[Key Prediction Genes of Nasopharyngeal Carcinoma:Screening Based on Systematic Bioinformatics and Validation by Cell Experiments].

Objective To screen out the potential prediction genes for nasopharyngeal carcinoma(NPC)from the gene microarray data of NPC samples and then verify the genes by cell experiments.Methods The NPC dataset was downloaded from Gene Expression Omnibus,and limma package was employed to screen out the differentially expressed genes.Weighted correlation network analysis package was used for weighted gene co-expression network analysis,and Venn diagram was drawn to find the common genes.The gene ontology annotation and Kyoto encyclopedia of genes and genomes pathway enrichment were then performed for the common genes.The biomarkers for NPC were further explored by protein-protein interaction network,LASSO regression,and non-parametric tests.Real-time quantitative PCR and Western blotting were employed to determine the mRNA and protein levels of key predictors of NPC,so as to verify the screening results.Results There were 622 up-regulated genes and 351 down-regulated genes in the GSE12452 dataset.A total of 116 common genes were obtained by limma analysis and weighted gene co-expression network analysis.The common genes were mainly involved in the biological processes of cell proliferation and regulation and regulation of intercellular adhesion.They were mainly enriched in Rap1,Ras,and tumor necrosis factor signaling pathways.Six key genes were screened out,encoding angiopoietin-2(ANGPT2),dual oxidase 2(DUOX2),coagulation factor Ⅲ(F3),interleukin-15(IL-15),lipocalin-2,and retinoic acid receptor-related orphan receptor B(RORB).Real-time quantitative PCR and Western blotting showed that the NPC cells had up-regulated mRNA and protein levels of ANGPT2 and IL-15 and down-regulated mRNA and protein levels of DUOX2,F3,and RORB,which was consistent with the results predicted by bioinformatics.Conclusion ANGPT2,DUOX2,F3,IL-15 and RORB are potential predictive molecular markers and therapeutic targets for NPC,which may be involved in Rap1,Ras,tumor necrosis factor and other signaling pathways.

Evidence-based novel changes in prevalence and symptom characteristics of spleen deficiency syndrome in persons of varied health status and different ages: a cross-sectional observational study.

Deficiency of the organs is a vital pathophysiologic characteristic in the elderly. A core TCM aging theory is known as aging caused by spleen deficiency syndrome (SDS) that can be found in ancient and modern literature. The key objectives of this study were to establish a full-scale trial to evaluate the prevalence, symptom severity, frequency, and distribution of SDS in different age groups as related to health status (healthy, subhealthy, and chronic disease) to elucidate the role of spleen deficiency in the aging process and deterioration of health status. This cross-sectional observational study was conducted in 4 hospitals in China. 1390 participants aged 20-79 were interviewed by investigators who completed questionnaires recording prevalence, severity, and frequency of symptoms as well as other relevant information. The results revealed that prevalence and symptom characteristics of SDS showed regularities with increasing age and deteriorating health status. It supports the TCM concept that spleen deficiency is an important mechanism of aging, subhealth, and chronic diseases. Early recognition of the warning signs and symptoms of SDS may lead to intervention and even prevention strategies for subhealth and chronic diseases as well as promotion of healthy aging.

Letrozole stimulation in endometrial preparation for cryopreserved-thawed embryo transfer in women with polycystic ovarian syndrome: a pilot study.

OBJECTIVE: To study the efficiency of letrozole, an aromatase inhibitor, in endometrial preparation for cryopreserved-thawed embryo transfer (FET) in women with polycystic ovarian syndrome (PCOS). DESIGN: Retrospective observational study. PATIENTS: One hundred and twenty patients with PCOS who met the inclusion criteria for the study. MEASUREMENTS: We assessed in vitro fertilization outcomes in one hundred and twenty patients with PCOS (148 cycles) who were prepared for and underwent FET between June 2011 and December 2012. Patients were prepared for FET using artificial hormone cycles induced with oestrogen and progesterone supplementation (n = 76), letrozole stimulation (n = 40) or hMG stimulation (n = 32). RESULTS: There were no differences in demographic characteristics between the groups, except that the letrozole group had a higher incidence of embryo transfer failure in the past. The letrozole stimulation group had a significantly higher maximal endometrial thickness and significantly higher rates of clinical pregnancy per transfer, ongoing pregnancy per transfer and implantation, compared with the artificial and hMG stimulation groups. Differences in these parameters between the artificial and hMG stimulation groups were not significant. CONCLUSION: Using letrozole stimulation in endometrial preparation for cryopreserved-thawed embryo transfer in patients with PCOS may be associated with better outcomes than using hormonal manipulation or hMG stimulation.

Increased expression of the adult stem cell marker Musashi-1 in the ectopic endometrium of adenomyosis does not correlate with serum estradiol and progesterone levels.

OBJECTIVE: To investigate whether abnormal expression of Musashi-1 occurs in eutopic and ectopic endometria from patients with adenomyosis and whether it is correlated with serum estradiol or progesterone levels. STUDY DESIGN: Musashi-1 expression in ectopic and paired eutopic endometrium of patients with adenomyosis (adenomyosis group, 30 cases) and in normal endometrium (control group, 29 cases) was studied with immunohistochemistry, and serum estradiol and progesterone levels in these cases were measured with electrochemiluminescence immunoassay. RESULTS: In all the normal endometrial tissues from control group and paired eutopic and ectopic endometrium of adenomyosis, epithelial and stromal Musashi-1 expression was observed throughout the menstrual cycle. Musashi-1 immunostaining was localized both in the nucleus and cytoplasm. The epithelial cells in normal endometrium showed a significantly higher staining index of Musashi-1 in the proliferative phase than in the secretory phase. The staining index of epithelial Musashi-1 in the ectopic endometrium was significantly higher than in the paired eutopic endometrium and normal endometrium throughout the menstrual cycle. In the secretory phase, the epithelial Musashi-1 immunoreactivity in eutopic endometrium and the stromal Musashi-1 immunoreactivity in ectopic endometrium were significantly higher than those in the normal endometrium. The Musashi-1 expression in the ectopic endometrium of adenomyosis was not correlated with the serum estradiol or progesterone levels. CONCLUSION: Aberrant Musashi-1 expression in adenomyosis may be involved in the pathogenesis and pathophysiology of adenomyosis, but it does not correlate with changes in serum estradiol or progesterone levels.

Low-dose mifepristone increases uterine expression of aquaporin 1/aquaporin 2 at the time of implantation.

BACKGROUND: The aim of this study was to investigate the mechanism by which low-dose mifepristone serves as an antiimplantation contraceptive drug. A human endometrial explant system was used to study the effects of low-dose mifepristone (65 nmol/L and 200 nmol/L) on expression of the water channel family aquaporins, aquaporin-1 and aquaporin-2 (AQP1/AQP2), at the time of implantation. STUDY DESIGN: Endometrial samples from 17 normally cycling patients at the "window of implantation" were treated with different concentrations of mifepristone. The protein and mRNA expression of AQP1/AQP2 in the endometrium was examined using immunohistochemistry (IHC) and reverse transcriptase-polymerase chain reaction (RT-PCR), respectively. RESULTS: The IHC and RT-PCR analyses demonstrated that expression of AQP1/AQP2 was increased by mifepristone in a dose-dependent manner, with the highest AQP1/AQP2 expression levels detected in subjects treated with 200-nmol/L mifepristone. CONCLUSION: Low-dose mifepristone may negatively regulate implantation by increasing AQP1/AQP2 protein and mRNA expression. The findings from this study provide further evidence to support the potential contraceptive activity of low-dose mifepristone.

Low-dose mifepristone increases uterine natural killer cell cytotoxicity and perforin expression during the receptive phase.

OBJECTIVE: To investigate the immunologic mechanism by which low-dose mifepristone serves as an anti-implantation contraceptive drug. DESIGN: In vitro study. SETTING: University hospital and research laboratory. PATIENT(S): Fifteen normally cycling patients at the "window of implantation." INTERVENTION(S): A human endometrial explant system was used to study the effects of low-dose mifepristone (65 and 200 nmol/L) on uterine natural killer (uNK) cells. Endometrial samples were treated with different concentrations of mifepristone. MAIN OUTCOME MEASURE(S): The cytotoxicity of uNK cells to K562 target cells and the expression of perforin (PFN) by uNK cells were examined using a methyl thiazolyl tetrazolium (MTT) assay and double immunohistochemistry, respectively. RESULT(S): Both uNK cell cytotoxicity and expression of PFN were increased after treatment with 65 or 200 nmol/L mifepristone, and these effects were dose-dependent. CONCLUSION(S): Mifepristone may negatively regulate implantation by increasing the cytotoxicity of uNK cells, and this increased cytotoxicity may result from increased PFN expression. These findings provide further evidence to support the potential contraceptive activity of low-dose mifepristone.