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Bowel problems Right after Sacrocolpopexy: An incident Collection.
BACKGROUND AND AIMS Genetic factors associated with non-alcoholic fatty liver disease (NAFLD) remain incompletely understood. To date, most GWAS studies have adopted radiologically assessed hepatic triglyceride content as reference phenotype and so cannot address steatohepatitis or fibrosis. We describe a genome-wide association study (GWAS) encompassing the full spectrum of histologically characterized NAFLD. METHODS The GWAS involved 1483 European NAFLD cases and 17781 genetically-matched population controls. see more A replication cohort of 559 NAFLD cases and 945 controls was genotyped to confirm signals showing genome-wide or close to genome-wide significance. RESULTS Case-control analysis identified signals showing p-values ≤ 5 x 10-8 at four locations (chromosome (chr) 2 GCKR/C2ORF16; chr4 HSD17B13; chr19 TM6SF2; chr22 PNPLA3) together with two other signals with p less then 1 x10-7 (chr1 near LEPR and chr8 near IDO2/TC1). Case-only analysis of quantitative traits steatosis, disease activity score, NAS and fibrosis showed that the PNPLA3 signal (rs738409) was genome-wide significantly associated with steatosis, fibrosis and NAS score and identified a new signal (PYGO1 rs62021874) with close to genome-wide significance for steatosis (p=8.2 x 10-8). Subgroup case-control analysis for NASH confirmed the PNPLA3 signal. The chr1 LEPR SNP also showed genome-wide significance for this phenotype. Considering the subgroup with advanced fibrosis (≥F3), the signals on chromosomes 2, 19 and 22 remained genome-wide significant. With the exception of GCKR/C2ORF16, the genome-wide significant signals replicated. CONCLUSIONS This study confirms PNPLA3 as a risk factor for the full histological spectrum of NAFLD at genome-wide significance levels, with important contributions from TM6SF2 and HSD17B13. PYGO1 is a novel steatosis modifier, suggesting relevance of Wnt signalling pathways in NAFLD pathogenesis. V.Phytochemical investigation of the roots of Pueraria lobata led to the isolation of two pairs of new isoflavone glucosides, 3'-hydroxyneopuerarin A/B (1-2) and 3'-methoxyneopuerarin A/B (3-4). A pair of known compounds (5-6), which possess a very similar structure, were obtained together. Their structures were elucidated on the basis of spectroscopic data interpretation. Compounds 3-6 dose-dependently blocked the production of TNF-α and IL-6 in LPS-stimulated RAW264.7 cells, which indicated the potential anti-inflammatory effect of these compounds. V.BACKGROUND Insertable cardiac monitors (ICMs) are often used for long-term monitoring of cardiac rhythm. The Medtronic's LINQ Reveal ™ is a new generation wireless, automated, and patient responsive subcutaneous ECG monitoring device. Despite several advantages to its small size we have noted an unusually high incidence of extrusion at our center. METHODS & Results We conducted a retrospective case analysis to review Reveal LINQs implanted at our center. All devices were inserted using the provided insertion tools. Patients with extruded devices were identified and details regarding the site and technique of insertion, incision closure, use of peri-operative antibiotics, and follow-up details were collected. 81 patients underwent 85 Reveal LINQ implants at a tertiary care University Hospital referral center. The most common reason for implant was suspected arrhythmia with or without structural heart disease or unexplained syncope. There were 4 spontaneous extrusions occurring within 7-24 days after insertion with an incidence rate of 4.7%. One extruded device was anchored to subcutaneous tissue, and no pocket/device infections or hematomas were noted. CONCLUSIONS Device migration and erosion through skin are important potential adverse events for the Reveal LINQ implantable loop recorder. This study reports an unexpectedly high rate of extrusion without infection. The authors suggest that the depth of the incision is the main factor impacting extrusions. Larger studies are recommended, however, and a proposed measure to avoid spontaneous extrusion is the design of a longer manufacturer's blade in order to increase the depth of the incision and insertion. OBJECTIVE We analysed the effect of expression of nucleolar spindle-associated protein 1 (NuSAP1) on the prognosis of breast cancer (BC) and investigated its potential mechanism of tumourigenicity in triple-negative breast cancer (TNBC) cell lines. MATERIALS AND METHODS We downloaded the RNA-seq breast cancer (BC) data from The Cancer Genome Atlas (TCGA) and screened for the NuSAP1 gene using R software. The clinical data for patients with BC were screened and analysed using R software. A survival curve was drawn using the Kaplan-Meier Plotter. Cell proliferation and invasion were verified by the Cell Counting Kit-8 and Transwell assays. Expression of NuSAP1, the Wnt/β-catenin pathway, and epithelial-mesenchymal-transition-related proteins in TNBC was detected using real-time quantitative polymerase chain reaction (qRT-PCR) and western blotting (WB). RESULTS Expression of NuSAP1 was upregulated in BC. The change in NuSAP1 expression levels was associated with multiple clinicopathological factors, and the higher the expression of NuSAP1 was, the shorter the survival time. In MDA-MB-231 and BT549 cells, knockdown of NuSAP1 expression resulted in a significant decrease in cell proliferation and invasion; a decrease in expression of cyclin D1, vimentin, Slug, Twist, wnt3a, and pβ-catenin; and an increase in expression of e-cadherin. The results of the sh-NuSAP1 + ov-NuSPA1 group were the opposite of the results of the sh-NuSAP1 group. CONCLUSION NuSAP1 is a carcinogen that facilitates progression of TNBC through the Wnt/β-catenin and epithelial-mesenchymal transition pathways. V.Lung squamous cell carcinoma (LUSC) is a common type of malignancy. The mechanism behind its tumor progression is not clear yet. The aim of this study is to use machine learning to identify the feature miRNAs, which can be reliably used as biomarkers for diagnosis LUSC. We downloaded microRNA expression data and clinical data from The Cancer Genome Atlas (TCGA) database and Gene Expression Omnibus(GEO) database to identify differences in microRNA expression of primary tumor tissues and para-carcinoma tissues from LUSC. Construction of miRNA-mRNA interaction network, GO, KEGG pathway analysis and Kaplan-Meier survival analysis were used to explore the biological functions of the identified microRNAs. 21 feature miRNAs were identified between lung SCC tumor tissues and para-carcinoma tissues with the support of SVM and PCA methods. Among them, ten feature miRNAs mir-143, mir-100, mir-101-1, mir-101-2, mir-182, mir-183, mir-205, mir-21, mir-30a, mir30-d were identified which could be used as a feature group to separate the cancer tissues from the adjacent tissues ultimately, and cross-validation of the obtained data showed that it can achieve extremely high accuracy and recall rate.
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