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A higher-order mode (HOM) pass filter is a key component in on-chip mode-division multiplexing (MDM) systems, enabling mode-selective transmission. In this study, a highly integrated silicon-based HOM pass filter is proposed based on "mode-scattering evolution." The proposed filter consists of a functional region and input/output waveguides, with a compact footprint of only 2â µm × 9â µm achieved through an inverse design. Experimental results demonstrate that the fabricated silicon-based HOM pass filter exhibits an insertion loss of 2.11â dB and a crosstalk of -10.63â dB at 1550â nm. The bandwidth with a loss <5â dB is measured to be 90â nm. The proposed device offers an efficient solution for on-chip mode-selective filtering, which can provide a promising technology for building integrated MDM systems.
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BACKGROUND: Pulsed field ablation (PFA) has emerged as a novel non-thermal modality with highly myocardium-specific. However, the PFA catheter based on contact force (CF)-sensing has not been reported. The study aimed to evaluate the efficacy and safety of a novel CF-sensing PFA catheter. METHODS: First, different CF (5, 15, 25, and 35 g) of the novel PFA catheter were evaluated on lesion dimensions during ablation on right and left ventricle in two pigs. Next, this catheter was further evaluated on four typical sites of superior vena cava (SVC), cavotricuspid isthmus (CTI), right superior pulmonary vein (RSPV), and right inferior pulmonary vein (RIPV) for atrial ablation in another six pigs. Electrical isolation was evaluated immediately after ablation and 30-day survival. Chronic lesions were assessed via histopathology after euthanasia. Acute and chronic safety outcomes were observed peri- and post-procedurally. RESULTS: In ventricular ablation, increased CF from 5 to 15 g produced significantly greater lesion depth but nonsignificant increases from 15 to 35 g. In atrial ablation, the novel CF-sensing PFA deliveries produced an acute attenuation of local electrograms and formation of a continuous line of block in all 6 pigs. The ablation line remained sustained blockage at the 30-day survival period. The CF of SVC, CTI, RSPV, and RIPV was 9.4 ± 1.5, 14.5 ± 3.2, 17.2 ± 2.6, and 13.4 ± 2.8 g, respectively. Moreover, no evidence of damage to esophagus or phrenic nerve was observed. CONCLUSION: The novel CF-sensing PFA catheter potentiated efficient, safe, and durable ablation, without causing damage to the esophagus or phrenic nerve.
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Ablación por Catéter , Vena Cava Superior , Humanos , Porcinos , Animales , Vena Cava Superior/cirugía , Catéteres , Ventrículos Cardíacos , MiocardioRESUMEN
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 4â µm × 2.2â 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 116â nm and 138â nm, respectively. The proposed mode MUX/DeMUX is scalable and could provide a feasible solution for constructing high-performance MDM systems.
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Rheumatoid arthritis (RA) is the most common chronic autoimmune disease worldwide. Although progress has been made in RA treatment in recent decades, remission cannot be effectively achieved for a considerable proportion of RA patients. Thus, novel potential targets for therapeutic strategies are needed. Semaphorin 5A (SEMA5A) plays a pivotal role in RA progression by facilitating pannus formation, and it is a promising therapeutic target. In this study, we sought to develop an antibody treatment strategy targeting SEMA5A and evaluate its therapeutic effect using a collagen-induced arthritis (CIA) model. We generated SYD12-12, a fully human SEMA5A blocking antibody, through phage display technology. SYD12-12 intervention effectively inhibited angiogenesis and aggressive phenotypes of RA synoviocytes in vitro and dose-dependently inhibited synovial hyperplasia, pannus formation, bone destruction in CIA mice. Notably, SYD12-12 also improved the Treg/Th17 imbalance in CIA mice. We confirmed through immunofluorescence and molecular docking that SYD12-12 integrated with the unique TSP-1 domain of SEMA5A. In conclusion, we developed and characterized a fully human SEMA5A-blocking antibody for the first time. SYD12-12 effectively alleviated disease progression in CIA mice by inhibiting pannus formation and improving the Treg/Th17 imbalance, demonstrating its potential for the RA treatment.
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Artritis Experimental , Artritis Reumatoide , Semaforinas , Sinoviocitos , Animales , Humanos , Ratones , Anticuerpos Monoclonales/inmunología , Anticuerpos Monoclonales/farmacología , Anticuerpos Monoclonales/uso terapéutico , Artritis Experimental/inducido químicamente , Artritis Reumatoide/tratamiento farmacológico , Simulación del Acoplamiento MolecularRESUMEN
This case report describes a teenager with a history of cardiomyopathy and recurrent syncope who was admitted to the pediatric unit with a urinary tract infection.
