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1.
Sci Total Environ ; 714: 136880, 2020 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-32018994

RESUMO

Here, a novel chemiluminescence (CL) immunoassay was fabricated for sensitive determination of tetrabromobisphenol A bis(2-hydroxyethyl) ether (TBBPA-DHEE), one of typical tetrabromobisphenol A derivatives. At the indirectly competitive method, the synthesized PS@hemin@Co2+ was labelled by secondary antibody (Ab2) instead of common natural enzymes, which showed excellent catalysis towards the decomposition of luminol-H2O2 for producing CL signal. Furthermore, the CL signal was greatly amplified owing to the synergistic catalysis of hemin and Co2+ in the detection system. Under the optimized conditions, the established method offered (i) low detection limit (LOD, 0.9 µg/L), which was almost 5 times lower than that using a conventional ELISA with the same antibody; (ii) a good linearity (1.6-14.3 µg/L); (iii) satisfactory accuracy and precision (recoveries, 89.67-125.33%; CV, 2.75-8.37%). The proposed CL immunoassay was applied for analysis of environmental samples from various sources collected from Jiangsu and Zhejiang province, China. And the detected concentrations were ranged in 2.4-3.7 µg/L in environmental waters and 1.8-2.4 ng/g (dry weight, dw) in soil samples, indicating great potential for trace TBBPA-DHEE detection from environmental samples.

2.
ChemSusChem ; 2020 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-32022410

RESUMO

Unlike traditional rechargeable rock-chair metal-ion batteries, dual-ion batteries (DIBs) involve redox reactions with anions rather than cations in p-type cathodes. In principle, regulating the electrochemical performance of the DIB by different anion species is highly feasible. Herein, the anion effect on the electrochemical performance of a DIB, aqueous Zn-organic radical battery (Zn-ORB) consisting of poly(2,2,6,6-tetramethylpiperidinyloxy-4-yl vinyl ether) cathode and Zn anode, is firstly investigated by density functional theory (DFT) calculations. SO 4 2- , CF 3 SO 3 - and ClO 4 - with different molecular electrostatic potential values are selected as anion models. DFT calculations reveal that the stronger electrostatic interaction of the anion with the organic radical, the higher operating voltage of the Zn-ORB, which are well consistent with experimental results. It brings new insight into the redox chemistry of p-type organic radical with anions and will promote the development of high-power aqueous Zn-ORBs as well as inspire more investigations for anion effect towards novel battery designs.

3.
Curr Neurovasc Res ; 2020 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-31987021

RESUMO

Endovascular treatment of intracranial aneurysms (IAs) by flow diverter (FD) stents depends on flow modification. Patient-specific modeling of FD deployment and computational fluid dynamics (CFD) could enable a priori endovascular strategy optimization. We developed a fast, simplistic, expansion-free balls-weeping algorithm to model FDs in patient-specific aneurysm geometry. However, since such strong simplification could result in less accurate simulations, we also developed a fast virtual stenting workflow (VSW) that explicitly models stent expansion using pseudo-physical forces. To test which of these two fast algorithms more accurately simulates real FDs, we applied them to virtually treat three representative patient-specific IAs. We deployed Pipeline Embolization Device into 3 patient-specific silicone aneurysm phantoms and simulated the treatments using both balls-weeping and VSW algorithms in computational aneurysm models. We then compared the virtually deployed FD stents against experimental results in terms of geometry and post-treatment flow fields. For stent geometry, we evaluated gross configurations and porosity. For post-treatment aneurysmal flow, we compared CFD results against experimental measurements by particle image velocimetry. We found that VSW created more realistic FD deployments than balls-weeping in terms of stent geometry, porosity and pore density. In particular, balls-weeping produced unrealistic FD bulging at the aneurysm neck, and this artifact drastically increased with neck size. Both FD deployment methods resulted in similar flow patterns, but the VSW had less error in flow velocity and inflow rate. In conclusion, modeling stent expansion is critical for preventing unrealistic bulging effects and thus should be considered in virtual FD deployment algorithms. Due to its high computational efficiency and superior accuracy, the VSW algorithm is a better candidate for implementation into a bedside clinical tool for FD deployment simulation.

4.
Chem Commun (Camb) ; 2020 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-31989132

RESUMO

A novel signal self-enhancement photoelectrochemical immuno-sensor has been developed based on the curing of sacrificial agent SO32- coated-Au NPs sensitizing Ag2S/CuS/α-Fe2O3 n-p-n hetero-structure films for the first time. This strategy has acquired high sensitivity and low background without addition of a sacrificial agent in solution in the detection of prostate antigen.

5.
BMC Neurol ; 20(1): 34, 2020 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-31973698

RESUMO

BACKGROUND: Progressive spinal deformity has become a well-recognized complication of intracanal tumors resection. However, the factors affecting post-operative spinal stability remain to be further research. Here, we described the current largest series of risk factors analysis for progressive spinal deformity following resection of intracanal tumors. METHODS: We retrospectively analyzed the medical records of the patients with resection of intracanal tumors between January 2009 and December 2018. All patients who underwent resection of intracanal tumors performed regular postoperative follow-up were identified and included in the study. Clinical, radiological, surgical, histopathological, and follow-up data were collected. The incidence of postoperative progressive kyphosis or scoliosis was calculated. The statistical relationship between postoperative progressive spinal deformity and radiographic, clinical, and surgical variables was assessed by using univariate tests and multivariate logistic regression analysis. RESULTS: Two hundred seventy-two patients (mean age 42.56 ± 16.18 years) with median preoperative modified McCormick score of 3 met the inclusion criteria. Among them, 7(2.6%)patients were found to have spinal deformity preoperatively, and the extent of spinal deformity in these 7 patients deteriorated after surgery. 36 (13.2%) were new cases of postoperative progressive deformity. The mean duration of follow-up was 21.8 months (median 14 months, range 6-114 months). In subsequent multivariate logistic regression analysis, age ≤ 18 years (p = 0.027), vertebral levels of tumor involvement (p = 0.019) and preoperative spinal deformity(p = 0.008) was the independent risk factors (p < 0.05), increasing the odds of postoperative progressive spinal deformity by 3.94-, 0.69- and 27.11-fold, respectively. CONCLUSIONS: The incidence of postoperative progressive spinal deformity was 15.8%, mostly in these patients who had younger age (≤18 years), tumors involved in multiple segments and preoperative spinal deformity. The risk factors of postoperative progressive spinal deformity warrants serious reconsideration that when performing resection of spinal cord tumors in these patients with such risk factors, the surgeons should consider conducting follow-ups more closely, and when patients suffering from severe symptoms or gradually increased spinal deformity, surgical spinal fusion may be a more suitable choice to reduce the risk of reoperation and improve the prognosis of patients.

6.
J Ethnopharmacol ; 252: 112536, 2020 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-31931161

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Previous studies have approved that Baoyuan decoction (BYD) exerted remarkable cardioprotective effects on heart failure (HF) due to its anti-apoptotic properties. As a novel biomarker and target of HF, Cardiac ankyrin repeat protein (CARP) can exacerbate apoptosis via activation by angiotensin type 1 receptor (AT1) and subsequently deteriorate heart function. Transcriptome results in our previous study indicated BYD was beneficial to HF post-acute myocardial infarction (AMI) with a promising effect on CARP. However, the mechanism remains to be validated. AIM OF THE STUDY: This study aims to elucidate whether BYD ameliorates apoptosis to protect against HF via AT1-CARP signaling pathway. MATERIALS AND METHODS: Left anterior descending ligation was applied to induce an HF rat model, Ang Ⅱ-stimulated H9C2 cells apoptotic model and overexpression of Ankrd1/CARP H9C2 cells were established to clarify the effects and potential mechanism of BYD. Ethanol extracts of BYD (0.64; 1.28; 2.57 g/kg) were orally administered for four weeks and Fosinopril (4.67 mg/kg) was selected as a positive group in vivo. In vitro, BYD (400, 600, 800 µg/ml) or RNH6270 (an inhibitor of AT1, 1 µM) was co-cultured with Ang Ⅱ stimulation for 48 h in H9C2 cells. Overexpression of Ankrd1/CARP was conducted by transient transfection with H9C2 cells to further confirm the exact mechanism. Finally, to define the active ingredients of anti-cardiomyocyte apoptosis in BYD, we furtherly used the Ang Ⅱ-induced cardiomyocyte apoptosis model to evaluate the effects. RESULTS: Echocardiography and TUNEL results showed that BYD in different doses remarkably improved heart function and inhibited apoptosis in vivo. Further study demonstrated that AT1 and CARP expressions in cardiac tissue were suppressed by BYD, accompanied with upregulation of B cell lymphoma-2 (Bcl-2) and downregulation of several pro-apoptotic molecules, including p53, Bcl-2 Associated X Protein (Bax) and Cleaved caspase 3. In parallel with the vivo experiment, in vitro research indicated BYD dramatically reduced the apoptotic cells and regulated expressions of critical apoptosis-related molecules mediated through downregulation of AT1 and CARP simultaneously which were consistent with the results in vivo experiment. Transiently transfected CARP over-expression further confirmed that BYD could suppress severe cardiomyocytes apoptosis induced by overexpression of CARP. Especially, the active ingredients of BYD including Astragaloside IV, Ginsenoside Rg3, Rb1, Rc and Re showed significantly anti-apoptosis effects. CONCLUSION: BYD improves cardiac function and protects against cardiomyocytes injury by inhibiting apoptosis via regulating the AT1-CARP signaling pathway.

7.
Nanoscale ; 12(3): 1448-1454, 2020 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-31829376

RESUMO

Intercalation has proven to be a powerful strategy for physical and chemical property modulation in two dimensional (2D) van der Waals (vdW) materials. Traditional gaseous and chemical intercalation methods offer the ability for mass production, and the electrochemical method provides reversible fine tuning for in situ material investigation. Spatial control, or even direct patterning, of ions is widely required for practical device fabrication and integration; yet it is not realized. Here we demonstrate a self-driven ion (Co2+, Sn4+, and Cu2+) intercalation approach with patterning ability on vdW α-MoO3. It is proved that the self-driven intercalation was enabled by the formation of a local galvanic cell and could be controlled by the metal electrode potential and the solution concentration. The universality of self-intercalation was confirmed in various types of 2D materials (MoS2, WS2, MoSe2, WSe2 and graphene). Furthermore, the feasibility of building heterostructures by multiple species (Sn & Co) intercalation in a single nanosheet was demonstrated for broadband photodetection. The enhancement of conductivity and photoresponse was found to be due to the synergistic effect of lattice distortion from Sn intercalation and the d orbital from the Co atom. This approach offers a feasible way for direct nano-fabrication in 2D vdW material and functional device integration.

8.
J Ethnopharmacol ; 248: 112328, 2020 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-31654799

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Dalbergia odorifera, a traditional herbal medicine, has long been used in China for dissipating blood stasis, regulating the flow of qi, and relieving pain. AIM OF THIS REVIEW: This review aims to provide comprehensive and up-to-date information about the traditional uses, phytochemistry, pharmacology, and quality control of D. odorifera. Additionally, perspectives for possible future investigations on D. odorifera are also discussed. MATERIALS AND METHODS: Information on D. odorifera was obtained from a library database and electronic searches (e.g., Elsevier, Springer, ScienceDirect, Wiley, Web of Science, PubMed, Google Scholar, China Knowledge Resource Integrated). RESULTS: According to classical Chinese herbal texts and the Chinese Pharmacopoeia, D. odorifera promotes blood circulation, relieves pain, and eliminates blood stasis, and it can be used to treat cardio-cerebrovascular diseases in traditional Chinese medicine prescriptions. The chemical constituents of D. odorifera have been well studied, with approximately 175 metabolites having been identified, including flavonoids, phenols, arylbenzofurans, and quinones. The species also contains well-studied volatile oil. Its flavonoids and volatile oil are generally considered to be essential for its pharmacological activity. Modern pharmacology research has confirmed that isolated components and crude extracts of D. odorifera possess wide-ranging pharmacological effects, including anti-inflammatory, anti-angina, anti-oxidative, and other activities. Additionally, there are few quality control studies on D. odorifera. CONCLUSIONS: To date, significant progress has been made in D. odorifera phytochemistry and pharmacology. Thus, modern pharmacological research has provided some evidence for local or traditional uses. D. odorifera also showed therapeutic potential in cardiovascular and coronary heart diseases. However, the present findings are insufficient to explain its mechanisms of action. Additionally, the mechanism of heartwood formation, artificial induction technology for heartwood production, and quality control of D. odorifera require further detailed research.

9.
Neurosurgery ; 86(Supplement_1): S21-S34, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31838536

RESUMO

Over the past decade, flow diverter technology for endocranial aneurysms has seen rapid evolution, with the development of new devices quickly outpacing the clinical evidence base. However, flow diversion has not yet been directly compared to surgical aneurysm clipping or other endovascular procedures. The oldest and most well-studied device is the Pipeline Embolization Device (PED; Medtronic), recently transitioned to the Pipeline Flex (Medtronic), which still has sparse data regarding outcomes. To date, other flow diverting devices have not been shown to outperform the PED, although information comes primarily from retrospective studies with short follow-up, which are not always comparable. Because of this lack of high-quality outcome data, no reliable recommendations can be made for choosing among flow diversion devices yet. Moreover, the decision to proceed with flow diversion should be individualized to each patient. In this work, we wish to provide a comprehensive overview of the technical specifications of all flow diverter devices currently available, accompanied by a succinct description of the evidence base surrounding each device.

10.
Cancer Nurs ; 2019 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-31789937

RESUMO

BACKGROUND: The treatment-related decision-making process is a highly emotional time for parents of children with incurable cancer, and they tend to continue the cancer-directed treatment even when they realize that there is no cure for their child. OBJECTIVE: To evaluate whether parents involved in different treatment decisions regretted their treatment decision after their child's death. METHODS: We collected prospective data from 418 parents of children who died of incurable cancer after receiving cancer care at 1 of 4 hospitals. We assessed parent decisional regret and its association with the type of treatment decision made (non-cancer-directed vs cancer-directed). Propensity score-matched analysis (at a ratio of 1:1) was performed. RESULTS: One hundred forty-eight parents (35.4%) reported heightened regret. Two isonumerical arms with 103 (non-cancer-directed) and 103 (cancer-directed) resulted after propensity score matching. Parents with a cancer-directed treatment decision (relative risk, 1.53; 95% confidence interval, 1.24-1.90; P = .002) were more likely to report decisional regret compared with those with a non-cancer-directed decision. CONCLUSION: Bereaved parents with a cancer-directed treatment decision are more likely to experience increased regret for their decision than bereaved parents involved in a non-cancer-directed treatment decision. IMPLICATIONS: Shared-decision aids should be prepared for young parents with low education to improve disease-related knowledge, accurate risk perceptions, and options congruent with parents' values.

11.
PLoS One ; 14(12): e0226421, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31881029

RESUMO

BACKGROUND: Computer modeling of endovascular coiling intervention for intracranial aneurysm could enable a priori patient-specific treatment evaluation. To that end, we previously developed a finite element method (FEM) coiling technique, which incorporated simplified assumptions. To improve accuracy in capturing real-life coiling, we aimed to enhance the modeling strategies and experimentally test whether improvements lead to more accurate coiling simulations. METHODS: We previously modeled coils using a pre-shape based on mathematical curves and mechanical properties based on those of platinum wires. In the improved version, to better represent the physical properties of coils, we model coil pre-shapes based on how they are manufactured, and their mechanical properties based on their spring-like geometric structures. To enhance the deployment mechanics, we include coil advancement to the aneurysm in FEM simulations. To test if these new strategies produce more accurate coil deployments, we fabricated silicone phantoms of 2 patient-specific aneurysms in duplicate, deployed coils in each, and quantified coil distributions from intra-aneurysmal cross-sections using coil density (CD) and lacunarity (L). These deployments were simulated 9 times each using the original and improved techniques, and CD and L were calculated for cross-sections matching those in the experiments. To compare the 2 simulation techniques, Euclidean distances (dMin, dMax, and dAvg) between experimental and simulation points in standardized CD-L space were evaluated. Univariate tests were performed to determine if these distances were significantly different between the 2 simulations. RESULTS: Coil deployments using the improved technique agreed better with experiments than the original technique. All dMin, dMax, and dAvg values were smaller for the improved technique, and the average values across all simulations for the improved technique were significantly smaller than those from the original technique (dMin: p = 0.014, dMax: p = 0.013, dAvg: p = 0.045). CONCLUSION: Incorporating coil-specific physical properties and mechanics improves accuracy of FEM simulations of endovascular intracranial aneurysm coiling.

12.
J Neurointerv Surg ; 2019 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-31848217

RESUMO

BACKGROUND: Recurrence of intracranial aneurysms after endovascular coiling is a serious clinical concern. OBJECTIVE: We hypothesized that recurrence is associated with aneurysm morphology and flow, as well as the coil intervention and the induced flow modifications. METHODS: We collected 52 primary-coiling aneurysm cases that were either occluded (n=34) or recurrent (n=18) at >1 year follow-up. We created aneurysm models from pre-coiling digital subtraction angiographic images, calculated aneurysm morphology, simulated pre-coiling hemodynamics, modeled coil deployment, and obtained post-coiling hemodynamics for each case. We performed univariable analysis on 26 morphologic, treatment-specific, and hemodynamic parameters to distinguish between recurrent and occluded groups, and multivariable analysis to identify independently significant parameters associated with recurrence. Univariable analysis was also performed on ruptured and unruptured aneurysm subcohorts separately to investigate if they shared specific significant parameters. RESULTS: Recurrence was associated with pre-coiling aneurysm morphologic and flow parameters including larger size (maximum dimension and volume), larger neck (diameter, area, and neck-to-parent-artery ratio), and higher flow momentum and kinetic energy. Recurrence was also associated with lower coil packing (packing density and uncoiled volume), higher post-treatment flow (velocity, momentum, and kinetic energy), lower post-treatment washout time, and higher post-treatment impingement force at the neck. Multivariable analysis identified two aneurysmal characteristics (neck diameter and pre-coiling flow kinetic energy), one coil packing parameter (uncoiled volume), and one post-treatment hemodynamic parameter (flow momentum) that were independently associated with recurrence. In ruptured aneurysms, recurrence was associated with larger neck (diameter and area), whereas in unruptured aneurysms, recurrence was associated with larger size (maximum dimension and volume). In both subcohorts, recurrence was associated with higher post-coiling flow momentum and kinetic energy. CONCLUSION: Recurrence at >1 year after coil treatment is associated with intrinsic aneurysm characteristics, coiling itself, and flow changes induced by coiling. Larger aneurysm size and neck, less coil packing, and higher intra-aneurysmal flow before and after coiling predict recurrence.

13.
Oxid Med Cell Longev ; 2019: 8218650, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31772710

RESUMO

Background/Aims: Polycystic ovary syndrome (PCOS) is an endocrine disorder characterized by abnormal hormone levels in peripheral blood and poor-quality oocytes. PCOS is a pathophysiological syndrome caused by chronic inflammation and oxidative stress. The aim of this study was to investigate the mechanism of melatonin regulation on androgen production and antioxidative damage in granulosa cells from PCOS patients with hypoestrogenia and hyperandrogenia. Methods: Cumulus-oocyte complexes were collected from PCOS patients who had low levels of estrogen in follicular fluids. Results: Melatonin triggered upregulation of cytochrome P450 family 19 subfamily A member 1 (CYP19A1) expression via the extracellular signal-regulated kinase pathway in luteinized granulosa cells. As a result, conversion of androgen to 17ß-estradiol was accelerated. We also found that melatonin significantly reduced the levels of inducible nitric oxide (NO) synthetase and NO in luteinized granulosa cells. Levels of transcripts encoding NF-E2-related factor-2 and its downstream target heme oxygenase-1 were also increased, leading to anti-inflammatory and antioxidant effects. We also found that melatonin could improve oocyte development potential. Conclusion: Our preliminary results showed that melatonin had a positive impact on oocyte quality in PCOS patients with hypoestrogenia and hyperandrogenia.

14.
Artigo em Inglês | MEDLINE | ID: mdl-31751214

RESUMO

OBJECTIVE: Bioluminescence tomography (BLT) is a non-invasive technique designed to enable three-dimensional (3D) visualization and quantification of viable tumor cells in living organisms. However, despite the excellent sensitivity and specificity of bioluminescence imaging (BLI), BLT is limited by the photon scattering effect and ill-posed inverse problem. If the complete structural information of a light source is considered when solving the inverse problem, reconstruction accuracy will be improved. METHODS: This paper proposed a block sparse Bayesian learning method based on K-nearest neighbor strategy (KNNBSBL), which incorporated several types of a priori information including sparsity, spatial correlations among neighboring points, and anatomical information to balance over-sparsity and morphology preservation in BLT. Furthermore, we considered the Gaussian weighted distance prior in a light source and proposed a KNN-GBSBL method to further improve the performance of KNN-BSBL. RESULTS: The results of numerical simulations and in vivo glioma-bearing mouse experiments demonstrated that KNNBSBL and KNN-GBSBL achieved superior accuracy for tumor spatial positioning and morphology reconstruction. CONCLUSION: The proposed method KNN-BSBL incorporated several types of a priori information is an efficient and robust reconstruction method for BLT.

15.
BMC Med Genomics ; 12(1): 149, 2019 10 30.
Artigo em Inglês | MEDLINE | ID: mdl-31666072

RESUMO

BACKGROUND: Genetics play an important role in intracranial aneurysm (IA) pathophysiology. Genome-wide association studies have identified several single nucleotide polymorphisms (SNPs) that are linked to IA but how they affect disease pathobiology remains poorly understood. We used Encyclopedia of DNA Elements (ENCODE) data to investigate the epigenetic landscapes surrounding genetic risk loci to determine if IA-associated SNPs affect functional elements that regulate gene expression and if those SNPs are most likely to impact a specific type of cells. METHODS: We mapped 16 highly significant IA-associated SNPs to linkage disequilibrium (LD) blocks within the human genome. Within these regions, we examined the presence of H3K4me1 and H3K27ac histone marks and CCCTC-binding factor (CTCF) and transcription-factor binding sites using chromatin immunoprecipitation-sequencing (ChIP-Seq) data. This analysis was conducted in several cell types relevant to endothelial (human umbilical vein endothelial cells [HUVECs]) and inflammatory (monocytes, neutrophils, and peripheral blood mononuclear cells [PBMCs]) biology. Gene ontology analysis was performed on genes within extended IA-risk regions to understand which biological processes could be affected by IA-risk SNPs. We also evaluated recently published data that showed differential methylation and differential ribonucleic acid (RNA) expression in IA to investigate the correlation between differentially regulated elements and the IA-risk LD blocks. RESULTS: The IA-associated LD blocks were statistically significantly enriched for H3K4me1 and/or H3K27ac marks (markers of enhancer function) in endothelial cells but not in immune cells. The IA-associated LD blocks also contained more binding sites for CTCF in endothelial cells than monocytes, although not statistically significant. Differentially methylated regions of DNA identified in IA tissue were also present in several IA-risk LD blocks, suggesting SNPs could affect this epigenetic machinery. Gene ontology analysis supports that genes affected by IA-risk SNPs are associated with extracellular matrix reorganization and endopeptidase activity. CONCLUSION: These findings suggest that known genetic alterations linked to IA risk act on endothelial cell function. These alterations do not correlate with IA-associated gene expression signatures of circulating blood cells, which suggests that such signatures are a secondary response reflecting the presence of IA rather than indicating risk for IA.

16.
Artigo em Inglês | MEDLINE | ID: mdl-31705175

RESUMO

PURPOSE: Accurate evaluation of hypoxia is particularly important in patients with nasopharyngeal carcinoma (NPC) undergoing radiotherapy. The aim of this study was to propose a novel imaging strategy for quantitative three-dimensional (3D) evaluation of hypoxia in a small animal model of NPC. METHODS: A carbonic anhydrase IX (CAIX)-specific molecular probe (CAIX-800) was developed for imaging of hypoxia. Mouse models of subcutaneous, orthotopic, and spontaneous lymph node metastasis from NPC (5 mice per group) were established to assess the imaging strategy. A multi-modality imaging method that consisted of a hybrid combination of fluorescence molecular tomography-computed tomography (FMT-CT) and multispectral optoacoustic tomography (MSOT) was used for 3D quantitative evaluation of tumour hypoxia. Magnetic resonance imaging, histological examination, and immunohistochemical analysis were used as references for comparison and validation. RESULTS: In the early stage of NPC (2 weeks after implantation), FMT-CT enabled precise 3D localisation of the hypoxia biomarker with high sensitivity. At the advanced stage (6 weeks after implantation), MSOT allowed multispectral analysis of the biomarker and haemoglobin molecules with high resolution. The combination of high sensitivity and high resolution from FMT-CT and MSOT could not only detect hypoxia in small-sized NPCs but also visualise the heterogeneity of hypoxia in 3D. CONCLUSIONS: Integration of FMT-CT and MSOT could allow comprehensive and quantifiable evaluation of hypoxia in NPC. These findings may potentially benefit patients with NPC undergoing radiotherapy in the future. Graphical abstract A novel multimodality imaging strategy for three-dimensional evaluation of tumour hypoxia in an orthotopic model of nasopharyngeal carcinoma.

17.
Arthritis Res Ther ; 21(1): 230, 2019 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-31706344

RESUMO

BACKGROUND: The response to treatment for juvenile idiopathic arthritis (JIA) can be staged using clinical features. However, objective laboratory biomarkers of remission are still lacking. In this study, we used machine learning to predict JIA activity from transcriptomes from peripheral blood mononuclear cells (PBMCs). We included samples from children with Native American ancestry to determine whether the model maintained validity in an ethnically heterogeneous population. METHODS: Our dataset consisted of 50 samples, 23 from children in remission and 27 from children with an active disease on therapy. Nine of these samples were from children with mixed European/Native American ancestry. We used 4 different machine learning methods to create predictive models in 2 populations: the whole dataset and then the samples from children with exclusively European ancestry. RESULTS: In both populations, models were able to predict JIA status well, with training accuracies > 74% and testing accuracies > 78%. Performance was better in the whole dataset model. We note a high degree of overlap between genes identified in both populations. Using ingenuity pathway analysis, genes from the whole dataset associated with cell-to-cell signaling and interactions, cell morphology, organismal injury and abnormalities, and protein synthesis. CONCLUSIONS: This study demonstrates it is feasible to use machine learning in conjunction with RNA sequencing of PBMCs to predict JIA stage. Thus, developing objective biomarkers from easy to obtain clinical samples remains an achievable goal.

18.
Br J Ophthalmol ; 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31615762

RESUMO

AIM: To investigate the protective behaviours of longer near work distance, discontinuing near work and more time outdoors in recess from parent self-report in the myopia prevalence and progression among myopic children aged 9-11 years. METHODS: Myopia Investigation study in Taipei is a longitudinal population-based study that enrolled elementary school students in Taipei. We provided vision and refraction examination every 6 months. Spherical equivalent (SE) of cycloplegic refraction ≤-0.50 Diopter (D) is defined as myopia. Total 10 743 (70.4%) students completed 2-year refraction data and questionnaire. The myopia prevalence and progression (difference of SE) in baseline, 6, 12, 18 and 24 months were compared by generalised estimating equations. RESULTS: Children with persistent protective behaviour had significant lower prevalence of myopia. The protective impact was statistically significant from 6 to 24 months. In 2 years follow-up, risk ratio after adjusting the background variables and the other two behaviours in near work distance, near work time and outdoor time were 0.71, 0.89 and 0.77. In SE analysis, after adjusting the other two behaviours, near work distance >30 cm (-0.7 vs -1.04 D; p<0.001), discontinuing near work every 30 min (-0.77 vs -0.96 D, p=0.005) and more time outdoors in recess from parent self-report (-0.75 vs -0.98 D; p=0.012) revealed protective impacts on diminishing myopia progression from 6 to 24 months. CONCLUSION: In myopic children aged around 10 years in Taipei, longer distance in near work, discontinuing near work every 30 min and more outdoor time from parent self-report are protective behaviours in myopia prevalence and progression in 6-24 months.

20.
Mol Cancer ; 18(1): 139, 2019 09 16.
Artigo em Inglês | MEDLINE | ID: mdl-31526368

RESUMO

Immunotherapy has been incorporated into the first- and second-line treatment strategies for non-small cell lung cancer (NSCLC), profoundly ushering in a new treatment landscape. However, both adaptive signaling and oncogenic (epidermal growth factor receptor (EGFR)-driven) signaling may induce PD-L1 upregulation in NSCLC. Nevertheless, the superiority of immune checkpoint inhibitors (ICIs) in advanced EGFR-mutant NSCLC is only moderate. ICIs appear to be well tolerated, but clinical activity for some advanced EGFR-mutant NSCLC patients has only been observed in a small proportion of trials. Hence, there are still several open questions about PD-L1 axis inhibitors in patients with NSCLC whose tumors harbor EGFR mutations, such as the effect of EGFR tyrosine kinase inhibitors (TKIs) or EGFR mutations in the tumor microenvironment (TME). Finding the answers to these questions requires ongoing trials and preclinical studies to identify the mechanisms explaining this possible increased susceptibility and to identify prognostic molecular and clinical markers that may predict benefits with PD-1 axis inhibition in this specific NSCLC subpopulation. The presence of multiple mechanisms, including dynamic immune TME profiles, changes in PD-L1 expression and low tumor mutational burdens, may explain the conflicting data regarding the correlation between PD-L1 axis inhibitors and EGFR mutation status. We conducted a review of this currently controversial topic in an attempt to aid in the decision-making process.

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