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1.
J Enzyme Inhib Med Chem ; 37(1): 451-461, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35012401

RESUMO

Different oleanolic acid (OA) oxime ester derivatives (3a-3t) were designed and synthesised to develop inhibitors against α-glucosidase and α-amylase. All the synthesised OA derivatives were evaluated against α-glucosidase and α-amylase in vitro. Among them, compound 3a showed the highest α-glucosidase inhibition with an IC50 of 0.35 µM, which was ∼1900 times stronger than that of acarbose, meanwhile compound 3f exhibited the highest α-amylase inhibitory with an IC50 of 3.80 µM that was ∼26 times higher than that of acarbose. The inhibition kinetic studies showed that the inhibitory mechanism of compounds 3a and 3f were reversible and mixed types towards α-glucosidase and α-amylase, respectively. Molecular docking studies analysed the interaction between compound and two enzymes, respectively. Furthermore, cytotoxicity evaluation assay demonstrated a high level of safety profile of compounds 3a and 3f against 3T3-L1 and HepG2 cells.HighlightsOleanolic acid oxime ester derivatives (3a-3t) were synthesised and screened against α-glucosidase and α-amylase.Compound 3a showed the highest α-glucosidase inhibitory with IC50 of 0.35 µM.Compound 3f presented the highest α-amylase inhibitory with IC50 of 3.80 µM.Kinetic studies and in silico studies analysed the binding between compounds and α-glucosidase or α-amylase.

3.
Bioengineered ; 13(2): 2981-2991, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35038957

RESUMO

To explore a new marker which can detect bacterial vaginosis (BV) with high sensitivity and specificity quantitatively. According to the Nugent Score, vaginal secretions from study participants were divided into BV, healthy, and BV-intermediate groups. First, we compared the obvious differences and high abundance of bacteria in the three groups using 16S rRNA-sequencing, and screened out candidate markers. Then, quantitative detection of these candidate markers from the three groups was done using real-time reverse transcription-quantitative polymerase chain reaction (RT-qPCR), followed by evaluation of the sensitivity and specificity. Finally, we verified the new markers using clinical cases. Gardnerella vaginalis, Atopobium vaginae, Lactobacillus, Megasphaera were screened out by 16S rRNA-sequencing. RT-qPCR data were transformed and analyzed through ROC curves. PCR results for these bacteria were log-transformed using Lactobacillus crispatus as the numerator and other BV-related bacteria as the denominator. Four new indicators were found. Of these, log L. crispatus/G. vaginalis (L/G) <0 was the best indicator. The sensitivity, specificity, positive predictive value, and negative predictive value of our system were 93.5%, 97.2%, 96.6 and 94.6%, respectively. Combination of data for 16S rRNA-sequencing and RT-qPCR revealed four indicators for BV detection. Of these, log L/G < 0 was the best indicator. Creating a molecular-diagnostic system independent of the Nugent Score for BV could have an important impact on the clinical management of BV.Abbreviation: log L. crispatus/G. vaginalis (logL/G); Bacterial vaginosis (BV); vaginal secretions (VSs); polymerase chain reaction (PCR); rRNA-sequencing (rRNA-seq); real-time reverse transcription-quantitative polymerase chain reaction (RT-qPCR); operational taxonomic unit (OTU); non-metric multidimensional scaling (NMDS); receiver operating characteristic (ROC).

4.
Adv Healthc Mater ; : e2102547, 2022 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-35034429

RESUMO

Theranostic system combined diagnostic and therapeutic modalities is critical for the real-time monitoring of disease-related biomarkers and personalized therapy. Microneedles, as a multifunctional platform, are promising for transdermal diagnostics and drug delivery. They have showed attractive properties including painless skin penetration, easy self-administration, prominent therapeutic effects, and good biosafety. Herein, we give an overview of the microneedles-based diagnosis, therapies, and theranostic systems. Four microneedles-based detection methods are concluded based on the sensing mechanism: i) electrochemistry, ii) fluorometric, iii) colorimetric, and iv) Raman methods. Additionally, robust microneedles are suitable for implantable drug delivery. Microneedles-assisted transdermal drug delivery can be primarily classified as passive, active, and responsive drug release, based on the release mechanisms. Microneedles-assisted oral and implantable drug delivery mechanisms are also presented in this review. Furthermore, the key frontier developments in microneedles-mediated theranostic systems as the major selling points are emphasized in this review. These systems are classified into open-loop and closed-loop theranostic systems based on the indirectness and directness of feedback between the transdermal diagnosis and therapy, respectively. Finally, conclusions and future perspectives for next-generation microneedles-mediated theranostic systems are also discussed. Taken together, microneedle-based systems are promising as the new avenue for diagnosis, therapy and disease-specific closed-loop theranostic applications. This article is protected by copyright. All rights reserved.

5.
Mater Horiz ; 2022 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-35037009

RESUMO

Bacterial infection has become a global concern owing to the significant morbidity and mortality. Although the phagocytosis of bacteria by immune cells acts as the front line to protect human body from invading pathogens, the relatively slow encounter and insufficient capture of bacteria by immune cells often lead to an inefficient clearance of pathogens. Herein, a supramolecular artificial receptor-modified macrophage (SAR-Macrophage) was developed to enhance the recognition and latch of bacteria in the systemic circulation, mediated via strong and multipoint host-guest interactions between the artificial receptors (cucurbit[7]uril) on the macrophage and the guest ligands (adamantane) selectively anchored on Escherichia coli (E. coli). As a result, the SAR-Macrophage could significantly accelerate the recognition of E. coli, catch and internalize more pathogens, which subsequently induced the M1 polarization of macrophages to generate ROS and effectively kill the intracellular bacteria. Therefore, the SAR-Macrophage represents a simple, yet powerful anti-bacterial approach.

6.
Cardiovasc Ultrasound ; 20(1): 2, 2022 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-35045881

RESUMO

BACKGROUND: This study aimed to investigate the relationship between echocardiography results and lung ultrasound score (LUS) in coronavirus disease 2019 (COVID-19) pneumonia patients and evaluate the impact of the combined application of these techniques in the evaluation of COVID-19 pneumonia. METHODS: Hospitalized COVID-19 pneumonia patients who underwent daily lung ultrasound and echocardiography were included in this study. Patients with tricuspid regurgitation within three days of admission were enrolled. Moreover, the correlation and differences between their pulmonary artery pressure (PAP) and LUS on days 3, 8, and 13 were analyzed. The inner diameter of the pulmonary artery root as well as the size of the atria and ventricles were also considered. RESULTS: The PAP on days 3, 8, and 13 of hospitalization was positively correlated with the LUS (r = 0.448, p = 0.003; r = 0.738, p < 0.001; r = 0.325, p = 0.036, respectively). On day 8, the values of both PAP and LUS were higher than on days 3 and 13 (p < 0.01). Similarly, PAP and LUS were significantly increased in 92.9% (39/42) and 90.5% (38/42) of patients, respectively, and at least one of these two values was positive in 97.6% (41/42) of cases. The inner diameters of the right atrium, right ventricle, and pulmonary artery also differed significantly from their corresponding values on days 3 and 13 (p < 0.05). CONCLUSIONS: PAP is positively correlated with LUS in COVID-19 pneumonia. The two values could be combined for a more precise assessment of disease progression and recovery status.


Assuntos
COVID-19 , Pneumonia , Ecocardiografia , Humanos , Pulmão/diagnóstico por imagem , Projetos Piloto , Pneumonia/diagnóstico por imagem , SARS-CoV-2 , Ultrassonografia
7.
Biomed Res Int ; 2022: 5544276, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35059464

RESUMO

Atherosclerosis is the most notable cardiovascular disease, the latter being the main cause of death globally. Endothelial cell dysfunction plays a major role in the pathogenesis of atherosclerosis. However, it is currently unclear which genes are involved between endothelial cell dysfunction and atherosclerosis. This study was aimed at identifying these genes. Based on the GSE83500 dataset, the quantification of endothelial cell function was conducted using single-sample gene set enrichment analysis; the coexpression modules were conducted using weighted correlation network analysis. After building module-trait relationships, tan and yellow modules were regarded as hub modules. 10 hub genes from each hub module were identified by the protein-protein interaction network analysis. The key genes (RAB5A, CTTN, ITGB1, and MMP9) were obtained by comparing the expression differences of the hub gene between atherosclerotic and normal groups from the GSE28829 and GSE43292 datasets, respectively. ROC analysis showed the diagnostic value of key genes. Moreover, the differential expression of key genes in normal and atherosclerotic aortic walls was verified. In vitro, we establish a model of ox-LDL-injured endothelial cells and transfect RAB5A overexpression and shRNA plasmids. The results showed that overexpression of RAB5A ameliorates the proliferation and migration function of ox-LDL-injured endothelial cells, including the ability of tubule formation. It was speculated that the interferon response, Notch signaling pathways, etc. were involved in this function of RAB5A by using gene set variation analysis. With the multiple bioinformatics analysis methods, we detected that yellow and tan modules are related to the abnormal proliferation and migration of endothelial cells associated with atherosclerosis. RAB5A, CTTN, ITGB1, and MMP9 can be used as potential targets for therapy and diagnostic markers. In vitro, overexpression of RAB5A can ameliorate the proliferation and migration function of ox-LDL-injured endothelial cells, and the possible molecules involved in this process were speculated.

8.
BMJ Open ; 12(1): e053488, 2022 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-34996792

RESUMO

INTRODUCTION: Atopic dermatitis (AD) is a chronic inflammatory skin disease and skin microbiota dysbiosis shows an important role in the pathogenesis of AD. Effects of treatment on skin microbiota for patients with AD have been evaluated in recent years; however, the results remained controversial across studies. This systematic review will summarise studies evaluating the effect of treatments on skin microbiota among patients with AD. METHODS AND ANALYSIS: We will search PubMed, EMBASE, Web of Science, ClinicalTrials.gov and Chinese Clinical Trial Registry in November 2021; other data sources will also be considered, including searching specific authors and screening references cited in the enrolled articles. Interventional studies, which enrolled patients with AD receiving treatments and reported treatment-related skin microbiota changes, will be included. Our primary outcomes include skin microbiota diversity and treatment-related differential microbes; the secondary outcomes include microbiota functions and microbial interactions. Risk of bias assessment will be performed using Cochrane risk-of-bias tool for randomised trials, risk of bias in non-randomised studies of interventions and methodological index for non-randomised studies. Two researchers will independently perform study selection, data extraction and risk of bias assessment, with disagreements resolved by group discussions. Subgroup analyses will be performed according to different types of treatment for AD. ETHICS AND DISSEMINATION: Ethics approval is not required for this systematic review. Findings will be disseminated via peer-reviewed publication or conference proceedings. PROSPERO REGISTRATION NUMBER: CRD42021246566.

9.
Phys Chem Chem Phys ; 2022 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-35023523

RESUMO

Terahertz functional devices have been instrumental in the development of terahertz technology. Moreover, the advent of metamaterials has greatly contributed to the advancement of terahertz devices. However, most of today's metamaterials in the terahertz band exhibit poor performance and are mono-functional. This greatly limits the scalability and application potential of the devices. To achieve diversification and tunability of device functionality, we propose a combination of metamaterial structures and vanadium dioxide film. A metamaterial absorber based on the thermotropic phase change material VO2 has been designed. Flexible switching of absorption performance (complete reflection and ultra-broadband perfect absorption) can be achieved through temperature adjustment. Moreover, the perfectly absorbed bandwidth is a staggering 3.3 THz. The thermal tuning of spectral absorbance has a maximal range of 0.01 to 0.999. The shift in absorption properties is explained by the phase change process of vanadium oxide (MIT). The electric field intensity on the absorber surface at different temperatures was monitored and analysed as a way to correlate the VO2 film phase transition process. The impedance matching theory is applied to explain the high level of absorption generated by the absorber. Finally, the effects of the structural parameters on the performance of the absorber are analysed. This work will have many applications in the terahertz field and offers a wide range of ideas for the design of terahertz-enabled devices.

10.
Artigo em Inglês | MEDLINE | ID: mdl-35055539

RESUMO

The aim of this study is to assess the impacts of urban green space on depressive symptoms among Chinese urban residents aged 45 and older. In total, 7397 urban respondents were included in this study. Each respondent participated in the China Health and Retirement Longitudinal Study Wave 3 (2015). Environmental-level variables were retrieved from the National Bureau of Statistics database. Both unadjusted and adjusted methods were used in the multilevel regression analysis. Almost one-third of the sample population suffered from depressive symptoms (31.20%). The multilevel logistic regression model showed that green coverage ratio of city-built districts is negatively associated with the prevalence of depressive symptoms among urban mid-aged (OR = 0.79, p < 0.05) and elderly (OR = 0.75, p < 0.05) residents, and the public recreational green space helps to reduce elderly people's depressive symptoms (OR = 0.77, p < 0.05). This study adds insights about the impact of green space and other environmental factors on depressive symptoms among mid-aged and elderly urban dwellers. It is important to provide enough and accessible overall urban green spaces; additionally, attention should also be paid to specific green space forms such as public recreational green space.

11.
ACS Biomater Sci Eng ; 8(1): 196-207, 2022 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-34927415

RESUMO

The use of cyclosporine A (CsA) in transplantation is frequently associated with nephrotoxicity, characterized by renal vascular injury, thrombotic microangiopathy, and striped interstitial fibrosis. Here, using human kidney-specific microvascular endothelial cells (HKMECs), we showed that CsA inhibited NFAT1 activation and impaired VEGF signaling in these ECs in a dose- and time-dependent manner. Integrated genome regulatory analyses identified key distinctions in the landscapes of HKMECs compared to human umbilical vein endothelial cells, particularly around genes related to the formation and maintenance of fenestrae. Using a bioengineered flow-directed 3D kidney microphysiological system, we revealed that CsA-induced kidney microvascular injury was associated with fenestrae and cell adhesion impairment, membrane swelling, and erythrocyte adhesion and extravasation into the interstitial space. Our data provide novel insights into kidney-specific molecular and structural mechanisms of CsA-induced microvascular injury. Our results also suggest VEGF-related pathways as potential targets for therapy during CsA treatment and emphasize the importance of leveraging species and organ-specific cells to better reflect human pathophysiology and the response to injury.

12.
Eur Radiol ; 32(1): 243-253, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34236464

RESUMO

OBJECTIVES: Accurate preoperative differentiation between squamous cell carcinoma (SCC) and non-Hodgkin's lymphoma (NHL) in the palatine tonsil is crucial because of their different treatment. This study aimed to construct and validate a contrast-enhanced CT (CECT)-based radiomics nomogram for preoperative differentiation of SCC and NHL in the palatine tonsil. METHODS: This study enrolled 135 patients with a pathological diagnosis of SCC or NHL from two clinical centers, who were divided into training (n = 94; SCC = 50, NHL = 44) and external validation sets (n = 41; SCC = 22, NHL = 19). A radiomics signature was constructed from radiomics features extracted from routine CECT images and a radiomics score (Rad-score) was calculated. A clinical model was established using demographic features and CT findings. The independent clinical factors and Rad-score were combined to construct a radiomics nomogram. Performance of the clinical model, radiomics signature, and nomogram was assessed using receiver operating characteristics analysis and decision curve analysis. RESULTS: Eleven features were finally selected to construct the radiomics signature. The radiomics nomogram incorporating gender, mean CECT value, and radiomics signature showed better predictive value for differentiating SCC from NHL than the clinical model for training (AUC, 0.919 vs. 0.801, p = 0.004) and validation (AUC, 0.876 vs. 0.703, p = 0.029) sets. Decision curve analysis demonstrated that the radiomics nomogram was more clinically useful than the clinical model. CONCLUSIONS: A CECT-based radiomics nomogram was constructed incorporating gender, mean CECT value, and radiomics signature. This nomogram showed favorable predictive efficacy for differentiating SCC from NHL in the palatine tonsil, and might be useful for clinical decision-making. KEY POINTS: • Differential diagnosis between SCC and NHL in the palatine tonsil is difficult by conventional imaging modalities. • A radiomics nomogram integrated with the radiomics signature, gender, and mean contrast-enhanced CT value facilitates differentiation of SCC from NHL with improved diagnostic efficacy.


Assuntos
Carcinoma de Células Escamosas , Linfoma não Hodgkin , Carcinoma de Células Escamosas/diagnóstico por imagem , Diferenciação Celular , Humanos , Linfoma não Hodgkin/diagnóstico por imagem , Nomogramas , Tonsila Palatina , Tomografia Computadorizada por Raios X
13.
Micron ; 152: 103176, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34763214

RESUMO

The fine structure of the larval eyes of the hangingfly Terrobittacus implicatus (Huang & Hua) was investigated using scanning and transmission electron microscopy. The results show that the larval eyes of T. implicatus each consist of seven spaced ommatidia. Each ommatidium is composed of a corneal lens with about 45 lamellae, a tetrapartite eucone type of crystalline cone, eight retinula cells, two primary pigment cells, and an undetermined number of secondary pigment cells. The rhabdomeres of eight retinula cells effectively fuse into a centrally-fused, tiered funnel-shaped rhabdom extending from the base of the crystalline cone deeply into the ommatidium. In light of different positions in the ommatidium, the retinula cells can be divided into four distal and four proximal retinula cells. Pigment cells envelop the entire ommatidium. Electron-lucent vesicles are abundant throughout the cytoplasm of the eight retinula cells. The larval ommatidia of T. implicatus are similar to those of the Panorpidae, except for the distal retinula cells that also participate in the formation of the proximal rhabdom. In this case, the larval eyes of T. implicatus may lie in the transitional stage during the larval eye evolution of insects from ommatidia to stemmata.


Assuntos
Córnea , Insetos , Animais , Citoplasma , Olho , Larva , Microscopia Eletrônica de Transmissão
14.
Future Oncol ; 2021 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-34865516

RESUMO

We aimed to assess the diagnostic and economic value of next-generation sequencing (NGS) versus single-gene testing, and of liquid biopsy (LBx) versus tissue biopsy (TBx) in non-small-cell lung cancer biomarker testing through literature review. Embase and MEDLINE were searched to identify relevant studies (n = 43) from 2015 to 2020 in adults with advanced non-small-cell lung cancer. For NGS versus single-gene testing, concordance was 70-99% and sensitivity was 86-100%. For LBx versus TBx, specificity was 43-100% and sensitivity was ≥60%. Turnaround times were longer for NGS versus single-gene testing (but not vs sequential testing) and faster for LBx versus TBx. NGS was cost-effective, and LBx reduced US per-patient costs. NGS versus single-gene testing and LBx versus TBx were concordant. NGS and LBx may be cost-effective for initial screening.

15.
Artigo em Inglês | MEDLINE | ID: mdl-34856098

RESUMO

3D porous structural materials are proved to be enticing candidates for the fabrication of high-performance organic phase change materials (PCMs), but the stringent fabrication process and poor processability greatly hampered their commercialization. Herein, flexible leakage-proof composite PCMs with pronounced comprehensive performance are fabricated by a scalable polymer swelling strategy without using any solvent, in which the paraffin wax (PW) segment is confined in a robust flexible 3D polymer network, giving rise to the composite PCMs with excellent form stability even at 160 °C, a high latent heat energy storage density of 133.6 J/g, and an outstanding thermal conductivity of up to ∼5.11 W/mK. More importantly, the mass production of the flexible composite phase change fiber, film, and bulk products can be achieved by adopting mature processing technologies. These resultant composite PCMs exhibit promising thermal management ability to solve the overheating problem of electronics and high-efficiency solar-thermal energy conversion capacity.

16.
Eur J Radiol ; 146: 110093, 2021 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-34890937

RESUMO

PURPOSE: Accurate prediction of the expression level of programmed death ligand 1 (PD-L1) in head and neck squamous cell carcinoma (HNSCC) is crucial before immunotherapy. The purpose of this study was to construct and validate a contrast-enhanced computed tomography (CECT)-based radiomics signature to discriminate between high and low expression status of PD-L1. METHODS: A total of 179 HNSCC patients who underwent immunohistochemical examination of tumor PD-L1 expression at one of two centers were enrolled in this study and divided into a training set (n = 122; 55 high PD-L1 expression and 67 low PD-L1 expression) and an external validation set (n = 57; 26 high PD-L1 expression and 31 low PD-L1 expression). The least absolute shrinkage and selection operator method was used to select the key features for a CECT-image-based radiomics signature. The performance of the radiomics signature was assessed using receiver operating characteristics analysis. RESULTS: Six features were finally selected to construct the radiomics signature. The performance of the radiomics signature in the discrimination between high and low PD-L1 expression status was good in both the training and validation sets, with areas under the receiver operating characteristics curve of 0.889 and 0.834 for the training and validation sets, respectively. CONCLUSIONS: The constructed CECT-based radiomics signature model showed favorable performance for discriminating between high and low PD-L1 expression status in HNSCC patients. It may be useful for screening out those patients with HNSCC who can best benefit from anti-PD-L1 immunotherapy.

18.
ACS Omega ; 6(48): 32508-32516, 2021 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-34901600

RESUMO

BACKGROUND: In this study, we developed a novel risk score named the blood routine test parameters (BRTP) score to predict the clinical outcomes in coronary artery disease (CAD) patients who had undergone percutaneous coronary intervention (PCI). METHODS: There were 6049 patients with CAD after PCI enrolled in CORFCHD-PCI from January 2008 to December 2016. We divided these patients into two groups according to diabetes (diabetic group, n = 3809, and nondiabetic group, n = 2240). During a follow-up time of 35.9 ± 22.6 months, we compared the incidences of all-cause mortality (ACM) and cardiac mortality (CM), which were assigned as the primary outcomes between patients with a high BRTP score (≥5 points) and those with a low BRTP score (<5 points). RESULTS: We found that the BRTP score independently predicted the risk for ACM and CM in both diabetic patients [ACM, hazard risk (HR) = 1.748 (95% confidence interval (CI): 1.186-2.575), P = 0.005; CM, HR = 1.728 (95% CI: 1.120-2.667), P = 0.014] and nondiabetic patients [ACM, HR = 1.682 (95% CI: 1.208-2.340), P = 0.002; CM, HR = 1.718 (95% CI: 1.188-2.484), P = 0.004]. However, the BRTP score was found to be an independent predictor for major adverse cardiovascular event (MACE) and major adverse cardiovascular and cerebrovascular event (MACCE) in diabetic patients [MACE, HR = 1.366 (95% CI: 1.076-1.734), P = 0.010; MACCE, HR = 1.330 (95% CI: 1.035-1.710), P = 0.026] but not in nondiabetic patients [MACE, HR = 1.241 (95% CI: 0.994-1.549), P = 0.056; MACCE, HR = 1.238 (95% CI: 0.981-1.562), P = 0.072]. CONCLUSIONS: This study suggests that the BRTP score is an independent and novel predictor of mortality in CAD patients who had undergone PCI, especially in patients with comorbidity of diabetes. TRIAL REGISTRATION: ChiCTR-ROC-16010153. Registered 14, December, 2016.

19.
Front Cardiovasc Med ; 8: 720597, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34966791

RESUMO

Objectives: A novel AFR- albumin-derived neutrophil to lymphocyte ratio (dNLR) score (ADS) were reported to associate with clinical outcome in various malignancies, However, the relation between the ADS score and outcomes in coronary artery disease (CAD) patients after percutaneous coronary intervention (PCI) has not been investigated. Methods: Three thousand five hundred and sixty-one patients were divided into two groups according to ADS score: low group (ADS score <2; n = 2,682) and high group (ADS score ≥ 2; n = 879). Overall, there were 133 all-cause mortality (ACM) during the following up. The incidence of ACM in the low group is 2.7% (72/2,682) and high group is 6.9% (61/879). The ACM incidence was significantly higher in high group compared to that in the low group (P < 0.001). Cardiac mortality (CM) occurred in 82 patients: 44(1.6%) in the low group and 38 (4.3%) in the high group. There was significant difference in the CM incidence between the low group and high group (P < 0.001). Major adverse cardiac and cerebrovascular events (MACCE) occurred in 520 patients: 366 (13.6%) in the low group and 154 (17.5%) in the high group. There was significant difference in the MACCE incidence between the low group and high group (P = 0.005). Major adverse cardiac and events (MACE) occurred in 395 patients: 281(10.5%) in the low group and 114 (13.0%) in the high group. There was significant difference in the MACE incidence between the low group and high group (P = 0.041). The multivariate Cox proportional hazards model showed that ADS score was independently correlated with the ACM [adjusted HR = 2.031 (1.357-3.039), P = 0.001]; CM [adjusted HR = 1.883 (1.127-3.147), P = 0.016]; MACCE [adjusted HR = 1.352 (1.096-1.668), P = 0.005], and MACE [adjusted HR = 1.260 (0.987-1.608), P = 0.063]. Conclusion: The present study indicated that the ADS score was associated with long-term mortality, the MACCE, and the MACE in CAD patients underwent PCI.

20.
Genet Med ; 2021 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-34906514

RESUMO

PURPOSE: Non-European populations are under-represented in genetics studies, hindering clinical implementation of breast cancer polygenic risk scores (PRSs). We aimed to develop PRSs using the largest available studies of Asian ancestry and to assess the transferability of PRS across ethnic subgroups. METHODS: The development data set comprised 138,309 women from 17 case-control studies. PRSs were generated using a clumping and thresholding method, lasso penalized regression, an Empirical Bayes approach, a Bayesian polygenic prediction approach, or linear combinations of multiple PRSs. These PRSs were evaluated in 89,898 women from 3 prospective studies (1592 incident cases). RESULTS: The best performing PRS (genome-wide set of single-nucleotide variations [formerly single-nucleotide polymorphism]) had a hazard ratio per unit SD of 1.62 (95% CI = 1.46-1.80) and an area under the receiver operating curve of 0.635 (95% CI = 0.622-0.649). Combined Asian and European PRSs (333 single-nucleotide variations) had a hazard ratio per SD of 1.53 (95% CI = 1.37-1.71) and an area under the receiver operating curve of 0.621 (95% CI = 0.608-0.635). The distribution of the latter PRS was different across ethnic subgroups, confirming the importance of population-specific calibration for valid estimation of breast cancer risk. CONCLUSION: PRSs developed in this study, from association data from multiple ancestries, can enhance risk stratification for women of Asian ancestry.

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