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Cardiomiopatía Hipertrófica , Síncope , Humanos , Adolescente , Síncope/etiología , Recurrencia , ElectrocardiografíaRESUMEN
AIMS: Although increased production of malondialdehyde (MDA), an end product of lipid oxidation caused by reactive oxygen species (ROS), has been found be elevated in hypertensive population, whether MDA contributed to a changed risk of hypertension is uncertain. We aimed to investigate whether elevated blood levels of MDA contribute to increased risk of hypertension and obesity has a modified effect on the association in an older Chinese population. METHODS: Data were obtained from 2011 to 2012 of the Chinese Longitudinal Healthy Longevity Survey (CLHLS), a national cohort of older adults in China. Associations between blood MDA level and systolic and diastolic blood pressure (BP) and risk of hypertension were performed by multivariable linear regression and logistic regression analysis. RESULTS: The results of smooth curve revealed a gradual upward trend on association of blood MDA level with diastolic BP (P < 0.001), but not with systolic BP (P > 0.05). Logistic regression analysis suggested that elevated blood MDA levels were associated with increased risk of diastolic hypertension (OR = 1.079, 95% CI 1.039-1.122, P < 0.001) rather than systolic hypertension (OR = 0.978, 95% CI 0.943-1.015, P = 0.247) after adjustments of related confounding factors were made. Furthermore, we found the significant modification effect of obesity on the association between MDA level and risk of diastolic hypertension evaluated by body mass index (BMI, interaction P = 0.015) and by waist circumference (interaction P = 0.016). CONCLUSION: Our results firstly identified that increased blood MDA levels were associated with elevated risk of diastolic hypertension, rather than systolic hypertension in the non-obese old population.
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Hipertensión , Obesidad , Humanos , Anciano , Estudios Transversales , Factores de Riesgo , Obesidad/complicaciones , Obesidad/epidemiología , Hipertensión/epidemiología , Presión Sanguínea/fisiología , Índice de Masa CorporalRESUMEN
The feasibility and safety of left bundle branch area pacing (LBBAP) used in pediatric patients with atrioventricular block (AVB) have not been well demonstrated. Currently, only several case reports for pediatric patients have been published since the advent of LBBAP, with 3 months to 1 year follow-up. Here, we present a case of LBBAP in a 6-year-old child with a high-degree AVB secondary to the transcatheter device closure of congenital ventricular septal defect. No procedure-related complications were observed, and the electrical parameters were stable at 2-year follow-up. Additionally, we performed a systematic literature review on pediatric patients with LBBAP. Fifteen cases were retrieved after systematically searching PubMed and Embase databases. No complications have been reported among these published cases. In conclusion, consistent with previous cases, our case with 2-year follow-up has demonstrated that LBBAP may be an alternative pacing modality from a very early age. However, given the limited evidence, the long-term outcomes of LBBAP in pediatric patients should be further investigated.
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Bloqueo Atrioventricular , Bloqueo Atrioventricular/etiología , Bloqueo Atrioventricular/terapia , Estimulación Cardíaca Artificial , Niño , Electrocardiografía , Estudios de Seguimiento , Sistema de Conducción Cardíaco , Humanos , Resultado del TratamientoRESUMEN
BACKGROUND: The influence of diabetes on the mortality and risk of implantable cardioverter defibrillator (ICD) therapies is still controversial, and a comprehensive assessment is lacking. We performed this systematic review and meta-analysis to address this controversy. METHODS: We systematically searched the PubMed, Embase, Web of Science and Cochrane Library databases to collect relevant literature. Fixed and random effects models were used to estimate the hazard ratio (HR) with 95% CIs. RESULTS: Thirty-six articles reporting on 162,780 ICD recipients were included in this analysis. Compared with nondiabetic ICD recipients, diabetic ICD recipients had higher all-cause mortality (HR = 1.45, 95% CI 1.36-1.55). The subgroup analysis showed that secondary prevention patients with diabetes may suffer a higher risk of all-cause mortality (HR = 1.89, 95% CI 1.56-2.28) (for subgroup analysis, P = 0.03). Cardiac mortality was also higher in ICD recipients with diabetes (HR = 1.68, 95% CI 1.35-2.08). However, diabetes had no significant effect on the risks of ICD therapies, including appropriate or inappropriate therapy, appropriate or inappropriate shock and appropriate anti-tachycardia pacing (ATP). Diabetes was associated with a decreased risk of inappropriate ATP (HR = 0.56, 95% CI 0.39-0.79). CONCLUSION: Diabetes is associated with an increased risk of mortality in ICD recipients, especially in the secondary prevention patients, but does not significantly influence the risks of ICD therapies, indicating that the increased mortality of ICD recipients with diabetes may not be caused by arrhythmias. The survival benefits of ICD treatment in diabetes patients are limited.
