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Aim: The aim of this study was to investigate the expression of Forkhead box M1 (FoxM1) in endometriosis and determine FoxM1’s possible effects on endometriotic epithelial cells (EECs) invasion and epithelial-mesenchymal transition (EMT). Methods: The expression of FoxM1 and E-cadherin in endometrium and ectopic tissues was analyzed by immunohistochemistry. The transforming growth factor-β1 (TGF-β1) was added to induce EMT of EECs, which were purified from ectopic tissues. The Short hairpin RNA (ShRNA) intervention technique was used to silence FoxM1. The morphological changes of EECs were observed by microscope. The invasion ability of EECs was determined by transwell invasion assay. The expression of FoxM1 and EMT-related gene (E-cadherin, N-cadherin, vimentin, and Snail) in EECs was detected by quantitative reverse transcription-polymerase chain reaction and western blot. Results: FoxM1 expression was significantly increased, while E-cadherin expression was significantly decreased in ectopic tissues than that in endometrium tissues. After TGF-β1 treatment, EECs showed a transformation from an epithelial sheet-like structure to a mesenchymal fibroblastic spindle shape; EECs invasion ability was enhanced; the level changes of EMT-related molecule also indicated an EMT phenotype of EECs. After FoxM1-shRNA intervention, TGF-β1-induced changes of EECs in morphology, invasion ability and EMT-related molecule expressions were partially reversed. Conclusions: Silencing of FoxM1 could reverse TGF-β1-induced invasion and EMT of EECs.

Histone deacetylase 6 (HDAC6) is a unique member of the histone deacetylase family. Although HDAC6 is mainly localized in the cytoplasm, it can regulate the activities of the transcription factors in the nucleus. However, a correlation of intracellular distribution of HDAC6 with tumor progression is lacking. In this study, we found that a low frequency of nuclear HDAC6-positive cells in tumors was associated with distant metastasis and a worse overall survival in 134 patients with non-small cell lung cancer (NSCLC). Ectopic expression of wild-type HDAC6 promoted migration and invasion of A549 and H661 cells. However, the enforced expression of nuclear export signal-deleted HDAC6 inhibited the invasion but not the migration of both cell lines. The inhibitory effect of nuclear HDAC6 on invasion was mediated by the deacetylation of the p65 subunit of nuclear factor-κB, which decreased its DNA-binding activity to the MMP2 promoter, leading to the downregulation of MMP2 expression. Our findings indicated that the loss of nuclear HDAC6 may be a potential biomarker for predicting metastasis in patients with NSCLC.

Objective The objective of this study was to assess the outcomes of preterm infants who failed to extubate following initial treatment with steroids. Materials and Methods This is a retrospective cohort study of ventilator-dependent preterm infants treated with first course of systemic steroids to facilitate extubation. Outcomes of infants who successfully extubated were compared with infants who failed to extubate. Results In this study, 74 infants (mean gestation 25.4 ± 1.4 weeks and mean birth weight 764 ± 163 g) met inclusion criteria. Of these, 41 (55%) were successfully extubated and 33 (45%) were not. Baseline demographics were similar between the two groups. The primary outcome of severe bronchopulmonary dysplasia (BPD) or death at 36 weeks was higher among infants who failed to extubate (94 vs. 63%, p = 0.002). Severe BPD remained significantly higher even after adjustment for potential confounders (odds ratio: 12.2, 95% confidence interval: 2.1–70.5, p = 0.005). Extubation failure was also associated with substantially higher rate of tracheostomy (32 vs. 5%, p = 0.003) and gastrostomy tube placement (61 vs. 22%, p = 0.001), as well as longer days of hospitalization (179 ± 72 vs. 129 ± 44 days, p = 0.001) and mechanical ventilation (112 ± 89 vs. 52 ± 42 days, p Conclusion Failure to extubate after first course of systemic steroids for BPD is associated with poor prognostic implications.

