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Epithelial ovarian cancer (EOC) is one of the most prevalent gynaecological cancers worldwide. The molecular mechanisms of serous ovarian cancer (SOC) remain unclear and not well understood. SOC cases are primarily diagnosed at the late stage, resulting in a poor prognosis. Advances in molecular biology techniques allow us to obtain a better understanding of precise molecular mechanisms and to identify the chromosome instability region and key driver genes in the carcinogenesis and progression of SOC. Whole-exome sequencing was performed on the normal ovarian cell line IOSE80 and the EOC cell lines SKOV3 and A2780. The single-nucleotide variation burden, distribution, frequency and signature followed the known ovarian mutation profiles, without chromosomal bias. Recurrently mutated ovarian cancer driver genes, including LRP1B, KMT2A, ARID1A, KMT2C and ATRX were also found in two cell lines. The genome distribution of copy number alterations was found by copy number variation (CNV) analysis, including amplification of 17q12 and 4p16.1 and deletion of 10q23.33. The CNVs of MED1, GRB7 and MIEN1 located at 17q12 were found to be correlated with the overall survival of SOC patients (MED1: p = 0.028, GRB7: p = 0.0048, MIEN1: p = 0.0051), and the expression of the three driver genes in the ovarian cell line IOSE80 and EOC cell lines SKOV3 and A2780 was confirmed by western blot and cell immunohistochemistry.
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Neoplasias Ovarianas , Humanos , Feminino , Carcinoma Epitelial do Ovário/genética , Neoplasias Ovarianas/genética , Linhagem Celular Tumoral , Variações do Número de Cópias de DNA/genética , Instabilidade Cromossômica/genética , Proteínas de Neoplasias/genética , Peptídeos e Proteínas de Sinalização Intracelular/genéticaRESUMO
BACKGROUND: Ovarian cancer is one of the most lethal cancers in women because it is often diagnosed at an advanced stage. The molecular markers investigated thus far have been unsatisfactory. METHODS: We performed whole-exome sequencing on the human ovarian cancer cell lines 3AO and ES2 and the normal ovarian epithelial cell line IOSE-80. Molecular markers of ovarian cancer were screened from shared mutation genes and copy number variation genes in the 6q21-qter region. RESULTS: We found that missense mutations were the most common mutations in the gene (93%). The MUC12, FLG and MUC16 genes were highly mutated in 3AO and ES2 cells. Copy number amplification occurred mainly in 4p16.1 and 11q14.3, and copy number deletions occurred in 4q34.3 and 18p11.21. A total of 23 hub genes were screened, of which 16 were closely related to the survival of ovarian cancer patients. The three genes CCDC170, THBS2 and COL14A1 are most significantly correlated with the survival and prognosis of ovarian cancer. In particular, the overall survival of ovarian cancer patients with high CCDC170 gene expression was significantly prolonged (P < 0.001). The expression of CCDC170 in normal tissues was significantly higher than that in ovarian cancer tissues (P < 0.05), and its expression was significantly decreased in advanced ovarian cancer. Western blotting and immunofluorescence assays also showed that the expression of CCDC170 in ovarian cancer cells was significantly lower than that in normal cells (P < 0.001, P < 0.01). CONCLUSIONS: CCDC170 is expected to become a new diagnostic molecular target and prognostic indicator for ovarian cancer patients, which can provide new ideas for the design of antitumor drugs.