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Desfibriladores Implantables , Diabetes Mellitus , Adenosina Trifosfato , Arritmias Cardíacas/etiología , Muerte Súbita Cardíaca/prevención & control , Desfibriladores Implantables/efectos adversos , Diabetes Mellitus/diagnóstico , Diabetes Mellitus/epidemiología , Diabetes Mellitus/terapia , Humanos , Modelos de Riesgos Proporcionales , Factores de RiesgoRESUMEN
Background: Existing evidence on the association between blood pressure (BP) and mortality risk in intensive care unit (ICU) patients with atrial fibrillation (AF) is scarce. Aim: This study aimed to assess the associations between blood pressure (BP) and risks of in-hospital and all-cause mortality in ICU patients with AF. Methods: A total of 2,345 records of patients with AF whose BP was monitored after admission to the ICU were obtained from the MIMIC-III database. Incidences were calculated for endpoints (hospital mortality, 7-day mortality, 30-day mortality, and 1-year mortality). We performed smooth curve and logistic regression analyses to evaluate the association between BP and the risk of each endpoint. Results: Smooth curve regression showed that systolic blood pressure (SBP), mean arterial pressure (MBP), and diastolic blood pressure (DBP) followed U-shaped curves with respect to endpoints (hospital mortality, 7-day mortality, 30-day mortality, and 1-year mortality). The incidence of these endpoints was lowest at 110/70/55 mm Hg. There was an increased risk of 1-year mortality observed with BP > 110/70/55 mm Hg (SBP, odds ratio [OR] = 1.008, 95% CI 1.001-1.015, p = 0.0022; MBP, OR = 1.010, 95% CI 1.005-1.016, p < 0.001) after adjusting for age, sex, and medical history. In contrast, an inverse association between BP and the risk of 1-year mortality was observed with BP ≤ 110/70/55 mm Hg (SBP, OR = 0.981, 95% CI 0.974-0.988, p < 0.001; MBP OR = 0.959, 95% CI 0.939-0.979, p < 0.001; and DBP, OR = 0.970, 95% CI 0.957-0.983, p < 0.001). Conclusions: We observed a U-shaped association between BP and in-hospital/all-cause mortality in ICU patients with AF. However, the underlying causes need to be investigated.
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Background: His bundle pacing (HBP) is a physiological pacing strategy, which aims to capture the His bundle-Purkinje system and synchronously activate the ventricles. Left bundle branch pacing (LBBP) is a newly discovered physiological pacing technique similar to HBP. We conducted this meta-analysis to compare the pacing parameters and clinical results between HBP and LBBP. Methods: We systematically retrieved studies using the PubMed, Embase database, and Cochrane Library. Mean difference (MD) and relative risk (RR) with their 95% confidence intervals [CIs] were used to measure the outcomes. A random-effect model was used when studies were of high heterogeneity. Results: A total of seven studies containing 867 individuals were included. Compared with HBP, LBBP was associated with higher implant success rates (RR: 1.12, 95% CI: 1.05-1.18; I 2 = 60%, P = 0.0003), lower capture threshold at implantation (V/0.5 ms) (MD: 0.63, 95% CI: 0.35-0.90, I 2 = 89%, P < 0.0001) and capture threshold at follow-up (V/0.5 ms) (MD: 0.76, 95% CI: 0.34-1.18, I 2 = 93%, P = 0.0004), and larger sensed R wave amplitude (mV) at implantation (MD: 7.23, 95% CI: 5.29-9.16, P < 0.0001) and sensed R wave amplitude (mV) at follow-up (MD: 7.53, 95% CI: 6.85-8.22, P < 0.0001). In LBBP recipients, greater QRS wave complex reduction was found in the paced QRS duration at follow-up compared with HBP recipients at follow-up (MD: 6.12, 95% CI: 1.23-11.01, I 2 = 0%, P = 0.01). No statistical differences were found in procedure duration, fluoroscopy time, native left ventricular ejection fractions (LVEF), LVEF improvement, native QRS duration, and QRS reduction from the native QRS duration vs. paced QRS duration at implantation. Conclusion: Current evidence suggests that pacing characteristics are better in LBBP compared with HBP. Further prospective studies are needed to validate the clinical advantages of LBBP.
