Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 576
Filtrar
1.
Opt Lett ; 44(21): 5181-5184, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31674961

RESUMO

We experimentally demonstrate turbulence effect mitigation in a 100-m round-trip orbital-angular-momentum (OAM)-multiplexed free-space optical communication link between a ground transmitter and a ground receiver via a retro-reflecting hovering unmanned aerial vehicle (UAV) using multiple-input-multiple-output (MIMO) equalization. In our demonstration, two OAM beams at 1550 nm are transmitted to the UAV through emulated atmospheric turbulence, each carrying a 20-Gbit/s signal. 2×2 MIMO equalization is used to mitigate turbulence-induced crosstalk between the two OAM channels. Bit error rates below the 7% overhead forward error correction limit of 3.8×10-3 are achieved for both channels.

2.
Int Urol Nephrol ; 2019 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-31667689

RESUMO

BACKGROUND: The relationship between the endothelial glycocalyx constituents and the early failure of autologous arteriovenous fistulas (AVFs) in ESRD patients is still unknown. METHODS: In this prospective cohort study, 181 ESRD patients (the mean age was 53.3 ± 11.8 years, 66.3% of them were males) received forearm AVFs surgery were consecutively enrolled with a median follow-up time of 10 months. The early AVF failure was defined as a fistula that never developed adequately for dialysis use or that failed within the first 3 months of use. The serum levels of glycocalyx constituents including glypicans-1 (GPC-1), syndecans-1 (SDC-1), and hyaluronan (HA), and the indicator of endothelial activation reflected by E-selectin (ES) were determined by ELISAs. RESULTS: The primary patencies of AVFs were 98.3%, 96.7%, 91.7%, and 89.5% at 3, 6, 12, and 18 months, respectively. The ROC curve was plotted and demonstrated that HA, not GPC-1, SDC-1 or ES, can diagnose the AVF failure, with the cut-off value of 6.37 ng/ml, the sensitivity of 87.5%, the specificity of 46.9%, and the Youden index of 0.34, respectively. The Kaplan-Meier survival analysis demonstrated that patients with HA < 6.37 ng/mL had better patency of AVFs than patients with HA ≥ 6.37 ng/mL (log-rank test, p = 0.008). In the Cox proportional hazards analysis, after adjusting for confounders, HA (≥ 6.37 ng/mL vs. < 6.37 ng/mL) was associated with the early AVFs failure, with the OR of 5.88 (1.21-28.60). CONCLUSIONS: This study demonstrated that HA can predict the early failure of forearm AVFs, when its serum level is more than 6.37 ng/mL.

3.
Biosci Rep ; 39(11)2019 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-31696225

RESUMO

Neuropathic pain is a common, debilitating clinical issue. Here, the weighted gene co-expression network analysis (WGCNA) was used to identify the specific modules and hub genes that are related to neuropathic pain. The microarray dataset of a neuropathic rat model induced by tibial nerve transection (TNT), including dorsal root ganglion (DRG) tissues from TNT model (n=7) and sham (n=8) rats, was downloaded from the ArrayExpress database (E-MTAB-2260). The co-expression network modules were identified by the WGCNA package. The protein-protein interaction (PPI) network was constructed, and the node with highest level of connectivity in the network were identified as the hub gene. A total of 1739 genes and seven modules were identified. The most significant module was the brown module, which contained 215 genes that were primarily associated with the biological process (BP) of the defense response and molecular function of calcium ion binding. Furthermore, C-C motif chemokine ligand 2 (Ccl2), Fos and tissue inhibitor of metalloproteinase 1 (Timp1) which were identified as the hub genes in the PPI network and two subnetworks separately. The in vivo studies validated that mRNA and protein levels of Ccl2, Fos and Timp1 were up-regulated in DRG and spinal cord tissues after TNT. The present study offers novel insights into the molecular mechanisms of neuropathic pain in the context of peripheral nerve injury.

4.
Blood ; 2019 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-31697815

RESUMO

T-cell activation releases inositol 1,4,5-trisphosphate (IP3), inducing cytoplasmic calcium (Ca2+) influx. In turn, inositol 1,4,5-trisphosphate 3-kinase B (Itpkb) phosphorylates IP3 to negatively regulate and thereby tightly control Ca2+ fluxes that are essential for mature T-cell activation, differentiation and protection from cell death. Itpkb pathway inhibition increases intracellular Ca2+, induces apoptosis of activated T-cells, and can control T-cell mediated autoimmunity. Here, we employed genetic and pharmacological approaches to inhibit Itpkb signaling as a means of controlling graft-versus-host disease (GVHD). Murine induced Itpkb deleted (Itpkb-/-) T-cells had attenuated acute GVHD in two models without eliminating A20-luciferase B-cell lymphoma graft-versus-leukemia (GVL). A highly potent, selective inhibitor, GNF362, ameliorated acute GVHD without impairing GVL against two acute myeloid leukemia lines (MLL-AF9-eGFP; C1498-luciferase). Compared to FK506, GNF362 more selectively deleted donor alloreactive versus nominal antigen responsive T-cells. Consistent with these data and as compared to FK506, GNF362 had favorable acute GVHD and GVL properties against MLL-AF9-eGFP cells. In chronic GVHD preclinical models that have a distinct pathophysiology from acute GVHD, Itpkb-/- donor T-cells reduced active chronic GVHD in a multi-organ system model with bronchiolitis obliterans (BO) driven by germinal center reactions, resulting in target organ fibrosis. GNF362 treatment reduced active chronic GVHD in both BO and scleroderma models. Thus, intact Itpkb signaling is required to drive acute GVHD pathogenesis and sustain active chronic GVHD, pointing toward a novel clinical application to prevent acute or treat chronic GVHD.

5.
J Med Genet ; 2019 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-31704776

RESUMO

BACKGROUND: Abnormal pronuclear formation during fertilisation and subsequent early embryonic arrest results in female infertility. In recent years, with the prevalence of assisted reproductive technology, a few genes have been identified that are involved in female infertility caused by abnormalities in oocyte development, fertilisation and embryonic development. However, the genetic factors responsible for multiple pronuclei formation during fertilisation and early embryonic arrest remain largely unknown. OBJECTIVE: We aim to identify genetic factors responsible for multiple pronuclei formation during fertilisation or early embryonic arrest. METHODS: Whole-exome sequencing was performed in a cohort of 580 patients with abnormal fertilisation and early embryonic arrest. Effects of mutations were investigated in HEK293T cells by western blotting and immunoprecipitation, as well as minigene assay. RESULTS: We identified a novel homozygous missense mutation (c.397T>G, p.C133G) and a novel homozygous donor splice-site mutation (c.546+5G>A) in the meiotic gene REC114. REC114 is involved in the formation of double strand breaks (DSBs), which initiate homologous chromosome recombination. We demonstrated that the splice-site mutation affected the normal alternative splicing of REC114, while the missense mutation reduced the protein level of REC114 in vitro and resulted in the loss of its function to protect its partner protein MEI4 from degradation. CONCLUSIONS: Our study has identified mutations in REC114 responsible for human multiple pronuclei formation and early embryonic arrest, and these findings expand our knowledge of genetic factors that are responsible for normal human female meiosis and fertility.

6.
Ther Apher Dial ; 2019 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-31705787

RESUMO

Failed autologous arteriovenous fistula (AVF) is a major issue in the creation of functional hemodialysis vascular access. To date, the relationship between D-dimer and AVF failure is still uncertain. So, we conducted a retrospective cohort study to explore the patency rate of forearm AVFs and to clarify whether plasma D-dimer level can predict the failure of AVFs. In this study, 290 ESRD patients (the mean age 54.1 ± 14.6 years, 63.8% of them were males) receiving forearm AVFs surgery were consecutively enrolled with a median follow-up time of 34 months. Primary patency rates and risk factors associated with AVFs failure were explored by the Kaplan-Meier method or Cox proportional hazards model. Patients were divided into 2 groups based on the median level of D-dimer (group 1<1.1mg/L and group 2≥1.1mg/L). The Kaplan-Meier survival analysis demonstrated that the patency of AVF in group 1 was similar in group 2, which were 92.4% vs. 88.9%, 84.8% vs. 84.0%, 80.0% vs. 79.2%, 76.7% vs. 78.5%, and 76.7% vs. 78.5% at 12, 24, 36, 48 and 60months (Log-rank test, P=0.8), respectively. In the crude analysis, D-dimer (per 1mg/L increase) was independently associated with AVFs failure, with OR of 1.08 (95% CI, 1.02-1.15). However, after adjusting for potential confounders, the D-dimer (per 1mg/L increase) was not associated with the AVFs failure (OR=1.06, 95% CI=0.99-1.13). This study did not find that the plasma D-dimer level can predict the failure of forearm AVFs. This article is protected by copyright. All rights reserved.

