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1.
Colloids Surf B Biointerfaces ; 189: 110831, 2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-32058252

RESUMO

Stent intervention as available method in clinic has been widely applied for cardiovascular disease treatment for decades. However, the restenosis caused by late thrombosis and hyperplasia still limits the stents long-term application, and the essential cause is usually recognized as endothelial functionalization insufficiency of the stent material surface. Here, we address this limitation by developing a pro-endothelial-functionalization surface that immobilized a natural factors-loaded nanoparticle, exosome, onto the poly-dopamine (PDA) coated materials via electrostatic binding. This PDA/Exosome surface not only increased the endothelial cells number on the materials, but also improved their endothelial function, including platelet endothelial cell adhesion molecule-1 (CD31) expression, cell migration and nitric oxide release. The pro-inflammation macrophage (M1 phenotype) attachment and synthetic smooth muscle cell proliferation as the interference factors for the endothelialization were not only inhibited by the PDA/Exosome coating, while the cells were also regulated to anti-inflammation macrophage (M2 phenotype) and contractile smooth muscle cell, which may contribute to endothelialization. Thus, it can be summarized this method has potential application on surface modification of cardiovascular biomaterials.

2.
J Thorac Oncol ; 2020 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-32036071

RESUMO

INTRODUCTION: Programmed death receptor-1 (PD-1) inhibitors have shown efficacy in first-line treatment of NSCLC; however, evidence of PD-1 inhibitor as neoadjuvant treatment is limited. This is a phase 1b study to evaluate the safety and outcome of PD-1 inhibitor in neoadjuvant setting. METHODS: Treatment-naive patients with resectable NSCLC (stage IA-IIIB) received two cycles of sintilimab (200 mg, intravenously, day 1 out of 22). Operation was performed between day 29 and 43. Positron emission tomography-computed tomography scans were obtained at baseline and before the operation. The primary end point was safety. Efficacy end points included rate of major pathologic response (MPR) and objective response rate. Expression of programmed cell death ligand 1 was also evaluated (registration number: ChiCTR-OIC-17013726). RESULTS: A total of 40 patients enrolled, all of whom received two doses of sintilimab and 37 underwent radical resection. A total of 21 patients (52.5%) experienced neoadjuvant treatment-related adverse events (TRAEs). Four patients (10.0%) experienced grade 3 or higher neoadjuvant TRAEs, and one patient had grade 5 TRAE. Eight patients achieved radiological partial response, resulting in an objective response rate of 20.0%. Among 37 patients, 15 (40.5%) achieved MPR, including six (16.2%) with a pathologic complete response in primary tumor and three (8.1%) in lymph nodes as well. Squamous cell NSCLC exhibited superior response compared with adenocarcinoma (MPR: 48.4% versus 0%). Decrease of maximum standardized uptake values after sintilimab treatment correlated with pathologic remission (p < 0.00001). Baseline programmed cell death ligand 1 expression of stromal cells instead of tumor cells was correlated with pathologic regression (p = 0.0471). CONCLUSIONS: Neoadjuvant sintilimab was tolerable for patients with NSCLC, and 40.5% MPR rate is encouraging. The decrease of maximum standardized uptake values after sintilimab might predict pathologic response.

3.
Oncologist ; 2020 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-32083766

RESUMO

BACKGROUND: The role of postoperative radiotherapy in pathological T2-3N0M0 esophageal squamous cell carcinoma is unknown. We aimed to evaluate the efficacy and safety of postoperative radiotherapy in patients with pathological T2-3N0M0 thoracic esophageal squamous cell carcinoma. MATERIALS AND METHODS: Patients aged 18-72 years with pathological stage T2-3N0M0 esophageal squamous cell carcinoma after radical surgery and without neoadjuvant therapy were eligible. Patients were randomly assigned to surgery alone or to receive postoperative radiotherapy of 50.4 Gy in supraclavicular field and 56 Gy in mediastinal field in 28 fractions over 6 weeks. The primary endpoint was disease-free survival. The secondary endpoints were local-regional recurrence rate, overall survival, and radiation-related toxicities. RESULTS: From October 2012 to February 2018, 167 patients were enrolled in this study. We analyzed 157 patients whose follow-up time was more than 1 year or who had died. The median follow-up time was 45.6 months. The 3-year disease-free survival rates were 75.1% (95% confidence interval [CI] 65.9-85.5) in the postoperative radiotherapy group and 58.7% (95% CI 48.2-71.5) in the surgery group (hazard ratio 0.53, 95% CI 0.30-0.94, p = .030). Local-regional recurrence rate decreased significantly in the radiotherapy group (10.0% vs. 32.5% in the surgery group, p = .001). The overall survival and distant metastasis rates were not significantly different between two groups. Grade 3 toxicity rate related to radiotherapy was 12.5%. CONCLUSION: Postoperative radiotherapy significantly increased disease-free survival and decreased local regional recurrence rate in patients with pathological T2-3N0M0 thoracic esophageal squamous cell carcinoma with acceptable toxicities in this interim analysis. Further enrollment and follow-up are warranted to validate these findings in this ongoing trial. IMPLICATIONS FOR PRACTICE: The value of adjuvant radiotherapy for patients with node-negative esophageal cancer is not clear. The interim results of this phase III study indicated that postoperative radiotherapy significantly improved disease-free survival and decreased local-regional recurrence rate in patients with pathological T2-3N0M0 thoracic esophageal squamous cell carcinoma compared with surgery alone with acceptable toxicities. The distant metastasis rates and overall survival rates were not different between the two groups. Adjuvant radiotherapy should be considered for pathologic T2-3N0M0 thoracic esophageal squamous cell carcinoma. Prospective trials to identify high-risk subgroups are needed.

4.
Talanta ; 209: 120569, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-31892050

RESUMO

As the concentration of Zn2+ in patients with prostate cancer is much less than that in healthy persons, Zn2+ concentration can be used as a marker to expediently screen prostate cancer. In this study, a sensitive and highly selective surface-enhanced Raman scattering (SERS) method to detect Zn2+ concentration in human prostatic fluids by utilizing water-insoluble 2-carboxyl-2'-hydroxyl-5'-sulfoformazylbenze (Zincon) as a SERS probe based on self-assembled Au nanoarrays at a liquid-liquid interface between n-hexane and Au colloids was proposed. Zincon showed remarkably different SERS bands before and after coordinating Zn2+ in the controlled conditions (70 µL of ethanol, 500 µL of n-hexane, pH value of 7.1 and 10 s of vortex mixing time), which can be used in quantifying Zn2+ with characteristic peaks. The proposed SERS method presented a good linear relationship ranging from 0.5 to 10 µmol/L and a satisfactory detection limit of 0.1 µmol/L as well as low interference with other metal ions. Moreover, the detection results are close to those of the conventional standard atomic absorption spectroscopy (AAS) method.

5.
Anal Chim Acta ; 1098: 102-109, 2020 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-31948572

RESUMO

Ratiometric analysis of dopamine (DA) in complex biological system is urgently desired. In this work, a novel dual-emission fluorescence probe was fabricated by embedding both gold nanoclusters (AuNCs) and poly(9,9-dioctylfluorenyl-2,7-diyl) (PFO) dots into zeolitic imidazolate framework-8 (ZIF-8) (abbreviated as ZIF-8@AuNCs-PFO) and applied to ratiometric analysis of DA. Remarkably, encapsulating AuNCs and PFO dots into ZIF-8 not only achieved an excellent aggregation induced emission (AIE) enhancement effect on AuNCs (5 times increase), but also brought about an unique DA-triggered asynchronous fluorescence changes of AuNCs and PFO dots. The as-prepared probe exhibited excellent performance toward DA in the concentrations range from 0.01 to 10000 µmol L-1 and good selectivity over interfering substances. The detection limit of DA was as low as 4.8 nmol L-1. Furthermore, good stability and practicability of the probe in human serum samples suggesting its great potential for diagnostic purposes. Moreover, the quenching mechanism of AuNCs was intensively studied and summarized as three synergistic processes: (i) electron transfer between AuNCs and DA; (ii) DA-triggered architecture change of ZIF-8; (iii) fluorescence resonance energy transfer (FRET) between AuNCs and polydopamine (PDA), which offered an important theory for ZIF-based fluorescent probes.

6.
Clin Respir J ; 14(2): 132-139, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31746542

RESUMO

BACKGROUND: During the bronchoscopy process, successful passage of the tracheoscope through the glottis can affect the following procedure of bronchoscopy. Therefore, safer, more effective and less painful anesthesia methods are particularly important for the bronchoscopy success rate. OBJECTIVE: This study aimed to evaluate the efficacy of 1% tetracaine hydrochloride injection pure solution aerosol inhalation combined with oral administration of dyclonine hydrochloride mucilage during bronchoscopy. METHODS: Patients who need bronchoscopy or bronchoscope treatment were randomly assigned to two groups; group A received pure tetracaine hydrochloride injection solution (3 mL of 1% tetracaine hydrochloride) aerosol inhalation combined with oral 5 mL of dyclonine hydrochloride mucilage and group B received diluted tetracaine hydrochloride injection (3 mL of 1% tetracaine hydrochloride injection + 3 mL of sterile water for injection) aerosol inhalation combined with oral 5 mL of dyclonine hydrochloride mucilage. The anesthetic effect and adverse reactions of these groups were observed and compared. RESULT: A total of 523 patients were randomized. The results showed that patient's tolerance, cough response, glottis opening during the bronchoscope into the glottis and the time required to the tracheoscope pass through the glottis were obviously significantly better in group A than in group B. Vital signs including blood pressure, heart rate and pulse oxygen saturation were more stable in group A than in group B. CONCLUSION: The 1% tetracaine hydrochloride injection pure liquid aerosol inhalation combined with oral administration of dyclonine hydrochloride mucilage as upper airway anesthesia is effective and safe for bronchoscopy. This method of local anesthesia is worthy of clinical application.

7.
Talanta ; 208: 120460, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31816722

RESUMO

Probing the level and activity of alkaline phosphatases (ALP) is of great significance for biomedical research on cellular functions and clinical diagnosis of cancers. Herein, a novel dual-colored carbon dots (CDs)-based ratiometric fluorescent sensor was constructed to accomplish high sensitive and accurate determination of ALP relyed on the difference of fluorescence resonance energy transfer (FRET) between blue light emitted CDs (B-CDs)-MnO2 nanohybrid and yellow light emitted CDs (Y-CDs)-MnO2 nanohybrid. The ratiometric fluorescent sensor enabled sensitive discrimination of ALP against other enzymes in a linear range of 0.1-500 U/L with a limit of detection of 0.02 U/L. The lower error and signal fluctuation, more satisfactory LODs and higher R value (R2 = 0.99552) of the ratiometric sensing platform than single signal detection mode (R2 = 0.85231; R2 = 0.64260) indicated the superiority of the ratiometric fluorescence detection mode.Besides, the excellent analytical performance towards ALP in biological system demonstrated the potential application in clinical diagnosis.

8.
Micromachines (Basel) ; 10(12)2019 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-31775279

RESUMO

A nano-stepping motor can translate or rotate when its piezoelectric element pair is electrically driven in-phase or anti-phase. It offers millimeter-level stroke, sub-micron-level stepping size, and sub-nanometer-level scanning resolution. This article proposes a visual servo system to control the nano-stepping motor, since its stepping size is not consistent due to changing contact friction, using a custom built microscopic instrument and image recognition software. Three kinds of trajectories-straight lines, circles, and pentagrams-are performed successfully. The smallest straightness and roundness ever tested are 0.291 µm and 2.380 µm. Experimental results show that the proposed controller can effectively compensate for the error and precisely navigate the rotor along a desired trajectory.

9.
Mater Sci Eng C Mater Biol Appl ; 105: 110042, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31546440

RESUMO

Influences of proteins on degradation of magnesium alloys are of great significance but not well understood. In particular the roles of amino acids, the basic unit of proteins in regulating the progress of biodegradation of magnesium based materials remain unclear. This study aims to investigate the impacts of alanine, glutamic acid and lysine on degradation of pure magnesium in phosphate buffer solution through SEM, XPS, FTIR, potentiodynamic polarisation curves, electrochemical impedance spectroscopy and immersion tests. The changed contents of amino acids in solutions were detected by UV-vis spectrophotometer. Results demonstrate that the charges of the selected amino acids imposed significant contribution to suppressing the degradation of pure magnesium in phosphate buffer solution. The presence of amino acids led to the formation of phosphate-based corrosion products, increasing free corrosion potential, and reduction in corrosion current density and solution pH depending on their isoelectric points and molecular structures. A plausible corrosion mechanism organised by amino acids on pure magnesium was proposed.


Assuntos
Aminoácidos/química , Magnésio/química , Fosfatos/química , Tampões (Química) , Corrosão , Espectroscopia Dielétrica , Eletroquímica , Humanos , Hidrogênio/análise , Ponto Isoelétrico , Conformação Molecular , Espectroscopia Fotoeletrônica , Espectroscopia de Infravermelho com Transformada de Fourier , Propriedades de Superfície , Difração de Raios X
10.
Med Gas Res ; 9(3): 153-159, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31552880

RESUMO

Nitric oxide (NO) released by vascular endothelial cells (VECs), as a functional factor and signal pathway molecule, plays an important role in regulating vasodilation, inhibiting thrombosis, proliferation and inflammation. Therefore, numerous researches have reported the relationship between the NO level in VECs and the cardiovascular biomaterials' structure/functions. In recent years, biomedical magnesium (Mg) alloys have been widely studied and rapidly developed in the cardiovascular stent field for their biodegradable absorption property. However, influence of the Mg alloys' degradation products on VEC NO release is still unclear. In this work, Mg-Zn-Y-Nd, an Mg alloy widely applied on the biodegradable stent research, was investigated on the influence of the degradation time, the concentration and reaction time of degradation products on VEC NO release. The data showed that the degradation product concentration and the reaction time of degradation products had positive correlation with NO release, and the degradation time had negative correlation with NO release. All these influencing factors were controlled by the Mg alloy degradation behaviors. It was anticipated that it might make sense for the cardiovascular Mg alloy design aiming at VEC NO release and therapy.

11.
Exp Mol Med ; 51(8): 88, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31371698

RESUMO

The number of patients with diabetic nephropathy (DN) is still on the rise worldwide, and this requires the development of new therapeutic strategies. Recent reports have highlighted genetic factors in the treatment of DN. Herein, we aimed to study the roles of long noncoding RNA (lncRNA) plasmacytoma variant translocation 1 (PVT1) and histone 3 lysine 27 trimethylation (H3K27me3) in DN. A model of DN was established by inducing diabetes in mice with streptozotocin. Mouse podocyte clone 5 (MPC5) podocytes and primary podocytes were cultured in normal and high glucose media to observe cell morphology and to quantify PVT1 expression. The roles of PVT1 and enhancer of zeste homolog 2 (EZH2) were validated via loss-of-function and gain-of-function in vitro experiments to identify the interactions among PVT1, EZH2, and forkhead box A1 (FOXA1). The podocyte damage and apoptosis due to PVT1 and FOXA1 were verified with in vivo experiments. PVT1 was highly expressed in MPC5 and primary podocytes in DN patients and in cultures grown in high glucose medium. A large number of CpG (C-phosphate-G) island sites were predicted at the FOXA1 promoter region, where PVT1 recruited EZH2 to promote the recruitment of H3K27me3. The silencing of PVT1 or the overexpression of FOXA1 relieved the damage and inhibited the apoptosis of podocytes in DN, as was evidenced by the upregulated expression of synaptopodin and podocin, higher expression of Bcl-2, and lower expression of Bax and cleaved caspase-3. The key findings of this study collectively indicate that the suppression of lncRNA PVT1 exerts inhibitory effects on podocyte damage and apoptosis via FOXA1 in DN, which is of clinical significance.

12.
Oncol Lett ; 18(2): 1023-1034, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31423162

RESUMO

The aim of the present study was to identify the hub genes and provide insight into the tumorigenesis and development of breast cancer. To examine the hub genes in breast cancer, integrated bioinformatics analysis was performed. Gene expression profiles were obtained from the Gene Expression Omnibus (GEO) database and the differentially expressed genes (DEGs) were identified using the 'limma' package in R. Gene Ontology enrichment analysis and Kyoto Encyclopedia of Genes and Genomes pathway analysis was used to determine the functional annotations and potential pathways of the DEGs. Subsequently, a protein-protein interaction network analysis and weighted correlation network analysis (WGCNA) were conducted to identify hub genes. To confirm the reliability of the identified hub genes, RNA gene expression profiles were obtained from The Cancer Genome Atlas (TCGA)-breast cancer database, and WGCNA was used to screen for genes that were markedly correlated with breast cancer. By combining the results from the GEO and TCGA datasets, 15 hub genes were identified to be associated with breast cancer pathophysiology. Overall survival analysis was performed to examine the association between the expression of hub genes and the overall survival time of patients with breast cancer. Higher expression of all hub genes was associated with significantly shorter overall survival in patients with breast cancer compared with patients with lower levels of expression of the respective gene.

13.
ACS Appl Mater Interfaces ; 11(31): 27924-27933, 2019 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-31291076

RESUMO

Single-layer fuel cells (SLFCs) based on mixed semiconductors and ionic conductors demonstrate  simplified material preparation and fabrication procedure and possess high performance potentially. However, the operational stability and principle of SLFCs have not yet been convinced of either commercialization or fundamental interests. We hereby report on the employment of a perovskite oxide-based phase-structured redox-stable semiconductor prior to determining a possible solution that improves the durability of the SLFC. Feasible working principles are established and an in-depth understanding of the short-circuit-free phenomenon in SLFCs with the mixed ionic and electronic conductors is provided. Additionally, a smart material design and cell structure processing are also proposed. An extended nonstop testing period of up to 2 days confirms the project feasibility and improved durability of the SLFCs, achieved by replacing the unstable lithiated oxide phase with redox-stable perovskite oxide, though the electrochemical performance is sacrificed. The precipitated metal/alloy nanoparticle on perovskite oxide not only improves the electrode reaction kinetics but also facilitates the charge separation and ionic conduction in SLFCs, consequently enhancing the fuel cell performance and electrical efficiency. The results confirmed the potential of stable operation for future practical deployment of SLFCs via appropriate selection of material and cell structure design. It is greatly believed that the physical junction plays a crucial role in overcoming the internal short-circuit issue of SLFCs.

14.
J Cardiothorac Surg ; 14(1): 143, 2019 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-31340823

RESUMO

BACKGROUNDS: The pulmonary ciliated muconodular papillary tumor (CMPT) is a very rare tumor with only several case reports in published literatures, and its clinicopathological features, standard treatment methods and prognosis has not been well defined. METHODS: Two cases of CMPT diagnosed and treated in our hospital and 39 cases reported in the published literature were analyzed retrospectively. RESULTS: The cohort of 41 CMPT patients comprised of 20 males and 21 females, aged 9-84 years. The diameter of the primary tumor was 0.3-4.5 cm. Most of these lesions were subsolid nodules, as observed on computed tomography and easily misdiagnosed as early lung adenocarcinoma. Tumors of 26 patients were stained by immunohistochemistry method, which revealed that CK7, CEA, and TTF-1 were positive and CK20 was negative in most patients. The results of gene alternation demonstrated mutations in EGFR, KRAS, and BRAF and ALK rearrangements in CMPT. All the patients underwent surgical treatment and did not receive postoperative adjuvant therapy. The follow-up duration was 0-120 months, and no case of tumor recurrence was found until the final follow-up. CONCLUSIONS: The incidence of CMPT was low and rate of image misdiagnosis high. Immunohistochemistry is helpful for accurate diagnosis of CMPT. Sub-lobectomy may be proper and adjuvant treatment should be avoided since the disease is now prone to benign lesions. Furthermore, since the biological behavior of this tumor is not yet fully elucidated, additional case data are essential for accurate conclusions.


Assuntos
Adenocarcinoma de Pulmão/patologia , Adenocarcinoma Mucinoso/patologia , Neoplasias Pulmonares/patologia , Adenocarcinoma de Pulmão/diagnóstico por imagem , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/cirurgia , Adenocarcinoma Mucinoso/diagnóstico por imagem , Adenocarcinoma Mucinoso/genética , Adenocarcinoma Mucinoso/cirurgia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Cílios/patologia , Feminino , Humanos , Imuno-Histoquímica , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/cirurgia , Masculino , Pessoa de Meia-Idade , Mutação , Prognóstico , Estudos Retrospectivos , Tomografia Computadorizada por Raios X , Adulto Jovem
15.
Acta Biomater ; 98: 196-214, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31154057

RESUMO

A Zinc-loaded montmorillonite (Zn-MMT) coating was hydrothermally prepared using Zn2+ ion intercalated sodium montmorillonite (Na-MMT) upon magnesium (Mg) alloy AZ31 as bone repairing materials. Biodegradation rate of the Mg-based materials was studied via potentiodynamic polarization curves, electrochemical impedance spectroscopy (EIS) and hydrogen evolution tests. Results revealed that both Na-MMT and Zn-MMT coatings exhibited better corrosion resistance in Dulbecco's modified eagle medium (DMEM) + 10% calf serum (CS) than bare Mg alloy AZ31 counterparts. Hemolysis results demonstrated that hemocompatibility of the Na-MMT and Zn-MMT coatings were 5%, and lower than that of uncoated Mg alloy AZ31 pieces. In vitro MTT tests and live-dead stain of osteoblast cells (MC3T3-E1) indicated a significant improvement in cytocompatibility of both Na-MMT and Zn-MMT coatings. Antibacterial properties of two representative bacterial strains associated with device-related infection, i.e. Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus), were employed to explore the antibacterial behavior of the coatings. The measured inhibitory zone and bacterial growth rate confirmed that Zn-MMT coatings exhibited higher suppression toward both E. coli and S. aureus than that of Na-MMT coatings. The investigation on antibacterial mechanism through scanning electron microscopy (SEM) and lactate dehydrogenase (LDH) release assay manifested that Zn-MMT coating led to severe breakage of bacterial membrane of E. coli and S. aureus, which resulted in a release of cytoplasmic materials from the bacterial cells. In addition, the good inhibition of Zn-MMT coatings against E. coli and S. aureus might be attributed to the slow but sustainable release of Zn2+ ions (up to 144 h) from the coatings into the culture media. This study provides a novel coating strategy for manufacturing biodegradable Mg alloys with good corrosion resistance, biocompatibility and antibacterial activity for future orthopedic applications. STATEMENT OF SIGNIFICANCE: The significance of the current work is to develop a corrosion-resistant and antibacterial Zn-MMT coating on magnesium alloy AZ31 through a hydrothermal method. The Zn-MMT coating on magnesium alloy AZ31 shows better corrosion resistance, biocompatibility and excellent antibacterial ability than magnesium alloy AZ31. This study provides a novel coating on Mg alloys for future orthopedic applications.

