Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 12 de 12
Filtrar
1.
Sci Rep ; 14(1): 10945, 2024 05 13.
Artigo em Inglês | MEDLINE | ID: mdl-38740919

RESUMO

To investigate the significance of atherosclerotic plaque location in hybrid surgery comprising both endovascular recanalization approaches and carotid endarterectomy for symptomatic atherosclerotic non-acute long-segment occlusion of the internal carotid artery (ICA), 162 patients were enrolled, including 120 (74.1%) patients in the proximal plaque group and 42 (25.9%) in the distal plaque group. Surgical recanalization was performed in all patients, with successful recanalization in 119 (99.2%) patients in the proximal and 39 (92.9%) in the distal plaque group. The total successful recanalization rate was 97.5% (158/162) with a failure rate of 2.5% (4/162). Periprocedural complications occurred in 5 (4.2% or 5/120) patients in the proximal plaque group, including neck infection in two (1.7%), recurrent nerve injury in 1 (0.8%), and laryngeal edema in 2 (1.7%), and 2 (4.8%) in the distal plaque group, including femoral puncture infection in 2 (4.8%). No severe complications occurred in either group. Univariate analysis showed plaque location was a significant (P = 0.018) risk factor for successful recanalization, and multivariate analysis indicated that the plaque location remained a significant independent risk factor for recanalization success (P = 0.017). In follow-up 6-48 months after the recanalization surgery, reocclusion occurred in two (2.8%) patients in the proximal plaque group and 4 (13.3%) in the distal plaque group. In conclusion, although hybrid surgery achieves similar outcomes in patients with ICA occlusion caused by either proximal or distal atherosclerotic plaques, plaque location may be a significant risk factor for successful recanalization of symptomatic non-acute long-segment ICA occlusion.


Assuntos
Artéria Carótida Interna , Estenose das Carótidas , Endarterectomia das Carótidas , Placa Aterosclerótica , Humanos , Masculino , Feminino , Idoso , Placa Aterosclerótica/cirurgia , Placa Aterosclerótica/patologia , Placa Aterosclerótica/complicações , Artéria Carótida Interna/cirurgia , Artéria Carótida Interna/patologia , Pessoa de Meia-Idade , Estenose das Carótidas/cirurgia , Estenose das Carótidas/patologia , Estenose das Carótidas/complicações , Endarterectomia das Carótidas/métodos , Resultado do Tratamento , Procedimentos Endovasculares/métodos , Idoso de 80 Anos ou mais , Fatores de Risco
2.
Int J Biol Sci ; 19(1): 167-182, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36594094

RESUMO

Drug resistance presents a major obstacle in the treatment of genitourinary cancers. Exosomes as the medium of intercellular communication serve important biological functions and play essential roles in pathological processes, including drug response. Through the transfer of bioactive cargoes, exosomes can modulate drug resistance via multiple mechanisms. This review attempts to elucidate the mechanisms of exosomal cargoes with reference to tumor drug resistance, their role in genitourinary cancers, and their potential clinical applications as candidate biomarkers in liquid biopsy.


Assuntos
Exossomos , Neoplasias , Neoplasias Urogenitais , Humanos , Biomarcadores , Resistencia a Medicamentos Antineoplásicos/genética , Biópsia Líquida , Neoplasias Urogenitais/patologia , Neoplasias/tratamento farmacológico , Biomarcadores Tumorais
3.
Kaohsiung J Med Sci ; 39(1): 26-39, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36448712

RESUMO

Ovarian cancer (OC) is a gynecological cancer with high mortality. OC-derived exosomal circRNAs can regulate angiogenesis. This study aims to explore the role and mechanism of exosomal circRNA nuclear factor I X (CircNFIX) derived from OC cells in angiogenesis. Quantitative real-time polymerase chain reaction was employed to evaluate the levels of circNFIX, miR-518a-3p, and tripartite motif protein 44 (TRIM44) in OC and adjacent tissues. Exosomes from the ovarian surface epithelial cell (HOSEpiC) and OC cells (SKOV3 or OVCAR3) were isolated by differential centrifugation. Exosomes were cocultured with the human umbilical vein endothelial cells (HUVECs). The angiogenesis capacity was analyzed by Tube formation assay. 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) and Transwell assays were used to determine the cell viability and migration ability. The dual-luciferase report, RNA immunoprecipitation (RIP), and RNA pull-down assays were applied to validate the gene's interaction. CircNFIX and TRIM44 expression were higher and miR-518a-3p was lower in OC tissues than in the adjacent tissues. Upregulated circNFIX and TRIM44 were significantly correlated with the tumor size and International Federation of Gynecology and Obstetrics (FIGO) stage of OC patients. HUVECs treated OC-derived exosomes had higher proliferation, migration, and angiogenesis capacities than the control group. While OC-derived exosomal circNFIX silencing restrained HUVECs' proliferation, migration, and angiogenesis, compared with the OC-derived exosomes group. OC-derived exosomal circNFIX positively regulated TRIM44 expression by targeting miR-518a-3p in HUVECs. OC-derived exosomal circNFIX promoted angiogenesis by regulating the Janus-activated kinase/signal transducer and activator of transcription 1 (JAK/STAT1) pathway via miR-518a-3p/TRIM44 axis in HUVECs.


Assuntos
MicroRNAs , Neoplasias Ovarianas , Humanos , Feminino , MicroRNAs/genética , MicroRNAs/metabolismo , Apoptose , Proteínas com Motivo Tripartido/metabolismo , Neoplasias Ovarianas/metabolismo , Linhagem Celular Tumoral , Células Endoteliais da Veia Umbilical Humana/metabolismo , Proliferação de Células/genética , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo
4.
Kaohsiung J Med Sci ; 39(3): 234-243, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36495291

RESUMO

We aimed to study the regulatory roles and mechanism of circular nuclear factor IX (circNFIX) in cancer growth and stemness properties of ovarian cancer (OC). CircNFIX and SH3RF3 levels in OC tissues and cells were tested by quantitative real-time PCR. RNase R treatment quantified circNFIX RNA stability. Molecular interaction among circNFIX, LIN28B, and SH3RF3 was predicted by bioinformatics software and validated through RNA immunoprecipitation (RIP) assay. The gain- or loss-experiments of circNFIX on capabilities of metastasis and stemness in vitro were assessed using Cell Counting Kit-8, Transwell, western blot, and sphere-formation assays. CircNFIX and SH3RF3 were markedly elevated in OC tissues and OC cells. Knocking down circNFIX repressed the proliferation, migration, invasion, and stemness properties of A2780 and SKOV3 cells. The RIP assay verified the direct binding relationship between LIN28B, circNFIX, and SH3RF3. Additionally, overexpression of circNFIX elevated the SH3RF3 expression, while this effect was reversed by LIN28B silence. Rescue experiments demonstrated that the overexpression of SH3RF3 reversed the knockdown of circNFIX on OC cells' proliferation, metastasis, and stemness properties. CircNFIX improved the mRNA stability and translation of SH3RF3 via recruiting LIN28B, thus promoting the proliferation, invasion, and stemness properties of OC cells in vitro.


Assuntos
MicroRNAs , Neoplasias Ovarianas , Humanos , Feminino , Neoplasias Ovarianas/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/genética , MicroRNAs/genética , Regulação Neoplásica da Expressão Gênica , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismo , Ubiquitina-Proteína Ligases/genética
5.
J Org Chem ; 87(17): 11899-11908, 2022 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-35957561

RESUMO

The direct cross-couplings of diaryl sulfoxides with aryl bromides via C-S bond cleavage could be readily accomplished using nickel(II) as the catalyst, 1,2-bis(diphenylphosphino)ethane (dppe) as the ligand, and magnesium turnings as the reducing metal in THF, leading to the corresponding biaryls in moderate to good yields. The reaction exhibited a broad substrate scope and could be applied to a gram-scale synthesis. The "one-pot" reaction, which avoids the utility of presynthesized and moisture-labile organometallic compounds, is operationally simple and step-economic.

6.
Oper Neurosurg (Hagerstown) ; 23(4): 334-341, 2022 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-36001745

RESUMO

BACKGROUND: MRI-guided laser interstitial thermal therapy (MRgLITT) is a novel treatment modality for focal cortical dysplasia (FCD). However, identifying the location and extent of subtle FCD by visual analysis during MRgLITT remains challenging. OBJECTIVE: To introduce voxel-based morphometric MRI postprocessing into the procedure of MRgLITT for FCD-suspected lesions and assess the complementary value of the MRI postprocessing technique for the trajectory design and thermal parameter setting of MRgLITT. METHODS: Junction and normalized fluid-attenuated inversion recovery signal intensity images were used to detect the gray-white matter junction blurring and cortical fluid-attenuated inversion recovery hyperintensity, respectively. According to the 2 postprocessing images, the region of interest (ROI) for ablation was drawn. The main principle of presurgical planning is that the trajectory of the laser fiber was designed as far as possible along the long axis of the ROI while the extent of planned ablation covered the entire ROI. The subsequent intraoperative procedure was performed under the guidance of the presurgical plan. RESULTS: Nine patients with epilepsy with FCD-suspected lesions underwent MRgLITT with the assistance of MRI postprocessing images. Among them, 4 patients were junction positive, 2 patients were normalized fluid-attenuated inversion recovery signal intensity positive, and the remaining 3 patients were positive for both. Postsurgical MRI demonstrated that the ROIs were ablated entirely in 7 patients. Engel Ia, Ib, and IV scores were obtained at 1-year follow-up for 6, 1, and 2 patients, respectively. CONCLUSION: MRI postprocessing provides complementary information for designing the laser fiber trajectory and subsequent ablation for FCDs.


Assuntos
Epilepsia , Terapia a Laser , Malformações do Desenvolvimento Cortical , Epilepsia/cirurgia , Humanos , Lasers , Imageamento por Ressonância Magnética/métodos , Malformações do Desenvolvimento Cortical/diagnóstico por imagem , Malformações do Desenvolvimento Cortical/cirurgia
7.
Radiology ; 304(1): 106-113, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35412367

RESUMO

Background Deep learning (DL) algorithms could improve the classification of ovarian tumors assessed with multimodal US. Purpose To develop DL algorithms for the automated classification of benign versus malignant ovarian tumors assessed with US and to compare algorithm performance to Ovarian-Adnexal Reporting and Data System (O-RADS) and subjective expert assessment for malignancy. Materials and Methods This retrospective study included consecutive women with ovarian tumors undergoing gray scale and color Doppler US from January 2019 to November 2019. Histopathologic analysis was the reference standard. The data set was divided into training (70%), validation (10%), and test (20%) sets. Algorithms modified from residual network (ResNet) with two fusion strategies (feature fusion [hereafter, DLfeature] or decision fusion [hereafter, DLdecision]) were developed. DL prediction of malignancy was compared with O-RADS risk categorization and expert assessment by area under the receiver operating characteristic curve (AUC) analysis in the test set. Results A total of 422 women (mean age, 46.4 years ± 14.8 [SD]) with 304 benign and 118 malignant tumors were included; there were 337 women in the training and validation data set and 85 women in the test data set. DLfeature had an AUC of 0.93 (95% CI: 0.85, 0.97) for classifying malignant from benign ovarian tumors, comparable with O-RADS (AUC, 0.92; 95% CI: 0.85, 0.97; P = .88) and expert assessment (AUC, 0.97; 95% CI: 0.91, 0.99; P = .07), and similar to DLdecision (AUC, 0.90; 95% CI: 0.82, 0.96; P = .29). DLdecision, DLfeature, O-RADS, and expert assessment achieved sensitivities of 92%, 92%, 92%, and 96%, respectively, and specificities of 80%, 85%, 89%, and 87%, respectively, for malignancy. Conclusion Deep learning algorithms developed by using multimodal US images may distinguish malignant from benign ovarian tumors with diagnostic performance comparable to expert subjective and Ovarian-Adnexal Reporting and Data System assessment. © RSNA, 2022 Online supplemental material is available for this article.


