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1.
Drug Discov Ther ; 18(1): 34-43, 2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38382932

RESUMO

To get a thorough understanding of PD-1/L1 inhibitor-related hypophysitis (PD-1/L1-irH), we utilized a combination of disproportionality analysis and case analysis to comprehensively characterize the clinical features of PD-1/L1-irH. Significant signals of hypophysitis were detected for all PD-1/PD-L1 inhibitors in the FAERS (FDA Adverse Event Reporting System). As revealed by both FAERS and the case analysis, PD-1/L1-irH occurred more commonly in males, PD-1 inhibitors users and patients older than 65 years. The median onset time was 101 days in FAERS and 8 cycles in the case analysis. In the case analysis, eight late-onset PD-1/L1-irHs occurred even after a discontinuation of several months (4-15 months). As revealed in FAERS, the outcome of PD-1/L1-irH tended to be poor, generally resulting in 64.66% hospitalization and 12.59% death. Fatigue was the most prominent symptom of PD-1/L1-irH, followed by anorexia, hyponatremia, and hypotension, as revealed by the analysis of 84 cases. Meanwhile isolated adrenocorticotropic (ACTH) deficiency was particularly prevalent for PD-1/L1-irH (85.71%), while gonadal hormones or posterior pituitary hormones deficiencies were rare. Glucocorticoids were administered to almost all cases (81/84), with a physiologic or stress dosage in 61.9% of cases, and a high-dose in 26.2% of cases. Most cases (58.3%) showed a favorable tumor response before diagnosis of PD-1/L1-irH. PD-1/L1-irH may occur throughout the whole therapy period even after discontinuation. Clinicians should pay more attention to PD-1 inhibitor users, males and older patients. Early diagnosis and prompt managements are crucial for PD-1/L1-irH as its potentially life-threatening nature.


Assuntos
Hipofisite , Neoplasias , Masculino , Humanos , Inibidores de Checkpoint Imunológico/uso terapêutico , Receptor de Morte Celular Programada 1 , Neoplasias/tratamento farmacológico , Glucocorticoides/uso terapêutico , Hipofisite/induzido quimicamente , Hipofisite/tratamento farmacológico
2.
Artigo em Inglês | MEDLINE | ID: mdl-38236668

RESUMO

The success of multiview raw data mining relies on the integrity of attributes. However, each view faces various noises and collection failures, which leads to a condition that attributes are only partially available. To make matters worse, the attributes in multiview raw data are composed of multiple forms, which makes it more difficult to explore the structure of the data especially in multiview clustering task. Due to the missing data in some views, the clustering task on incomplete multiview data confronts the following challenges, namely: 1) mining the topology of missing data in multiview is an urgent problem to be solved; 2) most approaches do not calibrate the complemented representations with common information of multiple views; and 3) we discover that the cluster distributions obtained from incomplete views have a cluster distribution unaligned problem (CDUP) in the latent space. To solve the above issues, we propose a deep clustering framework based on subgraph propagation and contrastive calibration (SPCC) for incomplete multiview raw data. First, the global structural graph is reconstructed by propagating the subgraphs generated by the complete data of each view. Then, the missing views are completed and calibrated under the guidance of the global structural graph and contrast learning between views. In the latent space, we assume that different views have a common cluster representation in the same dimension. However, in the unsupervised condition, the fact that the cluster distributions of different views do not correspond affects the information completion process to use information from other views. Finally, the complemented cluster distributions for different views are aligned by contrastive learning (CL), thus solving the CDUP in the latent space. Our method achieves advanced performance on six benchmarks, which validates the effectiveness and superiority of our SPCC.

3.
ACS Nano ; 18(5): 4360-4375, 2024 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-38277483

RESUMO

Targeting nutrient metabolism has been proposed as an effective therapeutic strategy to combat breast cancer because of its high nutrient requirements. However, metabolic plasticity enables breast cancer cells to survive under unfavorable starvation conditions. The key mammalian target regulators rapamycin (mTOR) and hypoxia-inducible-factor-1 (HIF-1) tightly link the dynamic metabolism of glutamine and glucose to maintain nutrient flux. Blocking nutrient flow also induces autophagy to recycle nutrients in the autophagosome, which exacerbates metastasis and tumor progression. Compared to other common cancers, breast cancer is even more dependent on mTOR and HIF-1 to orchestrate the metabolic network. Therefore, we develop a cascade-boosting integrated nanomedicine to reprogram complementary metabolism coupled with regulators in breast cancer. Glucose oxidase efficiently consumes glucose, while the delivery of rapamycin inside limits the metabolic flux of glutamine and uncouples the feedback regulation of mTOR and HIF-1. The hydroxyl radical generated in a cascade blocks the later phase of autophagy without nutrient recycling. This nanomedicine targeting orchestrated metabolism can disrupt the coordination of glucose, amino acids, nucleotides, lipids, and other metabolic pathways in breast cancer tissues, effectively improving the durable antitumor effect and prognosis of breast cancer. Overall, the cascade-boosting integrated system provides a viable strategy to address cellular plasticity and efficient enzyme delivery.


Assuntos
Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/patologia , Glutamina/metabolismo , Biomimética , Nanomedicina , Serina-Treonina Quinases TOR/metabolismo , Sirolimo , Glucose/metabolismo
4.
Artigo em Inglês | MEDLINE | ID: mdl-37738196

RESUMO

Multiview clustering has attracted increasing attention to automatically divide instances into various groups without manual annotations. Traditional shadow methods discover the internal structure of data, while deep multiview clustering (DMVC) utilizes neural networks with clustering-friendly data embeddings. Although both of them achieve impressive performance in practical applications, we find that the former heavily relies on the quality of raw features, while the latter ignores the structure information of data. To address the above issue, we propose a novel method termed iterative deep structural graph contrast clustering (IDSGCC) for multiview raw data consisting of topology learning (TL), representation learning (RL), and graph structure contrastive learning to achieve better performance. The TL module aims to obtain a structured global graph with constraint structural information and then guides the RL to preserve the structural information. In the RL module, graph convolutional network (GCN) takes the global structural graph and raw features as inputs to aggregate the samples of the same cluster and keep the samples of different clusters away. Unlike previous methods performing contrastive learning at the representation level of the samples, in the graph contrastive learning module, we conduct contrastive learning at the graph structure level by imposing a regularization term on the similarity matrix. The credible neighbors of the samples are constructed as positive pairs through the credible graph, and other samples are constructed as negative pairs. The three modules promote each other and finally obtain clustering-friendly embedding. Also, we set up an iterative update mechanism to update the topology to obtain a more credible topology. Impressive clustering results are obtained through the iterative mechanism. Comparative experiments on eight multiview datasets show that our model outperforms the state-of-the-art traditional and deep clustering competitors.

5.
Opt Lett ; 48(7): 1550-1553, 2023 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-37221707

RESUMO

Graphene supports both transverse magnetic and electric modes of surface polaritons due to the intraband and interband transition properties of electrical conductivity. Here, we reveal that perfect excitation and attenuation-free propagation of surface polaritons on graphene can be achieved under the condition of optical admittance matching. With both vanished forward and backward far-field radiation, incident photons are fully coupled to surface polaritons. This requires an exact match between the admittance difference of sandwiching media and the conductivity of graphene, resulting in no decay of propagating surface polaritons. The dispersion relation has a completely different line shape for structures that support compared to those that do not support admittance matching. This work promotes complete comprehension of the excitation and propagation behaviors of graphene surface polaritons and may further inspire ideas for research on surface waves on two-dimensional materials.

6.
Environ Sci Pollut Res Int ; 29(50): 76417-76431, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35670936

RESUMO

To facilitate removing As(III) from water through an "oxidation-adsorption" process, the double-shell CuOx@MnOy hollow spheres (DCMHS) have been fabricated via a two-step co-precipitation route combined with the soft-template method. The surface characterization results showed that Mn oxides were formed without segregation and uniformly distributed on the surface of CuOx hollow spheres. DCMHS could achieve outstanding performance to remove As(III) with an As maximum adsorption capacity of 32.15 mg/g. Meanwhile, the kinetics results illustrated that the oxidative activity of DCMHS was strengthened due to its specific structure, and part of As(III) was converted to As(V) during the adsorption process. Also, air aeration could further enhance As(III) oxidation and thus improving As removal. The As(III) removal performance could be maintained under neutral and weak alkaline conditions. Phosphate, silicate, and carbonate anions could depress the removal performance, while chloride ions and sulfate anions barely influenced As removal. Moreover, DCMHS could be regenerated using NaOH and KMnO4 solutions without breaking the hollow sphere structure. Based on the spectroscopic analysis results, As(III) molecules were converted to As(V) via two pathways, including the oxidation by Mn oxides or superoxide radicals. The Cu-Mn synergistic effect could not only enhance the oxidative activity of Mn oxides but also produce superoxide radicals via the activation of surface-adsorbed oxygen molecules. Afterwards, the newly formed As(V) could be attached to the hydroxyl groups through surface complexation. Therefore, this work has provided insights into the morphology design of Mn-oxide-containing adsorbents and supplemented the interface reaction mechanisms for enhancing As(III) removal.


Assuntos
Arsênio , Arsenitos , Poluentes Químicos da Água , Adsorção , Ânions , Arsênio/química , Arsenitos/química , Cloretos , Cobre , Compostos de Manganês/química , Oxirredução , Óxidos/química , Oxigênio , Fosfatos , Hidróxido de Sódio , Sulfatos , Superóxidos , Água , Poluentes Químicos da Água/análise
7.
Math Biosci Eng ; 19(4): 4120-4144, 2022 02 17.
Artigo em Inglês | MEDLINE | ID: mdl-35341290

RESUMO

Cancer is a serious threat to human health and life. Using anti-tumor drugs is one of the important ways for treating cancer. A large number of experiments have shown that the hormesis appeared in the dose-response relationship of various anti-tumor drugs. Modeling this phenomenon will contribute to finding the appropriate dose. However, few studies have used dynamical models to quantitatively explore the hormesis phenomenon in anti-tumor drug dose-response. In this study, we present a mathematical model and dynamical analysis to quantify hormesis of anti-tumor drugs and reveal the critical threshold of antibody dose. Firstly, a dynamical model is established to describe the interactions among tumor cells, natural killer cells and M2-polarized macrophages. Model parameters are fitted through the published experimental data. Secondly, the positivity of solution and bounded invariant set are given. The stability of equilibrium points is proved. Thirdly, through bifurcation analysis and numerical simulations, the hormesis phenomenon of low dose antibody promoting tumor growth and high dose antibody inhibiting tumor growth is revealed. Furthermore, we fit out the quantitative relationship of the dose-response of antibodies. Finally, the critical threshold point of antibody dose changing from promoting tumor growth to inhibiting tumor growth is obtained. These results can provide suggestions for the selection of appropriate drug dosage in the clinical treatment of cancer.


Assuntos
Antineoplásicos , Neoplasias , Antineoplásicos/farmacologia , Relação Dose-Resposta a Droga , Hormese , Humanos , Modelos Teóricos , Neoplasias/tratamento farmacológico
8.
ACS Appl Mater Interfaces ; 13(47): 56530-56543, 2021 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-34758621

RESUMO

Gas barrier membranes with impressive moisture permeability are highly demanded in air or nature gas dehumidification. We report a novel approach using polyetheramine oligomers covalently grafted on the carbon nanotubes (CNTs) to engineer liquid-like CNT nanofluids (CNT NFs), which are incorporated into a polyimide matrix to enhance the gas barrier and moisture permeation properties. Benefiting from the featured liquid-like characteristic of CNT NFs, a strong interfacial compatibility between CNTs and the polyimide matrix is achieved, and thus, the resulting membranes exhibit high heat resistance and desirable mechanical strength as well as remarkable fracture toughness, beneficially to withstanding creep, impact, and stress fatigue in separation applications. Positron annihilation lifetime spectroscopy measurements indicate a significant decrease in fractional free volume within the resulting membranes, leading to greatly enhanced gas barrier properties while almost showing full retention of moisture permeability compared to that of the pristine membrane. For membranes with 10 wt % CNT NFs, the gas transmission rates, respectively, decrease 99.9% for CH4, 94.4% for CO2, 99.2% for N2, and 97.9% for O2 compared with that of the pristine membrane. Most importantly, with the increasing amount of CNT NFs, the hybrid membranes demonstrate a simultaneous increase of barrier performance and permselectivity for H2O/CH4, H2O/N2, H2O/CO2, and H2O/O2. All these results make these membranes potential candidates for high-pressure natural gas or hyperthermal air dehydration.

9.
Arq. bras. cardiol ; 116(5): 959-967, nov. 2021. tab
Artigo em Inglês, Português | LILACS | ID: biblio-1248915

RESUMO

Resumo Fundamento: Para pacientes com infarto do miocárdio com elevação do segmento ST (IAMCST) que sofrem de obstrução coronariana microvascular funcional e estrutural (OCM) subsequente, nenhuma abordagem terapêutica específica e definitiva de atenuação foi comprovada como válida em testes de larga escala atuais, o que destaca a necessidade de abordar seu reconhecimento precoce. Objetivos: Este estudo teve como objetivo comparar o desempenho de dois escores de risco clínico com uma medida objetiva de OCM durante intervenção coronária percutânea (ICP) em casos de IAMCST Métodos: A medição do índice de resistência microcirculatória (IRM) foi realizada e os parâmetros clínicos e angiográficos basais também foram registrados. Os pacientes foram divididos em entre os grupos OM (obstrução microvascular) e NOM (não-obstrução microvascular), de acordo com o valor de IRM pós-procedimento. O risco de OCM foi avaliado para todos os participantes pelos escores preditivos SAK e ATI, respectivamente. Cada sistema foi calculado somando-se as pontuações de todas as variáveis. As curvas de características do operador receptor (ROC) e a área sob a curva (AUC) de dois modelos de risco foram utilizadas para avaliar o desempenho discriminatório. Um ecocardiograma foi realizado sete dias após o procedimento para avaliar a fração de ejeção do ventrículo esquerdo (FEVE). Um valor P bicaudal de <0,05 foi considerado estatisticamente significativo. Resultados: Entre os 65 pacientes elegíveis com IAMCST, 48 foram alocados no grupo NOM e 17 no grupo OM, com uma incidência de OCM de 26,15%. Não houve diferença significativa na AUC entre os dois escores. A FEVE avaliada para o grupo NOM foi maior do que para o grupo OM. Conclusão: Os escores SAK e ATI tiveram bom desempenho para estimar o risco de OCM após ICP primário para pacientes com IAMCST.


Abstract Background: For patients with ST-segment elevation myocardial infarction (STEMI) that are suffering from subsequent coronary microvascular functional and structural obstruction (CMVO), no specific and definitive therapeutic approaches of attenuation have been proven valid in up-to-date large-scale tests, which highlights the urge to address its early recognition. Objectives: This study aimed to compare the performance of two clinical risk scores with an objective measurement of CMVO during percutaneous coronary intervention (PCI) with STEMI. Methods: The Index of Microcirculatory Resistance (IMR) measurement was conducted and the baseline clinical and angiographic parameters were also recorded. The patients were divided into MO (Microvascular obstruction) or NMO (Non-microvascular obstruction) groups according to the post-procedure IMR value. The CMVO risk was evaluated for all participants by SAK and ATI predictive scores, respectively. Each system was calculated by summing the scores of all variables. The receiver operator characteristic (ROC) curves and the area under the curve (AUC) of two risk models were used to evaluate the discriminatory performance. An echocardiography was performed seven days after the procedure to evaluate left ventricular ejection fraction (LVEF). A two-sided P-value of <0.05 was considered statistically significant. Results: Among the 65 eligible STEMI patients, 48 patients were allocated in the NMO group and 17 in the MO group, with a CMVO incidence of 26.15%. There was no significant difference in the AUC between both scores. The LVEF evaluated for the NMO group was higher than that of MO group. Conclusion: Both SAK and ATI scores performed well in estimating CMVO risk after primary PCI for STEMI patients.


Assuntos
Humanos , Intervenção Coronária Percutânea/efeitos adversos , Infarto do Miocárdio com Supradesnível do Segmento ST/cirurgia , Infarto do Miocárdio com Supradesnível do Segmento ST/diagnóstico por imagem , Volume Sistólico , Fatores de Risco , Função Ventricular Esquerda , Resultado do Tratamento , Circulação Coronária , Microcirculação
10.
Arq Bras Cardiol ; 116(5): 959-967, 2021 05.
Artigo em Inglês, Português | MEDLINE | ID: mdl-34008822

RESUMO

BACKGROUND: For patients with ST-segment elevation myocardial infarction (STEMI) that are suffering from subsequent coronary microvascular functional and structural obstruction (CMVO), no specific and definitive therapeutic approaches of attenuation have been proven valid in up-to-date large-scale tests, which highlights the urge to address its early recognition. OBJECTIVES: This study aimed to compare the performance of two clinical risk scores with an objective measurement of CMVO during percutaneous coronary intervention (PCI) with STEMI. METHODS: The Index of Microcirculatory Resistance (IMR) measurement was conducted and the baseline clinical and angiographic parameters were also recorded. The patients were divided into MO (Microvascular obstruction) or NMO (Non-microvascular obstruction) groups according to the post-procedure IMR value. The CMVO risk was evaluated for all participants by SAK and ATI predictive scores, respectively. Each system was calculated by summing the scores of all variables. The receiver operator characteristic (ROC) curves and the area under the curve (AUC) of two risk models were used to evaluate the discriminatory performance. An echocardiography was performed seven days after the procedure to evaluate left ventricular ejection fraction (LVEF). A two-sided P-value of <0.05 was considered statistically significant. RESULTS: Among the 65 eligible STEMI patients, 48 patients were allocated in the NMO group and 17 in the MO group, with a CMVO incidence of 26.15%. There was no significant difference in the AUC between both scores. The LVEF evaluated for the NMO group was higher than that of MO group. CONCLUSION: Both SAK and ATI scores performed well in estimating CMVO risk after primary PCI for STEMI patients.


FUNDAMENTO: Para pacientes com infarto do miocárdio com elevação do segmento ST (IAMCST) que sofrem de obstrução coronariana microvascular funcional e estrutural (OCM) subsequente, nenhuma abordagem terapêutica específica e definitiva de atenuação foi comprovada como válida em testes de larga escala atuais, o que destaca a necessidade de abordar seu reconhecimento precoce. OBJETIVOS: Este estudo teve como objetivo comparar o desempenho de dois escores de risco clínico com uma medida objetiva de OCM durante intervenção coronária percutânea (ICP) em casos de IAMCST. MÉTODOS: A medição do índice de resistência microcirculatória (IRM) foi realizada e os parâmetros clínicos e angiográficos basais também foram registrados. Os pacientes foram divididos em entre os grupos OM (obstrução microvascular) e NOM (não-obstrução microvascular), de acordo com o valor de IRM pós-procedimento. O risco de OCM foi avaliado para todos os participantes pelos escores preditivos SAK e ATI, respectivamente. Cada sistema foi calculado somando-se as pontuações de todas as variáveis. As curvas de características do operador receptor (ROC) e a área sob a curva (AUC) de dois modelos de risco foram utilizadas para avaliar o desempenho discriminatório. Um ecocardiograma foi realizado sete dias após o procedimento para avaliar a fração de ejeção do ventrículo esquerdo (FEVE). Um valor P bicaudal de <0,05 foi considerado estatisticamente significativo. RESULTADOS: Entre os 65 pacientes elegíveis com IAMCST, 48 foram alocados no grupo NOM e 17 no grupo OM, com uma incidência de OCM de 26,15%. Não houve diferença significativa na AUC entre os dois escores. A FEVE avaliada para o grupo NOM foi maior do que para o grupo OM. CONCLUSÃO: Os escores SAK e ATI tiveram bom desempenho para estimar o risco de OCM após ICP primário para pacientes com IAMCST.


Assuntos
Intervenção Coronária Percutânea , Infarto do Miocárdio com Supradesnível do Segmento ST , Circulação Coronária , Humanos , Microcirculação , Intervenção Coronária Percutânea/efeitos adversos , Fatores de Risco , Infarto do Miocárdio com Supradesnível do Segmento ST/diagnóstico por imagem , Infarto do Miocárdio com Supradesnível do Segmento ST/cirurgia , Volume Sistólico , Resultado do Tratamento , Função Ventricular Esquerda
11.
RSC Adv ; 11(13): 7226-7230, 2021 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-35423244

RESUMO

In this work, we present a novel photothermal agent ICG-IBA-RGD based on albumin-binding strategy for enhanced tumor targeting imaging and photothermal therapy. In vitro and in vivo experiments demonstrated that ICG-IBA-RGD exhibits excellent photothermal conversion capability and high tumor ablation efficiency.

12.
Coron Artery Dis ; 31(6): 493-499, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32073417

RESUMO

OBJECTIVES: The study was designed to evaluate the effect of low-dose intracoronary prourokinase administration immediately after thrombus aspiration in patients with ST-segment elevation myocardial infarction (STEMI) presenting with a serious thrombus burden. METHODS: Consecutive STEMI patients with high thrombus burden received thrombus aspiration during primary percutaneous coronary intervention (PCI) were randomly assigned to study group (intracoronary prourokinase administration) or control group (intracoronary 0.9% sodium chloride administration). The primary endpoint was complete ST-segment resolution (STR) at 90 min after primary PCI, and the secondary endpoints included angiographic myocardial perfusion indexes. RESULTS: Patients in study group had a higher incidence of complete STR and myocardial blush grade 3 compared with those in control group (56.52% vs. 38.89%, P = 0.017 and 57.61% vs. 38.89%, P = 0.041). The peak cardiac troponin I value and corrected thrombolysis in myocardial infarction frame count were significantly lower in study group (52.16 ± 24.67 ng/mL vs. 60.91 ± 28.81 ng/mL, P = 0.029; and 19.57 ± 9.05 vs. 22.91 ± 10.22, P = 0.020). A significant improvement in left ventricular ejection fraction and major adverse cardiac events (MACEs)-free survival was observed in study group (55.22 ± 10.50% vs. 52.18 ± 9.39%, P = 0.041; 10.87% vs. 22.22%, P = 0.039) at the 6-month follow-up. The bleeding complication was similar in both groups (17.39% vs. 12.22%, P = 0.327). CONCLUSIONS: In STEMI patients with high thrombus burden, low-dose prourokinase intracoronary administered immediately after thrombus aspiration improves myocardial perfusion, cardiac function, and MACEs-free survival with no significant increase in major bleeding.


Assuntos
Trombose Coronária/tratamento farmacológico , Infarto do Miocárdio com Supradesnível do Segmento ST/tratamento farmacológico , Ativador de Plasminogênio Tipo Uroquinase/administração & dosagem , Função Ventricular Esquerda/fisiologia , Angiografia Coronária , Trombose Coronária/complicações , Trombose Coronária/diagnóstico , Vasos Coronários , Relação Dose-Resposta a Droga , Feminino , Fibrinolíticos/administração & dosagem , Seguimentos , Humanos , Injeções Intra-Arteriais , Masculino , Pessoa de Meia-Idade , Proteínas Recombinantes/administração & dosagem , Estudos Retrospectivos , Infarto do Miocárdio com Supradesnível do Segmento ST/etiologia , Infarto do Miocárdio com Supradesnível do Segmento ST/fisiopatologia , Volume Sistólico , Resultado do Tratamento
13.
J Anim Physiol Anim Nutr (Berl) ; 104(1): 371-378, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31724249

RESUMO

In order to investigate the mechanism of genistein (Gen) in the treatment of climacteric syndrome, an in vivo study was performed to investigate the beneficial effects of genistein on the expression of P450 aromatase (P450 arom) and follicle-stimulating hormone receptor (FSHR) in the mouse ovary and uterus. Fifty female ICR mice (45 ± 5g, n = 50), aged 12 months, were divided into the following five groups with 10 animals in each: blank control group (CG), low-dose genistein group (L-Gen), middle-dose genistein group (M-Gen) and high-dose genistein group (H-Gen) (received 15, 30 and 60 mg/kg of genistein, respectively), and oestrogen group (EG; received 0.5 mg/kg diethylstilbestrol). The expression levels of the FSHR protein were determined by an immunohistochemical staining method. The expression of P450 arom, Cytochrome P450 19 (CYP19) and FSHR was quantified by real-time PCR. Immunohistochemical results showed that the expression levels of the FSHR protein in the M-Gen (average stained area: 20.79) and the H-Gen (average stained area: 21.21) groups were significantly stronger than in the CG (average area was 17.24) group (p < .05). The expression levels of CYP19 mRNA and P450 arom were positively correlated with the dose of genistein. Specifically, the relative expression levels in the H-Gen and EG groups were more than 1.5 times higher than in the CG group (p < .05). Genistein played a significant role in regulating aromatase and FSHR gene expression to improve perimenopausal ovarian and uterine function.


Assuntos
Aromatase/metabolismo , Genisteína/farmacologia , Menopausa , Síndrome Metabólica/tratamento farmacológico , Receptores do FSH/metabolismo , Animais , Aromatase/genética , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos ICR , Ovário/efeitos dos fármacos , Ovário/metabolismo , Receptores do FSH/genética , Transcriptoma
14.
Med Sci Monit ; 25: 5864-5877, 2019 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-31387983

RESUMO

BACKGROUND Coronary microvascular functional and structural obstruction (CMVO) remains a major complication in patients with ST-segment elevation myocardial infarction (STEMI). This study was designed to develop and validate a nomogram model to predict CMVO risk during primary percutaneous catheterization procedure. MATERIAL AND METHODS Starting January 2014 to December 2016, a cohort of eligible candidates were enrolled and divided into a training or a validation database. Each database was divided into MO or NMO subgroups based on TIMI myocardial perfusion grade results after recanalization. Independent factors were identified by multivariate logistic regression, from which the nomogram was plotted. The echocardiography measurement of the left ventricular ejection fraction (LVEF) was arranged within 7 days after the procedure. RESULTS A nomogram was built for CMVO risk prediction for the first time. There were 446 participants in the training database with 319 cases in the NMO subgroup and 127 participants in the MO subgroup. The validation database included 99 participants with 25 cases in the NMO subgroup and 74 in the MO subgroup. The risk model was developed by 6 independently significant factors: age, symptom onset to balloon time, Killip classification, admission activated clotting time, neutrophil/lymphocyte ratio, and glucose value. Internal receiver operating characteristic displayed favorable performance with concordance index of 0.925, while external validation area under curve was 0.939. There were significant differences in LVEF values during hospitalization between the subgroups of each database (both P<0.001). CONCLUSIONS The nomogram model consisting of 6 factors could predict CMVO risk accurately for STEMI patients undergoing primary percutaneous catheterization.


Assuntos
Oclusão Coronária/etiologia , Infarto do Miocárdio com Supradesnível do Segmento ST/fisiopatologia , Idoso , China , Estudos de Coortes , Angiografia Coronária , Circulação Coronária , Oclusão Coronária/fisiopatologia , Ecocardiografia , Feminino , Humanos , Modelos Logísticos , Masculino , Microvasos/fisiopatologia , Pessoa de Meia-Idade , Infarto do Miocárdio/fisiopatologia , Nomogramas , Intervenção Coronária Percutânea/métodos , Medição de Risco , Fatores de Risco , Infarto do Miocárdio com Supradesnível do Segmento ST/complicações , Volume Sistólico , Função Ventricular Esquerda/fisiologia
15.
Coron Artery Dis ; 30(8): 555-563, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30998610

RESUMO

OBJECTIVE: This study aimed at evaluating efficacy and safety of thrombus aspiration and intracoronary-targeted thrombolysis on coronary thrombus burden in ST-elevation myocardial infarction (STEMI) patients undergoing primary percutaneous catheterization, comparing their effects on myocardial perfusion through index of microcirculatory resistance (IMR) and single-photon emission computed tomography (SPECT). PARTICIPANTS AND METHODS: From January 2017 to January 2018, STEMI patients with high thrombus burden undergoing primary catheterization were enrolled and randomly assigned to receiving thrombus aspiration (TA group) or intracoronary thrombolysis (IT group). IMR, SPECT, and other conventional measurements were adopted to assess myocardial perfusion. Major adverse cardiovascular events (MACEs) and complications were recorded over a 90-day follow-up and a 12-month follow-up after the procedure. RESULTS: The study consisted of 38 patients in the IT group and 33 in the TA group. After recanalization, thrombus burden score, corrected thrombolysis in myocardial infarction (TIMI) frame count, the proportion of TIMI myocardial perfusion 3 grade, and IMR in the IT group were significantly better than those of the TA group (P<0.05). During the 90-day follow-up, no difference was observed in cardiac function and MACEs. During the 12-month follow-up, there were significant differences in infarct size of SPECT (18.56±8.56 vs. 22.67±7.66, P=0.046), left ventricular ejection fraction of echocardiography (58.13±5.92 vs. 55.17±5.68, P=0.043), and the composite MACEs between the two groups (P=0.034). CONCLUSION: Thrombus aspiration and intracoronary-targeted thrombolysis are effective and safe strategies in managing high coronary thrombus burden in STEMI patients. Compared with aspiration, intracoronary-targeted thrombolysis is more beneficial in improving myocardial microcirculation perfusion.


Assuntos
Trombose Coronária/terapia , Intervenção Coronária Percutânea , Infarto do Miocárdio com Supradesnível do Segmento ST/terapia , Trombectomia , Terapia Trombolítica , Idoso , China , Circulação Coronária , Trombose Coronária/diagnóstico por imagem , Trombose Coronária/fisiopatologia , Feminino , Humanos , Masculino , Microcirculação , Pessoa de Meia-Idade , Imagem de Perfusão do Miocárdio/métodos , Intervenção Coronária Percutânea/efeitos adversos , Estudos Prospectivos , Fatores de Risco , Infarto do Miocárdio com Supradesnível do Segmento ST/diagnóstico por imagem , Infarto do Miocárdio com Supradesnível do Segmento ST/fisiopatologia , Sucção , Trombectomia/efeitos adversos , Terapia Trombolítica/efeitos adversos , Fatores de Tempo , Tomografia Computadorizada de Emissão de Fóton Único , Resultado do Tratamento
16.
Angiology ; 68(7): 633-639, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-27815334

RESUMO

We evaluated the effect of long-term administration of nicorandil on endothelial function of the radial artery in patients with angina undergoing elective transradial coronary intervention (TRI). A total of 127 patients were randomly assigned to nicorandil (standard medication plus nicorandil 5 mg twice daily, n = 64) or control group (standard medication except nicorandil, n = 63) immediately after TRI procedure. Radial artery diameter (RAD), flow-mediated dilation (FMD), and nitroglycerin-mediated dilation (NMD) of radial artery were measured 1 day before TRI as well as 1 day and 3 months after TRI by Ultrasound-Doppler. No significant difference was observed in the baseline RAD, FMD, and NMD between the 2 groups (all P > .05). In cannulated arm, at 3-month follow-up, RAD in nicorandil group was much larger than that in the control group (2.78 ± 0.27 mm vs 2.61 ± 0.30 mm, P = .001). Besides, FMD and NMD were much higher in nicorandil group than those in the control group (10.38% ± 2.43% vs 6.81% ± 1.86%; 15.94% ± 6.28% vs 10.46% ± 5.37%, respectively, all Ps < .001). In conclusion, long-term administration of nicorandil after TRI could improve the endothelial function of the cannulated radial artery.


Assuntos
Angina Pectoris/tratamento farmacológico , Células Endoteliais/efeitos dos fármacos , Nicorandil/uso terapêutico , Artéria Radial/efeitos dos fármacos , Idoso , Idoso de 80 Anos ou mais , Angiografia/métodos , Feminino , Coração/efeitos dos fármacos , Humanos , Masculino , Pessoa de Meia-Idade , Nitroglicerina/uso terapêutico , Intervenção Coronária Percutânea/métodos , Tempo
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