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Background Circular RNAs (circRNAs) have been indicated as potentially critical mediators in various types of tumor progression, generally acting as microRNA (miRNA) sponges to regulate downstream gene expression. However, the aberrant expression profile and dysfunction of circRNAs in human clear cell renal cell carcinoma (ccRCC) need to be further investigated. This study mined key prognostic circRNAs and elucidates the potential role and molecular mechanism of circRNAs in regulating the proliferation and metastasis of ccRCC. Methods circCHST15 (hsa_circ_0020303) was identified by mining two circRNA microarrays from the Gene Expression Omnibus database and comparing matched tumor versus adjacent normal epithelial tissue pairs or matched primary versus metastatic tumor tissue pairs. These results were validated by quantitative real-time polymerase chain reaction and agarose gel electrophoresis. We demonstrated the biological effect of circCHST15 in ccRCC both in vitro and in vivo. To test the interaction between circCHST15 and miRNAs, we conducted a number of experiments, including RNA pull down assay, dual-luciferase reporter assay and fluorescence in situ hybridization. Results The expression of circCHST15 was higher in ccRCC tissues compared to healthy adjacent kidney tissue and higher in RCC cell lines compared to normal kidney cell lines. The level of circCHST15 was positively correlated with aggressive clinicopathological characteristics, and circCHST15 served as an independent prognostic indicator for overall survival and progression-free survival in patients with ccRCC after surgical resection. Our in vivo and in vitro data indicate that circCHST15 promotes the proliferation, migration, and invasion of ccRCC cells. Mechanistically, we found that circCHST15 directly interacts with miR-125a-5p and acts as a microRNA sponge to regulate EIF4EBP1 expression. Conclusions We found that sponging of miR-125a-5p to promote EIF4EBP1 expression is the underlying mechanism of hsa_circ_0020303-induced ccRCC progression. This prompts further investigation of circCHST15 as a potential prognostic biomarker and therapeutic target for ccRCC.

In patients with PAH, RV regional volume was enlarged and systolic function was impaired with distinct characteristics; regional EF in the inflow compartment and global EF were inversely correlated with PASP and PVR. Evaluation of RV regional systolic function using RT3DE may play a potential role in the noninvasive assessment of the severity of PAH.

The aim of this study was to investigate subclinical LV changes in patients with maintenance hemodialysis (MHD) using three-dimensional speckle-tracking echocardiography (3DSTE) and to explore its prognostic value. A total of 88 individuals were consecutively enrolled, including 66 subjects with MHD and 22 age- and sex-matched controls. Conventional and Real-time three-dimensional echocardiography was performed and analyzed. Left ventricular volume, strain and time parameters were calculated and compared. The MHD cohort was then followed to record cardiovascular events (CVE). Univariate and multivariate logistic regression analysis was used to identify independent predictors of CVE. Compared with the controls, MHD patients had significantly lower global longitudinal and radial strain (GLS and GRS), and LVEF (GLS: -17.0 ± 2.3 vs -18.8 ± 2.3 %; GRS: 37.0 ± 3.5 vs 39.4 ± 3.4 %; LVEF: 57.3 ± 4.2 vs 59.5 ± 3.5 %, p < 0.05 for all), as well as enlarged LV volume (EDV: 51.3 ± 14.2 vs 40.4 ± 7.3 ml/m(2); ESV: 22.0 ± 6.9 vs 16.3 ± 3.2 ml/m(2); SV: 29.2 ± 8.0 vs 24.0 ± 4.7 ml/m(2), p < 0.01 for all) and LV mass index (LVMi) (107.7 ± 28.6 vs 83.7 ± 20.6 g/m(2)). Time to minimum end-systolic volume and to peak longitudinal strain (T-msv and T-ls) were delayed in the MHD group (T-msv: 38.1 ± 5.2 vs 41.4 ± 6.4 %; T-ls: 38.1 ± 4.6 vs 42.1 ± 6.8 %, p < 0.05). Systolic dyssynchrony index (SDI) of the MHD group was significant larger than that of the controls (6.4 ± 1.5 vs 4.9 ± 1.8 %, p < 0.01). CVE occurred in 23 patients within a follow-up of 2 years. GLS and LVMi remained significant predictors of CVE [OR = 3.94, 95 % CI (1.33-11.66) for GLS and OR = 1.04, 95 % CI (1.01-1.07) for LVMi, p = 0.013 and 0.009, respectively]. Subclinical LV deformation and dysfunction exist in MHD patients with preserved LVEF. GLS and LVMi are two important predictors of CVE in MHD patients. Strain assessment in MHD patients may contribute to better vascular risk stratification.