Assuntos
Aprendizado Profundo , Neoplasias Ovarianas , Algoritmos , Feminino , Humanos , Pessoa de Meia-Idade , Neoplasias Ovarianas/diagnóstico por imagem , Curva ROC , Estudos Retrospectivos
8.
Front Immunol ; 12: 666909, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34149702

RESUMO

Background: Atezolizumab plus chemotherapy has been recommended as a first-line treatment option for patients with advanced non-small cell lung carcinoma (NSCLC) irrespective of programmed cell death-ligand 1 (PD-L1) expression. Currently, little is known about the efficacy and treatment-related adverse effects (TRAEs) of subtracting chemotherapy from the combination for patients with high PD-L1 expression. Thus, we performed an indirect comparison between atezolizumab plus chemotherapy and atezolizumab alone. Methods: A total of five eligible randomized controlled trials (RCTs) were identified from PubMed, EMBASE, and Cochrane Central controlled trial registries, using keywords including atezolizumab, PD-1, PD-L1, NSCLC, and RCT. The clinical outcomes of objective response rate (ORR), progression-free survival (PFS), OS, and TRAEs were extracted and evaluated. Using indirect analysis, the efficacy and TRAEs were compared between arm A (atezolizumab plus chemotherapy) and arm C (atezolizumab), linked by arm B (chemotherapy). Results: Direct comparison revealed that both atezolizumab plus chemotherapy (HR 0.65, P = 0.003) and atezolizumab alone (HR 0.59, P = 0.010) significantly improved OS compared with chemotherapy. More importantly, the indirect comparison showed that atezolizumab plus chemotherapy was not superior to atezolizumab regarding OS (RR 1.10, P =0.695) and ORR (RR 1.11, P = 0.645). However, patients who received atezolizumab combined with chemotherapy experienced more ≥ grade 3 TRAEs (RR 4.23, P<0.001) and TRAEs leading to drug discontinuation (RR 3.60, P<0.001) than those treated with atezolizumab monotherapy. Conclusions: Atezolizumab monotherapy might be a better treatment option for patients with advanced NSCLC and high PD-L1 expression than atezolizumab plus chemotherapy.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Anticorpos Monoclonais Humanizados/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Antígeno B7-H1/metabolismo , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , Humanos , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Intervalo Livre de Progressão , Ensaios Clínicos Controlados Aleatórios como Assunto
9.
Epilepsy Behav ; 121(Pt A): 108028, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34058496

RESUMO

OBJECTIVE: To summarize the clinical and electrophysiological observations of epilepsy originating from the inferior perisylvian cortex, and analyze the potential epileptic networks underlying the semiological manifestations. METHODS: We retrospectively analyzed patients with refractory inferior perisylvian epilepsy (IPE) who had undergone resective surgery, and then reviewed the demographic, clinical, neuroelectrophysiological, neuroimaging, surgical, histopathological, and follow-up data of the patients from the respective medical records. The selected patients were then categorized in accordance with the results of semiological analysis. Quantitative 18F-fluorodeoxyglucose-positron emission tomography (FDG-PET) analysis was performed to investigate the underlying neural network. RESULTS: Of the 18 IPE patients assessed in this study, ipsilateral frontotemporal epileptic discharges or its onsets were the dominant interictal or ictal scalp EEG observations. In addition, oroalimentary or manual automatism was the most frequently documented manifestation, followed by facial tonic or clonic movements. Moreover, the semiological analysis identified and classified the patients into 2 patterns, and the PET statistical analyses conducted on these 2 groups revealed differences in the neural network between them. CONCLUSION: Inferior perisylvian epilepsy possesses semiological manifestations similar to those of mesial temporal lobe epilepsy or rolandic opercular epilepsy, hence these conditions should be carefully differentiated. Performing lesionectomy or cortectomy, sparing the mesial temporal structures, was found to be an effective and safe treatment modality for IPE.


Assuntos
Epilepsia do Lobo Frontal , Epilepsia do Lobo Temporal , Eletroencefalografia , Fluordesoxiglucose F18 , Humanos , Imageamento por Ressonância Magnética , Tomografia por Emissão de Pósitrons , Estudos Retrospectivos , Resultado do Tratamento
10.
J Ovarian Res ; 14(1): 53, 2021 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-33865445

RESUMO

BACKGROUND: Ovarian sex cord stromal tumours (OSCSTs) are rare ovarian tumours and include different histopathologic subtypes. This study aimed to analyse the clinical and sonographic characteristics of different histopathologic OSCST subtypes. METHODS: A total of 63 patients with surgically proven OSCSTs were enrolled in this retrospective study to analyse their clinical and sonographic features. Ultrasound examinations and predictive models were performed before surgery. The clinical and sonographic findings were compared according to the type of OSCST based on the histopathological diagnosis. RESULTS: The mean age of 63 patients was 52.17 years (range: 17-78 years). Eighteen patients experienced irregular vaginal bleeding (28.57% 18/63), 7 patients exhibited abnormal body hair (11.11%). 2 patients (3.17%) showed an increased level of CA125, and 25 patients (39.68%, 25/63) showed an increased level of testosterone. Forty-two patients had ovarian thecoma-fibroma groups (OTFGs). Six patients had Sertoli-Leydig cell tumours (S-LCTs), 4 patients had Leydig cell tumours (LCTs), 8 patients had ovarian granulosa cell tumours (OGCTs), 2 patients had ovarian steroid cell tumours, not otherwise specified (OSCTs-NOS), and one patient had sclerosing stromal tumours (SSTs). The mean diameter of the tumour was 47.9 mm (range: 10-258 mm). Forty-seven masses were hypoechoic (74.60%). Twenty-eight masses had posterior echo attenuation, 22 masses exhibited abundant Doppler flow signals (34.92%), and one patient had ascites (1.59%). The diagnostic accuracy of the Simple Rules (SR) and the Assessment of Different NEoplasias in the adneXa (ADNEX) model in distinguishing benign and malignant OSCSTs was 44% (30/63) and 84% (53/63), respectively. The diagnostic accuracy of the SR for OTFGs, S-LCTs & LCTs & OSCTs-NOS, OGCTs, and SSTs was 47.6% (20/42), 16.67% (2/12), 100% (8/8), and 0% (0/1), respectively. The diagnostic accuracy of the ADNEX model for OTFGs, S-LCTs & LCTs & OSCTs-NOS, OGCTs, and SSTs was 93% (31/42), 58.33% (7/12), 75% (6/8), and 100% (1/1), respectively. CONCLUSIONS: OSCSTs generally appear as a solid mass on ultrasound. Posterior echo attenuation indicates an OTFG. A solid mass with abundant Doppler flow signals indicates an S-LCT, LCT, OSCT-NOS or OGCT. Current predictive models are not very effective, but symptoms, sonographic features and serum hormones are helpful for diagnosis.


Assuntos
Tumores do Estroma Gonadal e dos Cordões Sexuais/diagnóstico por imagem , Ultrassonografia/métodos , Adolescente , Adulto , Idoso , Feminino , Humanos , Pessoa de Meia-Idade , Adulto Jovem
11.
J Refract Surg ; 35(5): 333-339, 2019 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-31059583

RESUMO

PURPOSE: To evaluate the ocular biological parameter difference between scleral corneal cross-linking (CXL) and control eyes in rhesus monkeys by using a rebound tonometer, A-scan ultrasonography, retinoscopy, optical coherence tomography, and electroretinography (ERG). METHODS: Six rhesus monkeys were used in this study, with ages ranging from 3 to 3.5 years. One eye of each rhesus monkey was randomly selected to receive riboflavin/ultraviolet-A CXL in the temporal quadrant of the equatorial sclera and the contralateral eye served as an intra-individual control. The ocular biological parameters were repeatedly measured in both eyes of the monkeys before scleral CXL and 1 week, 1 month, and 3 months postoperatively. RESULTS: The intraocular pressure, refractive state, total axial length, and axial dimensions of the anterior chamber, crystalline lens, vitreous chamber, and central corneal thickness were not statistically significantly different between the control and cross-linked specimens at the different time periods (each P > .05). No obvious changes in the waveform of the standard full-field ERGs were observed in the control and cross-linked specimens. There were no statistically significant differences between the control and cross-linked specimens in the dark-adapted 0.01 ERG, the dark-adapted 3.0 ERG, the light-adapted 3.0 ERG, and the amplitudes of the a-wave and b-wave for the different time periods (each P >.05). CONCLUSIONS: The scleral CXL laboratory technique might not significantly affect the ocular biological parameters of the rhesus monkey in the early postoperative period, but long-term effects and histological changes still need to be investigated further. [J Refract Surg. 2019;35(5):333-339.].


Assuntos
Colágeno/metabolismo , Reagentes de Ligações Cruzadas , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/farmacologia , Riboflavina/farmacologia , Esclera/efeitos dos fármacos , Animais , Fenômenos Biomecânicos , Biometria , Eletrorretinografia , Pressão Intraocular/fisiologia , Macaca mulatta , Masculino , Retina/fisiologia , Esclera/metabolismo , Tomografia de Coerência Óptica , Tonometria Ocular , Raios Ultravioleta
12.
World Neurosurg ; 111: e661-e667, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29294393

RESUMO

BACKGROUND: The effects and safety of transradial access for stenting of carotid artery stenosis in patients with bovine-type and type III aortic arch are currently unknown and are the purpose of this study. METHODS: Patients who were treated with stenting via transradial (n = 28) compared with transfemoral (n = 30) access of carotid artery stenosis complicated with bovine-type and type III aortic arch were enrolled. The clinical data were studied for comparison. RESULTS: The success rate of transradial access for carotid artery stenting was 100%. During the transradial access procedure, 3 patients experienced a temporary blood pressure drop and bradycardia that was resolved with atropine injection. No radial artery occlusion or severe cardiac or cerebral events occurred. The success rate of transfemoral access for carotid artery stenting was 90% with failure in 3 patients. No complications occurred during or after the stenting procedure. The irradiation duration was significantly (P = 0.001) smaller in transradial than in transfemoral access stenting (8.6 ± 0.87 vs. 11.4 ± 1.25 minutes). The arterial stenosis ranged 71.25%-96.50% (mean, 86.50% ± 10.15%) for transradial and 78%-97.75% (85.1% ± 10.42%) for transfemoral access groups before treatment, and the residual stenosis following treatment was significantly smaller in either the transradial (2.4%-17.75%; mean, 11.2% ± 6.03%) or transfemoral (4%-18.6%; mean, 12.4% ± 6.3%) groups compared with before treatment, respectively. CONCLUSIONS: The transradial access for stenting of patients with type III aortic arch plus left carotid artery stenosis or in the bovine-type aortic arch combined with right carotid artery stenosis can decrease the stenting difficulty, risks of embolization, and radiation time and increase the success rate.


Assuntos
Aorta Torácica/anormalidades , Implante de Prótese Vascular/métodos , Estenose das Carótidas/cirurgia , Artéria Radial/cirurgia , Stents , Idoso , Pressão Sanguínea , Implante de Prótese Vascular/efeitos adversos , Bradicardia , Artérias Carótidas , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Artéria Radial/diagnóstico por imagem , Stents/efeitos adversos , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Ultrassonografia Doppler Dupla
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA