Dioscin, a natural steroid saponin, has been shown to have anti-inflammatory effects, but its protective mechanism against mastitis is still unknown. NLRP3 inflammasome and pyroptosis play important roles in the pathogenesis of many inflammatory diseases, including mastitis. The purpose of this study was to explore the effect of dioscin on lipopolysaccharide- (LPS-) induced mastitis in vivo and in vitro and its mechanism of action. In vivo experiments, dioscin can reduce the inflammatory lesions and neutrophil motility in mammary tissue. Moreover, dioscin also can reduce the production of proinflammatory factors such as interleukin-1 beta (IL-1β) and inhibit the activation of NLRP3 inflammasome in LPS-induced mice mastitis. In vitro experiments, the results showed that dioscin inhibited the inflammatory response and the activation of NLRP3 inflammasome, but the survival rate of mouse mammary epithelial cells (mMECs) induced by LPS+ATP is increased. Subsequently, the experiment convinces that dioscin can reduce LPS+ATP-induced mMEC pyroptosis by adding Ac-DEVD-CHO (a caspase-3 inhibitor). Further mechanistic studies demonstrate that dioscin can activate AMPK/Nrf2 to inhibit NLRP3/GSDMD-induced mMEC pyroptosis. In summary, this paper reveals a novel function of dioscin on mMEC pyroptosis and provides a new potential therapy of dioscin for the treatment and prevention of mastitis.
There are controversies on optimal stenting strategy regarding true left main (LM) bifurcation lesions. The present study compared 1- and 2-stenting strategy for patients with true LM bifurcation lesions as differentiated by DEFINITION criteria. 928 patients with true LM bifurcation lesions (Medina 1,1,1 or 0,1,1) treated with DES were enrolled consecutively. 297 (32.0%) patients were identified as complex LM bifurcation, and 631 (68.0%) patients into simple LM bifurcation group according to DEFINTION criteria. Patients in complex vs. simple LM bifurcation group had significantly higher major adverse cardiac event (MACE, including cardiac death, myocardial infarction [MI] and ischemia-driven target vessel revascularization) rate at 30 days (7.8% vs. 4.0%, p = 0.01), 1 year (10.3% vs. 6.4%, p = 0.04), and numerically at 3 years (14.2% vs. 10.1%, p = 0.07), which was mainly driven by increased MI. Moreover, patients in the 2-stent strategy group had strong trend towards lower incidence of cardiac death in both complex LM bifurcation group (2.0% vs. 5.9%, p = 0.08) and simple LM bifurcation group (1.9% vs. 4.5%, p = 0.07). In conclusion, the complex bifurcation lesion criteria established in DEFINITION study was able to risk-stratify LM bifurcation patients. Two-stent technique yielded numerically lower 3-year cardiac mortality regardless of LM bifurcation complexity.
This set of consensus quality indicators can be used as a standard list to be monitored by providers of acute myocardial infarction care in an effort to continuously evaluate and improve their performance.
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