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Neoplasias Ovarianas , Feminino , Humanos , Neoplasias Ovarianas/patologia , Exoma/genética , Variações do Número de Cópias de DNA , Mutação , Linhagem Celular Tumoral , BiomarcadoresRESUMO
BACKGROUND: Acute myocardial infarction (AMI) complicated by cardiogenic shock (AMI-CS) or heart failure is associated with an unacceptably high in-hospital mortality of 33%-55% and a lost chance to accept PCI (Percutaneous Coronary Intervention). AIM: The aim of the study was to find out whether percutaneous hemodynamic support device Impella 2.5 improves prognosis of high-risk PCI patients or not. METHODS: This study was a case series involving six patients who underwent a Left Ventricular Assist Device (LVAD, Impella 2.5, Abiomed, Danvers, MA) implantation after suffering from AMI with a very low ejection fraction and acute heart failure. The clinical experience and outcomes of the patients are hereby discussed. RESULTS: All PCI procedures were safely completed under LVAD support. The hemodynamic parameters of all patients improved clinically over the next 30 days and following 12 months after Impella insertion except in two patients, of which one patient (Case number 6) died 4 days post-Impella protected PCI procedure due to acute left ventricle heart failure with cardiogenic shock and pulmonary oedema; and another one died at 12 months after Impella protected PCI procedure (Case number 4) due to decompensated heart failure and infected pneumonia. CONCLUSION: Percutaneous hemodynamic support is favorable and feasible during high risk Percutaneous Coronary Intervention (PCI). A bigger study is needed to substantiate the claims of the current study.
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Insuficiência Cardíaca , Coração Auxiliar , Infarto do Miocárdio , Intervenção Coronária Percutânea , Humanos , Choque Cardiogênico/cirurgia , Choque Cardiogênico/complicações , Intervenção Coronária Percutânea/efeitos adversos , Infarto do Miocárdio/etiologia , Coração Auxiliar/efeitos adversos , Insuficiência Cardíaca/complicações , Insuficiência Cardíaca/cirurgia , Resultado do Tratamento , Estudos RetrospectivosRESUMO
Stem cell therapy has shown therapeutic benefit in dilated cardiomyopathy (DCM), but doubt remains about the most appropriate stem cell subpopulation. The current study compared the efficacy of intracoronary administration of bone marrow mononuclear cells (BMMC) or mesenchymal stem cells (BMSC) in patients with DCM.Fifty-three patients with DCM and reduced (< 40%) left ventricular ejection fraction (LVEF), were randomized to intracoronary infusion of BMMC (BMMC group, n = 16) or BMSC (BMSC group, n = 17) or equal volume normal saline (CTRL group, n = 20). LVEF, New York Heart Association (NYHA) class, left ventricular end-diastolic diameter (LVEDd), and myocardial perfusion were assessed at baseline and at 3-month and 12-month follow-ups. Major adverse cardiovascular events (MACE) were also recorded.At the 3-month follow-up, LVEF, NYHA class, and myocardial perfusion had improved significantly in the BMSC group (P = 0.004, 0.020 and 0.019, respectively) along with significant changes in LVEF and NYHA class in the BMMC group compared with CTRL (P = 0.042 and 0.047, respectively), however, LVEDd remained unchanged. In comparison with CTRL, LVEF, NYHA class, and myocardial perfusion improved significantly in the BMSC group at the 12-month follow-up (P = 0.005, 0.050 and 0.038 respectively), but not in the BMMC group (P > 0.05). There were no significant differences between the transplantation groups during follow-up (P > 0.05). There were no differences in MACE among the 3 groups (P = 0.817).Intracoronary bone marrow stem cell transplantation in DCM is safe and effective, while BMSC and BMMC infusion possess comparable effectiveness.
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Transplante de Medula Óssea , Cardiomiopatia Dilatada/terapia , Transplante de Células-Tronco Mesenquimais , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Volume Sistólico , Transplante Autólogo , Resultado do TratamentoRESUMO
BACKGROUND: The inhibition of the proliferation and migration of vascular smooth muscle cells (VSMC) is one cholesterol-independent effect of statins that could lower the rate of in-stent restenosis (ISR), even if the exact mechanism remains unclear. The aim of this study was to explore the exact inhibitory mechanisms of simvastatin on ISR in vivo. METHODS: Forty-five rabbits were randomized into 3 feeding groups of equal size (n=15): normal rabbit chow (normal group), a high-cholesterol diet (control group), and a simvastatin-enriched high-cholesterol diet (simvastatin group). Balloon de-endothelialization was first performed in the control and simvastatin groups after 3 days, followed by stent deployment at week 14. All rabbits were killed at week 18, and the histological changes of the ISR segments were observed. The expressions of cyclin-dependent kinase inhibitor p27 (p27kip1), proliferating cell nuclear antigen (PCNA), and α-smooth muscle (α-SM) actin were measured. RESULTS: In the simvastatin group compared to the control group, the neointimal thickness, neointimal area, and degree of stenosis decreased, while the residual lumen area increased significantly (P<0.05). Moreover, the expression of α-SM actin in the control group decreased by 55.4% compared to the normal group, while it increased by 29.7% with respect to the simvastatin group (P<0.05). Finally, the expression of p27kip1 increased, while that of PCNA decreased significantly in the simvastatin group compared to the control group (P<0.05). CONCLUSIONS: Simvastatin may inhibit VSMC phenotype modulation and proliferation by downregulating the expression of PCNA and upregulating that of p27kip1.