7.
Int Immunopharmacol ; 77: 105955, 2019 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-31678866

RESUMO

The saponin active fraction from the stem bark of Albizia julibrissin (AJSAF) is an ideal vaccine adjuvant, but its mechanism of action remains unclear. The recent evidences indicate that long noncoding RNAs (lncRNAs) play essential roles in regulating the activation and function of macrophages. The current experiments were designed to investigate the effects of AJSAF on the activation of RAW264.7 macrophages and to explore its intracellular molecular mechanisms using a global gene expression microarray. AJSAF could significantly enhance phagocytic activity, induce reactive oxygen species (ROS), promote surface molecule expression, and up-regulate the mRNA and protein expression of cytokines and chemokines in RAW264.7 cells. AJSAF induced the differential expression of 223 mRNAs and 103 lncRNAs in RAW264.7 cells. Bioinformatics were used to predict the potential target mRNAs and function of up-regulated lncRNA A_30_P01018532 in RAW264.7 cells induced by AJSAF. The total 99 co-expressed mRNAs were classified as putative target genes of A_30_P01018532. A_30_P01018532 was associated with the inflammatory and immune response. AJSAF significantly increased the intracellular free Ca2+ levels and induced the phosphorylation of ERK1/2 and CREB in RAW264.7 cells. Moreover, Ca2+ chelator BAPTA-AM, ERK1/2 inhibitor PD98059 and CREB inhibitor KG-501 significantly inhibited the up-regulation of TNF-α, CCL2, CXCL2, CCL22, and A_30_P01018532 in RAW264.7 cells induced by AJSAF. These results suggested that AJSAF could activate RAW264.7 cells via Ca2+-ERK1/2-CREB pathways and that A_30_P01018532 might be an important regulator of mRNA expression in AJSAF-activated macrophage. This study may provide insights into the molecular mechanisms of action of AJSAF.

8.
Life Sci ; 239: 116877, 2019 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-31669575

RESUMO

AMP-activated protein kinase (AMPK) is induced by the exhaustion of cellular energy and activates adaptive alterations in cellular metabolism, which is the basis for cell survival during different environmental stresses. We aimed to investigate the biological functions of AMPK and its molecular mechanism in regulating thyroid cancer (TC) progression. In current study, we found that activation of AMPK by multiple agonists suppresses TC cell proliferation. However, AMPK activation also led to TC cell migration at the same time. Depletion of AMPK abolished the effect of its agonist on cell multiplication and migration. Mechanistic investigations revealed that the impact of AMPK in terms of cell migration is dependent on its nuclear translocation, since site mutation of AMPK in its nuclear translocation domain (K244A) abolished TC cell migration but did not affect the inhibition of cell proliferation by AMPK agonist. Moreover, the nuclear AMPK recruits PKM2 and ß-catenin by their interaction, which promotes the transcription of cell migration related genes, including MMP7 and c-Myc. Furthermore, depletion of PKM2/ß-catenin abolished the migration effect of AMPK agonists, but did not affect their effects on suppression of cell proliferation. Our results provided a novel function of AMPK in cancer migration, and suggested that a combination of AMPK activation and PKM2 depletion or inhibition can be a new strategy to achieve better therapeutic effects for TC patients.

9.
Front Immunol ; 10: 2470, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31681336

RESUMO

Allogeneic hematopoietic stem cell transplant (allo-HSCT) is often used to treat acute leukemia or defects of hematopoiesis. Its widespread use is hampered by graft-vs.-host disease (GVHD), which has high morbidity and mortality in both acute and chronic subtypes. Chronic GVHD (cGVHD) occurs most frequently in skin and often is characterized by pathogenic fibrosis. Mast cells (MCs) are known to be involved in the pathogenesis of other fibrotic diseases. In a murine model of cGVHD after allo-HSCT, C57BL/6J recipients of allogeneic LP/J donor cells develop sclerodermatous dermal cGVHD which is significantly decreased in mast cell-deficient B6.Cg-KitW-sh/HNihrJaeBsmGlliJ recipients. The presence of MCs is associated with fibrosis, chemokine production, and recruitment of GVHD effector cells to the skin. Chemokine production by MCs is blocked by drugs used to treat cGVHD. The importance of MCs in skin cGVHD is mirrored by increased MCs in the skin of patients with dermal cGVHD. We show for the first time a role for MCs in skin cGVHD that may be targetable for preventive and therapeutic intervention in this disease.