Biochanin A is a major isoflavone in red clover and a potent chemopreventive agent against cancer. However, the effects of biochanin A on human osteosarcoma cells have never been clarified. This study investigated the anti-proliferative potential of biochanin A in osteosarcoma cells. The results indicate that biochanin A inhibited cell growth and colony formation in a dose-dependent manner with a minimal toxicity to normal cells. The combination of doxorubicin and biochanin A could synergistically inhibit osteosarcoma cell growth. The cytotoxic effect of biochanin A via the induction of apoptosis as evidenced by formation of apoptotic bodies, externalization of phosphatidylserine, accumulation of sub-G1 phase cells, caspase 3 activation, and cleavage of PARP. Apoptosis was associated with loss of the mitochondrial membrane potential, release of cytochrome c, caspase 9 activation, increased Bax expression, and reduced Bcl-2 and Bcl-XL expression. Pre-treatment with a caspase-9 specific inhibitor (Z-LEHD-FMK) partially attenuated cell death, suggesting involvement of the intrinsic mitochondrial apoptotic cascade. However, pre-treatment with the JNK inhibitor SP600125, the MEK inhibitor PD-98059, and the p38 MAPK inhibitor SB203580 or the antioxidants vitamin E, N-acetylcysteine, and glutathione failed to prevent biochanin A-induced cell death. Our results suggest that biochanin A inhibits cell growth and induces apoptosis in osteosarcoma cells by triggering activation of the intrinsic mitochondrial pathway and caspase-9 and -3 and increasing the Bax: Bcl-2/Bcl-XL ratio.

With the development of science and technology, Samrt Home system has become more and more widely used. In this paper, Smart Home system, based on the handheld device, using ZigBee and WIFI technology to build the internal network, and with the detailed design of the handheld device as the controller center, realizes its control of Smart Home, which also provides an universal solution to the Smart Home.

Recently, two-way relay network has been taken attention. In this paper, the two-way relayprotocols of ultra-wideband (UWB) network based on code-multiplexed transmitted-reference (CMTR)impulse radio have been studied. Based on code-multiplexed scheme, a new two-way relayingstrategy for two-slots protocol is designed. The corresponding bit error rate (BER) performance isevaluated via simulations and compared with three-slots scheme which can get path diversity gainfrom direct link between terminals. Simulation results reveal that the performance of the two-slotsrelaying scheme is almost same with that of the three-slots scheme. Meanwhile the throughput ispromoted about 33% over three-slots scheme.

e15638 Background: Alterations of histone deacetylases (HDACs) and related signaling have been increasingly associated with cancer development and treatment. Among those HDACs, HDAC6 uniquely functions in maintaining mRNA stability of certain genes. The aim of this study was to determine the clinical impacts and associated mechanisms of HDAC6 in hepatocellular carcinoma (HCC). Methods: Immunohistochemistry is firstly applied to analyze the distribution patterns of HDAC6 in 122 patients and the obtained results are statistically analyzed with clinicopathological characteristics and patient survival. XTT, flowcytometery, transwell assay, real-time PCR, IF, IB, immunoprecipitation (IP), and RNA-IP are used to determine the bio-impacts and underlying mechanisms of HDAC6 in liver cancer cells. Results: Both cytoplasmic and nuclear staining of HDAC6 proteins were mainly decreased in cancerous lesions. Nevertheless, increased cytoplasmic HDAC6 staining was positively correlated with disease recurrence (p = 0.002). Increased nuclear frequency, but not cytoplasmic intensity, of HDAC6 was associated with a poor survival rate in HCC patients (p = 0.041). Restoration of HDAC6 expression increased the proliferation, S phase, migration and invasion of the HepJ5, Huh7 and Mahlavu cells, lacking detectable HDAC6 expression. More interestingly, ectopic HDAC6 overexpression increased a ligand-independent expression of p-AKT, beta-catenin and cyclin D, and subsequently promoted the entry of beta-catenin into the nucleus. Both transcripts and proteins of the EGFR, a dominant trigger of AKT signaling, were unexpectedly increased upon HDAC6 restoration in HepJ5, Huh7 and Mahlavu cells. The expression of EGFR was not restored by treatment with MG132 (proteasome inhibitor) in HepJ5, Huh7 and Mahlavu cells, and HDAC6-specific siRNA decreased both HDAC6 and EGFR expression in Hep3B and SK-Hep1 cells, having detectable HDAC6 and EGFR expression. IP and RNA-IP analysis revealed that HDAC6 interacted with HuR and increased EGFR mRNA stability. Accordingly, the expression of HDAC6 and EGFR were positively correlated in cancerous lesions. Conclusions: Our results suggest that the contribution of HDAC6 to recurrent HCC may act through its maintenance of EGFR mRNA stability. HDAC6 may serve as a rational treatment target in recurrent HCC.

Background: The nuclear factor-ĸB (NF-ĸB) pathway activates many of the target genes that are critical to the initiation and establishment of endometriosis. We sought to examine the potential application of pyrrolidine dithiocarbamate (PDTC), a potent NF-ĸB inhibitor, in the treatment of endometriosis. Methods: The phosphorylation of IĸB, expression of nuclear p65 protein and NF-ĸB DNA binding in endometriotic epithelial cells (EECs), endometriotic eutopic epithelial cells (EuECs) and normal epithelial cells (NECs) were detected by Western blot analysis and electrophoretic mobility shift assay. Cyclooxgenase-2 (COX-2) gene and protein expressions in EECs were measured by RT-PCR and Western blot analysis. Prostaglandin E2 (PGE2) production of EECs was measured by ELISA. Results: PDTC in the absence or presence of tumor necrosing factor-α (TNF-α) showed stronger inhibitory effects on IĸB phosphorylation, expression of nuclear p65 protein and NF-ĸB DNA-binding activity in EECs than in EuECs or NECs. Pretreatment of EECs with PDTC resulted in a dose-dependent reduction in the TNF-α-induced expressions of COX-2 at gene and protein levels, as well as a reduction of PGE2 synthesis. Conclusion: PDTC may represent a novel therapeutic strategy for treatment of endometriosis.

The activation of nuclear factor-κB (NF-κB) has been implicated in the development and progression of endometriosis. The aim of this study is to investigate the potential application of pyrrolidine dithiocarbamate (PDTC), a potent NF-κB inhibitor, in the treatment of endometriosis. NF-κB-DNA-binding activity, IκB phosphorylation and expression of nuclear p65 protein in endometriotic ectopic stromal cells (EcSCs), endometriotic eutopic stromal cells (EuSCs) and normal endometrial stromal cells (NESCs) were detected by electrophoretic mobility shift assay and western blot analysis. Adhesion, migration, invasion and apoptosis of EcSCs were observed by means of adhesion, migration, invasion and terminal deoxynucleotidyl transferase-mediated dUDP nick-end labeling assay, respectively. Gene and protein expressions of CD44s, matrix metalloproteinase (MMP)-2, MMP-9 and survivin in EcSCs were measured by RT-PCR and western blot analysis. The results showed that PDTC in the absence or presence of interleukin (IL)-1β showed stronger inhibitory effects on NF-κB-DNA-binding activity, IκB phosphorylation and expression of nuclear p65 protein in EcSCs than those in EuSCs or NESCs. PDTC enhanced apoptosis, and suppressed IL-1β-induced cellular adhesion, migration and invasion of EcSCs. Pretreatment of EcSCs with PDTC attenuated IL-1β-induced expressions of CD44s, MMP-2, MMP-9 and survivin at gene and protein levels. All these findings suggest that PDTC induces apoptosis and down-regulates adhesion, migration and invasion of EcSCs through the suppression of various molecules. Therefore, PDTC could be used as a therapeutic agent for the treatment of endometriosis.

OBJECTIVE To evaluate the diagnostic and therapeutic efficacy of using cold knife conization for cervical intraepithelial neoplasia (CIN).METHODS We retrospectively analyzed 186 cases with CIN diagnosed and treated in our hospital; compared the histologic diagnoses from cervical conization and from colposcopic multiple punch biopsies, and then evaluated their postoperative hiistologic findings and clinical outcomes. RESULTS Of the 186 cases, there was a correlation in histologic findings between cervical conization and colposcopic multiple punch biopsies in 138 cases (74.2%), and there was no correlation in the other 48 cases (25.8%). Incomplete excision was performed in 8 cases (4.3%), but the failure rate was only 1.1%; the cure rate was 98.9%. Five cases with early invasive cancer were found. Eleven patients underwent subsequent hysterectomy. The main complications associated with conization were hemorrhage and cervical stenosis. Bleeding occurred in 8 (4.3%) of the patients, and cervical stenosis occurred in 3 (1.6%).CONCLUSION Cervical intraepithelial neoplasia was diagnosed more accurately using conization than by colposcopic multiple punch biopsies. Conization can also play an important role in the treatment for CIN. If properly performed, the procedure has a low risk of complications. It can provide an accurate histologic representation of the disease process, and be curative in most cases.

The nuclear factor-κB (NF-κB) pathway activates many of the target genes that are critical to the initiation and establishment of endometriosis. We sought to examine the potential application of pyrrolidine dithiocarbamate (PDTC), a potent NF-κB inhibitor, in the treatment of endometriosis.The phosphorylation of IκB, expression of nuclear p65 protein and NF-κB DNA binding in endometriotic epithelial cells (EECs), endometriotic eutopic epithelial cells (EuECs) and normal epithelial cells (NECs) were detected by Western blot analysis and electrophoretic mobility shift assay. Cyclooxgenase-2 (COX-2) gene and protein expressions in EECs were measured by RT-PCR and Western blot analysis. Prostaglandin E(2) (PGE(2)) production of EECs was measured by ELISA.PDTC in the absence or presence of tumor necrosing factor-α (TNF-α) showed stronger inhibitory effects on IκB phosphorylation, expression of nuclear p65 protein and NF-κB DNA-binding activity in EECs than in EuECs or NECs. Pretreatment of EECs with PDTC resulted in a dose-dependent reduction in the TNF-α-induced expressions of COX-2 at gene and protein levels, as well as a reduction of PGE(2) synthesis.PDTC may represent a novel therapeutic strategy for treatment of endometriosis.

This study demonstrated that pyrrolidine dithiocarbamate (PDTC), a potent nuclear factor-κB inhibitor, showed stronger inhibitory effects on nuclear factor-κB activation in endometriotic stromal cells than in normal endometrial stromal cells as determined by electrophoretic mobility shift assay and Western blot analysis. Pretreatment of endometriotic stromal cells with PDTC attenuated tumor necrosis factor-α–induced expressions of CD44s, matrix metalloproteinase-9, and vascular endothelial growth factor whereas reversed tumor necrosis factor-α–reduced expressions of tissue inhibitor of metalloproteinase-1 revealed by reverse transcriptase polymerase chain reaction and Western blot analysis, suggesting that PDTC may represent a novel therapeutic strategy for treatment of endometriosis.

To investigate the relationship between -344T polymorphism in aldosterone synthetase (CYP11B2) gene promoter region and the pathogenesis of polycystic ovary syndrome (PCOS).Ninety two patients with PCOS and controls were genotyped according to the fragment length (273 bp and or 202 bp) of CYP11B2 gene promoter by the technique of polymerase chain reaction-restriction fragment length polymorphism. The levels of luteinizing hormone, follicular stimulating hormone, estrodiol, progesterone, prolactin, testosterone, plasma renin activity (PRA), plasma angiotensin II (PANG II) and aldosterone in the basal state were also determined. Different genotypes between PCOS were compared about their levels of PRA, PANG II, aldosterone and testosterone.(1) The C allele frequencies of CYP11B2 gene in control and PCOS was 22% and 36%, respectively. (2) The frequency of variants (TC, CC) of CYP11B2 gene -344T polymorphism site in PCOS (57%) was significantly higher than that of control subjects (37%). (3) The level of PRA, PANG II, aldosterone, testosterone were all significantly higher in the genotype of -344CC than in that of -344TT in PCOS and normal women (P0.01).(1) The variants (T--C) of -344T polymorphism site of CYP11B2 gene predisposes increased risk of PCOS. (2) The genotype of -344CC, -344TC may be susceptible genotype of PCOS and has related to the enhanced functional activity of ovarian renin angiotensin system in PCOS.