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Reestenose Coronária/prevenção & controle , Inibidor de Quinase Dependente de Ciclina p27/metabolismo , Imunossupressores/farmacologia , Antígeno Nuclear de Célula em Proliferação/metabolismo , Sinvastatina/farmacologia , Stents/efeitos adversos , Animais , Western Blotting , Ciclo Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Doença da Artéria Coronariana/metabolismo , Reestenose Coronária/etiologia , Reestenose Coronária/metabolismo , Modelos Animais de Doenças , Regulação para Baixo/efeitos dos fármacos , Imuno-Histoquímica , Masculino , Músculo Liso Vascular/citologia , Coelhos , Distribuição Aleatória , Regulação para Cima/efeitos dos fármacosRESUMO
Post-fermented tea (PFT) is one of the most commonly consumed beverages worldwide. Rapid microbial growth and significant changes in the microbial composition of PFT during processing and storage pose a potential risk of contamination with mycotoxins such as zearalenone (ZEN). Screening for ZEN contamination in a simple, rapid, and inexpensive manner is required to ensure that PFT is safe for consumption. To monitor ZEN in PFT, ZEN was conjugated with bovine serum albumin to prepare egg yolk immunoglobulins (IgY). A specific indirect competitive enzyme-linked immunosorbent assay (ic-ELISA) based on IgY was developed and validated. ZEN was extracted with acetonitrile and water (50:50, v/v) containing 5% acetic acid and purified using a mixture of primary and secondary amines and graphitized carbon black to remove matrix interference from the PFT samples. Under optimal conditions, the linear range of this assay was 13.8-508.9 ng mL-1, the limit of detection was 9.3 ng mL-1, and the half-maximal inhibitory concentration was 83.8 ng mL-1. Cross-reactivity was negligible, and the assay was specific for ZEN-related molecules. The recovery rate of ZEN in the control blanks of PFT samples spiked with a defined concentration of ZEN of 89.5% to 98.0%. The recovery and accuracy of the method were qualified for PFT matrices. No significant differences were evident between the results of the actual PFT samples analyzed by high-performance liquid chromatography and ic-ELISA. The collective data indicate that the developed ic-ELISA can be used for the rapid and simple detection of ZEN in PFT products.
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OBJECTIVE: The prognostic value of corrected QT interval (QTc), corrected Tp-e interval (Tp-ec) and Tp-e/QT ratio on occurrence of malignant arrhythmia events (MAE) in acute ST-segment elevation myocardial infarction (STEMI) patients underwent successful thrombolysis was explored and the potential association of these indices with MAE was analyzed. METHODS: Fifty-seven STEMI patients underwent successful thrombolytic therapy within 6 hours after admission and conservative medical treatment were included. QTc, Tp-ec, Tp-e/QT ratio were obtained and calculated in infarct-related electrocardiograph leads and non-infarct-related leads before thrombolysis, (7±1) days and (30±3) days after thrombolysis respectively, and incidence of MAE up to 30 days after thrombolysis was analyzed. Sixty age and gender matched normal subjects served as control group. RESULTS: (1) QTc, Tp-ec, Tp-e/QT in infarct-related and non-infarct-related leads in STEMI group before thrombolysis were significantly higher than those in control group (all P<0.05), and values from the infarct-related leads were significantly higher than those from non-infarct-related leads in STEMI group (all P<0.05). QTc, Tp-ec and Tp-e/QT all significantly and continuously reduced from 7 days and at 30 days post thrombolysis compared the before thrombolysis (P<0.05 vs. before thrombolysis). (2) Tp-ec≥100 ms and Tp-e/QT ratio≥0.25 before thrombolysis in infarct-related leads were linked with higher incidence of MAE within 30 days post thrombolysis in this patient cohort [28.1% (9/32) vs. 40% (1/25), 27.8% (10/36) vs.0, respectively, all P<0.05]. CONCLUSION: QTc, Tp-ec and Tp-e/QT values decreased post successful thrombolysis in STEMI patients and higher Tp-ec and Tp-e/QT values before thrombolysis in STEMI patients were related with higher MAE incidence up to 30 days post successful thrombolysis in this patient cohort.
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Eletrocardiografia/métodos , Infarto do Miocárdio/tratamento farmacológico , Infarto do Miocárdio/fisiopatologia , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Terapia Trombolítica , Resultado do TratamentoRESUMO
OBJECTIVE: To compare the effects of intracoronary infusion of mononuclear stem cells (MNCs) or mesenchymal stem cells (MSCs) in patients with dilated cardiomyopathy (DCM). METHODS: DCM patients with left ventricular ejection fraction(LVEF) < 40% were randomized to intracoronary infusion of MNCs [(5.1 ± 2.0) × 10(8), n = 16] or MSCs [(4.9 ± 1.7) × 10(8), n = 17] or equal volume normal saline (n = 20) through the guiding catheter. Changes of left ventricular end-diastolic diameter (LVEDd), LVEF and myocardium perfusion defects were assessed before and at (30 ± 3) days and (90 ± 7) days after the procedure. Malignant cardiovascular events were also recorded. RESULTS: (1) One month after the procedure, LVEF in transplantation groups significantly increased compared to before procedure (all P < 0.05), and significant increase of LVEF was observed only in MSCs transplantation group compared to control group (P < 0.05). However, absolute changes of LVEDd and perfusion defects of myocardium were similar among and within groups (P > 0.05). (2) Comparing with before procedure and control group, LVEF in transplantation groups increased significantly in three months after the procedure (P < 0.05), but there were no significant differences between transplantation groups (P > 0.05). LVEDd and myocardium perfusion defects in transplantation groups improved significantly compared with that of before procedure (P < 0.05), while significant decrease of myocardium perfusion defects was only observed in patients treated with MSCs compared with control group at three months after procedure (P < 0.05). (3) There were no significant differences in major cardiovascular events between transplantation group and control during follow-up (P > 0.05). CONCLUSIONS: Intracoronary bone marrow stem cells transplantation is safe and effective for DCM patients while the efficacy of MSCs and MNCs transplantation is comparable.
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Transplante de Medula Óssea , Cardiomiopatia Dilatada/cirurgia , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do TratamentoRESUMO
Leg stiffness is considered a prevalent parameter used in data analysis of leg locomotion during different gaits, such as walking, running, and hopping. Quantification of the change in support leg stiffness during stair ascent and descent will enhance our understanding of complex stair climbing gait dynamics. The purpose of this study is to investigate a methodology to estimate leg stiffness during stair climbing and subdivide the stair climbing gait cycle. Leg stiffness was determined as the ratio of changes in ground reaction force in the direction of the support leg Fl (leg force) to the respective changes in length Ll during the entire stance phase. Eight subjects ascended and descended an instrumented staircase at different cadences. In this study, the changes of leg force and length (force-length curve) are described as the leg stiffness curve, the slope of which represents the normalized stiffness during stair climbing. The stair ascent and descent gait cycles were subdivided based on the negative and positive work fluctuations of the center-of-mass (CoM) work rate curve and the characteristics of leg stiffness. We found that the leg stiffness curve consists of several segments in which the force-length relationship was similarly linear and the stiffness value was relatively constant; the phase divided by the leg stiffness curve corresponds to the phase divided by the CoM work rate curve. The results of this study may guide biomimetic control strategies for a wearable lower-extremity robot for the entire stance phase during stair climbing.
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Subida de Escada , Fenômenos Biomecânicos , Marcha , Humanos , Perna (Membro) , Locomoção , CaminhadaRESUMO
MicroRNAs (miRNAs) emerge as important regulators for myocardial infarction (MI). However, the function of miR-708-3p during MI is unclear. H9c2 cells were cultured in a hypoxic environment and Sprague-Dawley rats experienced surgical ligation of the left anterior descending coronary artery to establish MI models. qPCR was used to measure the expression level of miR-708-3p and ADAM17 mRNA. ELISA was used to detect inflammatory cytokines TNF-α, IL-6, and IL-1ß, and myocardial injury markers LDH, CK-MB, and cTnI. Cell apoptosis and viability were monitored by flow cytometry analysis and MTT assay. ADAM17 expression was detected by Western blot. Dual-luciferase reporter gene experiments were carried out to identify binding sites between miR-708-3p and ADAM17 3'UTR. In vivo, left ventricle functions and myocardial remodeling of the rats were measured by echocardiography. MiR-708-3p was found to be significantly decreased in H9c2 cells after hypoxia induction and in heart tissues of rats with MI or serum samples of patients with MI, while ADAM17 was upregulated. Overexpression of miR-708-3p inhibited inflammation and injury of H9c2 cells cultured in hypoxia and the heart of the rats with MI. ADAM17 was verified as a direct target of miR-708-3p and restoration of ADAM17 reversed the effects of miR-708-3p. MiR-708-3p alleviated the inflammation and injury of cardiomyocytes via targeting ADAM17.
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Proteína ADAM17/metabolismo , Citocinas/metabolismo , Mediadores da Inflamação/metabolismo , MicroRNAs/metabolismo , Infarto do Miocárdio/metabolismo , Miócitos Cardíacos/metabolismo , Proteína ADAM17/genética , Idoso , Animais , Apoptose , Estudos de Casos e Controles , Hipóxia Celular , Linhagem Celular , Modelos Animais de Doenças , Regulação para Baixo , Feminino , Humanos , Masculino , MicroRNAs/genética , Pessoa de Meia-Idade , Infarto do Miocárdio/genética , Infarto do Miocárdio/patologia , Miócitos Cardíacos/patologia , Ratos Sprague-Dawley , Transdução de SinaisRESUMO
Steel designs with superior mechanical properties have been urgently needed in automotive industries to achieve energy conservation, increase safety, and decrease weight. In this study, the aging process is employed to enhance the yield strength (YS) by tailoring the distribution of V-rich precipitates and to improve ductility by producing high volume fractions of recrystallized ferrite in cold-rolled medium-Mn steel. A reliable method to acquire ultra-high strength (1.0-1.5 GPa), together with ductility (>40%), is proposed via utilizing non-recrystallized austenite and recrystallized ferrite. Similarly to conventional medium-Mn steels, the TRIP effect, along with the mild TWIP effect, is responsible for the main deformation mechanisms during tensile testing. However, the coupled influence of precipitation strengthening, grain refinement strengthening, and dislocation strengthening contributes to an increase in YS. The studied steel, aged at 650 °C for 5 h, demonstrates a YS of 1078 MPa, ultimate tensile strength (UTS) of 1438 MPa, and tensile elongation (TE) of 30%. The studied steel aged at 650 °C for 10 h shows a UTS of 1306 MPa and TE of 42%, resulting in the best product in terms of of UTS and TE, at 55 GPa·%. Such a value surpasses that of the previously reported medium-Mn steels containing equal mass fractions of various microalloying elements.
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AIMS: Myocardial infarction is the leading cause of death worldwide. The aim of this study was to investigate the function and mechanism of lncRNA RMST in myocardial infarction. MATERIALS AND METHODS: H/R and H2O2 models were established to assess the function of lncRNA RMST in vitro. Mouse myocardial infarction was used to analyze the function of lncRNA RMST in vivo. Bioinformatics analysis was performed to predict the potential binding target of lncRNA RMST. Rescue experiments were performed to verify the relationship between RMST and its target. RESULTS: The expression of lncRNA RMST was significantly increased with H/R or H2O2 treatment. Knockdown of lncRNA RMST improved cell death and protected mitochondria from H/R injury in vitro. In vivo, cardiac function was significantly attenuated by knockdown of lncRNA RMST. We also provided evidence that miR-5692 was a direct target of lncRNA RMST. Rescue experiments showed that knockdown of miR-5692 could restore the function of RMST. CONCLUSION: Our study is the first to prove the function and mechanism of lncRNA RMST in myocardial infarction. Thus, a deeper understanding of the role of lncRNA RMST in myocardial infarction may provide new insights for the clinical intervention of MI.
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Visual information is indispensable to human locomotion in complex environments. Although amputees can perceive the environmental information by eyes, they cannot transmit the neural signals to prostheses directly. To augment human-prosthesis interaction, this article introduces a subvision system that can perceive environments actively, assist to control the powered prosthesis predictively, and accordingly reconstruct a complete vision-locomotion loop for transfemoral amputees. By using deep learning, the subvision system can classify common static terrains (e.g., level ground, stairs, and ramps) and estimate corresponding motion intents of amputees with high accuracy (98%). After applying the subvision system to the locomotion control system, the powered prosthesis can help amputees to achieve nonrhythmic locomotion naturally, including switching between different locomotion modes and crossing the obstacle. The subvision system can also recognize dynamic objects, such as an unexpected obstacle approaching the amputee, and assist in generating an agile obstacle-avoidance reflex movement. The experimental results demonstrate that the subvision system can cooperate with the powered prosthesis to reconstruct a complete vision-locomotion loop, which enhances the environmental adaptability of the amputees.
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Membros Artificiais , Aprendizado Profundo , Processamento de Imagem Assistida por Computador/métodos , Robótica/instrumentação , Adulto , Técnicas de Apoio para a Decisão , Meio Ambiente , Feminino , Humanos , Masculino , Processamento de Sinais Assistido por Computador , Caminhada/fisiologiaRESUMO
The demand for aromatics, especially benzene, toluene, and xylene, has been increased in recent years as the crucial feedstocks of coatings and pharmaceutical industry. In this work, a modified Fischer-Tropsch synthesis (FTS) catalyst FeNaMg was fabricated via a sol-precipitation method and integrated with an HZSM-5 aromatization catalyst for the aromatics synthesis from syngas by a one-step process. Syngas was first converted to lower olefins as intermediates on the active component of the FeNaMg catalyst followed by aromatization on zeolite. Different characterization approaches, such as BET, XRD, XPS, hydrogen temperature-programmed reduction, temperature-programmed desorption of CO, TG, and SEM, revealed that Mg efficiently optimized physicochemical properties of the Fe-based catalyst by generating a MgFe2O4 spinel structure. Further investigation demonstrated that the MgFe2O4 spinel structure could increase the syngas adsorption area, facilitating the reduction and carburization of the Fe phase, while Mg decreased CO2 selectivity (31.26 to21%) by restraining the water-gas shift reaction and improved the utilization efficiency of carbon. At the same time, alkali metal Na changed the surface electronic environment of the FTS catalyst to enhance CO adsorption as an electronic promoter, which suppressed methane formation by restraining over hydrogenation. Therefore, the synergism that existed between Mg and Na during the reaction escalated the CO conversion and aromatics selectivity to 96.19 and 51.38%, respectively.
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Powered prostheses are effective for helping amputees walk in a single environment, but these devices are inconvenient to use in complex environments. In order to help amputees walk in complex environments, prostheses need to understand the motion intent of amputees. Recently, researchers have found that vision sensors can be utilized to classify environments and predict the motion intent of amputees. Although previous studies have been able to classify environments accurately in offline analysis, the corresponding time delay has not been considered. To increase the accuracy and decrease the time delay of environmental classification, the present paper proposes a new decision fusion method. In this method, the sequential decisions of environmental classification are fused by constructing a hidden Markov model and designing a transition probability matrix. The developed method is evaluated by inviting five able-bodied subjects and three amputees to perform indoor and outdoor walking experiments. The results indicate that the proposed method can classify environments with accuracy improvements of 1.01% (indoor) and 2.48% (outdoor) over the previous voting method when a delay of only one frame is incorporated. The present method also achieves higher classification accuracy than with the methods of recurrent neural network (RNN), long-short term memory (LSTM), and gated recurrent unit (GRU). When achieving the same classification accuracy, the method of the present paper can decrease the time delay by 67 ms (indoor) and 733 ms (outdoor) in comparison to the previous voting method. Besides classifying environments, the proposed decision fusion method may be able to optimize the sequential predictions of the human motion intent.
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Desenho de Prótese , Tecnologia Assistiva , Caminhada , Adulto , Algoritmos , Amputados , Eletromiografia , Meio Ambiente , Feminino , Voluntários Saudáveis , Humanos , Masculino , Cadeias de Markov , Modelos Teóricos , Redes Neurais de Computação , Reprodutibilidade dos Testes , Adulto JovemRESUMO
Studies have shown that matrine showed cardiovascular protective effects; however, its role and mechanism in myocardial ischemia/reperfusion (I/R) injury remain unknown. The Janus kinase 2/signal transducer and activator of transcription 3â(JAK2/STAT3) pathway activation and elevated heat shock protein (HSP) 70 are closely related to the prevention of myocardial I/R injury. The cardioprotective effects of matrine were determined in hypoxia/reoxygenation (H/R)-treated primary rat cardiomyocytes and left anterior descending coronary artery ligation and reperfusion animal models. The molecular mechanisms of matrine in myocardial I/R injury were focused on JAK2/STAT3 pathway activation and HSP70 expression. We found that matrine significantly increased H/R-induced the suppression of cell viability, decreased lactate dehydrogenase release, creatine kinase activity, and cardiomyocytes apoptosis in vitro. Moreover, matrine notably reduced the serum levels of creatine kinase-myocardial band (CK-MB) and cardiac troponin I, lessened the infarcted area of the heart, and decreased the apoptotic index of cardiomyocytes induced by I/R in vivo. Matrine activated the JAK2/STAT3 signaling, upregulated HSP70 expression both in vitro and in vivo. The cardioprotective effects of matrine were abrogated by AG490, a JAK2 inhibitor, and HSP70 siRNA. In addition, AG490 reduced HSP70 expression increased by matrine. In conclusion, matrine attenuates myocardial I/R injury by upregulating HSP70 expression via the activation of the JAK2/STAT3 pathway.
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Alcaloides/uso terapêutico , Proteínas de Choque Térmico HSP70/metabolismo , Janus Quinase 2/metabolismo , Traumatismo por Reperfusão Miocárdica/tratamento farmacológico , Traumatismo por Reperfusão Miocárdica/metabolismo , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , Quinolizinas/uso terapêutico , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismo por Reperfusão/metabolismo , Fator de Transcrição STAT3/metabolismo , Animais , Masculino , Miocárdio/metabolismo , Ratos , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos , MatrinasRESUMO
OBJECTIVE: Diabetes substantially increases the risk of cardiovascular disease (CAD) and is associated with an increased risk of CAD mortality. The purpose of this study was to investigate the differences in coronary artery plaque, coronary artery calcification (CAC) measured in outpatients with and without type 2 diabetes, and the occurrence rate of a major adverse cardiac event (MACE) throughout follow-up with the same patients. METHODS: Five hundred eighty-eight outpatients with suspected CAD comprising 208 diabetic and 380 non-diabetic patients were enrolled in this study. Coronary artery plaque and CAC scores were detected and measured by dual-source computed tomography. The major MACE during the follow-up period (4.0-20 months) was recorded and its relationship to type 2 diabetes and CAC was investigated. RESULTS: The diabetes group had higher CAC scores in the left anterior descending, left circumflex, and right coronary arteries and total CAC burden than the group without diabetes. The diabetes group had more diseased coronary segments and more obstructed vessels than the non-diabetes group. Logistic regression analysis demonstrated that diabetes is positively associated with mixed coronary plaque and non-calcified plaque. All patients in the diabetes group and all patients with higher CACs in both groups had a higher incidence rate of MACEs. CONCLUSION: Patients with type 2 diabetes have a higher prevalence of obstructive CAD, higher CAC scores, and a higher incidence rate of MACEs than those without diabetes. Diabetes and higher CAC scores were the important predictors of the occurrence of MACEs throughout follow-up with patients.