11.
Sci Rep ; 9(1): 14887, 2019 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-31624317

RESUMO

Bone adapts to the change of mechanical stimulus by bone remodeling activities. A number of numerical algorithms have been developed to model the adaptive bone remodeling under mechanical loads for orthopedic and dental applications. This paper examines the effects of several model parameters on the computed apparent bone density in mandible under normal chewing and biting forces. The density change rate was based on the strain energy density per unit mass. The algorithms used in this study containing an equilibrium zone (lazy zone) and saturated values of density change rate provides certain stability to result in convergence without discontinuous checkerboard patterns. The parametric study shows that when different boundary conditions were applied, the bone density distributions at convergence were very different, except in the vicinity of the applied loads. Compared with the effects of boundary conditions, the models are less sensitive to the choice of initial density values. Several models starting from different initial density values resulted in similar but not exactly the same bone density distribution at convergence. The results also show that higher reference value of mechanical stimulus resulted in lower average bone density at convergence. Moreover, the width of equilibrium zone did not substantially affect the average density at convergence. However, with increasing width, the areas with the highest and the lowest bone density areas were all reduced. The limitations of the models and challenges for future work were discussed for the better agreement between the computed results and the in vivo data.

12.
Epigenomics ; 11(12): 1399-1412, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31596135

RESUMO

Aim: To investigate DNA methylation changes in placenta tissues associated with small for gestational age (SGA). Materials & methods: A prospective cohort study consisting of 1292 pregnant women from China (including 39 SGA with placenta tissues) was performed, microarray and pyrosequencing were conducted. Results: Total 2012 methylation variable positions stood out from all probes (p < 0.05; Δß > 0.2). In SGA cases, a CpG site within ANKRD20B showed lower methylation level (p = 0.032) than appropriate for gestational age in validation cohort. Five sites within FAM198A (p = 0.047, 0.050, 0.039, 0.026 and 0.043, respectively) had a reduced methylation in male newborns whose mother had preconception folic acid supplementation. Conclusion: DNA methylation changes in placenta tissues may be associated with SGA, maternal preconception folic acid supplementation status and also be fetal sex-specific.

13.
Transplantation ; 2019 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-31634333

RESUMO

BACKGROUND: Gastrointestinal acute graft-versus-host disease (aGVHD) occurring after allogeneic hematopoietic cell transplant (allo-HCT) is an alloreactive T cell- and inflammatory cytokine driven organ injury with epithelial apoptosis as one of its hallmark findings, and is associated with significant mortality. Tumor necrosis factor (TNF)-alpha-induced protein 8 (TNFAIP8 or TIPE) acts as a negative mediator of apoptosis via inhibition of caspase-3 activation, promotes cell proliferation and Tipe deficiency is associated with increased inflammation. METHODS: To evaluate the role of TIPE in acute GVHD, naive C57BL/6 and Tipe C57BL/6 mice were conditioned with 1000cGy single dose total-body irradiation, followed by transplantation of 10 million bone marrow (BM) cells and 20 million splenocytes from either syngeneic C57BL/6 or allogeneic BALB/c donors. RESULTS: Allo TIPE-deficient mice developed exacerbated gut GVHD compared to allo controls and had significantly decreased survival (6 weeks OS: 85% vs 37%; p<0.05), higher clinical GVHD scores, more profound weight loss, increased serum proinflammatory cytokines (IL-17A, TNF, IL-6, IFN-y). T cell infiltration into the ileum was increased; epithelial proliferation was decreased along with significantly higher levels of chemokines KC and MIG. Using BM chimeric experiments, TIPE was found to have a role in both hematopoietic and nonhematopoietic cells. CONCLUSIONS: Absence of TIPE results in excessive inflammation and tissue injury after allo HCT, supporting that TIPE confers immune homeostasis and has tissue-protective function during the development of gut GVHD, and may be a potential future target to prevent or treat this complication after allogeneic HCT.

14.
Sci Rep ; 9(1): 13272, 2019 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-31520004

RESUMO

Classified as Regosols in the Food and Agriculture Organization (FAO) Taxonomy, purple soils formed from purple rocks and are mainly distributed in the Sichuan Basin of southwestern China. A number of studies have focused on the soil water, nutrients, texture and erosion of purple soils. This study was conducted to understand the lithological features of the related purple rocks and their effects on the pedogenesis of purple soils in the Sichuan Basin. The results showed the following: due to variability in the paleoenvironment, purple rocks mainly consist of sandstone and mudstone with various stratal thicknesses and various particle sizes. The lithology of the purple rocks leads the purple soils have an obvious inheritance from their parent rocks. An apparent purple color and numerous rock fragments derived from the purple parent rock are observed throughout the profile, with no clear soil stratification. The particle size contents of the purple soils are closely related to those of their parent rocks. The clay-sized fractions in the purple soils are generally dominated by illite, vermiculite, chlorite, and montmorillonite with little quartz and with or without kaolinite, which is generally the same as that in the parent purple rocks. In addition, the purple soils are characterized by obvious inherited mineralogy, chemical composition, pH value, OM content and nutrient content. Therefore, the diagenetic environment determined the lithology of the purple rock, and the lithology of the purple rock determined the pedogenic characteristics of the purple soil to some extent. Purple soils are characterized by rapid physical weathering and pedogenetic processes and slow chemical pedogenetic processes.

15.
Artigo em Inglês | MEDLINE | ID: mdl-31545873

RESUMO

Cerebral ischemia is caused by various disorders, such as stroke, myocardial infarction, or peripheral vascular disease. The purpose of this paper was to investigate the effects of glycyrrhizic acid (GA) on cerebral ischemia/reperfusion (I/R) injury. Middle cerebral artery occlusion was established to evaluate the effects of GA on cerebral ischemia. In this study, our results showed that GA could dramatically decrease cerebral edema, reduce the neurological deficits, and smaller brain infarct volume was found in the GA treatment group. In serum and brain tissue, GA also increased superoxide dismutase activity. In addition, in serum and brain tissue, GA also dramatically inhibited the secretion of inflammatory cytokines, including interleukin-1ß (IL-1ß), IL-6, and tumor necrosis factor-α. Moreover, GA inhibited the expressions of high-mobility group protein box-1 (HMGB1)-mediated TLR4/NF-κB pathway. Our data determined that GA may provide protective effect on the I/R-induced cerebral ischemia disease.

16.
Ecotoxicol Environ Saf ; 185: 109662, 2019 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-31550568

RESUMO

Phenol, as a representative organic pollutant in aquatic environments, has posed a serious threat to humans and ecosystem. In this work, a novel integration system combined coal-based carbon membrane with sulfate radicals-based advanced oxidation processes (SR-AOPs) was designed for degradation of phenol. The integrated system achieved 100% removal efficiency under the optimal condition (peroxydisulfate dosage is 0.2 g/L, at alkaline condition with 2 mL/min flow velocity). The quenching experiments revealed that the efficient removal of phenol by the integrated system were attributed to the co-existence of radical and nonradical mechanisms. This study proposes a green and efficient technique for the removal of phenol.

17.
Artigo em Inglês | MEDLINE | ID: mdl-31562112

RESUMO

OBJECTIVE: We evaluated the prognostic value of lymph node ratio (LNR) for the survival of breast cancer patients using Bayesian inference. METHODS: Data on 5,279 women with infiltrating duct and lobular carcinoma breast cancer, diagnosed from 2006-2010, was obtained from the NCI SEER Cancer Registry. A prognostic modeling framework was proposed using Bayesian inference to estimate the impact of LNR in breast cancer survival. Based on the proposed model, we then developed a web application for estimating LNR and predicting overall survival. RESULTS: The final survival model with LNR outperformed the other models considered (C-statistic 0.71). Compared to directly measured LNR, estimated LNR slightly increased the accuracy of the prognostic model. Model diagnostics and predictive per- formance confirmed the effectiveness of Bayesian modeling and the prognostic value of the LNR in predicting breast cancer survival. CONCLUSION: The estimated LNR was found to have a significant predictive value for the overall survival of breast cancer patients. SIGNIFICANCE: We used Bayesian inference to estimate LNR which was then used to predict overall survival. The models were developed from a large population-based cancer registry. We also built a user-friendly web application for individual patient survival prognosis. The diagnostic value of the LNR and the effectiveness of the proposed model were evaluated by comparisons with existing prediction models.

18.
Int J Immunopathol Pharmacol ; 33: 2058738419872621, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31456452

RESUMO

Endometrial carcinoma (EC) is one of the most common gynecological cancers in many developing countries. Although tremendous advances have been made in the diagnosis and treatment of EC, there is still no adequate biomarker currently available for predicting the prognosis of this cancer. In this study, we found that miR-103 expression was significantly upregulated in EC tissues than their paired non-carcinoma tissues. Overexpression of miR-103 significantly promoted EC cell proliferation, while downregulation of miR-103 significantly suppressed EC cell proliferation. In addition, ZO-1 expression was significantly downregulated in the EC tissues than their paired non-carcinoma tissues. We also found an inverse correlation between ZO-1 and miR-103. Moreover, ZO-1 was validated as the direct target of miR-103. The downregulation of ZO-1 significantly enhanced EC cell proliferation. In conclusion, miR-103 could regulate EC cell proliferation through directly targeting ZO-1. Our results provide a potential development of microRNA-based targeted approaches for the treatment of EC.

19.
Fertil Steril ; 112(4): 749-757.e2, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31371045

RESUMO

OBJECTIVE: To examine whether sequence variants within the FSHR and CYP19A1 genes are related to the ovarian response to controlled ovarian stimulation (COS). DESIGN: Genetic association study using both single-gene and combined analyses of women with sequence variants undergoing in vitro fertilization treatment. SETTING: Academic research institute hospital. PATIENT(S): Seven hundred and five women undergoing ovarian stimulation with recombinant follicle-stimulating hormone (FSH). INTERVENTION(S): Peripheral blood extraction, DNA purification, and FSHR c.919G>A (rs6165, p.Thr307Ala) and CYP19A1 c.*19C>T (rs10046) sequence variants analyses. MAIN OUTCOME MEASURE(S): Single-gene statistical analysis and combined statistical analysis with the SPSS17.0 software; FSHR c.919G>A and CYP19A1 c.*19C>T sequence variant genotypes and clinical parameters related to the COS response as oocyte retrieval and hormone levels, doses of exogenous FSH. RESULT(S): Women with genotype Ala/Ala at FSHR position 307 had higher basal levels of FSH and were more likely to have a low ovarian response compared with other genotypes. Women with genotype TT at CYP19A1 yielded fewer oocytes after ovarian stimulation. The combined analysis of these two sequence variants revealed that these two single-nucleotide variants have a synergistic effect in conferring the risk of a low ovarian response. CONCLUSION(S): Our results support an association of sequence variants in the genes that participate in estrogen synthesis, notably the FSHR and CYP19A1 genes, with the outcome of COS.

20.
Artigo em Inglês | MEDLINE | ID: mdl-31441082

RESUMO

BACKGROUND: Fine-needle aspiration (FNA) of thyroid nodules leads to nearly 25% indeterminate nodules, while BRAFV600E mutation helps to predicting papillary thyroid carcinoma (PTC). However, the clinical validity and utility of the BRAFV600E mutation detected using preoperative FNA samples in a large cohort were rarely reported. AIM: To explore the clinical significance of the BRAFV600E mutation on preoperative diagnosis and decision-making in a large FNA cohort in China. DESIGN: This was a prospective study of BRAFV600E mutation analysis using an amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) in FNA samples. PATIENTS: The study involved 2640 samples from 2307 patients undergoing FNA procedures in a Chinese medical centre. RESULTS: A high mutation rate of 86.7% was found in the PTC population. For indeterminate thyroid nodules, the malignant rate of BRAFV600E+ and BRAFV600E- was 87.8% and 39.5% in the Bethesda System for Reporting Thyroid Cytopathology (BSRTC) III, and 88.2% and 31.8% in the BSRTC IV, respectively. A cost-effective diagnostic model combining both BSRTC grading and BRAFV600E mutation status showed the highest sensitivity of 82.9% and specificity of 85.4%. Central lymph node metastasis (CLNM) was independent of the BRAF mutation status and accounted for 34.2% of the patients with PTC. CT values of BRAFV600E of patients with PTMC were significantly lower in young patients and patients with CLNM. CONCLUSIONS: The combined analysis of cytological results and BRAFV600E mutation is highly recommended in BRAFV600E high-prevalence regions, including China. Prophylactic central neck dissection should be performed in selected patients without regard to the BRAF mutation status.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA