BackgroundDuctal carcinoma in situ with microinvasion (DCISM) represents ~1% of all breast cancer cases. Risk factors for lymph node (LN) metastasis and appropriate adjuvant therapy for DCISM are still widely debated.MethodsWe retrieved DCISM data from the National Cancer Institute’s Surveillance, Epidemiology, and End Results registry database (1998–2013). Chi-squared tests and logistic regression models were applied to investigate the potential risks of LN metastasis. Univariate and multivariate Cox proportional hazards regressions were performed to estimate the prognostic factors of DCISM. Survival outcomes were estimated using the Kaplan–Meier method. A 1:1 propensity score matching was used to minimize potential bias.ResultsOverall, 6,219 patients with DCISM met our inclusion criteria. Younger age and higher grade disease were identified as risk factors for LN metastasis. In the multivariable analysis, LN metastasis and chemotherapy were prognostic factors for worse overall survival and breast cancer-specific survival. Furthermore, propensity score matching and subgroup analysis showed that chemotherapy may not be effective for DCISM patients.ConclusionYounger patients with high-grade disease tend to have LN involved in DCISM. Adjuvant chemotherapy might not be necessary for patients with DCISM.
Cobalt-based spinel oxide is a promising electrocatalyst for oxygen evolution reaction (OER) because of its low cost, excellent activity and stability. Herein, we designed the CuMn x Co 2 O 4 electrocatalyst with tunable electronic structure via Mn-doping to enhance OER performance. Results showed that the CuMn 0.5 Co 2 O 4 catalyst prepared by calcined at 600°C exhibited high crystalline without impurity phase, and possessed the enhanced Co 2 + /Co 3 + ratio and high concentration of oxygen vacancies, which were facilitated to enhance OER performance. Electrochemical test results showed the CuMn 0.5 Co 2 O 4 catalyst had high OER performance with a low overpotential of 340 mV at the current density of 10 mA • cm À 2 and a smaller Tafel slope of 69.8 mV • dec À 1 . TOF and ECSA results illustrated that the more intrinsic catalytic activity on the CuMn 0.5 Co 2 O 4 catalyst. After 1000 cycles, the catalyst exhibited high stability with the 8 1.7 % of current retention rate. The OER activity enhancement mechanism of was further analyzed, which were mainly ascribed to the conversion of variable Co 2 + / Co 3 + and enhanced oxygen vacancies.
This study investigated the association of genetic variants of EPHA4, a receptor tyrosine kinase, with hypertension, and the role of EPHA4 in vascular smooth muscle cell (VSMC) contractility. Methods: Data from two human genetic studies, ADVANCE and HCHS/SOL, were analysis for association of EPHA4 single nucleotide variants (SNVs) with hypertension risks. The effect of EPHA4 signalling and sex hormones on mouse vascular smooth muscle cells contractility was assessed. Results: We identified a single-nucleotide variant (rs75843691 hg19 chr2:g.222395371 C>G), located in the 3rd intron of EPHA4 gene, as significantly associated with hypertension in human female subjects (p-value = 8.3 x 10-4, below the Bonferroni-corrected critical p-value) but not male subjects with type 2 diabetes from the ADVANCE clinical trial. We found that EPHA4 was expressed in VSMCs and its stimulation by solid-phase anti-EPHA4 antibody led to reduced VSMC contractility triggered by phenylephrine. Estrogen enhanced the contractility-lowering effect of EPHA4 stimulation. Conversely, small interfering RNA knockdown of Epha4 expression in VSMCs resulted in increased contractility of VSMCs from female but not from male mice. Conclusion: EPHA4 is a sex-specific hypertension risk gene. Forward EPHA4 signalling reduces VSMC contractility, and estrogen is a modifier of this effect. The effect of EPHA4 on VSMCs contractility explains the association of EPHA4 gene with hypertension risks in females.
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