BRAF V600E as an accurate marker to complement fine needle aspiration (FNA) cytology in the guidance of thyroid surgery in the Chinese population: evidence from over 1000 consecutive FNAs with follow-up.
BRAF V600E作为中国人群甲状腺手术指导中补充细针穿刺 (FNA) 细胞学的准确标志物: 来自超过1000个连续FNA随访的证据。
- 作者列表："Zhao Q","Wang Y","Ye Q","Wang P","Rao J
BACKGROUND:Currently, several commercial molecular tests have been developed for reclassifying thyroid nodules with indeterminate fine needle aspiration cytology. These tests are quite expensive and not available in China. Previous studies demonstrated a very high prevalence of the BRAF V600E mutation in Asian people. A high incidence may result in a robust sensitivity. We conducted this study to determine the prevalence of BRAF V600E mutation and its ability to reclassify cytologically indeterminate thyroid nodules in the Chinese population. METHODS:Between January 2016 and October 2018, consecutive patients who underwent a fine needle aspiration procedure and agreed to provide materials for molecular analysis in our hospital were recruited in this study. All were followed up until they had a thyroidectomy and a final pathological diagnosis or until January 2019 (those did not have surgery). RESULTS:A total of 1960 patients were included in this study. Until January 2019, 1240 patients underwent surgery. Using histopathological diagnosis as a gold standard, the overall sensitivity and specificity of the BRAF V600E mutational analysis for the discrimination of benign nodules from cancer in thyroid fine needle aspiration samples were 83.3% (81.0-85.3%) and 96.0% (77.7-99.8%), respectively, with an area under the ROC curve of 0.90 (95% CI 0.85-0.95, P < 0.001). Among cases with indeterminate cytology, BRAF-positive cases were showing malignancy in the final pathology, and BRAF-negative cases were showing safer to be followed up. CONCLUSION:The BRAF V600E mutation is highly prevalent in the Chinese population and can accurately complement cytopathology in the guidance of thyroid surgery.Mini-abstract: The BRAF V600E mutation has both high specificity and sensitivity to predict thyroid malignancy in the Chinese population. It can accurately complement cytopathology in the guidance of thyroid surgery.
背景: 目前，已经开发了几种商业分子检测方法，用不确定的细针穿刺细胞学对甲状腺结节进行重新分类。这些测试相当昂贵，在中国还没有。以前的研究表明，在亚洲人中BRAF V600E突变的患病率非常高。高发病率可能导致稳健的灵敏度。我们进行了这项研究，以确定中国人群中BRAF V600E突变的患病率及其重新分类细胞学不确定甲状腺结节的能力。 方法: 在2016年1月至2018年10月期间，在本研究中招募接受细针穿刺术并同意为我们医院的分子分析提供材料的连续患者。所有患者均接受随访，直到他们接受了甲状腺切除术和最终病理诊断，或直到2019年1月 (那些没有接受手术的患者)。 结果: 本研究共纳入1960例患者。至2019年1月，1240例患者接受了手术治疗。以组织病理学诊断为金标准，BRAF V600E突变分析对甲状腺细针穿刺标本中良性结节与癌鉴别的总体敏感性和特异性分别为83.3% (81.0-85.3%) 和96.0% (77.7-99.8%)，ROC曲线下面积为0.90 (95% CI 0.85-0.95，P <0.001)。在细胞学不确定的病例中，BRAF阳性病例在最终病理中显示恶性，BRAF阴性病例显示随访更安全。 结论: BRAF V600E突变在中国人群中高度流行，在甲状腺手术指导中可准确补充细胞病理学。在甲状腺手术的指导下，能准确地补充细胞病理学。
METHODS::The ATP binding-cassette superfamily corresponds the mostly transmembrane transporters family found in humans. These proteins actively transport endogenous and exogenous substrates through biological membranes in body tissues, so they have an important role in the regulation of many physiological functions necessary for human homeostasis, as well as in response regulation to several pharmacological substrates. The development of multidrug resistance has become one of the main troubles in conventional chemotherapy in different illnesses including cancer, being the increased efflux of antineoplastic drugs the main reason for this multidrug resistance, with a key role of the ABC superfamily. Likely, the interindividual variability in the pharmacological response among patients is well known, and may be due to intrinsically factors of the disease, genetic and environmental ones. Thus, the understanding of this variability, especially the genetic variability associated with the efficacy and toxicity of drugs, can provide a safer and more effective pharmacological treatment, so ABC genes are considered as important regulators due to their relationship with the reduction in pharmacological response. In this review, updated information about transporters belonging to this superfamily was collected, the possible role of these transporters in cancer, the role of genetic variability in their genes, as well as some therapeutic tools that have been tried to raise against main transporters associated with chemoresistance in cancer.
METHODS:BACKGROUND:Cholinergic neurotransmission regulates neuroinflammation in Parkinson disease (PD). RESEARCH DESIGN AND METHODS:The authors conducted a delayed-start study of donepezil for cognitive decline in non-demented PD patients. The study consisted of a 96-week randomized placebo-controlled double-blind phase 1, followed by a 24-week donepezil extension phase 2. The primary outcome measure was a change in the Mini-Mental State Examination (MMSE) at week 120. RESULTS:A total of 98 patients were randomly allocated to the early-start (donepezil-to-donepezil) and delayed-start (placebo-to-donepezil) groups. Mean (SD) of the baseline MMSE was 27.6 (2.0) and 28.0 (2.1), respectively. MMSE change at week 120 was better in the early-start group than in the delayed-start group, but the difference was not significant. The MMSE declined in apolipoprotein ε4 carriers, but not in non-carriers, and the factor interaction (intervention × ε4 genotype) was highly significant (P < 0.001). Analyzed with the interaction, the difference was significant (group difference 1.95 [0.33 to 3.57], P = 0.018). The MMSE decline slope in phase 1 was significantly better in the early-start group than in the delayed-start group (P = 0.048). CONCLUSIONS:Cognitive function deteriorated in ε4 carriers, but not in non-carriers, and early-start donepezil may postpone cognitive decline in the former.
METHODS::Since the discovery of dental pulp stem cells, a lot of teams have expressed an interest in dental pulp regeneration. Many approaches, experimental models and biological explorations have been developed, each including the use of stem cells and scaffolds with the final goal being clinical application in humans. In this review, the authors' objective was to compare the experimental models and strategies used for the development of biomaterials for tissue engineering of dental pulp with stem cells. Electronic queries were conducted on PubMed using the following terms: pulp regeneration, scaffold, stem cells, tissue engineering and biomaterial. The extracted data included the following information: the strategy envisaged, the type of stem cells, the experimental models, the exploration or analysis methods, the cytotoxicity or viability or proliferation cellular tests, the tests of scaffold antibacterial properties and take into account the vascularization of the regenerated dental pulp. From the 71 selected articles, 59% focused on the "cell-transplantation" strategy, 82% used in vitro experimentation, 58% in vivo animal models and only one described an in vivo in situ human clinical study. 87% used dental pulp stem cells. A majority of the studies reported histology (75%) and immunohistochemistry explorations (66%). 73% mentioned the use of cytotoxicity, proliferation or viability tests. 48% took vascularization into account but only 6% studied the antibacterial properties of the scaffolds. This article gives an overview of the methods used to regenerate dental pulp from stem cells and should help researchers create the best development strategies for research in this field.