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Clinical annotations for the actionable pharmacogenetic variants affecting the efficacy of cardiovascular drugs have been collected, yet their impacts on elderly patients with coronary artery disease (CAD) undergoing polypharmacy remain uncertain. We consecutively enrolled 892 elderly patients (mean age 80.7 ± 5.2) with CAD and polypharmacy. All the included patients underwent genotyping for 13 variants in 10 pharmacogenes (CYP2C19, CYP2C9, CYP4F2, CYP2D6, VKORC1, SLCO1B1, APOE, ACE, ADRB1, and MTHFR), which have the clinical annotations for 12 drugs that are commonly prescribed for patients with CAD. We found that 80.3% of the elderly CAD patients had at least one drug–gene pair associated with a therapeutical drug change. After adjusting for covariates, the number of drug–gene pairs was independently associated with a decreased risk of both major cardiovascular events (MACEs) (adjusted hazard ratio [HR]: 0.803, 95% confidence interval [CI]: 0.683–0.945, p = 0.008) and all-cause mortality (adjusted HR: 0.848, 95% CI: 0.722–0.996, p = 0.045), but also with an increased risk of adverse drug reactions (ADRs) (adjusted HR: 1.170, 95% CI: 1.030–1.329, p = 0.016). The Kaplan–Meier survival curves showed that compared to patients without a drug–gene pair, a significantly lower risk of MACEs could be observed in patients with a drug–gene pair during a 4-year follow-up (HR: 0.556, 95% CI: 0.325–0.951, p = 0.013). In conclusion, the carrier status of the actionable drug–gene pair is predictive for the clinical outcomes in elderly patients with CAD and polypharmacy. Implementing early or preemptive pharmacogenetic panel-guided polypharmacy holds the potential to enhance clinical outcomes for these patients. [ABSTRACT FROM AUTHOR]

Processing fine and ultrafine coal particles from primary resources is essential for sustainable development. As one of the most recently developed enrichment equipment, cyclonic microbubble flotation columns (FCMC) showed high efficiency in upgrading various fine minerals. However, understanding the effect of FCMC operating variables on coal upgrading process responses remains a black box and needs fundamental assessments. To fill the gap, this study examined the influence of circulating pump pressure and froth height on the recovery of different coal particle size ranges to assess and explore fundamental FCMC performance. The experimental results established that increased froth height would simultaneously reduce the collection and froth recovery. Coarse particles in the high froth height were detached due to bubble coalescence or rupture, while the liquid drainage reduced fine particle pollution of froth products. Increasing circulating pump pressure would increase the collection zone's turbulence, lead to coarse particle detachment, and reduce collection recovery. Meanwhile, increasing circulating pump pressure could promote froth stability and decrease froth detachment in the froth zone. The calculated first-order rate constant (kc) confirmed that the flotation rate constants of coarse (−0.5 + 0.25 mm) and fine (−0.074 mm) particles were low, while the intermediate particles (−0.125 + 0.074 mm) had faster flotation kinetics. [ABSTRACT FROM AUTHOR]

Astilbin, a flavonoid compound, was isolated from the rhizome of Smilax glabra Roxb. (with red cross-section) grown in Guizhou Province, China. We accessed its effect and potential mechanism on attenuation of the inflammatory response in CFA-induced AA rats. Our results showed that daily oral administration of astilbin at 5.3 mg/kg reduced joint damage in the hind paw of AA rats. Accordingly, astilbin exhibited remarkable inhibitory effects on TNF-α, IL-1β, and IL-6 mRNA expression. Significant decrease of serum cytokine levels of TNF-α, IL-1β, and IL-6 was also observed in astilbin-treated AA rats compared to the vehicle-treated AA rats. The reduced expression of these cytokines was associated with protein activity suppression of three key molecular targets in the pathogenesis of RA, including IKKβ, NF-κB p65 subunit, and TLR adaptor MyD88. Furthermore, the therapeutic effects of astilbin on the inhibition of cytokines production as well as the reduction of inflammatory response in AA rats are close to a commonly used antirheumatic drug, leflunomide. Collectively, our data suggest that the action mechanism of astilbin, as an anti-inflammatory agent for RA treatment, is associated with modulating the production of proinflammatory cytokines and inhibiting the expression of key elements in NF-κB signaling pathway mediated by TLR. [ABSTRACT FROM AUTHOR]