Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 105
Filtrar
1.
Opt Express ; 31(20): 33253-33263, 2023 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-37859109

RESUMO

A mode multiplexer/demultiplexer (MUX/DeMUX) is a crucial component for constructing mode-division multiplexing (MDM) systems. In this paper, we propose and experimentally demonstrate a wide-bandwidth and highly-integrated mode MUX/DeMUX based on an inverse-designed counter-tapered coupler. By introducing a functional region composed of subunits, efficient mode conversion and evolution can be achieved, greatly improving the mode conversion efficiency. The optimized mode MUX/DeMUX has a size of only 4 µm × 2.2 µm. An MDM-link consisting of a mode MUX and a mode DeMUX was fabricated on the silicon-on-insulator (SOI) platform. The experimental results show that the 3-dB bandwidth of the TE fundamental mode and first-order mode can reach 116 nm and 138 nm, respectively. The proposed mode MUX/DeMUX is scalable and could provide a feasible solution for constructing high-performance MDM systems.

2.
Opt Express ; 31(20): 33343-33354, 2023 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-37859117

RESUMO

A compact 5-mode (de)multiplexer [(De)MUX] is proposed and experimentally demonstrated based on the principle of multi-phase matching. The proposed device comprises a cascaded asymmetric directional coupler (ADC) based on 3-mode phase-matching, a polarization beam combiner, and a taper waveguide connecting them. The multiple modes in the access waveguides are matched to different modes in the same bus waveguide, which eliminates the need for additional taper structures and results in a total coupling length of only 18.9 µm. Experimental results exhibit that the insertion losses of the five modes are below 3.4 dB, and the mode crosstalks are below -15 dB at the central wavelength. The 3-dB bandwidths of TM0, TM1, TE0, TE1, and TE2 modes are greater than 100 nm, 46 nm, 100 nm, 28 nm, and 37 nm, respectively. The proposed device can serve as a key functional component in highly integrated on-chip mode-division multiplexing systems.

3.
Europace ; 25(3): 783-792, 2023 03 30.
Artigo em Inglês | MEDLINE | ID: mdl-36734272

RESUMO

Treatment of atrial fibrillation (AF) remains challenging despite significant progress in understanding its underlying mechanisms. The first detailed, quantitative theory of functional re-entry, the 'leading circle' model, was developed more than 40 years ago. Subsequently, in decades of study, an alternative paradigm based on spiral waves has long been postulated to drive AF. The rotor as a 'spiral wave generator' is a curved 'vortex' formed by spin motion in the two-dimensional plane, identified using advanced mapping methods in experimental and clinical AF. However, it is challenging to achieve complementary results between experimental results and clinical studies due to the limitation in research methods and the complexity of the rotor mechanism. Here, we review knowledge garnered over decades on generation, electrophysiological properties, and three-dimensional (3D) structure diversity of the rotor mechanism and make a comparison among recent clinical approaches to identify rotors. Although initial studies of rotor ablation at many independent centres have achieved promising results, some inconclusive outcomes exist in others. We propose that the clinical rotor identification might be substantially influenced by (i) non-identical surface activation patterns, which resulted from a diverse 3D form of scroll wave, and (ii) inadequate resolution of mapping techniques. With rapidly advancing theoretical and technological developments, future work is required to resolve clinically relevant limitations in current basic and clinical research methodology, translate from one to the other, and resolve available mapping techniques.


Assuntos
Fibrilação Atrial , Ablação por Cateter , Humanos , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/cirurgia , Sistema de Condução Cardíaco , Resultado do Tratamento , Ablação por Cateter/métodos , Eletrofisiologia Cardíaca
4.
Europace ; 25(5)2023 05 19.
Artigo em Inglês | MEDLINE | ID: mdl-37050858

RESUMO

AIMS: The optimal strategy for persistent atrial fibrillation (PerAF) is poorly defined. We conducted a multicentre, randomized, prospective trial to compare the outcomes of different ablation strategies for PerAF. METHODS AND RESULTS: We enrolled 450 patients and randomly assigned them in a 1:1:1 ratio to undergo pulmonary vein isolation and subsequently undergo the following three different ablation strategies: anatomical guided ablation (ANAT group, n = 150), electrogram guided ablation (EGM group, n = 150), and extensive electro-anatomical guided ablation (EXT group, n = 150). The primary endpoint was freedom from atrial fibrillation (AF) lasting longer than 30 s at 12 months after a single ablation procedure. After 12 months of follow-up, 72% (108) of patients in the EXT group were free from AF recurrence, as compared with the 64% (96) in the EGM group (P = 0.116), and 54% (81) in the ANAT group (P = 0.002). The EXT group showed less AF/atrial tachycardia recurrence than the EGM group (60% vs. 50%, P = 0.064) and the ANAT group (60% vs. 37.3%, P < 0.001). The EXT group showed the highest rate of AF termination (66.7%), followed by 56.7% in the EGM group, and 20.7% in the ANAT group. The AF termination signified less AF recurrence at 12 months compared to patients without AF termination (30.1% vs. 42.7%, P = 0.008). Safety endpoints did not differ significantly between the three groups (P = 0.924). CONCLUSIONS: Electro-anatomical guided ablation achieved the most favourable outcomes among the three ablation strategies. The AF termination is a reliable ablation endpoint.


Assuntos
Fibrilação Atrial , Ablação por Cateter , Veias Pulmonares , Humanos , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/cirurgia , Estudos Prospectivos , Resultado do Tratamento , Ablação por Cateter/efeitos adversos , Ablação por Cateter/métodos , Técnicas Eletrofisiológicas Cardíacas/métodos , Veias Pulmonares/cirurgia , Recidiva
5.
Chemistry ; 27(41): 10693-10699, 2021 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-33886157

RESUMO

Regulating the structure of metal-organic frameworks (MOFs) by adjusting the ligands reasonably is expected to enhance the interaction of MOFs on special molecules/ions, which has significant application value for the selective adsorption of guest molecules. Herein, two tricarboxylic ligands H3 L-Cl and H3 L-NH2 were designed and synthesized based on the ligand H3 TTCA by replacing part of the benzene rings with C=C bonds and modifying the chlorine and amino groups on the 4-position of the benzene ring. Two 3D Fe-MOFs (UPC-60-Cl and UPC-60-NH2 ) with the new topology types were constructed. As the C=C bonds of the ligands have flexible torsion angles, UPC-60-Cl features three types of irregular 2D channels, while UPC-60-NH2 has a cage with two types of windows on the surface. The synergistic effect of unique channels and modification of functional groups endows UPC-60-Cl and UPC-60-NH2 with high adsorption capacity for organic dyes. Compound UPC-60-Cl shows high adsorption capacity for CV (147.2 mg g-1 ), RHB (100.3 mg g-1 ), and MO (220.9 mg g-1 ), whereas UPC-60-NH2 exhibits selective adsorption of MO (158.7 mg g-1 ). Meanwhile, based on the diverse pore structure and modification of active sites, UPC-60-Cl and UPC-60-NH2 show the selective separation of equimolar C2 H2 /CO2 . Therefore, reasonable regulation of organic ligands plays a significant role in guiding the structure diversification and performance improvement of MOFs.

6.
Europace ; 23(5): 701-709, 2021 05 21.
Artigo em Inglês | MEDLINE | ID: mdl-33554255

RESUMO

AIMS: The aim of this study was to determine whether driver ablation effectively treats persistent atrial fibrillation (AF) in obese patients. METHODS AND RESULTS: We randomly assigned 124 persistent AF obese patients to two groups, one undergoing conventional ablation (n = 62) and the other undergoing driver ablation (n = 62). Sixty-two non-obese patients with persistent AF undergoing driver ablation served as matched controls. Bipolar electrogram dispersion was analysed for driver mapping. Epicardial adipose tissue (EAT) volume was measured using cardiac computed tomography. Obese patients had a higher proportion of driver regions in the posterior wall (56.5% vs. 32.3%, P = 0.007). Driver complexity, measured as the average number and area of driver regions, was higher in the obese group than in the non-obese group (3.5 ± 1.0 vs. 2.9 ± 0.9, P < 0.001; 15.5% ± 4.2% vs. 9.8 ± 2.6%, P < 0.001, respectively). Left atrial EAT volume correlated better with the proportion of area of driver regions than did body mass index (BMI) and total EAT (BMI: r2 = 0.250, P < 0.001; total EAT: r2 = 0.379, P < 0.001; and left atrial EAT: r2 = 0.439, P < 0.001). The rate of AF termination was significantly higher in the driver ablation group than in the conventional ablation group (82.9% vs. 22.8%, P < 0.001). During the follow-up period of 16.9 ± 6.5 months, patients in the driver ablation group had significantly better AF-free survival (91.91% vs. 79.0%, log rank test, P = 0.026) and AF/atrial tachycardia-free survival (83.9% vs. 64.5%, log rank test, P = 0.011) than did patients in the conventional ablation group. CONCLUSION: Obesity is associated with increased driver complexity. Driver ablation improves long-term outcomes in obese patients with persistent AF.


Assuntos
Fibrilação Atrial , Ablação por Cateter , Veias Pulmonares , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/cirurgia , Átrios do Coração/diagnóstico por imagem , Átrios do Coração/cirurgia , Humanos , Obesidade/complicações , Obesidade/diagnóstico , Veias Pulmonares/diagnóstico por imagem , Veias Pulmonares/cirurgia , Recidiva , Resultado do Tratamento
7.
Appl Opt ; 60(5): 1164-1170, 2021 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-33690546

RESUMO

A broadband three-dimensional (3D) mode (de) multiplexer [(De)MUX] is proposed based on the subwavelength grating (SWG) for 3D photonic integrated circuits (PICs). The proposed 3D mode (De)MUX consists of three SWG waveguides on two vertical layers. The coupling strength and operating bandwidth can be increased benefitting from both the subwavelength structure and offset between bus and access SWGs. The proposed 3D mode (De)MUX is optimized based on the 3D full-vectorial finite difference time domain method. The 1-dB bandwidths of the optimized device are over >300, 107, and 128 nm for demultiplexing TE0, TE1, and TE2 modes, respectively. The coupling lengths are only 5.0 and 1.75 µm for demultiplexing the TE1 and TE2 modes, respectively. The insertion losses are 0.12, 0.27, and 0.29 dB, respectively. The proposed 3D mode (De)MUX is also fabrication tolerant.

8.
J Cardiovasc Electrophysiol ; 31(1): 48-60, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31701626

RESUMO

OBJECTIVE: To investigate the role of driver mechanism and the effect of electrogram dispersion-guided driver mapping and ablation in atrial fibrillation (AF) at different stages of progression. METHODS: A total of 256 consecutive patients with AF who had undergone pulmonary vein isolation (PVI) plus driver ablation or conventional ablation were divided into three groups: paroxysmal atrial fibrillation (PAF; group A, n = 51); persistent atrial fibrillation (PsAF; group B, n = 38); and long standing-persistent atrial fibrillation (LS-PsAF; group C, n = 39). PVI was performed with the guidance of the ablation index. The electrogram dispersion was analyzed for driver mapping. RESULTS: The most prominent driver regions were at roof (28.0%), posterior wall (17.6%), and bottom (21.3%). From patients with PAF to those with PsAF and LS-PsAF: the complexity of extra-pulmonary vein (PV) drivers including distribution, mean number, and area of dispersion region increased (P < .001). Patients who underwent driver ablation vs conventional ablation had higher procedural AF termination rate (76.6% vs 28.1%; P < .001). With AF progression, the termination rate gradually decreased from group A to group C, and the role of PVI in AF termination was also gradually weakened from group A to group C (39.6%, 7.4%, and 4.3%; P < .001) in patients with driver ablation. At the end of the follow-up, the rate of sinus rhythm maintenance was higher in patients with driver ablation than those with conventional ablation (89.1% vs 70.3%; P < .001). CONCLUSION: The formation of extra-PV drivers provides an important mechanism for AF maintenance with their complexity increasing with AF progression. Electrogram dispersion-guided driver ablation appears to be an efficient adjunctive approach to PVI for AF treatment.


Assuntos
Potenciais de Ação , Fibrilação Atrial/cirurgia , Ablação por Cateter , Técnicas Eletrofisiológicas Cardíacas , Frequência Cardíaca , Veias Pulmonares/cirurgia , Idoso , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/fisiopatologia , Ablação por Cateter/efeitos adversos , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Veias Pulmonares/fisiopatologia , Fatores de Tempo , Resultado do Tratamento
9.
J Cardiovasc Electrophysiol ; 31(3): 621-628, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31930545

RESUMO

BACKGROUND: Catheter ablation (CA) is a promising option in most patients with refractory atrial fibrillation (AF). However, data on over 5 years' outcomes with larger numbers in hypertrophic cardiomyopathy (HCM) patients with AF have not been reported. We assessed the outcome of 120 HCM patients following CA compared with a non-CA group and general patients without AF matched by HCM type with a 61.9 ± 31.6-month follow-up. METHODS AND RESULTS: A total of 120 patients (age 61 ± 9.8 years, female n = 43, 35.8%) with paroxysmal AF (n = 60, 50%) and persistent AF (n = 60, 50%) were enrolled. Of the 120 patients, 48 (40%) required redo procedures, and 82 (68.3%) were in sinus rhythm at the last evaluation. The composite clinical events rate following the initial CA was lower than that in the non-CA group (P = .023) and was also comparable to that in general patients without AF matched by HCM type (P = .729). Female (HR 2.358, 95% CI, 1.151-4.831; P = .019), NYHA functional class III-IV (HR 2.422, 95% CI, 1.032-5.685; P = .042) and left atrial diameter ≥50 mm (HR 3.319, 95% CI, 1.469-7.499; P = .004) were predictors of AF recurrence after multiple procedures. CONCLUSIONS: CA was successful in restoring long-term sinus rhythm and improving symptomatic status in most HCM patients with refractory AF especially for those patients with small atrial size and mild symptoms. In addition, CA may contribute to the prevention of major clinical adverse events in the long-term clinical course.


Assuntos
Fibrilação Atrial/cirurgia , Cardiomiopatia Hipertrófica/complicações , Ablação por Cateter , Frequência Cardíaca , Idoso , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/etiologia , Fibrilação Atrial/fisiopatologia , Cardiomiopatia Hipertrófica/diagnóstico por imagem , Cardiomiopatia Hipertrófica/fisiopatologia , Ablação por Cateter/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva , Reoperação , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento
10.
Langmuir ; 36(19): 5176-5185, 2020 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-32340458

RESUMO

Accurate evaluation of the shell elastic modulus of microcapsules is of great significance to understanding their performance during production, processing, and applications. In this work, microcompression was employed to investigate the elastic behaviors of a single microcapsule. It was modeled as a microsphere with a core-shell structure compressed between two rigid plates. Based on the assumption that the contact pressure between the microsphere and plates obeys parabolic distribution, a microcompression method derived from the Reissner's theory and the modified Hertz contact theory was established to evaluate the shell elastic modulus. Applications were carried out on poly(methylmethacrylate) (PMMA) microcapsules containing n-octadecane. The average elastic modulus of PMMA shells measured by the proposed microcompression method agrees well with that of the bulk PMMA sample. Furthermore, the elastic modulus of PMMA shells was found to have size dependence on the diameter of the microcapsules. Finally, finite element models combined with the newly proposed method were constructed to accurately predict the microcompression behaviors of microcapsules with different sizes.

11.
Appl Opt ; 59(20): 5924-5929, 2020 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-32672735

RESUMO

An efficient three-dimensional (3D) quasi-TE0 and quasi-TE1 mode (de)multiplexer [(De)MUX] is proposed and optimized based on a dual-waveguide 3D-coupler, in which the sidewalls of a bottom silicon waveguide and an upper poly-silicon waveguide are aligned vertically. The full-vectorial finite element method and 3D full-vectorial finite difference time domain method are utilized to study the performances of the proposed 3D mode (De)MUX. The results indicate that the proposed mode (De)MUX can achieve a compact coupling length of 6.88 µm, a mode crosstalk of -30.04dB, an insertion loss of 0.02 dB, and an ultra-broad 1 dB bandwidth of 300 nm. The proposed 3D mode (De)MUX based on a sidewall-aligned vertical coupler has the potential to extend the functionality and to increase the integration of the mode division multiplexing (MDM) systems.

12.
Genet Mol Biol ; 43(4): e20200142, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33306779

RESUMO

TBX5 has been linked to Holt-Oram syndrome, with congenital heart defect (CHD) and atrial fibrillation (AF) being two major cardiac phenotypes. However, the prevalence of a TBX5 variation in patients with CHD and AF remains obscure. In this research, by sequencing analysis of TBX5 in 178 index patients with both CHD and AF, a novel heterozygous variation, NM_000192.3: c.577G>T; p.(Gly193*), was identified in one index patient with CHD and AF as well as bicuspid aortic valve (BAV), with an allele frequency of approximately 0.28%. Genetic analysis of the proband's pedigree showed that the variation co-segregated with the diseases. The pathogenic variation was not detected in 292 unrelated healthy subjects. Functional analysis by using a dual-luciferase reporter assay system showed that the Gly193*-mutant TBX5 protein failed to transcriptionally activate its target genes MYH6 and NPPA. Moreover, the mutation nullified the synergistic transactivation between TBX5 and GATA4 as well as NKX2-5. Additionally, whole-exome sequencing analysis showed no other genes contributing to the diseases. This investigation firstly links a pathogenic variant in the TBX5 gene to familial CHD and AF as well as BAV, suggesting that CHD and AF as well as BAV share a common developmental basis in a subset of patients.

13.
Cardiology ; 142(3): 158-166, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31189165

RESUMO

AIM: During cardiac resynchronization therapy (CRT), optimized programming of the atrioventricular (AV) delay and ventricular-to-ventricular (VV) interval can lead to improved hemodynamics, symptomatic response, and left ventricular systolic function. Currently, however, there is no recommendation for the best optimization method. This study aimed to compare the long-term clinical outcomes of 4 different CRT optimization methods. METHODS: One hundred and twenty-four consecutive CRT patients with severe heart failure and left bundle-branch block configuration were randomly assigned into four groups to undergo AV/VV delay optimization through echocardiogram (ECHO; n = 30), electrocardiogram (ECG; n = 32), QuickOpt algorithm (n = 28), and nominal AV/VV (n = 36) groups. Patients were followed up and underwent examinations, including New York Heart Association (NYHA) cardiac functional classification, 6-min walking distance (6MWD), and echocardiography, at 6, 12, 24, 36, and 48 months, respectively. The patients' survival and clinical outcomes were compared among the four groups. RESULTS: Kaplan-Meier survival analyses showed that the median survival was the same in the 4 groups: ECHO, 43 months; ECG, 44 months; QuickOpt, 44 months, and nominal, 41 months. At the 6-month follow-up, the reduction in left ventricular end diastolic diameter (LVEDD) was significantly less in the nominal group (-1.91 ± 2.58 mm) than that in the other three groups (ECHO: -3.70 ± 2.78 mm, p = 0.012; ECG: -3.53 ± 3.14 mm, p = 0.020; QuickOpt: -3.46 ± 2.65 mm, p = 0.032); 6MWD was significantly shorter in the nominal group (87.88 ± 34.76 m) than that in the other three groups (ECHO: 120.63 ± 56.93 m, p = 0.006; ECG: 114.97 ± 54.95 m, p = 0.020; QuickOpt: 114.57 ± 35.41 m, p = 0.027). Left ventricular ejection fraction (LVEF) significantly increased in ECHO (7.23 ± 2.76%, p = 0.010), ECG (8.50 ± 3.17%, p < 0.001), and QuickOpt (8.39 ± 2.90%, p < 0.001) compared with the nominal group (5.35 ± 2.59%). There were no significant differences among the groups in the aforementioned parameters at 24, 36, and 48 months, respectively. CONCLUSION: While LVEDD, LVEF, 6MWD, and NYHA were significantly improved in ECHO, ECG, and QuickOpt at 6 months, there were no significant improvements in any of the groups at 12, 24, and 48 months. These findings suggested that the long-term effect of the four CRT methods for heart failure was not significantly different.


Assuntos
Terapia de Ressincronização Cardíaca/métodos , Ecocardiografia , Eletrocardiografia , Insuficiência Cardíaca/terapia , Idoso , Algoritmos , Terapia de Ressincronização Cardíaca/efeitos adversos , China , Feminino , Insuficiência Cardíaca/mortalidade , Insuficiência Cardíaca/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Análise de Sobrevida , Fatores de Tempo , Resultado do Tratamento , Função Ventricular Esquerda , Teste de Caminhada
14.
Appl Opt ; 58(33): 9290-9296, 2019 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-31873608

RESUMO

An on-chip silicon dual-mode multiplexer (MUX) is proposed via a subwavelength grating (SWG)-based directional coupler and a mode blocker. The proposed mode MUX is optimized by utilizing the three-dimensional full-vectorial finite-difference time-domain-based band structure and propagation calculations. The simulated results indicate that an ultralow mode cross talk of $ - {40}\,\,{\rm dB}$-40dB at the operating wavelength of 1550 nm can be achieved by introducing a ${{\rm TE}_0}$TE0 mode blocker. Benefiting from the triple SWG coupler, the mode-coupling strength can be significantly enhanced inside the proposed mode MUX, which can achieve a compact coupling length of 8.75 µm, a low insertion loss of 0.39 dB at 1550 nm, an ultrabroad bandwidth of 310 nm for the mode CT $ \lt - {15.0}\,\,{\rm dB}$<-15.0dB, and insensitivity to fabrication errors.

15.
Opt Express ; 26(20): 26257-26271, 2018 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-30469716

RESUMO

A reconfigurable mode (de)multiplexer/switch (RMDS) is a pivotal component for the mode routing in mode-division multiplexing (MDM) networks. Here, we propose a three-dimensional (3D) RMDS via a triple-waveguide directional coupler, consisting of a lower doped silicon waveguide, a central plasmonic horizontal-slot waveguide with indium-tin-oxide (ITO) and an upper doped polycrystalline-silicon waveguide. The enhanced light-matter-interactions can be achieved via the central plasmonic metal-oxide-semiconductor (MOS) mode. The multiplexing states of the proposed 3D-RMDS can be switched by adjusting the applied voltage bias on the ITO layer. The simulation results reveal that a 3D quasi-TM0 and quasi-TM1 RMDS is with a compact length of 8.429 µm, the mode crosstalk of -20.3 dB (-9.2 dB) and the insertion loss of 0.06 dB (1.47dB) at the wavelength of 1550 nm for the "OFF" ("ON") state, respectively. The proposed 3D-RMDS can be applied in future 3D on-chip MDM networks to achieve a flexible mode-routing and further enhance the transmission capacity.

16.
Clin Chem Lab Med ; 56(3): 502-511, 2018 02 23.
Artigo em Inglês | MEDLINE | ID: mdl-28902616

RESUMO

BACKGROUND: The MADS-box transcription factor myocyte enhancer factor 2C (MEF2C) is required for the cardiac development and postnatal adaptation and in mice-targeted disruption of the MEF2C gene results in dilated cardiomyopathy (DCM). However, in humans, the association of MEF2C variation with DCM remains to be investigated. METHODS: The coding regions and splicing boundaries of the MEF2C gene were sequenced in 172 unrelated patients with idiopathic DCM. The available close relatives of the index patient harboring an identified MEF2C mutation and 300 unrelated, ethnically matched healthy individuals used as controls were genotyped for MEF2C. The functional effect of the mutant MEF2C protein was characterized in contrast to its wild-type counterpart by using a dual-luciferase reporter assay system. RESULTS: A novel heterozygous MEF2C mutation, p.Y157X, was detected in an index patient with adult-onset DCM. Genetic screen of the mutation carrier's family members revealed that the mutation co-segregated with DCM, which was transmitted as an autosomal dominant trait with complete penetrance. The non-sense mutation was absent in 300 control individuals. Functional analyses unveiled that the mutant MEF2C protein had no transcriptional activity. Furthermore, the mutation abolished the synergistic transactivation between MEF2C and GATA4 as well as HAND1, two other transcription factors that have been associated with DCM. CONCLUSIONS: This study indicates MEF2C as a new gene responsible for human DCM, which provides novel insight into the mechanism underpinning DCM, suggesting potential implications for development of innovative prophylactic and therapeutic strategies for DCM, the most prevalent form of primary myocardial disease.


Assuntos
Cardiomiopatia Dilatada/genética , Adulto , Cardiomiopatia Dilatada/metabolismo , Feminino , Células HeLa , Humanos , Fatores de Transcrição MEF2/deficiência , Fatores de Transcrição MEF2/genética , Fatores de Transcrição MEF2/metabolismo , Masculino , Pessoa de Meia-Idade , Mutação , Células Tumorais Cultivadas
17.
Pacing Clin Electrophysiol ; 41(2): 172-178, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29023875

RESUMO

BACKGROUND: In longstanding persistent atrial fibrillation (LPeAF), the ideal endpoint of ablation remains to be determined. This study was to explore the value of pursuing AF termination or no with the same strategy during ablation on the long-term outcomes in patients with LPeAF. METHODS: Utilized "CCL" strategy is a fixed ablation approach consisting of circumferential pulmonary vein antrum isolation, ablation of complex fractionated atrial electrogram, and linear ablation between two anatomical structures (the mitral isthmus, left atrial roof). Note that 400 patients were randomized to group A (technical endpoint) and group B (pursuing AF termination). RESULTS: A group with technical endpoint had lower rate of acute AF termination (AF→sinus rhythm, 3.5% vs 18.1%; AF→atrial tachycardia, 23.7% vs 44.7%; P < 0.01) and shorter duration of ablation (164.9 ± 20.8 vs 223.4 ± 24.9, P < 0.01), radiofrequency delivery time (69.8 ± 18.1 vs 102.2 ± 26.3, P < 0.01), and x-ray exposure time (18.2 ± 8.8 vs 27.9 ± 12.4, P < 0.01) than those in B group (pursuing AF termination). During follow-up, freedom from atrial arrhythmias did not differ between the two groups after a single ablation procedure (46.5% vs 54.3%, P=0.12) and the final ablation procedure (60.1% vs 65.8%, P  =  0.24). CONCLUSION: In patients of LPeAF, pursuing AF termination during ablation was associated with similar long-term clinical outcome compared to that with technical endpoint. Ablation to termination is not the best strategy during ablation.


Assuntos
Fibrilação Atrial/cirurgia , Ablação por Cateter/métodos , Veias Pulmonares/cirurgia , Eletrocardiografia , Determinação de Ponto Final , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reoperação , Resultado do Tratamento
18.
Clin Lab ; 64(6): 915-921, 2018 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-29945308

RESUMO

BACKGROUND: Breast cancer is the second leading cause of cancer-related death among women worldwide. The aim of this study is to investigate the role of miR-142-3p in breast cancer cells and the related mechanism. METHODS: Sixty paired breast cancer tissues were collected and 60 breast tissues from patients with mammary hyperplasia served as the control group. The expression of miR-142-3p was examined using RT-qPCR methods; moreover, we also performed receiver operating characteristic (ROC) curve analysis to determine whether miR142-3p can distinguish breast cancer patients from the controls. Next, HMGA1 and FZD7 have been predicted as target genes of miR-142-3p, and the expressions of HMGA1 and FZD7 in breast cancer tissue and the control group were examined using RT-qPCR and western blot methods. RESULTS: miR-142-3p was significantly down-regulated in breast cancer tissue compared with the controls, and the levels of miR-142-3p was negatively correlated with the tumor size, degree of differentiation, and metastasis (p < 0.01). Moreover, results of ROC curve analysis indicated that the expression of miR-142-3p can distinguish between patients with breast cancer and the control group (AUC = 0.819, 95% CI, 0.756 - 0.881). Furthermore, the expressions of HMGA1 and FZD7 were significantly up-regulated in patients with breast cancer compared with the controls. The level of miR-142-3p was negatively correlated with expressions of HMGA1 (r = -0.3507, p = 0.006) and FZD7 (r = -0.3410, p = 0.0077) in patients with breast cancer. CONCLUSIONS: Our results proved that miR-142-3p may serve as a tumor suppressor in breast cancer by suppressing the expression of oncogene HMGA1 and FZD7, suggesting that miR-142-3p has the potential to become a diagnostic marker and therapeutic target for the early diagnosis and treatment of breast cancer.


Assuntos
Neoplasias da Mama/genética , Receptores Frizzled/genética , Regulação Neoplásica da Expressão Gênica , Proteína HMGA1a/genética , Adolescente , Adulto , Biomarcadores Tumorais/genética , Mama/metabolismo , Mama/patologia , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/metabolismo , Diagnóstico Diferencial , Feminino , Receptores Frizzled/metabolismo , Proteína HMGA1a/metabolismo , Humanos , Hiperplasia/diagnóstico , Hiperplasia/genética , Hiperplasia/metabolismo , MicroRNAs/genética , Adulto Jovem
19.
Europace ; 19(10): 1670-1675, 2017 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-28073882

RESUMO

AIMS: The superior vena cava (SVC) has been established as an important source of atrial fibrillation (AF). The role of SVC in long-standing persistent AF and the efficacy of empiric electrical isolation of the SVC are still unclear. The purpose of this study was to judge the role of SVC in catheter ablation of long-standing persistent AF. METHODS AND RESULTS: A total of 102 consecutive patients with long-standing persistent AF were enrolled. All patients underwent circumferential pulmonary vein isolation, complex fractionated atrial electrograms ablation, and linear ablation during the index procedure. Superior vena cava-triggered AF and an SVC associated with the maintenance of AF were evaluated by mapping catheters during the procedure. The arrhythmogenicity of the SVC was confirmed in only 1 of the patients (0.98%). At the end of 12 months follow-up, the arrhythmia-free survival rate after a single procedure was 43.1%. After the last procedure (mean 1.47 ± 0.58 procedures), sinus rhythm was maintained in 71 (69.6%) patients, 63 of whom without antiarrhythmic drugs. The patients in AF recurrence group had higher rates of right atrium enlargement (71 vs. 34%, P = 0.03), ≥2 procedures (65 vs. 34%, P < 0.05), longer AF duration (84 ± 46 vs. 45 ± 34 months, P < 0.05), and larger left atrium diameter (50 ± 5 vs. 45 ± 6 mm, P < 0.05). In the multivariate analysis, left atrium diameter and AF duration were independent predictors of AF recurrence. CONCLUSION: The arrhythmogenic SVC is rarely detected in patients with long-standing persistent AF. Empiric SVC electrical isolation in the stepwise approach of long-standing persistent AF seems unnecessary.


Assuntos
Fibrilação Atrial/cirurgia , Ablação por Cateter/métodos , Veias Pulmonares/cirurgia , Veia Cava Superior/cirurgia , Potenciais de Ação , Idoso , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/fisiopatologia , Ablação por Cateter/efeitos adversos , Distribuição de Qui-Quadrado , China , Intervalo Livre de Doença , Técnicas Eletrofisiológicas Cardíacas , Feminino , Frequência Cardíaca , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Razão de Chances , Veias Pulmonares/fisiopatologia , Recidiva , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Procedimentos Desnecessários , Veia Cava Superior/fisiopatologia
20.
Cardiology ; 138(1): 55-62, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28571007

RESUMO

OBJECTIVES: Eplerenone (EPL), an antagonist of the mineralocorticoid receptor, is beneficial for atrial fibrillation and atrial fibrosis. However, the underlying mechanism remains less well known. We aimed to investigate the effect of EPL on atrial fibrosis using a mouse with selective atrial fibrosis and to explore the underlying mechanisms. METHODS: EPL-treated MHC-TGFcys33ser transgenic mice that have selective atrial fibrosis (Tx+EPL mice), as well as control mice, were used for in vivo studies including histological analyses, Western blotting, and qRT-PCR studies. TGF-ß1-stimulated atrial fibroblasts were treated with EPL or vehicle for the in vitro studies including Western blotting and qRT-PCR studies. In addition, Smad7 siRNA was used to knock down Smad7. RESULTS: EPL inhibited atrial fibrosis in the Tx mice. In addition, EPL suppressed the expression of fibrosis-related molecules induced by TGF-ß1 in vivo and in vitro. This occurred in concert with a downregulation of Smad7 protein expression and an upregulation of p-Smad2/3 protein expression. In addition, knockdown of Smad7 by siRNA abolished the protective roles of EPL. CONCLUSIONS: EPL inhibited atrial fibrosis in Tx mice. The underlying mechanism may involve increased protein expression of Smad7, which enhances the inhibitory feedback regulation of TGF-ß1/Smad signaling.


Assuntos
Fibrilação Atrial/patologia , Átrios do Coração/patologia , Antagonistas de Receptores de Mineralocorticoides/farmacologia , Proteína Smad7/genética , Espironolactona/análogos & derivados , Animais , Fibrilação Atrial/tratamento farmacológico , Células Cultivadas , Eplerenona , Fibroblastos/efeitos dos fármacos , Fibrose , Átrios do Coração/efeitos dos fármacos , Camundongos , Camundongos Transgênicos , Transdução de Sinais/efeitos dos fármacos , Espironolactona/farmacologia , Fator de Crescimento Transformador beta1/farmacologia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA