Correlation between Metabolic Parameters and Warfarin Dose in Patients with Heart Valve Replacement of Different Genotypes.

Background: Warfarin has become the first choice for anticoagulation in patients who need lifelong anticoagulation due to its clinical efficacy and low price. However, the anticoagulant effect of warfarin is affected by many drugs, foods, etc. accompanied by a high risk of bleeding and embolism. The Vitamin K epoxide reductase complex 1 (VKORC1) and Cytochrome P450 2C9 (CYP2C9) genotypic variation can influence the therapeutic dose of warfarin. However, it is not clear whether there is a correlation between warfarin dose and liver function, kidney function and metabolic markers such as uric acid (UA) in patients with different genotypes. We performed a single-center retrospective cohort study to evaluate the factors affecting warfarin dose and to establish a dose conversion model for warfarin patients undergoing heart valve replacement. Methods: We studied 343 patients with a mechanical heart valve replacement, compared the doses of warfarin in patients with different warfarin-related genotypes (CYP2C9 and VKORC1), and analyzed the correlation between liver function, kidney function, UA and other metabolic markers and warfarin dose in patients with different genotypes following heart valve replacement. Results: Genotype analysis showed that 72.01% of patients had CYP2C9*1/*1 and VKORC1 mutant AA genotypes. Univariate regression analysis revealed that the warfarin maintenance dose was significantly correlated with gender, age, body surface area (BSA), UA and genotype. There was no correlation with liver or kidney function. Multiple linear regression analysis showed that BSA, genotype and UA were the independent factors influencing warfarin dose. Conclusions: There is a significant correlation between UA content and warfarin dose in patients with heart valve replacement genotypes CYP2C9*1/*1/VKORC1(GA+GG), CYP2C9*1/*1/VKORC1AA and CYP2C9*1/*1/VKORC1AA.

GPR30 Alleviates Pressure Overload-Induced Myocardial Hypertrophy in Ovariectomized Mice by Regulating Autophagy.

The incidence of heart failure mainly resulting from cardiac hypertrophy and fibrosis increases sharply in post-menopausal women compared with men at the same age, which indicates a cardioprotective role of estrogen. Previous studies in our group have shown that the novel estrogen receptor G Protein Coupled Receptor 30 (GPR30) could attenuate myocardial fibrosis caused by ischemic heart disease. However, the role of GPR30 in myocardial hypertrophy in ovariectomized mice has not been investigated yet. In this study, female mice with bilateral ovariectomy or sham surgery underwent transverse aortic constriction (TAC) surgery. After 8 weeks, mice in the OVX + TAC group exhibited more severe myocardial hypertrophy and fibrosis than mice in the TAC group. G1, the specific agonist of GPR30, could attenuate myocardial hypertrophy and fibrosis of mice in the OVX + TAC group. Furthermore, the expression of LC3II was significantly higher in the OVX + TAC group than in the OVX + TAC + G1 group, which indicates that autophagy might play an important role in this process. An in vitro study showed that G1 alleviated AngiotensionII (AngII)-induced hypertrophy and reduced the autophagy level of H9c2 cells, as revealed by LC3II expression and tandem mRFP-GFP-LC3 fluorescence analysis. Additionally, Western blot results showed that the AKT/mTOR pathway was inhibited in the AngII group, whereas it was restored in the AngII + G1 group. To further verify the mechanism, PI3K inhibitor LY294002 or autophagy activator rapamycin was added in the AngII + G1 group, and the antihypertrophy effect of G1 on H9c2 cells was blocked by LY294002 or rapamycin. In summary, our results demonstrate that G1 can attenuate cardiac hypertrophy and fibrosis and improve the cardiac function of mice in the OVX + TAC group through AKT/mTOR mediated inhibition of autophagy. Thus, this study demonstrates a potential option for the drug treatment of pressure overload-induced cardiac hypertrophy in postmenopausal women.

Intraluminal thrombus attached to the lesser curvature of the aortic arch and cerebral ischemic stroke after its surgical removal.

Some cases of thrombi at the ascending and descending aorta have been reported, but there are only a few reports of intraluminal aortic arch thrombi. Most intraluminal thrombi are associated with atherosclerotic lesions at the aortic wall. Here, we report a case of an intraluminal thrombus attached to the lesser curvature of the aortic arch. The thrombus was successfully and completely excised, and the pathologic study suggested no obvious atherosclerotic changes in the aortic wall. Two months after surgical removal of the thrombus, the patient suffered a severe cerebral ischemic stroke caused by a newly formed thromboembolism in the innominate artery.

Influence of repeated cut-off and rescanning on the trueness of the intraoral digital scans.

OBJECTIVES: To evaluate the effects of repeated cut-off and rescan procedures on the trueness of three intraoral scanners (IOS). METHODS: A tooth model (#16) with a standard class II cavity was prepared, and the complete-arch was scanned using a laboratory scanner (D2000, 3Shape A/S) to obtain a reference scan. Then the typodont was scanned with three IOSs (3Shape TRIOS 3, CEREC Omnicam, and Medit i500) under two rescanning strategies (full-cut and partial-cut), with varying numbers of repeated cut-off and rescanning procedures (0, 1, 3, 5, 7, or 10). The trueness discrepancy between the reference and experimental digital scan was estimated using root mean square (RMS) calculations. Three regions of interest were selected to represent the rescanning, identification, and non-rescan area. And the discrepancies were analyzed using a linear mixed model (α=0.05). RESULTS: Cut-off and rescanning procedures significantly decreased the trueness of digital scans in all test conditions compared to the reference. However, no progressive increase in discrepancy was observed under any rescan conditions. Significant influences on trueness were found based on the IOS used, with the 3Shape system exhibiting lower RMS values. The partial-cut strategy showed lower RMS values compared to the full-cut strategy, albeit without statistical significance. CONCLUSIONS: While repeated cut-off and rescanning procedures led to a decline in the quality of digital impressions, they did not result in discrepancy accumulation with repeated rescanning. CLINICAL SIGNIFICANCE: To ensure high scanning accuracy in dental practice, it is advisable to minimize the rescanning area when correcting imperfections in digital scans. Additionally, selecting an appropriate scanner can help mitigate the negative effects of the rescanning technique.