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The cross-slot geometry plays an important role in the study of nonlinear effects of viscoelastic fluids. The flow of viscoelastic fluid in a micro cross-slot with a high channel aspect ratio (AR, the ratio of channel depth to width) can be divided into three types, which are symmetric flow, steady-state asymmetric flow and time-dependent flow under the inlet condition with a constant velocity. However, the flow pattern of a viscoelastic fluid in the cross-slot when a stimulation is applied at inlets has been rarely reported. In this paper, the response of cross-slot flow under an external sinusoidal stimulation is studied by numerical simulations of a two-dimensional model representing the geometry with a maximum limit of AR. For the cases under constant inlet velocity conditions, three different flow patterns occur successively with the increase of Weissenberg number (Wi). For the cases under sinusoidal varying inlet velocity conditions, when the stimulation frequency is far away from the natural frequency of a viscoelastic fluid, the frequency spectrum of velocity fluctuation field shows the characteristics of a fundamental frequency and several harmonics. However, the harmonic frequency disappears when the stimulation frequency is close to the natural frequency of the viscoelastic fluid. Besides, the flow pattern shows spatial symmetry and changes with time. In conclusion, the external stimulation has an effect on the flow pattern of viscoelastic fluid in the 2D micro cross-slot channel, and a resonance occurs when the stimulation frequency is close to the natural frequency of the fluid.
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The outbreak of new viruses, such as serve acute respiratory syndrome coronavirus 2 (SARS-CoV-2), as well as the emerging of drug-resistance viruses highlight the urgent need for the development of broad-spectrum antiviral drugs. Herein, we report the discovery of a plant-derived small molecule, 6,8-dihydroxy-9-isobutyl-2,2,4,4-tetramethyl-7-(3-methylbutanoyl)-4,9-dihydro-1H-xanthene-1,3(2H)-dione (rhodomyrtone, RDT), which exhibited potent broad-spectrum antiviral activities against several RNA and DNA viruses, including SARS-CoV-2, respiratory syncytial virus (RSV), herpes simplex virus type 1 (HSV-1), herpes simplex virus type 2 (HSV-2), varicella-zoster virus (VZV), human cytomegalovirus (HCMV), and Kaposis sarcoma-associated herpesvirus (KSHV). RDT can significantly suppress viral gene expression and show the low possibility to elicit drug-resistant variants. Mechanistic study implied that RDT inhibited viral infection by disturbing the cellular factors that essential for viral gene expression. Our results suggested that RDT might be a promising lead compound for the development of broad-spectrum antiviral drugs.
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Approaches for energy harvesting from rotating vehicle tires have been investigated for years; however, where the harvestable energy is actually generated has not been discussed so far. For the first time, the potentially harvestable energy under vehicle wheels, as a real energy source, is discovered. Estimations show that the global potentially harvestable energy from the vehicle wheels could be 3.26 × 1011 kW, equivalent to 14 500 times the installed capacity of the worldwide largest hydraulic power plant, Three Gorges Dam of China; 36.7% saving of a vehicle's fuel consumption could be achieved if this potential energy could be totally harvested. State-of-the-art energy harvesting techniques can only extract a negligibly small amount of the energy under vehicle wheels, calling for revolutionary new energy harvesting techniques.
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Objective: To investigate the efficiency and safety of domestic tyrosine kinase inhibitor (TKI) dasatinib (Yinishu) as second-line treatment for patients with chronic myeloid leukemia in chronic phase (CML-CP). Methods: A retrospective analysis of clinical data of CML-CP patients who received domestic dasatinib as second-line treatment in the CML collaborative group hospitals of Hubei province from March 2016 to July 2018 was performed. The optimal response rate, the cumulative complete cytogenetic response (CCyR), the cumulative major molecular responses (MMR), progression free survival (PFS), event free survival (EFS) and adverse effects (AEs) of the patients were assessed at 3, 6 and 12 months of treatment. Results: A total of 83 CML-CP patients were enrolled in this study. The median follow-up time was 23 months. The optimal response rates at 3, 6 and 12 months in 83 CML-CP patients treated with dasatinib were 77.5% (54/71), 72.6% (61/75) and 60.7% (51/69), respectively. By the end of follow-up, the cumulative CCyR and MMR rates were 65.5% (55/80) and 57.1% (48/73), respectively. The median time to achieving CCyR and MMR was 3 months. During follow-up time, the PFS rate was 94.0% (79/83) and the EFS rate was 77.4% (65/83). The most common non-hematological AEs of dasatinib were edema (32.5%), rash itching (18.1%) and fatigue (13.3%). The common hematological AEs of dasatinib were thrombocytopenia (31.3%), leukopenia (19.3%) and anemia (6.0%). Conclusion: Domestic dasatinib was effective and safe as the second-line treatment of CML-CP patients and it can be used as an option for CML-CP patients.
