ABSTRACT
Purpose: Our objective was to evaluate the diagnostic performance of BRAFV600E mutation for malignant, and to identify clinical characteristics associated with positive BRAFV600E mutation in low-risk cytological and ultrasound diagnostic thyroid nodules. This aims to identify patients who may benefit from BRAFV600E mutation testing and subsequent surgical intervention. Patients and Methods: We analysis the clinical characteristics correlated with BRAFV600E mutation in our detection cohort, including 204 patients with 217 thyroid nodules, and separate analyses were performed in 103 thyroid nodules with benign cytological result. Signaling pathway and immune response associated with age and BRAFV600E mutation status were also evaluated in Asian patients with thyroid cancer from the Cancer Genome Atlas (TCGA) dataset. Results: The positive BRAFV600E mutation was significantly associated with higher Ultrasound (US) classification (p<0.001) and fine-needle aspiration (FNA) categories (p<0.001). BRAFV600E mutation as a risk factor for malignancy, showing the optimal diagnostic efficacy for malignancy combined with FNA categories, with the AUC was 0.923. Otherwise, BRAFV600E mutation is a risk factor in screening malignancy in low-risk FNA and US classification, which is significant correlation with patients age. Patients over 50 years old exhibiting a higher percentage of positive BRAFV600E mutation when both ultrasound and FNA results indicate benign conditions, with higher risk of malignancy. Conclusion: BRAFV600E mutation is an accurate adjunctive diagnostic marker on FNA to screen malignancy. In low risk of both ultrasound and FNA results, the positive BRAFV600E was significant increased in patients over 50 years old, which have higher risk of malignancy. Thus, the BRAFV600E mutation detection and further surgery should be strengthened in older patients with benign cytological and US results thyroid nodules.
ABSTRACT
Quercetin (QCT) has antioxidant, anti-inflammatory, anti-tumor and other important pharmacological activities, but the poor water solubility limits its application. In this work, the amphiphilic dextran (ADEX) was prepared by grafting L-cysteine and octadecylamine onto carboxymethyl dextran with the grafting rate of 21.29 % and 19.35 %. Then, the QCT-loaded nanomicelles (QNMs) were prepared by using ADEX as wall material and the QCT as core material via ultrasonic self-assembly method. The particle size and zeta potential of QNMs were 372 nm and 31.4 mV. Under simulated gastric and simulated intestinal fluids, the cumulative release QNMs were 37.54 % and 52.13 % within 180 min, and the QNMs showed better stability in simulated gastric fluid. The QNMs showed significantly better PTIO, OH and O2- scavenging activities than QCT. In addition, QNMs could effectively down-regulate the expression of pro-inflammatory cytokines and promoted the expression of anti-inflammatory cytokine. The cellular uptake results proved that the QNMs were more easily absorbed by cells than free QCT, indicating that the nano-encapsulation procedure effectively improved the uptake efficiency of QCT by cells.