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BACKGROUND: As an antioxidant, serum superoxide dismutase (SOD) have been found to be associated with hypertension. METHODS: The data were derived from the Chinese Longitudinal Healthy Longevity Survey (CLHLS), a prospective cohort study in China. We explored the association between serum SOD and blood pressure (BP) using multivariable correction analysis in an older Chinese population. RESULTS: We observed a significantly gradual downward trend in the association between serum SOD levels and diastolic BP (DBP) in participants with lower serum SOD levels (< 58 IU/mL), while no associations were observed between serum SOD levels and DBP in participants with higher serum SOD levels (> 58 IU/mL). Similar results showed a significant gradual downward trend in associations between serum SOD levels and the risk of diastolic hypertension only at SOD < 58 IU/mL. Multiple linear regression analysis suggested that serum SOD was negatively correlated with DBP (Sß = -0.088,P < 0.001) but not with SBP (Sß = 0.013, P = 0.607). Multiple logistic regression analysis suggested that serum SOD was independently associated with the risk of diastolic hypertension (OR = 0.984, 95% CI: 0.973-0.996, P = 0.010) but not with the risk of systolic hypertension (OR = 1.001, 95% CI: 0.990-1.012,P = 0.836)) after adjusting for relevant confounding factors. Serum SOD levels (< 58 IU/mL, > 58 IU/mL) were an effect modifier of the association between serum SOD and DBP (interactionP = 0.0038) or the risk of diastolic hypertension (interaction P = 0.0050). CONCLUSIONS: Our study indicated for the first time that there was an L-shaped association between serum SOD levels and the risk of diastolic hypertension in the older Chinese population.
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BACKGROUND: The comparative effects of different types of cardiac resynchronization therapy (CRT) delivered by biventricular pacing (BVP), His bundle pacing (HBP), and left bundle branch area pacing (LBBAP) remain inconclusive. HYPOTHESIS: HBP and LBBAP may be advantageous over BVP for CRT. METHODS: PubMed, Embase, Web of Science, and the Cochrane Library were systematically searched for studies that reported the effects after BVP, HBP, and LBBAP for CRT. The effects between groups were compared by a frequentist random-effects network meta-analysis (NMA), by which the mean differences (MDs) and 95% confidence intervals (CIs) were calculated. RESULTS: Six articles involving 389 patients remained for the final meta-analysis. The mean follow-up of these studies was 8.03 ± 3.15 months. LBBAP resulted in a greater improvement in LVEF% (MD = 7.17, 95% CI = 4.31 to 10.04), followed by HBP (MD = 4.06, 95% CI = 1.09 to 7.03) compared with BVP. HBP resulted in a narrower QRS duration (MD = 31.58 ms, 95% CI = 12.75 to 50.40), followed by LBBAP (MD = 27.40 ms, 95% CI = 10.81 to 43.99) compared with BVP. No significant differences of changes in LVEF improvement and QRS narrowing were observed between LBBAP and HBP. The pacing threshold of LBBAP was significantly lower than those of BVP and HBP. CONCLUSION: The NMA first found that LBBAP and HBP resulted in a greater LVEF improvement and a narrower QRS duration compared with BVP. Additionally, LBBAP resulted in similar clinical outcomes but with lower pacing thresholds, and may therefore offer advantages than does HBP for CRT.