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Humanos , Antineoplásicos , Dasatinibe/uso terapêutico , Mesilato de Imatinib , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Inibidores de Proteínas Quinases , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Objective:To investigate the electrophysiology effects and mechanism of iron overload on the slow response autorhythmic cells in the left ventricular outflow tract of guinea pigs.Methods:Standard microelectrode cell recording techniques were adopted to observe the electrophysiological effects of different concentrations of FeResults:FeConclusions:Fe
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Objective: To investigate the electrophysiology effects and mechanism of iron overload on the slow response autorhythmic cells in the left ventricular outflow tract of Guinea pigs. Methods: Standard microelectrode cell recording techniques were adopted to observe the electrophysiological effects of different concentrations of Fe
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Pharmacological data have suggested the involvement of mitogen-activated protein kinase (MPK) cascades in dark-induced stomatal closure, but which specific MPK cascade participates in the darkness guard cell signaling and its relationship with hydrogen peroxide (H2O2) and nitric oxide (NO) remain unclear. In this paper, we observed that darkness induced activation of MPK6 in leaves of wild-type Arabidopsis (Arabidopsis thaliana) and mutants for nitrate reductase 1 (NIA1), but this effect was inhibited in mutants for MPK Kinase 1 (MEK1) and ATRBOHD/F. Mutants for MEK1, MPK6 and NIA1 showed defect of dark-induced NO production in guard cells and stomatal closure, but were normal in the dark-induced H2O2 generation, while stomata of mutant AtrbohD/F showed defect of dark-induced H2O2 and NO production and subsequent closure. Moreover, exogenous NO rescued the defect of dark-induced stomatal closure in mutants of AtrbohD/F, mek1 and mpk6, while exogenous H2O2 could not rescue the defect of dark-induced stomatal closure in mutants of mek1, mpk6 and nia1. These genetic and biochemical evidences not only show that MEK1-MPK6 cascade, AtRBOHD/F-dependent H2O2 and NIA1-dependent NO are all involved in dark-induced stomatal closure in Arabidopsis, also indicate that MEK1-MPK6 cascade functions via working downstream of H2O2 and upstream of NO.
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Proteínas de Arabidopsis/metabolismo , Arabidopsis/metabolismo , Arabidopsis/fisiologia , Escuridão , Peróxido de Hidrogênio/metabolismo , MAP Quinase Quinase 1/metabolismo , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Óxido Nítrico/metabolismo , Estômatos de Plantas/metabolismo , Estômatos de Plantas/fisiologia , Proteínas de Arabidopsis/genética , MAP Quinase Quinase 1/genética , Proteínas Quinases Ativadas por Mitógeno/genética , Nitrato Redutase/genética , Nitrato Redutase/metabolismoRESUMO
Ultraviolet B (UV-B) radiation induces the activation of MITOGEN-ACTIVATED PROTEIN KINASE PHOSPHATASE1 (MKP1) and its targets MPK3 and MPK6, but whether they participate in UV-B guard cell signaling is not clear. Here, evidence shows that UV-B-induced stomatal closure in Arabidopsis (Arabidopsis thaliana) is antagonistically regulated by MKP1 and MPK6 via modulating hydrogen peroxide (H2O2)-induced nitric oxide (NO) production in guard cells. The mkp1 mutant was hypersensitive to UV-B-induced stomatal closure and NO production in guard cells but not to UV-B-induced H2O2 production, suggesting that MKP1 negatively regulates UV-B-induced stomatal closure via inhibiting NO generation in guard cells. Moreover, MPK3 and MPK6 were activated by UV-B in leaves of the wild type and hyperactivated in the mkp1 mutant, but the UV-B-induced activation of MPK3 and MPK6 was largely inhibited in mutants for ATRBOHD and ATRBOHF but not in mutants for NIA1 and NIA2 mpk6 mutants showed defects of UV-B-induced NO production and stomatal closure but were normal in UV-B-induced H2O2 production, while stomata of mpk3 mutants responded to UV-B just like those of the wild type. The defect of UV-B-induced stomatal closure in mpk6 mutants was rescued by exogenous NO but not by exogenous H2O2 Furthermore, double mutant mkp1/mpk6 and the single mutant mpk6 showed the same responses to UV-B in terms of either stomatal movement or H2O2 and NO production. These data indicate that MPK6, but not MPK3, positively regulates UV-B-induced stomatal closure via acting downstream of H2O2 and upstream of NO, while MKP1 functions negatively in UV-B guard cell signaling via down-regulation of MPK6.
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Proteínas de Arabidopsis/metabolismo , Óxido Nítrico/metabolismo , Estômatos de Plantas/fisiologia , Arabidopsis/citologia , Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Regulação da Expressão Gênica de Plantas , Peróxido de Hidrogênio/metabolismo , Quinases de Proteína Quinase Ativadas por Mitógeno/genética , Quinases de Proteína Quinase Ativadas por Mitógeno/metabolismo , Fosfatases da Proteína Quinase Ativada por Mitógeno/genética , Fosfatases da Proteína Quinase Ativada por Mitógeno/metabolismo , Proteínas Quinases Ativadas por Mitógeno/genética , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Mutação , NADPH Oxidases/genética , NADPH Oxidases/metabolismo , Células Vegetais/metabolismo , Células Vegetais/efeitos da radiação , Estômatos de Plantas/efeitos da radiação , Proteínas Tirosina Fosfatases/genética , Proteínas Tirosina Fosfatases/metabolismo , Transdução de Sinais , Raios UltravioletaRESUMO
The present paper presents direct numerical simulations of Rayleigh-Bénard convection (RBC) in an enclosed cell filled with the polymer solution in order to investigate the viscoelastic effect on the characteristics of heat transport and large-scale circulation (LSC) of RBC. To overcome the difficulties in numerically solving a high Weissenberg number (Wi) problem of viscoelastic fluid flow with strong elastic effect, the log-conformation reformulation method was implemented. Numerical results showed that the addition of polymers reduced the heat flux and the amount of heat transfer reduction (HTR) behaves nonmonotonically, which firstly increases but then decreases with Wi. The maximum HTR reaches around 8.7% at the critical Wi. The nonmonotonic behavior of HTR as a function of Wi was then corroborated with the modifications of the period of LSC and turbulent energy as well as viscous boundary layer thickness. Finally, a standard turbulent kinetic energy (TKE) budget analysis was done for the whole domain, the boundary layer region, and the bulk region. It showed that the role change of elastic stress contributions to TKE is mainly responsible for this nonmonotonic behavior of HTR.
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OBJECTIVE@#To investigate the electrophysiological changes of autonomic cells in left ventricular outflow tract in guinea pigs with iron deficiency anemia complicated with chronic heart failure.@*METHODS@#Guinea pigs model of iron deficiency anemia complicated with chronic heart failure in 10 guinea pigs of the experimental group was made by feeding a low iron diet, pure water and subcutaneous injection of isoproterenol. The control group consisting of 11 guinea pigs was given normal food, normal water and injected with normal saline. The left ventricular outflow tract model specimen was also prepared. The standard microelectrode technique was used to observe electrophysiological changes of autonomic cells in the outflow tract of left ventricular heart failure complicated with iron deficiency anemia in guinea pig model. The indicators of observation were maximal diastolic potential, action potential amplitude, 0 phase maximal depolarization velocity, 4 phase automatic depolarization velocity, repolarization 50% and 90%, and spontaneous discharge frequency.@*RESULTS@#Compared with the control group, 4 phase automatic depolarization velocity, spontaneous discharge frequency and 0 phase maximal depolarization velocity decreased significantly (P < 0.01) and action potential amplitude reduced (P < 0.01) in model group. Moreover, repolarization 50% and 90% increased (P < 0.01).@*CONCLUSIONS@#There are electrophysiological abnormalities of the left ventricular outflow tract in guinea pigs with iron deficiency anemia complicated with heart failure.
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Objective To investigate the electrophysiological changes of autonomic cells in left ventricular outflow tract in guinea pigs with iron deficiency anemia complicated with chronic heart failure. Methods Guinea pigs model of iron deficiency anemia complicated with chronic heart failure in 10 guinea pigs of the experimental group was made by feeding a low iron diet, pure water and subcutaneous injection of isoproterenol. The control group consisting of 11 guinea pigs was given normal food, normal water and injected with normal saline. The left ventricular outflow tract model specimen was also prepared. The standard microelectrode technique was used to observe electrophysiological changes of autonomic cells in the outflow tract of left ventricular heart failure complicated with iron deficiency anemia in guinea pig model. The indicators of observation were maximal diastolic potential, action potential amplitude, 0 phase maximal depolarization velocity, 4 phase automatic depolarization velocity, repolarization 50% and 90%, and spontaneous discharge frequency. Results Compared with the control group, 4 phase automatic depolarization velocity, spontaneous discharge frequency and 0 phase maximal depolarization velocity decreased significantly (P < 0.01) and action potential amplitude reduced (P < 0.01) in model group. Moreover, repolarization 50% and 90% increased (P < 0.01). Conclusions There are electrophysiological abnormalities of the left ventricular outflow tract in guinea pigs with iron deficiency anemia complicated with heart failure.
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Deformability is an effective property that can be used in the separation of colloidal particles and cells. In this study, a microfluidic device is proposed and tested numerically for the sorting of deformable particles of various degrees. The separation process is numerically investigated by a direct numerical simulation of the fluidâ»particleâ»electric field interactions with an arbitrary Lagrangianâ»Eulerian finite-element method. The separation performance is investigated with the shear modulus of particles, the strength of the applied electric field, and the design of the contracted microfluidic devices as the main parameters. The results show that the particles with different shear moduli take different shapes and trajectories when passing through a microchannel contraction, enabling the separation of particles based on their difference in deformability.
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Objective To learn the infection status and genotype of Hantavirus carried by rodents in Yuyao City.Methods From May,2014 to May,2015,a total of 248 rodents were captured from four kinds of characteristic topographies (plains, mountains,coastal and urban areas)with clip night method in Yuyao.The real time fluorescence quantitative PCR method was used to detect the Hantavirus from lung specimens of rodents.The RT-PCR method was used to sequence and analyze the M fragment gene.Results Hantavirus nucleic acid was detected positive in 12 samples from a total of 248 specimens, and the positive rate was 4.84%,and they were all detected in Rattus norvegicus and were all Seoul virus (SEOV).Eight samples were sequenced and analyzed,and phylogenetic tree was constructed.The result showed SEOV S3 subtype with high homology.Conclusion Hantavirus carried by rodents in Yuyao City is mainly SEOV S3 subtype,and the distribution of gene subtype is single.Rattus norvegicus is the main host of this virus.
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It has been well established that droplets could be produced by various microchannels in many research and application areas. In this paper, we experimentally study the formation of droplets by flow focusing of two immiscible liquids in cross-flow microchannels. The used microchannels are featured by width of 100 µm and depth of 60 µm, which are fabricated with poly-dimethylsiloxane. The process of droplet formation is described in detail by changing the parameters which control the droplet size and generation rate. Different characteristic regimes are achieved over a large range of flow rates. We also numerically simulate the behaviors of droplets in the tested microfluidic device. The variation tendency of droplet formation frequency with different flow rates and transport properties of the continuous and dispersed phases are illustrated. The important parameters resulted from different flow conditions and configurations at the junctions and flow focusing section are also presented.
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<p><b>BACKGROUND</b>There are no conclusive studies evaluating the interaction between icariin and exercise for treatment of osteoporosis; the efficacy and safety of this treatment combination remains to be evaluated. The purpose of this study was to investigate the effects of icariin treatment combined with exercise therapy on bone parameters and body weight of ovariectomized rats.</p><p><b>METHODS</b>Ovariectomized rats were used as a model of postmenopausal osteoporosis and were exposed to either icariin treatment, exercise, hormone replacement therapy, or a combination of the above. Untreated, ovariectomized rats and sham operated rats were used as controls. After 3 months of experimental interventions the effects of the treatments on the body and uterine weights, the physical and biomechanical properties of bones, and the expression of the osteoblast-specific gene Osterix (Osx), were assessed.</p><p><b>RESULTS</b>The weight gain of the ovariectomized rats was greater than that of the treated experimental groups. Uterine weight and serum estradiol levels were significantly greater in sham operated and estrogen-treated ovariectomized rats than in the other groups. Biomechanical parameters were improved significantly in ovariectomized rats treated with exercise alone or treated with exercise and icariin. Osx expression was increased in ovariectomized rats treated with exercise and icariin or treated with just icariin.</p><p><b>CONCLUSIONS</b>Exercise combined with icariin had a synergistic effect in the early prevention of osteoporosis in ovariectomized rats. The effects of icariin and exercise on osteoporosis are worth further exploration.</p>
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Animais , Feminino , Humanos , Ratos , Flavonoides , Usos Terapêuticos , Osteoporose Pós-Menopausa , Tratamento Farmacológico , Terapêutica , Ovariectomia , Condicionamento Físico Animal , Fisiologia , Ratos WistarRESUMO
<p><b>OBJECTIVE</b>To study the effects of dihydromyricetin (DMY) on tumor necrosis factor (TNF-alpha) and NF-kappaB p65 cells of the recurrent aphthous ulcer (RAU) rat.</p><p><b>METHOD</b>Sixty of Sprague Dawley (SD) rats are randomly divided into 6 groups. The rat RAU models was established by injection of immunogen composed of the homogenate supernate of homogeneous oral mucosa from SD rats and Freund's complete adjuvant (FCA) into rat backs subcutaneously once every two weeks for 5 times, and the only FCA injected as normal control. DMY(50,100, 200 mg x kg(-1)) and licorzine (67.5 mg x kg(-1)) were given intragastrically once daily for 7 days on the day of the last immunogen injection, respectively. Water was given instead of drugs in normal and model control groups. The blood was got from the fundus oculi vein of rats on the day after last administration, the serum was separated. Then the rats were put to death with the cervical dislocation and decollated on the ice stage. Two sides of rat buccal mucosal tissue were cut. One side of them was put into 4% neutral formalin and another was added into 10 times of phosphate buffer to homogenize it homogenate. The oral mucosa ulcer occurrence of rats was observed by the histopathology. The content of TNF-alpha in serum and oral mucosa was assayed with ELISA; the expression of NF-kappaB cells was determined by the immunohistochemisty and macrophagus was determined by azure-feosin-dyeing in oral mucosa tissue. The expression of TNF-alpha mRNA in serum and oral mucosa was detected by reverse transcription polymerase chain reaction.</p><p><b>RESULT</b>In RAU rats, oral mucosa ulcer occurred, the content of TNF-alpha raised and the expression of TNF-alpha mRNA increased in serum and oral mucosa, the expression of positive NF-kappaB p65 cells and the amount of macrophages went up in oral mucosa. DMY and licorzine significantly reduced occurrence of oral mucosa ulcer in RAU rats, lowered content of TNF-alpha and the expression of TNF-alpha mRNA in serum and oral mucosa, reduced expression of positive NF-kappaB p65 cells and the amount of macrophages.</p><p><b>CONCLUSION</b>It is considered that DMY could inhibited occurrence of oral mucosa ulcer in RAU rats. One principle of it's effects could be that DMY controlled NF-kappaB p65 regulation on transcription and release of TNF-alpha mRNA in macrophages in oral mucosa ulcer tissue and lead to fall of TNF-alpha content in oral mucosa tissue causing role of anti-oral mucosa ulcer.</p>
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Animais , Feminino , Humanos , Masculino , Ratos , Modelos Animais de Doenças , Flavonóis , Macrófagos , Alergia e Imunologia , Mucosa Bucal , Metabolismo , Ratos Sprague-Dawley , Estomatite Aftosa , Tratamento Farmacológico , Genética , Alergia e Imunologia , Fator de Transcrição RelA , Genética , Alergia e Imunologia , Fator de Necrose Tumoral alfa , Genética , Alergia e ImunologiaRESUMO
<p><b>OBJECTIVE</b>To evaluate the value of oblique-sagittal black-blood contrast-enhanced magnetic resonance imaging (OB-CEMRI) in atherosclerotic carotid artery (CA) assessment before carotid endarterectomy (CEA).</p><p><b>METHODS</b>Twenty-five patients with symptomatic atherosclerotic stenosis in the carotid artery (involving 26 arteries) were scheduled for CEA. OB-CEMRI and digital subtraction angiography (DSA) were conducted within 1 week prior to CEA, and two radiologists independently assessed the location of maximal lumen stenosis, plaque rupture, degree of maximal lumen stenosis and plaque involvement on DSA and OB-CEMRI images. The differences of DSA and the OB-CEMRI in analyzing the plaque conditions were assessed in comparison with matched histological sections of the excised specimens.</p><p><b>RESULTS</b>Compared with the corresponding histological specimens, both DSA (κ=0.807) and OB-CEMRI (κ=0.812) showed a good consistency in defining the location of the maximal lumen stenosis. OB-CEMRI showed a better performance in detecting plaque rupture with higher sensitivity (90.0%) and specificity (83.3%) than DSA (40.0% and 66.7%, respectively). No significant difference was found between DSA and the OB-CEMRI in evaluating the degree of maximal lumen stenosis [(77.33∓3.79)% vs (76.02∓3.95)%, P=0.648]. Compared with the histological examination, OB-CEMRI appeared to underestimate the stenosis. The plaque extent on OB-CEMRI was larger than that on DSA (18.96∓4.96 mm vs 14.80∓3.78 mm, P=0.004), and similar to that by histological examination (18.13∓4.57 mm, P=0.506).</p><p><b>CONCLUSIONS</b>OB-CEMRI allows noninvasive and objective detection of the location of the maximal lumen stenosis, plaque rupture, and plaque extent, though with a lower accuracy than DSA in the assessment of the maximal lumen stenosis. OB-CEMRI combined with DSA offers a more reliable means for preoperative evaluation of the carotid artery plaques for CEA.</p>
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Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Angiografia Digital , Doenças das Artérias Carótidas , Patologia , Estenose das Carótidas , Endarterectomia das Carótidas , Métodos , Angiografia por Ressonância Magnética , Imageamento por Ressonância Magnética , MétodosRESUMO
<p><b>OBJECTIVE</b>To explore the specialty of diagnosis and surgery of tight carotid stenosis.</p><p><b>METHOD</b>From January 2000 to December 2009, 53 patients with tight carotid stenosis (> 95%) were operated on. All 53 patients had tight carotid stenosis more than 95% on one side in whom 28 had contralateral carotid stenosis or occlusion. The clinical and imaging data as well as surgical outcomes of the patients were retrospectively analyzed.</p><p><b>RESULTS</b>Forty-five patients had postoperatively done well without any complications. There were 3 cases of hemodynamic instability and one case of cardiac ischemia which resolved in one to two days. One patient developed mild hoarseness. One complicated with bacteremia due to deep vein catheter insertion. Two patients experienced brain hemorrhage. None of this series occurred perioperative brain ischemia.</p><p><b>CONCLUSIONS</b>Tight carotid stenosis indicates a need for expeditious carotid endarterectomy with very low rates of brain ischemia. Intraoperative shunting is seldom necessary. Postoperative hyperperfusion syndrome and brain hemorrhage should be worried. Micro-endarterectomy can effectively prevent from restenosis.</p>
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Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estenose das Carótidas , Diagnóstico , Cirurgia Geral , Endarterectomia das Carótidas , Estudos Retrospectivos , StentsRESUMO
<p><b>OBJECTIVE</b>To explore the electrophysiological effects of antiarrhythmic drugs on pacemaker cells of left ventricular outflow tract.</p><p><b>METHODS</b>By using conventional intracellular microelectrode technique to record action potentials, series antiarrhythmic drugs were used to investigate the electrophysiological features and regularities of spontaneous activity of left ventricular outflow tract.</p><p><b>RESULTS</b>(1) Perfusion with 1 micromol/L quinidine resulted in a significant decrease in rate of pacemaker firing (RPF, P < 0.05), velocity of diastolic depolarization (VDD, P < 0.05), amplitude of action potential (APA, P < 0.05), and maximal rate of depolarization (V(max), P < 0.05), and a marked prolonging in 50% and 90% of duration of action potential (APD50 and APD90, P < 0.05). (2) 1 micromol/L lidocaine decreased RPF, VDD, MDP, APA and V(max) significantly (P < 0.05), shortened APD50 and APD90 notably (P < 0.05). (3) 1 micromol/L propafenone led to a significant decrease in RPF (P < 0.01), VDD (P < 0.05), APA (P < 0.05), V(max) (P < 0.01), and a marked prolonging in APD50 (P < 0.01) and APD90 (P < 0.05). (4) Application of 5 micromol/L propranolol resulted in a significant decrease in RPF and VDD (P < 0.01), MDP and APA (P < 0.01), V(max) (P < 0.05) and a notable prolonging in APD50 and APD90 (P < 0.05). (5) Perfusion with 1 micromol/L amiodarone resulted in a significant decrease in RPF and VDD (P < 0.01), APA (P < 0.01), V(max) (P < 0.05), a marked prolonging in APD50 (P < 0.01) and APD90 (P < 0.05). (6) 1 micromol/L verapamil significantly decreased RPF and VDD (P < 0.01), MDP and APA (P < 0.05), V(max) (P < 0.05), notably prolonged APD50 and APD90 (P < 0.01). (7) 50 micromol/L adenosine significantly decreased RPF and VDD (P < 0.05), APA (P < 0.05), V(max) (P < 0.01), markedly shortened APD50 and APD90 (P < 0.05).</p><p><b>CONCLUSION</b>All kinds of antiarrhythmic drugs can decrease the autorhythmicity of guinea pig left ventricular outflow tract. By altering APD50 and APD90, they can affect effective refractory period (ERP) and having a significant effect on autorhythmicity of left ventricular outflow tract.</p>
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Animais , Antiarrítmicos , Farmacologia , Eletrocardiografia , Cobaias , Ventrículos do CoraçãoRESUMO
<p><b>OBJECTIVE</b>To construct hypoxic induction factor-1alpha (HIF-1alpha) siRNA expression cassette containing U6 promoter, alpha HIF-1alpha sense or antisense target sequence, and to observe its influence on the expression of cardiomyocytic HIF-1alpha during hypoxic state.</p><p><b>METHODS</b>Neonatal murine cardiomyocytes cultured in the mixed gas were employed as the hypoxic model and were divided into normal control (cultured in normal oxygen), RNAi control (invalidated transfection interference sequence IV) and RNAi effective inhibition (effective transfection interference sequence, which was further divided into I, II and III groups according to the difference of downstream primer) groups. Three pairs (I, II and III) of PCR downstream primer containing HIF-1alpha encoded gene fragments (sense and antisense) and one pair of randomize sequence (IV) PCR downstream primer were designed and synthesized. U6 starter expression frame was constructed by PCR method. The cardiomyocytes were transfected simultaneously by sense and antisense sequence expression frame. Five plates of the cells were set at each time points in each group. The expression of HIF-1alpha mRNA was detected by RT-PCR at 6 hours of hypoxia. The change in the protein expression level at 1 hour of hypoxia was determined by Western blot, and the interference effects were monitored by immunohistochemistry.</p><p><b>RESULTS</b>The best inhibition fragment screened was group II sequence. After the transfection and hypoxic culture, it was found that the cardiomyocytic HIF1alpha mRNA and protein levels in RNAi effective inhibition group were evidently lower than those in normal control and RNAi control groups (P < 0.01). While the protein inhibition rate (60% - 80%) between the former group and normal and RNAi control groups was no difference (P > 0.05).</p><p><b>CONCLUSION</b>The expression of the HIF1alpha in hypoxic rat cardiomyocytes could be effectively inhibited by our constructed HIF1alpha siRNA expression cassette group II.</p>