We performed a genome-wide association study for primary open-angle glaucoma (POAG) in 1,007 cases with high-pressure glaucoma (HPG) and 1,009 controls from southern China. We observed genome-wide significant association at multiple SNPs near ABCA1 at 9q31.1 (rs2487032; P = 1.66 × 10(-8)) and suggestive evidence of association in PMM2 at 16p13.2 (rs3785176; P = 3.18 × 10(-6)). We replicated these findings in a set of 525 HPG cases and 912 controls from Singapore and a further set of 1,374 POAG cases and 4,053 controls from China. We observed genome-wide significant association with more than one SNP at the two loci (P = 2.79 × 10(-19) for rs2487032 representing ABCA1 and P = 5.77 × 10(-10) for rs3785176 representing PMM2). Both ABCA1 and PMM2 are expressed in the trabecular meshwork, optic nerve and other ocular tissues. In addition, ABCA1 is highly expressed in the ganglion cell layer of the retina, a finding consistent with it having a role in the development of glaucoma.

Generalized pustular psoriasis (GPP) is a rare and severe auto-inflammatory skin disease that is characterized by recurrent, acute onset, and generalized pustular eruptions on erythematous, inflamed skin. GPP is traditionally classified as a variant of psoriasis vulgaris, even though recent clinical, histological and genetic evidence suggests that it is a heterogeneous disease and requires a separate diagnosis. In recent years, variants of IL36RN, CARD14, AP1S3 and MPO genes have been identified as causative or contributing to genetic defects in a proportion of patients affected by GPP. These disease-related genes are involved in common inflammatory pathways, in particular in the IL-1/IL-36-chemokines-neutrophil pathogenic axis. At present, no standard therapeutic guidelines have been established for GPP management, and there is a profound need for novel efficacious treatments of GPP. Among them, biological agents antagonizing the IL-36 pathway are promising therapeutics. The aim of the present review is to provide the most recent updates on the genetics, genotype-phenotype correlation and pathological basis of GPP, as well as on biologic treatments available for GPP and relative clinical courses.

Our analysis showed that CPAP significantly improved insulin resistance in non-diabetic patients with moderate to severe OSA, while no significant change in body mass index was detected. Compared with fasting blood glucose at baseline, there was no change in glycemic control with CPAP. Further large-scale, randomized, and controlled studies are needed to evaluate the longer treatment and its possible effects on weight loss and glycemic homeostasis.

ClinicalTrials.gov NCT02059993.

No abstract

This study established a numerical model to investigate the degradation mechanism and behavior of bioabsorbable cardiovascular stents. In order to generate the constitutive degradation material model, the degradation characteristics were characterized with user-defined field variables. The radial strength bench test and analysis were used to verify the material model. In order to validate the numerical degradation model, in vitro bench test and in vivo implantation studies were conducted under physiological and normal conditions. The results showed that six months of degradation had not influenced the thermodynamic properties and mechanical integrity of the stent while the molecular weight of the stents implanted in the in vivo and in vitro models had decreased to 61.8% and 68.5% respectively after six month's implantation. It was also found that the degradation rate, critical locations and changes in diameter of the stents in the numerical model were in good consistency in both in vivo and in vitro studies. It implies that the numerical degradation model could provide useful physical insights and prediction of the stent degradation behavior and evaluate, to some extent, the in-vivo performance of the stent. This model could eventually be used for design and optimization of bioabsorbable stent.

No abstract

Ubiquitin C-terminal hydrolase-L1 (UCHL1) belongs to the family of deubiquitinating enzymes (DUBs), which is involved in the ubiquitin-dependent proteolytic system. Previously, we have reported that the upregulation of UCHL1 is related to lymph node metastasis in colorectal cancer (CRC). However, its molecular mechanisms remain elusive. In this study, we transfected pcDNA3.1/UCHL1 and the pcDNA3.1/UCHL1-C90S mutant into HCT8 cells. The changes in biological features in these stable transfectants were examined both in vitro and in vivo. Western blot analysis was used to analyze the changes in the β-catenin/T cell factor (TCF) pathway. We demonstrated that UCHL1 re-expression promoted the proliferation, migration and metastasis potential of HCT8 cells both in vitro and in vivo. We also found that UCHL1 could decelerate β-catenin degradation depending on its deubiquitinating activity. The accumulated β-catenin consequently activated the β-catenin/TCF pathway and induced the expression of cyclin D1 and uPA. These observations imply that UCHL1 may contribute to CRC progression by activating the β-catenin/TCF pathway through its deubi-quitinating activity.