Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 276
Filtrar
1.
Cardiovasc Diabetol ; 19(1): 15, 2020 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-32041617

RESUMO

BACKGROUND: Heart-type fatty acid-binding protein (H-FABP) is a novel marker of myocardial injury and has been reported to be associated with cardiovascular diseases (CVD) including patients with diabetes mellitus (DM). Unfortunately, its prognostic value in patients with CVD and impaired glucose metabolism (IGM) is unclear. The objective of this study was to investigate the prognostic value of H-FABP in CVD patients with IGM. METHODS: A total of 4594 patients with angiography-proven coronary artery disease (CAD) were enrolled and divided into subgroup according to glucose metabolism status (normal glucose regulation [NGR], pre-DM, and DM). Baseline levels of H-FABP were measured using latex immunoturbidimetric method. The cardiovascular events (CVE) were defined as cardiovascular death, myocardial infarction, stroke and coronary revascularization. Cox regression and Kaplan-Meier analysis were used to evaluate the relations of H-FABP and glucose metabolism status to CVEs. RESULTS: During the follow-up period with up to 7.1 years, 380 CVEs occurred. Patients with CVE had higher levels of H-FABP compared to those without CVE (p < 0.001). Interestingly, H-FABP levels were also elevated in DM and pre-DM groups compared with NGR group (p < 0.001), when combined glucose metabolism status with H-FABP stratification, patients in the highest tertile of H-FABP appeared to have higher risk of CVEs with pre-DM (adjusted hazard ratio [HR]: 1.855, 95% confidential intervals [CIs] 1.076-3.214; p = 0.033) and DM (adjusted HR: 2.560, 95% CIs 1.409-4.650; p = 0.002). The Kaplan-Meier curve indicated that DM patients with the highest H-FABP levels were associated with the greatest risk of CVEs (p < 0.05). CONCLUSIONS: Our data firstly showed that elevated H-FABP levels were associated with worse outcomes in CAD patients with pre-DM and DM, which provided the novel information that H-FABP might be a prognostic marker for clinical outcomes among patients with CAD and IGM.

2.
J Am Heart Assoc ; 9(3): e014581, 2020 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-32013705

RESUMO

Background Although several studies have indicated that lipoprotein(a) is a useful prognostic predictor for patients following percutaneous coronary intervention (PCI), previous observations have somewhat been limited by either small sample size or short-term follow-up. Hence, this study aimed to evaluate the impact of lipoprotein(a) on long-term outcomes in a large cohort of stable coronary artery disease patients after PCI. Methods and Results In this multicenter and prospective study, we consecutively enrolled 4078 stable coronary artery disease patients undergoing PCI from March 2011 to March 2016. They were categorized according to both the median of lipoprotein(a) levels and lipoprotein(a) values of <15 (low), 15 to 30 (medium), and ≥30 mg/dL (high). All patients were followed up for occurrence of cardiovascular events, including cardiovascular death, nonfatal myocardial infarction, and stroke. During an average of 4.9 years of follow-up, 315 (7.7%) cardiovascular events occurred. The events group had significantly higher lipoprotein(a) levels than the nonevents group. Compared with the low lipoprotein(a) group, Kaplan-Meier analysis showed that the high lipoprotein(a) group had a significantly lower cumulative event-free survival rate, and multivariate Cox regression analysis further revealed that the high lipoprotein(a) group had significantly increased cardiovascular events risk. Moreover, adding continuous or categorical lipoprotein(a) to the Cox model led to a significant improvement in C-statistic, net reclassification, and integrated discrimination. Conclusions With a large sample size and long-term follow-up, our data confirmed that high lipoprotein(a) levels could be associated with a poor prognosis after PCI in stable coronary artery disease patients, suggesting that lipoprotein(a) measurements may be useful for patient risk stratification before selective PCI.

3.
Food Res Int ; 128: 108778, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31955752

RESUMO

Oolong tea is a partially fermented tea with distinct tastes and aromas. However, the dynamic biochemical changes during oolong tea processing are not well understood. In this study, we performed metabolomics-based profiling of non-volatile and volatile constituents of oolong tea during its entire processing procedures by UPLC-QTOF MS and GC-TOF MS. A step-wise change of tea metabolome was observed, where catechins and oxidized products, flavonol glycosides and amino acids were identified as key discriminate metabolites. The ZuoQing process comprising alternating YaoQing and TanQing steps was deemed most critical for key metabolic transformation. Extensive YaoQing facilitated the oxidative polymerizations of catechins into theaflavins and proanthocyanidins, lowering the astringency in raw tea. Two direct terpene precursors farnesyl pyrophosphate and geranyl pyrophosphate accumulated to high levels during ZuoQing, which provided more substrates for the synthesis of downstream volatile terpenes. Moreover, both YaoQing and prolonged TanQing facilitated the formation of terpenes as well as fatty acid and benzenoid-derived volatiles, which contributed to the fruity and floral fragrances in oolong tea. The fixation step not only converted amino acids into aromatic compounds, but also lowered the amounts of flavonol glycosides, potentially improving the flavor quality of the final tea product. This study provides a comprehensive profile of flavor-related metabolic changes during oolong tea processing and will contribute to better quality control and flavor improvement of oolong tea.

4.
Artigo em Inglês | MEDLINE | ID: mdl-31939012

RESUMO

Passive sampling technology has been considered as a promising tool to measure the concentration of environmental contaminants. With this technology, sampling rate (Rs) is an important parameter. However, as experimental methods employed to obtain the Rs value of a given compound were time-consuming, laborious, and expensive. A cost-effective method for deriving Rs is urgent. In addition, considering the great dependence of Rs value on water matrix properties, the laboratory measured Rs may not be a good alternative for field Rs. Thus, obtaining the field Rs is very necessary. In this study, a multiparameter quantitative structure-property relationship (QSPR) model was constructed for predicting the field Rs of 91 polar to semi-polar organic compounds. The determination coefficient (R2Train), leave-one-out cross-validated coefficient (Q2LOO), bootstrap coefficient (Q2BOOT), and root mean square error (RMSETrain) of the training set were 0.772, 0.706, 0.769, and 0.230, respectively, while the external validation coefficient (Q2EXT) and RMSEEXT of the validation set were 0.641 and 0.253, respectively. According to the acceptable criteria (Q2 > 0.600, R2 > 0.700), the model had good robustness, goodness-of-fit, and predictive performances. Therefore, we could use the model to fill the data gap for substances within the applicability domain on their missing Rs value.

5.
Chemosphere ; 242: 125135, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31669991

RESUMO

The anionic form-dependent binding interaction of halo-phenolic substances with human transthyretin (hTTR) has been observed previously. This indicates that ionizable compounds should be the primary focus in screening potential hTTR disruptors. Here, the potential binding potency of halo-benzoic acids, halo-benzenesulfonic acids/sulfates and halo-phenylboronic acids with hTTR was determined and analyzed by competitive fluorescence displacement assay integrated with computational methods. The laboratorial results indicated that the three test groups of model compounds exhibited a distinct binding affinity to hTTR. All the tested halo-phenylboronic acids, some of the tested halo-benzoic acids and halo-benzenesulfonic acids/sulfates were shown to be inactive with hTTR. Other halo-benzoic acids and halo-benzenesulfonic acids/sulfates were moderate and/or weak hTTR binders. The binding affinity of halo-benzoic acids and halo-benzenesulfonic acids/sulfates with hTTR was similar. The low distribution ability of the model compounds from water to hTTR may be the reason why they exhibited the binding potency observed with hTTR. By introducing other highly hydrophobic compounds, we observed that the binding affinity between compounds and hTTR increased with increasing molecular hydrophobicity. Those results indicated that the highly hydrophobic halo-benzoic acids and halo-benzenesulfonic acids/sulfates may be high-priority hTTR disruptors. Finally, a binary classification model was constructed employing three predictive variables. The sensitivity (Sn), specificity (Sp), predictive accuracy (Q) values of the training set and validation set were >0.83, indicating that the model had good classification performance. Thus, the binary classification model developed here could be used to distinguish whether a given ionizable compound is a potential hTTR binder or not.

6.
Arch Microbiol ; 202(1): 191-196, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31595323

RESUMO

A novel Gram-negative, aerobic, rod-shaped bacterium, RS19T, was isolated from rose rhizosphere soil. The strain was psychrophilic and showed good growth over a temperature range of 1-37 â„ƒ. Colonies on TSB agar were circular, smooth, mucoid, convex with clear edges and yellow. Phylogenetic analysis based on 16S rRNA gene sequences characterized RS19T in the genus Dyadobacter and showed that strain RS19T was most closely related to Dyadobacter psychrophilus CGMCC 1.8951T (97.4%) and Dyadobacter alkalitolerans CGMCC 1.8973T (97.1%). The average nucleotide identity values to the closest related species type strains were less than 84.0%. The DNA G + C content was 43.1 mol%, and the predominant respiratory menaquinone was MK-7. The major fatty acids were summed features 3 (C16:1ω7c and/or C16:1ω6c), iso-C15:0, C16:1ω5c and iso-C17:0 3-OH. Based on genotypic, phenotypic and chemotaxonomic data, strain RS19T is different from closely related species of the genus Dyadobacter. RS19T represents a novel species within the genus Dyadobacter, for which the name Dyadobacter luteus sp. nov. is proposed. The type strain is RS19T (= CGMCC 1.13719T = ACCC 60381T = JCM 32940T).


Assuntos
Cytophagaceae/classificação , Filogenia , Rizosfera , Microbiologia do Solo , Técnicas de Tipagem Bacteriana , Composição de Bases , Cytophagaceae/química , Cytophagaceae/genética , DNA Bacteriano/genética , Ácidos Graxos/análise , RNA Ribossômico 16S/genética , Rosa/microbiologia , Análise de Sequência de DNA , Especificidade da Espécie , Vitamina K 2/análise
7.
Talanta ; 208: 120359, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31816689

RESUMO

A versatile protocol has been developed for highly sensitive magnetic relaxation detection of the analyte based on the fabrication of MnO nanoparticles (NPs) assemblies. Based on the strategy that positively charged analyte could induce the assembly of negatively charged MnO NPs through electrostatic interaction, which will generate the change of magnetic relaxation rate of MnO NPs, we achieved highly sensitive and convenient detection of the analytes. By applying the detection of melamine as an example, we found that the detection limit can be as low as 0.733 ppb. Furthermore, this strategy has been applied for the initially detection of commercially available milk spiked with melamine as proof of its potential applicability of detection in complicated food samples.

8.
Neurosci Lett ; 714: 134536, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31589904

RESUMO

Spiral ganglion neurons (SGNs) are primary afferent auditory neurons activated by inner hair cells in mammalian cochlea. Here, for the convenience of SGN studies such as patch-clamp or single cell RNA-sequence studies, a knock-in mouse (ShhCreEGFP/+; Rosa26-Tdtomatoloxp/+) was generated for the purpose of obtaining fluorescence SGNs. Auditory brainstem response (ABR) and Tuj1 immunohistochemistry staining were performed to verify the hearing function and the morphological characteristics. The results showed that there was no significant difference between shh and wild type mice. In electrophysiological studies, we verified a series of electrophysiological characteristics including the amplitude of sodium and potassium currents and action potential characteristics of shh and wild type mice and no significant differences were found either. From the above, shh mice have the same cell function and morphology as their littermate control wild type mice and could be used as an ideal tool to study the function and characteristics of spiral ganglion neurons. Potassium channels of SGNs play an important role in resolving time accuracy. We obtained similar amplitude of IK+ in neonatal and mature mice in the aging competition experiment, however, the density of IK+ from mature mice were significantly different from those of neonatal mice, a phenomenon that may play a key role in the nervous system. Potassium channels have been shown to contribute to apoptosis induced by cisplatin administration in various cell lines. Here we used cisplatin administration to study the ototoxicity and found that the effects of a low dose of cisplatin (0.5 mM correspond to therapeutic doses) causes a decrease in currents and is reversible after a short administration time. Moreover, we propose the activated state of potassium channels has changed but the characteristic and number remain still after cisplatin administration. The excess potassium ions may accumulate in the cell body, which had affected the firing properties and induce cytotoxicity and apoptosis. We suggest that the electrophysiological properties of acutely isolated SGNs may support further research on the mechanics of auditory propagation and ion channel pharmacology.

9.
Am J Transl Res ; 11(11): 6877-6889, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31814894

RESUMO

In recent years, molecular biology and biochemistry have been a focus of studies on the ototoxic side effects of cisplatin. In this paper, the application of cisplatin for 4 h and 72 h was studied from the perspective of electrophysiological function. Patch clamp experiments and immunofluorescence staining were performed on inner hair cells of the cochlea. The patch-clamp results showed that the calcium current amplitude decreased significantly at 4 h and 72 h after cisplatin treatment, the reversal potential was negatively polarized, and the activation time decreased. We suspected that intracellular calcium accumulation was responsible for this result and confirmed this hypothesis by using calpain to measure intracellular calcium concentrations. We tested membrane capacitive function, whose levels after cisplatin application were significantly lower than those in the control group, thus indicating dysfunctional cytoplasmic effervescent function. CtBP2 staining was used to verify this result and indicated a decrease in ribbon synapses. Simultaneously, we observed dysfunction of vesicle circulation after cisplatin application. We found that cisplatin induces the accumulation of calcium ions in inner hair cells by calpain staining and fluoresce intensity calculation, thus decreasing calcium current and synaptic vesicle release, and impairing vesicles cycling, all of which are important mechanisms of cisplatin-induced hearing loss.

10.
Phys Rev Lett ; 123(21): 216101, 2019 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-31809167

RESUMO

The phase stability of ZnO in a quantum-confinement size regime (sub-2-nm) remains fiercely debated. Applying in situ (scanning) transmission electron microscopy, we present the atomistic view of the phase transitions from the original wurtzite structure to an intermediate body-centered tetragonal and h-MgO structure under tensile strain in quantum-confined ZnO nanowires. Strikingly, such structural transitions are reversible after releasing the stress. Further theoretical calculations mirror the transition pathway and provide basic insight into the overall landscape regarding surface- and strain-dependent phase transition behavior. Our results provide the critical piece to solve the puzzle in phase stability of ZnO, which may prove essential for advancing a variety of nanotechnologies, e.g., quantum-dot light-emitting devices.

11.
Artigo em Inglês | MEDLINE | ID: mdl-31880257

RESUMO

In the body, millions of cells die and proliferate each day to maintain normal function and cooperation of all tissues, organs, and systems. Thus, programmed cell death, or apoptosis, is critical to sustain growth, development, and body health. The vital role of B-cell leukemia/lymphoma-2 (BCL-2) family proteins in apoptosis has been identified. The BCL-2 family includes both pro- and anti-apoptotic proteins, which are structurally and functionally related, containing up to four BCL-2 homology (BH) motifs (BH1-4). There are also nutritional factors that regulate apoptosis via the BCL-2 family proteins. In this review, the BCL-2 family proteins and their apoptosis-inducing mechanism have been discussed, along with the nutrient factors that regulating apoptosis through the BCL-2 family proteins.

12.
BMC Infect Dis ; 19(1): 1080, 2019 Dec 26.
Artigo em Inglês | MEDLINE | ID: mdl-31878888

RESUMO

BACKGROUND: Current studies regarding glucocorticosteroid treatment of influenza have only estimated risk of critical illness or death which can be easily confounded by timing of treatment administration. We used severe acute respiratory infection (sARI) as an endpoint and investigated risk associated with receiving glucocorticosteroids before sARI onset. METHODS: sARI cases were defined as influenza-like illness (ILI) with pH1N1 infection and respiratory distress. Controls were defined as pH1N1 cases other than sARI and randomly selected from the community. We compared glucocorticosteroids and other medications used before sARI onset using a matched case control study adjusted for age group as well as underlying disease. Time-dependent risk and dose responses at different time periods over the course of sARI cases were also examined. RESULTS: Of the sARI cases, 34% received glucocorticosteroids before sARI onset compared to 3.8% of controls during equivalent days (ORM-H = 17,95%CI = 2.1-135). Receiving glucocorticosteroids before sARI onset increased risk of developing subsequent critical illness or death (ORM-H = 5.7,95%CI = 1.6-20.2), and the ORM-H increased from 5.7 to 8.5 for continued glucocorticosteroid use after sARI onset. However, only receiving glucocorticosteroids after sARI onset did not increase risk of severe illness (ORM-H = 1.1,95%CI = 0.3-4.6). Each increase in glucocorticosteroids dose of 1 mg/kg/day before sARI onset resulted in an increase of 0.62 (R2 = 0.87) in the pMEWS score at the time of sARI onset. CONCLUSIONS: Early glucocorticosteroid treatment increased risk of sARI and subsequent critical illness or death; however, only receiving glucocorticosteroids after sARI onset did not increase risk of severe illness.

13.
Artigo em Inglês | MEDLINE | ID: mdl-31874808

RESUMO

OBJECTIVES: The aim was to identify the change in gene expression between mesenchymal stem cells (MSCs) and induced endothelial cells (ECs) and to investigate the potential mechanism of endothelial differentiation based on ribonucleic acid sequencing (RNA-Seq) analysis. METHODS: MSCs were isolated from bone marrow and exposed to inducing medium. The dynamic transcription profiles of MSCs were identified and ECs were induced through RNA-seq. Differentially expressed genes (DEGs) were identified. Enrichment of functions and signalling pathways analysis were performed based on Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. Quantitative real time polymerase chain reaction (qRT-PCR) was used to validate the genes selected from RNA-Seq. RESULTS: In total, 2769 DEGs were identified, of which 1117 genes were upregulated and 1652 genes were downregulated. GO and KEGG pathway analyses identified significantly enriched pathways in DEGs, including extracellular matrix organisation, blood vessel morphogenesis, angiogenesis, extracellular matrix binding, growth factor binding and glycosaminoglycan binding extracellular matrix-receptor interaction pathway, cytokine-receptor interaction pathway and transforming growth factor (TGF)-ß signalling pathway. All genes found to be associated with the TGF-ß pathway were significantly downregulated. Eleven novel genes were also identified that most likely are involved in endothelial differentiation and were upregulated with more than 10 fold change, which were further validated by qRT-PCR. CONCLUSIONS: The GO and KEGG analysis revealed that extracellular matrix, cytokines and the TGF-ß pathway play an important role in the process of endothelial differentiation. Furthermore, 11 genes were found that may be involved in the differentiation of MSCs into ECs and contribute to current understanding of the differentiation mechanism.

14.
J Chem Inf Model ; 59(12): 5104-5110, 2019 Dec 23.
Artigo em Inglês | MEDLINE | ID: mdl-31756297

RESUMO

Hepatitis B virus (HBV) infections are a major global health concern, for which heteroaryldihydropyrimidines (HAPs) have been developed. HAPs accelerate and/or result in aberrant capsid assembly; however, their effect on the assembly mechanism is unknown. This study aimed to compare the effects of three representative HAPs on core protein dimer assembly through molecular dynamics simulations and free energy calculations. Molecular docking and equilibrium simulations showed that different HAPs bind at the same binding site and are involved in different interactions. The observed conformational changes in HAPs deter the calculation of binding affinity. Herein, the reduced free energy perturbation/Hamiltonian replica exchange molecular dynamics method was used to enhance sampling during binding affinity calculations, indicating consistency between the binding free energies of HAPs and pEC50. Furthermore, binding pattern analysis revealed that the tetramer could sample flat structures after binding HAPs. The present results suggest a mechanism wherein HAPs accelerate capsid assembly by increasing the binding affinity of dimers, leading to aberrant assembly by altering the binding orientation of dimers.

15.
Pest Manag Sci ; 2019 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-31749278

RESUMO

BACKGROUND: The gene doublesex (dsx) plays pivotal roles in sex determination and controls sexually dimorphic development in certain insects. Importantly, it also displays a potential candidate target for pest management due to its sex-specific splicing. Therefore, we used CRISPR/Cas9-mediated gene disruption to investigate the function of dsx in Hyphantria cunea, an invasive forest pest. RESULT: In the present study, we identified the dsx gene from H. cunea which showed a sex-biased expression pattern that was different from other lepidopteran insects. Referring to sex-specific functional analyses in Bombyx mori, we performed a site-specific knockout of the Hcdsx gene by using a CRISPR/Cas9 system, which induced severe abnormalities in external genitalia and some incomplete sex reversal phenotypes, which in turn led to reduced sex-specific fecundity. An alternative splicing pattern of Hcdsx was altered by CRISPR/Cas9-induced mutation, and alterations in splicing affected expression of downstream genes encoding pheromone binding protein 1, vg1 and vg2 (encoding vitellogenin), which contributed to the sex-specific sterility phenotypes in the Hcdsx mutants. CONCLUSION: The Hcdsx gene plays important roles in sexual differentiation in H. cunea. Disruption of Hcdsx induced sex-specific sterility, demonstrating a potential application in control of this pest. © 2019 Society of Chemical Industry.

16.
Hematol Oncol ; 37(5): 617-625, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31701557

RESUMO

Immortalized cell lines are useful for deciphering the pathogenesis of acute leukemia and developing novel therapeutic agents against this malignancy. In this study, a new human myeloid leukemia cell line YBT-5 was established. After more than 1-year cultivation from the bone marrow of a patient with acute monocytic leukemia, YBT cell line was established. Then a subclone, YBT-5, was isolated from YBT using single cell sorting. Morphological and cytogenetical characterizations of the YBT-5 cell line were determined by cytochemical staining, flow cytometry analysis, and karyotype analysis. Molecular features were identified by transcriptomic analysis and reverse transcription-polymerase chain reaction. To establish a tumor model, 5 × 106 YBT-5 cells were injected subcutaneously in nonobese diabetic/severe combined immune-deficiency (NOD/SCID) mice. DOT1L has been proposed as a potential therapeutic target for KMT2A-related leukemia; therefore, to explore the potential application of this new cell line, its sensitivity to a specific DOT1L inhibitor, EPZ004777 was measured ex vivo. The growth of YBT-5 does not depend on granulocyte-macrophage colony-stimulating factor. Cytochemical staining showed that α-naphthyl acetate esterase staining was positive and partially inhibited by sodium fluoride, while peroxidase staining was negative. Flow cytometry analysis of YBT-5 cells showed positive myeloid and monocytic markers. Karyotype analysis of YBT-5 showed 48,XY,+8,+8. The breakpoints between KMT2A exon 10 and exon 11 (KMT2A exon 10/11) and MLLT3 exon 5 and exon 6 (MLLT3 exon 5/6) were identified, which was different from all known breakpoint locations, and a novel fusion transcript KMT2A exon 10/MLLT3 exon 6 was formed. A tumor model was established successfully in NOD/SCID mice. EPZ004777 could inhibit the proliferation and induce the differentiation of YBT-5 cells. Therefore, a new acute monocytic leukemia cell line with clear biological and molecular features was established and may be used in the research and development of new agents targeting KMT2A-associated leukemia.


Assuntos
Antineoplásicos/farmacologia , Resistencia a Medicamentos Antineoplásicos/genética , Histona-Lisina N-Metiltransferase/antagonistas & inibidores , Histona-Lisina N-Metiltransferase/genética , Proteína de Leucina Linfoide-Mieloide/genética , Proteínas Nucleares/genética , Proteínas de Fusão Oncogênica/genética , Animais , Biomarcadores , Células da Medula Óssea , Linhagem Celular Tumoral , Modelos Animais de Doenças , Humanos , Imunofenotipagem , Hibridização in Situ Fluorescente , Cariotipagem , Leucemia Monocítica Aguda/tratamento farmacológico , Leucemia Monocítica Aguda/genética , Leucemia Monocítica Aguda/metabolismo , Masculino , Camundongos , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase em Tempo Real , Ensaios Antitumorais Modelo de Xenoenxerto
17.
J Transl Med ; 17(1): 367, 2019 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-31711505

RESUMO

BACKGROUND: Proprotein convertase subtilisin/kexin 9 (PCSK9) has been proposed as a novel target for coronary artery disease (CAD). Familial hypercholesterolemia (FH) is characterized by high prevalence of CAD and major cardiovascular events (MACEs). However, no data is available on the association between PCSK9 levels and MACEs in FH patients with standard lipid lowering therapy. METHODS: A total of 338 consecutive heterozygous FH (Dutch Lipid Clinic Network score ≥ 6) was enrolled and followed up for the occurrence of MACEs. Multidetector CT and coronary angiography were performed to determine coronary artery calcification score (CACS) and Gensini score (GS). Multivariable Cox regression analyses were used to calculate hazard ratios (HRs) with 95% confidence intervals (CIs). Plasma PCSK9 concentrations were determined by enzyme immunoassay. RESULTS: PCSK9 was independently and positively associated CACS and GS at baseline. During a mean follow-up of 3 years, 33 (9.8%) events occurred. Patients with MACEs had higher median PCSK9 compared with those without (332.47 vs. 311.89 ng/mL, p = 0.038). Kaplan-Meier analysis revealed that patients with higher PCSK9 presented lower event-free survival (p = 0.0017). PCSK9 was statistically correlated with MACEs after adjusting for confounding factors, with the HR per SD being 1.86 (1.31-2.65) and 3.70 (1.16-11.82) for the highest tertile compared with the lowest tertile. Adding PCSK9 to Cox prediction model led to a statistical improvement in net reclassification and integrated discrimination. CONCLUSION: Elevated levels of PCSK9 were positively associated with the development of CAD and future cardiovascular events, suggesting that measurement of PCSK9 concentration might be useful for cardiovascular risk stratification. Further studies are needed to confirm our results.

18.
Atherosclerosis ; 291: 27-33, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31683090

RESUMO

BACKGROUND AND AIMS: Lipoprotein(a) [Lp(a)] has been considered as a causal risk factor for cardiovascular disease (CVD) in the general population and levels vary in different ethnicities. However, no systemic analysis is currently available regarding the relation of plasma Lp(a) levels to cardiovascular events (CVEs) in Chinese patients with heterozygous familial hypercholesterolemia (HeFH). METHODS: Three hundred and ninety-three patients with HeFH undergoing Lp(a) measurement at baseline were consecutively enrolled and followed prospectively for an average of 36.5 months. Lp(a) levels were determined using an immunoturbidimetry assay. Cox regression analysis with adjusted hazard ratios (HRs) and Kaplan-Meier analysis were used to evaluate the prognostic value of Lp(a) on CVEs. RESULTS: Thirty-five events occurred during follow-up. Lp(a) was significantly higher in patients with CVEs (53.3 mg/dL versus 31.7 mg/dL, p < 0.001). In Kaplan-Meier analysis, patients with upper tertile of Lp(a) had a significant lower event-free survival (p = 0.004). After adjusting for confounding risk factors, per log unit increase in baseline Lp(a) was independently associated with CVEs [HR: 2.03(1.28-3.21), p = 0.002]. HRs remained unchanged after accounting for hard endpoints and did not vary too much in several relevant subgroups. Adding Lp(a) to the Cox model led to a significant improvement in C-statistic, net reclassification and integrated discrimination. Moreover, HR for upper versus lower tertile of change in Lp(a) was 2.68 (1.11-6.48) for CVEs after one year. CONCLUSIONS: Both baseline and on-statin treatment Lp(a) levels were associated with an increased risk of CVEs in patients with HeFH, suggesting that Lp(a) measurement might clinically help further risk stratification of FH patients.

19.
Front Neurol ; 10: 1073, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31649615

RESUMO

Background: Pre-morbid chronic hyperglycemia is associated with the poor outcome of ischemic stroke, but the association between chronic hyperglycemia, and the long-term outcome of acute intracerebral hemorrhage is still poor understood. Methods: Data on patients with acute intracerebral hemorrhage in the ACROSS-China registry (Abnormal Glucose Regulation in Patients With Acute Stroke Across China) were reviewed. Elevated hemoglobin A1c (HbA1c) level on admission was indicative of chronic hyperglycemia. According to the clinical categories of HbA1c, patients were divided into three groups. Multivariable logistic regression or Cox method was performed to analyze the association of HbA1c and the prognosis of patients with acute intracerebral hemorrhage (poor functional outcome [modified Rankin scale score 3-6] and mortality) at 1 year. Results: A total of 416 patients were included in this study. Fifty-two (12.5%) patients died and 130 (31.8%) had poor functional outcome at 1-year follow-up. The higher levels of HbA1c (≥6.5%) was associated with a poor functional outcome (OR 2.35, 95% CI, 1.28-4.29) and increased mortality (OR 2.63, 95% CI 1.34-5.15), compared with the lowest category. When further stratified by diabetic or non-diabetic medical history, higher HbA1c (≥6.5%) still increased the risk of poor functional outcome (OR 3.42, 95% CI 1.39-8.44) and mortality (OR 4.48, 95% CI 1.64-12.24) in patients with non-diabetic medical history. However, higher HbA1c didn't have the association with the increased risk of poor functional outcome (OR 1.06, 95% CI 0.37-3.03) and mortality (OR 1.20, 95% CI 0.39-3.72) in patients with diabetic medical history. Conclusions: Higher HbA1c was associated with a higher risk of death and poor functional outcome 1 year after intracerebral hemorrhage, especially in patients without a diabetic history.

20.
Anal Chem ; 91(21): 13508-13513, 2019 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-31608618

RESUMO

The physical properties of microparticles, such as mass, size, and density, are critical for their functions. The comprehensive characterization of these physical parameters, however, remains a fundamental challenge. Here, we developed a particle mass spectrometry (PMS) methodology for determining the mass, size, and density of microparticles simultaneously. The collisional cross-section (CCS) and mass spectrometry (MS) measurements were performed in a single quadrupole ion trap (QIT), and the two modes can be switched easily by tuning the electric and gas hydrodynamic fields of the QIT. The feasibility of the method was demonstrated through a series of monodispersed polystyrene (PS) and silica (SiO2) particle standards. The SiO2/polypyrrole core-shell particles were also successfully characterized, and the measured results were verified by using conventional methods.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA