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

Recurrent spontaneous abortion (RSA) is thought to be mostly triggered by immune-related causes. Mesenchymal stem cells (MSCs), 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 hAMSCs or PBS 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 hAMSCs significantly increased the expression of interleukin 10 (IL-10) and transforming growth factor beta (TGF-ß), while significantly decreased the expression of interleukin 1 beta (IL-1ß) and interleukin 6 (IL-6), improved vascular formation and angiogenesis, minimized the embryo absorption rate and inflammatory cell infiltration in the RSA + hAMSCs group. In any case, hAMSCs 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 RSA.

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.

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.

Deformation and Phase Transformation of Disordered α Phase in the (α + γ) Two-Phase Region of a High-Nb TiAl Alloy.

In this paper, the deformation and phase transformation of disordered α phase in the (α + γ) two-phase region in as-forged Ti-44Al-8Nb-(W, B, Y) alloy were investigated by hot-compression and hot-packed rolling. The detailed microstructural evolution demonstrated that the deformed microstructure was significantly affected by the deformation conditions, and the microstructure differences were mainly due to the use of a lower temperature and strain rate. Finer α grains were formed by the continuous dynamic recrystallization of α lamellae and α grains distributed around lamellar colonies. Moreover, the grooved γ grains formed by the phase transformation from α lamellae during hot rolling cooperated with and decomposed α lamellae. A microstructure evolution model was built for the TiAl alloy at 1250 °C during hot rolling.

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.

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.

Factors affecting failed trial of labor and countermeasures: A retrospective analysis.

BACKGROUND: Vaginal delivery is the ideal mode of delivery for the termination of a pregnancy. However, the cesarean section rate in China is much higher than the published by the World Health Organization in the Lancet in 2010. AIM: To retrospectively analyze the factors related to failed trial of labor and the clinical indications for cesarean section conversion, explore how to promote the trial of labor success rate, and determine the feasibility of reducing the rate of conversion to cesarean section. METHODS: A retrospective analysis was performed on 9240 maternal women who met vaginal delivery conditions and required a trial of labor from January 2016 to December 2018 at our hospital. Among them, 8164 pregnant women who had a successful trial of labor were used as a control group, and 1076 pregnant women who had a failed trial of labor and converted to an emergency cesarean section were used as an observation group. The patients' clinical data during hospitalization were collected for comparative analysis, the related factors of the failed trial of labor were discussed, and reasonable prevention and resolution strategies were proposed to increase the success rate of trial of labor. RESULTS: The analysis revealed that advanced age (≥ 35 years old), macrosomia (≥ 4000 g), delayed pregnancy (≥ 41 wk), use of uterine contraction drugs, primipara, and fever during labor were associated with conversion to an emergency cesarean section in the failed trial of labor. Multivariate regression analysis showed that age, gestational age, primipara, use of uterine contraction drugs, fever during birth, and newborn weight led to a higher probability of conversion to an emergency cesarean section in the failed trial of labor. The analysis indicated that the following clinical indications were associated with the conversion to cesarean section in the failed trial of labor: Fetal distress (44.3%), social factors (12.8%), malpresentation (face presentation, persistent occipitoposterior position, and persistent occipitotransverse position) (9.4%), and cephalopelvic disproportion (8.9%). CONCLUSION: The conversion to emergency cesarean section in failed trial of labor is affected by many factors. Medical staff should take appropriate preventive measures for the main factors, increase the trial of labor success rate, improve the quality of delivery, ensure the safety of mother and child during the perinatal period, and improve the relationship between doctors and patients.

Risk scores, prevention, and treatment of maternal venous thromboembolism.

BACKGROUND: At present, the preventive treatment for pregnancy-related venous thromboembolism (VTE) in China is in its infancy, and there is no uniform or standardized industry guide. Drug prevention and treatment of pregnancy-related VTE rely highly on foreign guidelines; however, due to the differences in ethnicity and national conditions, there are many controversies over the indications for drug treatment, drug selection, and dose selection for anticoagulant therapy. AIM: To investigate the risk scores, prevention, and treatment of maternal VTE to promote the prevention and standardized treatment of maternal thrombosis. METHODS: A retrospective analysis was performed on 7759 patients who gave birth at our hospital from June 2018 to June 2019. Risk factors for pregnancy-related VTE, prenatal and postpartum VTE risk scores, prophylactic anticoagulant therapy, side effects after medication, and morbidity were analysed. RESULTS: The risk factors for VTE were mainly caesarean delivery, obesity, and advanced maternal age. Regarding pregnancy-related VTE risk scores, there were 7520 patients in the low-risk group with a prenatal score < 3 points and 239 in the high-risk group with a score ≥ 3, and 44 patients received drug prevention and treatment during pregnancy. There were 4223 patients in the low-risk group with a postpartum score < 2 points and 3536 in the high-risk group with a score ≥ 2 points, and 824 patients received drug prevention and treatment for 10 d. Among the patients who did not present with VTE before delivery, we found one case each of pulmonary embolism secondary to lower extremity venous thrombosis, intracranial venous sinus thrombosis, and asymptomatic lower extremity venous thrombosis during the postpartum follow-up. CONCLUSION: VTE poses a serious threat to maternal safety, and the society should increase its vigilance against pregnancy-related VTE.

Ability of human umbilical cord mesenchymal stem cells to repair chemotherapy-induced premature ovarian failure.

BACKGROUND: Premature ovarian insufficiency (POI) and premature ovarian failure (POF) have become one of the major problems threatening women of childbearing age. Studies have shown that stem cells transplanted from bone marrow, umbilical cord, peripheral blood and amniotic fluid can migrate and proliferate to the ovary, promote ovarian function repair, increase the number of follicles and granulosa cells at all levels of ovary, improve endocrine function, and can differentiate into oocytes in specific ovarian environment to restore fertility to some extent. AIM: To study the ability of human umbilical cord mesenchymal stem cells (hUCMSCs) to repair ovarian injury after chemotherapy. METHODS: A total of 110 female BALB/c mice (aged 7-8 wk old) with body masses of 16.0-20.0 g were selected. The mice were fed until 12 wk of age, and cyclophosphamide was administered by intraperitoneal injection for 14 consecutive days to induce premature ovarian failure in mice. Seventy-five mice with estrous cycle disorder were screened and randomly divided into 3 groups according to their body weight: model group, positive control group and hUCMSC group, and each group had 25 mice. Another 25 mice were used as negative controls. The mice in the hUCMSC group were injected with hUCMSCs in the tail vein, and the mice in the positive control group were given an oestradiol valerate solution and a medroxyprogesterone acetate solution in the tail vein. On the 1st, 15th, 30th, 45th, and 60th days after intravenous administration, vaginal smears were made to monitor the estrous cycles of the mice. The ovaries were weighed, and pathological sections were made to observe the morphology of the follicles; blood samples were collected to monitor the concentration of sex hormones (oestradiol and follicle-stimulating hormone). RESULTS: The estrous cycles of the model group mice were disrupted throughout the experiment. Mice in the hUCMSC group and the positive control group resumed normal estrous cycles. The ovarian weight of the model group mice continued to decline. The ovarian weight of the hUCMSC group mice and the positive control group mice decreased first and then gradually increased, and the ovarian weight of the hUCMSC group mice was heavier than that of the positive control group mice. The difference was statistically significant (P < 0.05). Compared with the negative control group, the model group experienced a decrease in oestradiol and an increase in follicle-stimulating hormone, and the difference was statistically significant (P < 0.05). Compared with the model group, the hUCMSC and positive control groups experienced a slight increase in oestradiol and a decrease in follicle-stimulating hormone; the difference was statistically significant (P < 0.05). The pathological examination revealed that the mouse ovaries from the model group were atrophied, the volume was reduced, the cortical and medullary structures were disordered, the number of follicles at all stages was significantly reduced, the number of atretic follicles increased, the number of primordial follicles and corpus luteum significantly decreased, and the corpus luteum had an irregular shape. Compared with those of the model group, the lesions of the hUCMSC and positive control groups significantly improved. CONCLUSION: hUCMSCs can repair ovarian tissue damaged by chemotherapy to a certain extent, can improve the degree of apoptosis in ovarian tissue, and can improve the endocrine function of mouse ovaries.

Severe venous thromboembolism in the puerperal period caused by thrombosis: A case report.

BACKGROUND: The incidence of venous thromboembolism (VTE) in pregnant women is significantly higher than that in non-pregnant women. VTE is more common after delivery than before delivery, and this condition can be hidden and develops rapidly. VTE mainly includes deep vein thrombosis and pulmonary embolism. Thrombophilia is an important risk factor for VTE in pregnant women and includes acquired thrombophilia and hereditary thrombophilia. CASE SUMMARY: A 24-year-old nulliparous female patient underwent cesarean section of the lower uterus due to fetal distress. Anti-inflammatory rehydration was given after the operation to prevent thrombosis. The patient had no obvious discomfort after surgery. Ten days after the operation, the patient developed a fever. The patient's mother revealed that she had a previous history of a lower extremity venous thrombosis. Color Doppler ultrasound showed deep vein thrombosis in the left lower extremity. The results of computed tomography angiography showed that the patient had a double pulmonary artery embolism. Bilateral lower extremity antegrade venography, inferior vena cava angiography and filter placement were performed. The patient continued to receive anticoagulant therapy. After 2 wk, the patient's condition improved. An anticoagulant protein test was performed 2 mo after discharge, and the results showed that both the patient and her mother had reduced protein S. CONCLUSION: Clinicians should learn to recognize the high-risk factors for VTE, improve their understanding of VTE, and actively prevent and diagnose VTE as early as possible.

Circular RNA Circ-ITCH Inhibits the Malignant Behaviors of Cervical Cancer by microRNA-93-5p/FOXK2 Axis.

Growing evidence has been demonstrated that circular RNA circ-ITCH plays an important role in the development of several cancers. However, the role of circ-ITCH in cervical cancer has not been evaluated. The aim of the present study was to investigate the biological function of circ-ITCH in cervical cancer both in vitro and in vivo. Our results showed that circ-ITCH was lowly expressed in both human cervical cancer tissues and cell lines. Overexpression of circ-ITCH in HeLa cells significantly suppressed cell proliferation, migration, and invasion. A xenograft tumor model was established to evaluate the role of circ-ITCH in vivo. The results showed that overexpression of circ-ITCH significantly inhibited tumorigenesis of cervical cancer. Mechanism investigations proved that circ-ITCH executed its tumor suppressive activity through sponging microRNA-93-5p (miR-93-5p) and regulating the expression of forkhead box K2 (FOXK2). These findings suggest that circ-ITCH may be a therapeutic target for the management of cervical cancer.

Microstructural Evolution and Refinement Mechanism of a Beta-Gamma TiAl-Based Alloy during Multidirectional Isothermal Forging.

Multidirectional isothermal forging (MDIF) was used on a Ti-44Al-4Nb-1.5Cr-0.5Mo-0.2B (at. %) alloy to obtain a crack-free pancake. The microstructural evolution, such as dynamic recovery and recrystallization behavior, were investigated using electron backscattered diffraction and transmission electron microscopy methods. The MDIF broke down the initial near-lamellar microstructure and produced a refined and homogeneous duplex microstructure. γ grains were effectively refined from 3.6 µm to 1.6 µm after the second step of isothermal forging. The ultimate tensile strength at ambient temperature and the elongation at 800 °C increased significantly after isothermal forging. ß/B2→α2 transition occurred during intermediate annealing, and α2 + γ→ß/B2 transition occurred during the second step of isothermal forging. The refinement mechanism of the first-step isothermal forging process involved the conversion of the lamellar structure and discontinuous dynamic recrystallization (DDRX) of γ grains in the original mixture-phase region. The lamellar conversion included continuous dynamic recrystallization and DDRX of the γ laths and bugling of the γ phase. DDRX behavior of γ grains dominated the refinement mechanism of the second step of isothermal forging.

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.

HOXB4 knockdown enhances the cytotoxic effect of paclitaxel and cisplatin by downregulating ABC transporters in ovarian cancer cells.

Therapeutic effects of anti-cancer drugs for ovarian cancer were limited due to the rapid development of chemotherapy resistance. The aim of this study was to test whether knockdown of Homeobox B4 (HOXB4) enhanced the cytotoxic effect of paclitaxel and cisplatin in ovarian cancer cells. HOXB4 expressions at mRNA and protein levels were upregulated in Taxol-resistant A2780 (A2780/Taxol) and DDP-resistant SKOV-3 (SKOV-3/DDP) cells. HOXB4 knockdown enhanced the cytotoxic effects of Taxol and DDP in A2780/Taxol and SKOV-3/DDP cells, respectively. HOXB4 silencing suppressed the phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway and reduced the expression of ABCB1, ABCC1 and ABCG2 in ovarian cancer cells. PI3K inhibitor LY294002 or siRNA targeting Akt (si-Akt) treatment inhibited cell viability, decreased protein levels of ABCB1, ABCC1 and ABCG2, and increased LDH release in A2780/Taxol and SKOV-3/DDP cells. These findings revealed that HOXB4 knockdown enhanced the cytotoxic effects of Taxol and DDP by downregulating ABC transporters via inhibiting the PI3K/Akt pathway in ovarian cancer cells.

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.

[Changes of maternal plasma and umbilical cord plasma inhibin and epidermal growth factor in patients with hypertensive disorder complicating pregnancy].

OBJECTIVE: To study the levels of inhibin (INH) and epidermal growth factor (EGF) in maternal plasma and umbilical cord plasma of patients with hypertensive disorder complicating pregnancy, and to explore their influence on the disease and fetal growth. METHODS: Enzyme linked immunosorbent assay (ELISA) was used to detect maternal and umbilical cord plasma INH and EGF levels in 65 patients with hypertensive disorder complicating pregnancy (test groups) and 21 normal pregnant women (control group). RESULTS: Plasma level of INH in test groups (499 +/- 52) ng/L was significantly higher than that (421 +/- 36) ng/L in control group (P < 0.01); however, the umbilical cord plasma level of INH had no significant difference (P > 0.05). Plasma level of EGF in test groups (408 +/- 60) ng/L was significantly lower than that (463 +/- 87) ng/L in control group (P < 0.05), also there was significant difference in umbilical cord plasma level of two groups (232 +/- 99) ng/L vs (380 +/- 97) ng/L (P < 0.01). The level of EGF in umbilical cord blood was positively correlated with newborn's body weight and placental weight. CONCLUSIONS: Plasma levels of INH and EGF in pregnancy women are related with hypertensive disorder complicating pregnancy. EGF level of umbilical cord blood affects the growth of fetus and placenta.