16.
Anal Chim Acta ; 1068: 52-59, 2019 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-31072477

RESUMO

Early detection of carcinoembryonic antigen (CEA) is of great significance for the screening, diagnosis, monitoring and prognosis analysis of lung cancer. Herein, a novel fluorescence aptasensor with high signal-noise ratio (SNR) was constructed to achieve highly-sensitive detection of CEA relied upon the fluorescence resonance energy transfer (FRET) between near-infrared carbon dots (NIR-CDs) and gold nanorods (AuNRs). Initially, AuNRs@SiO2-Aptamer and NIR-CDs-DNA probe were prepared via the covalent bonding reaction between their corresponding carboxyl and amino groups, respectively. After DNA hybridization, the aptasensor was formed, meanwhile, the fluorescence of NIR-CDs was quenched by AuNRs@SiO2. Once CEA encountered the aptasensor, it would selectively combine with CEA aptamer to unwind the preformed DNA double-strand architecture thereby resulting in the NIR-CDs-DNA detach from the surface of AuNRs@SiO2. The attendant fluorescence recovery of NIR-CDs was linearly correlated with the concentration of CEA. According to this relationship, the NIR-CDs based "turn on" sensing system was constructed and exhibited prominent responses toward CEA in the concentration range of 0.1-5000 pg/mL and a relatively low detection limit (0.02 pg/mL). Moreover, it displayed high specificity against other biomarkers or proteins, good reproducibility and acceptable accuracy regarding human pleural effusion samples.


Assuntos
Aptâmeros de Nucleotídeos/química , Carbono/química , Antígeno Carcinoembrionário/análise , Fluorescência , Derrame Pleural/diagnóstico por imagem , Pontos Quânticos/química , Transferência Ressonante de Energia de Fluorescência , Ouro/química , Humanos , Nanotubos/química , Tamanho da Partícula , Propriedades de Superfície
17.
J Mol Diagn ; 21(4): 677-686, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31026599

RESUMO

The absence of interpretation guidelines and limited data on BRCA1/2 mutations in the Chinese population have impeded the detection of BRCA variants based on next-generation sequencing (NGS) in China. This study was performed to establish a reference system for performance evaluation of BRCA genetic testing and variant interpretation, which includes interpretation rules, reference materials (RMs), and a reference database (RD). BRCA1/2 mutations identified in cell lines and clinical cases were selected to establish RMs. All mutations were detected by NGS and validated by Sanger sequencing. Variant call format files and standard variant data sets were collected and annotated to build the RD. Participant laboratories were invited to validate this reference system. Interpretation rules for BRCA variants in the Chinese population were generated as a standard for BRCA variant interpretation. Mutational analysis demonstrated that BRCA2 mutations (55%) were more common than BRCA1 mutations (45%) in Chinese patients. Eliminating duplicates from 19,886 variants, the RD contained 750 unique BRCA mutations. Most BRCA1/2 mutations in the reference system were pathogenic or likely pathogenic (RMs, 77.5%; RD, 57%). In total, 91 novel pathogenic/likely pathogenic variants were identified in the RD. The reference system can contribute to NGS performance and high-quality interpretation to facilitate clinical decision making. It could also accelerate the development and application of BRCA mutation detection technologies in China.

18.
Commun Biol ; 2: 72, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30820467

RESUMO

Shrimp nodaviruses, including Penaeus vannamei (PvNV) and Macrobrachium rosenbergii nodaviruses (MrNV), cause white-tail disease in shrimps, with high mortality. The viral capsid structure determines viral assembly and host specificity during infections. Here, we show cryo-EM structures of T = 3 and T = 1 PvNV-like particles (PvNV-LPs), crystal structures of the protrusion-domains (P-domains) of PvNV and MrNV, and the crystal structure of the ∆N-ARM-PvNV shell-domain (S-domain) in T = 1 subviral particles. The capsid protein of PvNV reveals five domains: the P-domain with a new jelly-roll structure forming cuboid-like spikes; the jelly-roll S-domain with two calcium ions; the linker between the S- and P-domains exhibiting new cross and parallel conformations; the N-arm interacting with nucleotides organized along icosahedral two-fold axes; and a disordered region comprising the basic N-terminal arginine-rich motif (N-ARM) interacting with RNA. The N-ARM controls T = 3 and T = 1 assemblies. Increasing the N/C-termini flexibility leads to particle polymorphism. Linker flexibility may influence the dimeric-spike arrangement.

19.
Cell Biol Toxicol ; 35(1): 59-66, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30430365

RESUMO

Circulating tumor cells (CTCs) have important application prospects in the early diagnosis, treatment evaluation, and prognostic prediction of tumors. In this study, we enrolled a total of 65 patients with different stages and molecular subtypes of breast cancer and isolated and enriched for CTCs from peripheral blood using the ClearCell FX1 platform, which is based on a label-free spiral microfluidic method. The ClearCell platform can successfully isolate CTCs from peripheral blood with different detection rates in breast cancer patients. We also compared the difference between the ClearCell and CellSearch platforms for isolating CTCs. To further determine the genetic information of CTCs, we performed single-cell whole-exome sequencing (WES) in three CTCs isolated from one patient. The sequencing results indicated the presence of a few hundreds of single-nucleotide variants (SNVs) in each CTC, with only 16 SNVs being shared by all three CTCs. These shared SNVs may have a crucial impact on the development of breast cancer. Here, we report, for the first time, the complete process and results of performing single-cell WES on CTCs isolated by the ClearCell FX1 platform.

20.
Clin Chem Lab Med ; 57(5): 707-715, 2019 04 24.
Artigo em Inglês | MEDLINE | ID: mdl-30471216

RESUMO

Background Platelet-neutrophil aggregates (PNAs) are fundamental mechanisms linking hemostasis and inflammatory processes. Elevated level of PNAs have been reported in inflammatory diseases and coronary artery diseases. However, studies on the correlation between PNAs formation and deep venous thrombosis (DVT) are not available. Methods A total of 92 participants were involved in this study, including 32 cases with DVT and 60 cases without DVT. Blood samples coagulated by K2-EDTA or sodium citrate were prepared for blood cell count and blood smears. PNAs and platelet activation were measured using flow cytometry. The correlation between platelet activation level and PNAs level was analyzed by linear regression. Receiver operating characteristic (ROC) analysis was performed, assessing the prognostic performance of PNAs to predict potential risk of DVT occurrence. Results PNAs was found in the blood smears of patients with DVT. Significant increased level of PNAs was identified in DVT group (medium 8.43%, interquartile range [IQR] 4.11%-15.69%), compared with that in control group (5.16%, IQR 2.40-9.60, p<0.01). The DVT group also showed a dramatic elevated level of total platelet activation (medium 16.06%, IQR 6.04-22.05) vs. control group (11.26%, IQR 5.54-19.99, p<0.05). The PNAs level was correlated with total platelet activation (r2=0.58, p<0.0001). A significantly high odds ratio (OR) of DVT occurrence was identified when the level of PNAs was higher than 7.4% (OR 3.60, 95% confidence interval [CI] 1.463-8.838, p<0.01). Conclusions An elevated level of PNAs was associated with risk of DVT occurrence, which might be a suitable marker predicting DVT development.


Assuntos
Plaquetas/metabolismo , Neutrófilos/metabolismo , Trombose Venosa/sangue , Trombose Venosa/epidemiologia , Idoso , Plaquetas/fisiologia , Agregação Celular , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Ativação Plaquetária/fisiologia , Curva ROC , Fatores de Risco
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