESCs with the FOXC1-plasmid or vector. We found that FOXC1 overexpression evidently reversed the results caused by a miR-106a-5p mimic in ESCs. Additionally, our results demonstrated that miR-106a-5p mimic inhibited the expression of p-Akt and p-PI3K. Collectively, these results revealed that miR-106a-5p inhibited the proliferative, migratory, and invasive ability of ESCs via directly binding to FOXC1, likely through the suppression of the PI3K and its downstream signaling pathway, which offered a potential and novel therapeutic strategy for EMS treatment.