Fetal Ductus Arteriosus Premature Constriction.

This study aimed to investigate the connections between the echocardiography indices of fetal ductus arteriosus premature constriction and newborn prognosis by analyzing 22 cases of spontaneous fetal ductus arteriosus premature constriction.An ultrasonic instrument was used to observe prenatal fetal heart state, combine clinical examination data and echocardiographic results after delivery, summarize the ultrasound manifestations and imaging characteristics, and analyze the prognosis of the fetus.In all cases, fetal ductus arteriosus premature constriction occurred in the third trimester of pregnancy (34 + 1 to 41 weeks), and no abnormality in extracardiac organs were observed. Seven neonates required respiratory support due to the accompanying severe tricuspid regurgitation. The remaining 15 neonates did not receive respiratory support, including 4 with severe tricuspid regurgitation, 5 with moderate regurgitation, and 6 with mild regurgitation. Significant differences were observed in the fetal right atrium size and tricuspid regurgitation severity between the neonatal respiratory support group and non-respiratory support group. Furthermore, there were statistical differences in the ductus arteriosus inner diameter and pulsation index between the two groups.The severity of fetal ductus arteriosus premature contraction accompanied by tricuspid regurgitation and right atrium enlargement can predict the immediate prognosis of the newborn and provide guidance for the clinical judgment of the timing of pregnancy termination.

LncRNA CRNDE acts as an oncogene in cervical cancer through sponging miR-183 to regulate CCNB1 expression.

Studies have identified a series of lncRNAs that contributed to various tumors, although the underlying mechanisms remain largely unclear. We proposed a ceRNA network and investigate relations among lncRNA/miRNA/mRNA in cervical cancer (CC). The genes of differential expression and lncRNA/miRNA/mRNA network were identified by combining TCGA, miRcode, starBase, miRTarBase, miRDB, TargetScan and STRING databases. Meanwhile, the function enrichment was recognized with Gene Ontology and Kyoto Encyclopedia of Genes and Genomes. Quantitative real time-PCR (qRT-PCR) was performed to determine colorectal neoplasia differentially expressed (CRNDE) expression in CC tissues and cell lines. The effects of CRNDE on the CC biological functions and cyclin B1 (CCNB1) expression were detected by conducting in vitro and in vivo experiments. Quantitative real time-PCR, western blot and dual-luciferase reporter assay were used to predict the target of miR-183. Furthermore, rescue experiments were conducted to further confirm the regulation of CCNB1 by CRNDE. Systematic analyses of bioinformatics from several databases predicted that CRNDE, miR-183 and CCNB1 were in the same network path. Their expressions were up-regulated in CC tissues and cells. Silencing CRNDE-inhibited cell proliferation, migration and invasion, restricted solid tumor growth and promoted cell apoptosis. Moreover, our results suggested that miR-183 targeted the CCNB1 3'UTR and regulated its expression. Additionally, miR-183 mimic could inverse the antitumor function of CRNDE inhibition and partially eliminated the attenuated expression of CCNB1 induced by silencing CRNDE, indicating that CRNDE could positively regulate CCNB1 expression by sponging miR-183. Our study highlighted a role for the CRNDE/miR-183/CCNB1-axis in CC and offered a promising diagnostic strategy for CC treatment.

BKCa participates in E2 inducing endometrial adenocarcinoma by activating MEK/ERK pathway.

BACKGROUND: The large-conductance, voltage-gated, calcium (Ca (2+))-activated potassium channel (BKCa) plays an important role in regulating Ca (2+) signaling and cell physiological function, and is aberrantly expressed in some types of cancers. The present study focuses on identifying the oncogenic potential and clinical significance of BKCa in endometrial adenocarcinoma, as well as exploring the mechanistic relevance by 17ß -estradiol (E2) inducing aberrant activation of MEK1/2 and ERK1/2 via BKCa. METHODS: The expression of BKCa, ERK1/2 and p-ERK1/2 were examined by immunohistochemical staining in 263 cases, including 185 primary types I endometrial cancer tissues, 38 atypical endometrial hyperplasia tissues and 40 normal endometrium tissues. Cell growth, cycle, apoptosis rate, migration and invasion was separately tested in Ishikawa cells using siRNA-BKCa and/or E2 treatment, as well as the expression of these interested proteins by western blot analysis. RESULTS: We showed that expression of BKCa is significantly elevated in 185 types I endometrial adenocarcinoma tissues compared to those of the normal endometrium and atypical endometrial hyperplasia tissues. Furthermore, in vitro observations revealed that down-regulation of BKCa expression inhibited cell growth by both enhancing apoptosis and blocking G1/S transition, suppressed cell migration and invasion in Ishakiwa cells, and decreased the expression of p-MEK1/2 and p-ERK1/2. Additionally, RNAi-mediated knockdown of BKCa attenuated the increased cellular growth and invasion, as well as the elevated expression of p-MEK1/2 and p-ERK1/2 proteins, induced by E2 stimulation. More importantly, the aberrant expression of BKCa and p-ERK1/2 were closely related with poor prognostic factors in type I endometrial cancer, and up-regulated expression of p-ERK1/2 was significantly associated with shorter disease-free survival (DFS) and overall survival (OS) and was an independent prognostic factor in type I endometrial cancer patients. CONCLUSION: Our results demonstrated that BKCa and the key downstream effectors p-ERK1/2 could be involved in important signaling pathways in initiation and development of endometrial adenocarcinoma and may provide a new therapeutic approach for women with endometrial cancer.

The efficacy and safety of clotrimazole vaginal tablet vs. oral fluconazole in treating severe vulvovaginal candidiasis.

To compare the efficacy and safety of two doses of clotrimazole vaginal tablet 500 mg with two doses of oral fluconazole 150 mg in treating severe vulvovaginal candidiasis (SVVC), 240 consecutive patients with SVVC were studied at the Department of Obstetrics and Gynaecology of Peking University Shenzhen Hospital between June 2014, and September 2015. Patients were randomly assigned in a 1 : 1 ratio to receive treatment with either two doses of clotrimazole vaginal tablet or two doses of oral fluconazole. The clinical cure rates in the clotrimazole group and the fluconazole group at days 7-14 follow-up were 88.7% (102/115) and 89.1% (98/110) respectively; the clinical cure rates at days 30-35 in the two groups were 71.9% (82/114) and 78.0% (85/109) respectively. The mycological cure rates at days 7-14 follow-up in the two groups were 78.3% (90/115) and 73.6% (81/110) respectively. The mycological cure rates of the patients at days 30-35 in the two groups were 54.4% (62/114) and 56.0% (61/109) respectively (P > 0.05). The adverse events of clotrimazole were mainly local. This study demonstrated that two doses of clotrimazole vaginal tablet 500 mg were as effective as two doses of oral fluconazole 150 mg in the treatment of patients with SVVC and could be an appropriate treatment for this disorder.

WNT1, a target of miR-34a, promotes cervical squamous cell carcinoma proliferation and invasion by induction of an E-P cadherin switch via the WNT/ß-catenin pathway.

PURPOSE: Persistent infection with high-risk human papillomavirus (HR-HPV) is thought to play a prominent role in the initiation and progression of almost all cases of cervical cancer. Previously, we and others found that microRNA 34a (miR-34a) may be regulated by HR-HPV E6 to contribute to the development of cervical cancer. Here, we aimed to identify the oncogenic potential and clinical significance of a known miR-34a target, WNT1, in cervical squamous cell carcinoma (SCC) development and to investigate the associated mechanisms underlying cervical SCC cell proliferation and invasion. METHODS: WNT1 and miR-34a expression levels were assessed in primary cervical lesions using immunohistochemistry and qRT-PCR, respectively. The cellular effects and the expression of its associated genes were examined in cervical SCC-derived Siha and Caski cells after siRNA-WNT1 (downregulation) or miR-34a mimic (upregulation) treatment. A cervical SCC xenograft mouse model was used to investigate the in vivo effects of miR-34a overexpression. HPV-16 E6/E7 expression was inhibited by gene promoter siRNA targeting, after which the levels of miR-34a and WNT1 were examined. RESULTS: WNT1 protein upregulation was found to be associated with a poor prognosis in cervical SCC patients. In vitro assays in Siha and Caski cells revealed that WNT1 downregulation decreased cell proliferation and invasion, inhibited WNT/ß-catenin activation and affected the expression of E-cadherin and P-cadherin. MiR-34a upregulation resulted in decreased WNT1 expression. An inverse correlation between miR-34a and WNT1 expression was also observed in primary cervical SCC tissues. In addition, we found that MiR-34a could regulate an E-cadherin to P-cadherin switch (E-P cadherin switch) to inhibit cell proliferation and tumorigenesis in vitro and in vivo via inactivation of the WNT1/ß-catenin pathway. Finally, we found that decreased HPV-16 E6/E7 expression resulted in miR-34a upregulation and WNT1 downregulation in Siha and Caski cells. CONCLUSIONS: From our results we conclude that WNT1, as a target of miR-34a, can promote cervical SCC cell proliferation and invasion by induction of an E-P cadherin switch via the WNT1/ß-catenin pathway. Our results may provide new options for the treatment of patients with cervical SCC.

Evaluating the Effect of Hydrophobic Nanosilica on the Viscoelasticity Property of Asphalt and Asphalt Mixture.

Viscoelasticity property of bitumen is closely related to the service life of bituminous pavement. This paper evaluated the impact of one of the most efficient and widely used nanomaterials in various industries called hydrophobic nanosilica on the viscoelasticity property of bitumen and asphalt mixture. In this paper, three hydrophobic nanosilica modified bitumens and asphalt mixtures were researched by conventional physical properties test, SEM test, FTIR test, DSC test, DSR test, static creep test and dynamic creep test. The results showed that the introduction of hydrophobic nanosilica could strengthen the viscosity of asphalt more effectively and had better dispersion than hydrophilic nanosilica in asphalt. From conventional physical properties test and rheological performance test, hydrophobic nanosilica could weaken the temperature susceptibility of bitumen observably. From DSR test, hydrophobic nanosilica modified asphalt had a lower sensitivity and dependence on temperature and frequency than hydrophilic nanosilica modified asphalt. The Cole⁻Cole diagrams indicated that hydrophobic nanosilica exhibited good compatibility with asphalt compared with hydrophilic nanosilica. Newly formed chemical bonds were found in the hydrophobic nanosilica modified asphalt and its mixture with stone according to SEM test, FTIR test, and DSC test, which is the biggest difference from the modification mechanism of hydrophilic nanosilica modified asphalt. Through static and dynamic creep test, it found that the addition of hydrophobic nanosilica can significantly reduce the creep strain at the same temperature.

Kelch repeat protein interacts with the yeast Galpha subunit Gpa2p at a site that couples receptor binding to guanine nucleotide exchange.

The kelch repeat-containing proteins Krh1p and Krh2p are negative regulators of the Gpa2p signaling pathway that directly interact with the G protein alpha-subunit Gpa2p in the yeast Saccharomyces cerevisiae. A screen was carried out to identify Gpa2p variants that are defective in their ability to bind Krh1p but retain the ability to bind another Gpa2p-interacting protein, Ime2p. This screen identified amino acids Gln-419 and Asn-425 as being important for the interaction between Gpa2p and Krh1p. Gpa2p variants with changes at these positions are defective for Krh1p binding in vivo. Cells containing these forms of Gpa2p display decreased heat shock resistance and increased expression of a gene required for pseudohyphal growth. These findings indicate that the substitutions at positions 419 and 425 confer a degree of constitutive activity to the Gpa2p alpha-subunit. Residues Gln-419 and Asn-425 are located in the beta6-alpha5 loop and alpha5 helix of Gpa2p, which is the region that couples receptor binding to guanine nucleotide exchange. The results suggest that binding of Gpa2p to Krh1p does not resemble the binding of Galpha subunits to either Gbeta subunits or effectors, but it instead represents a novel type of functional interaction.