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Terapia de Resincronización Cardíaca , Fascículo Atrioventricular , Estimulación Cardíaca Artificial/métodos , Terapia de Resincronización Cardíaca/métodos , Electrocardiografía/métodos , Humanos , Metaanálisis en Red , Resultado del TratamientoRESUMEN
Left bundle branch area pacing (LBBAP) has developed in an effort to improve cardiac resynchronization therapy (CRT). We aimed to compare the long-term clinical outcomes between LBBAP and biventricular pacing (BIVP) in patients with heart failure (HF) and complete left bundle branch block (CLBBB). Consecutive patients with HF and CLBBB requiring CRT received either LBBAP or BIVP were recruited at the Second Affiliated Hospital of Nanchang University from February 2018 to May 2019. We assessed their implant parameters, electrocardiogram (ECG), clinical outcomes at implant and during follow-up at 1, 3, 6, 12, and 24 months. Forty-one patients recruited including 21 for LBBAP and 20 for BIVP. Mean follow-up duration was 23.71 ± 4.44 months. LBBAP produced lower pacing thresholds, shorter procedure time and fluoroscopy duration compared to BIVP. The QRS duration was significantly narrower after LBBAP than BIVP (129.29 ± 31.46 vs. 156.85 ± 26.37 ms, p = 0.005). Notably, both LBBAP and BIVP significantly improved LVEF, LVEDD, NYHA class, and BNP compared with baseline. However, LBBAP significantly lowered BNP compared with BIVP (416.69 ± 411.39 vs. 96.07 ± 788.71 pg/ml, p = 0.007) from baseline to 24-month follow-up. Moreover, patients who received LBBAP exhibited lower number of hospitalizations than those in the BIVP group (p = 0.019). In addition, we found that patients with moderately prolonged left ventricular activation time (LVAT) and QRS notching in limb leads in baseline ECG respond better to LBBAP for CLBBB correction. LBBAP might be a relative safe and effective resynchronization therapy and as a supplement to BIVP for patients with HF and CLBBB.
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Terapia de Resincronización Cardíaca , Insuficiencia Cardíaca , Fascículo Atrioventricular , Bloqueo de Rama/diagnóstico , Bloqueo de Rama/terapia , Estimulación Cardíaca Artificial/métodos , Terapia de Resincronización Cardíaca/efectos adversos , Terapia de Resincronización Cardíaca/métodos , Electrocardiografía/métodos , Insuficiencia Cardíaca/diagnóstico , Insuficiencia Cardíaca/terapia , Humanos , Resultado del TratamientoRESUMEN
With the steadily increasing amount of leadless pacemaker implantations performed worldwide, it has called attention to the delivery difficulty in patients with severe large right heart. Nevertheless, limited studies have reported leadless pacemaker implantation in patients with tricuspid stenosis. Here, we report the successful implantation of leadless pacemaker in a 60-year-old female patient with giant right atrium and tricuspid valve stenosis. It is highlighted that leadless pacemaker should not be discouraged even if there are tricuspid valve stenosis and giant right atrium.
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Marcapaso Artificial , Estenosis de la Válvula Tricúspide , Electrocardiografía , Femenino , Atrios Cardíacos/diagnóstico por imagen , Humanos , Persona de Mediana Edad , Estenosis de la Válvula Tricúspide/complicaciones , Estenosis de la Válvula Tricúspide/diagnóstico por imagen , Estenosis de la Válvula Tricúspide/terapiaRESUMEN
BACKGROUND: Although the associations of antioxidant micronutrients, such as carotenoids and vitamins, with cardiovascular diseases (CVDs) have been studied extensively, blood concentrations of antioxidant micronutrients and heart rate variability (HRV), which has been proven to be an indicator of cardiac autonomic control, has not been reported. We aimed to explore whether blood concentrations of antioxidant micronutrients, including carotenoids and vitamins, are associated with elevated heart rate variability (HRV (beneficial change) in a cross-sectional analysis. METHODS: Data were obtained from the Midlife in the United States (MIDUS) study that includes a general adult population. A total of 1074 (aged 34-84) individuals were included. Multivariable analyses were performed to investigate the association between main blood carotenoids (total lutein, zeaxanthin, beta-cryptoxanthin, 13-cis-beta-carotene, alpha-carotene, all-trans-beta-carotene and total lycopene) and vitamins A (retinol) and E (gamma-tocopherol and alpha-tocopherol) and HRV after adjustments were made for lifestyle factors and age-related confounders. RESULTS: Pearson correlation analyses showed that the increased levels of carotenoids and vitamins were positively correlated with higher HRV (all P < 0.05). After adjustments were made for age, gender, race, body mass index(BMI), ever-smoker, number of drinking years and exercise, blood alpha-carotene, all-trans-beta-carotene and total lycopene levels were independently associated with higher HRV in the linear regression model (all P < 0.05). Sensitivity analysis by adding "ever chronic respiratory diseases" as a covariate suggested that blood concentrations of these three carotenoids were still associated with higher low-frequency (LF)-HRV and high-frequency (HF)-HRV (all P < 0.05). Furthermore, stratified analyses suggested that the associations were affected by adding "heart disease" and "hypertension" as covariates. CONCLUSIONS: We provide the first evidence that elevated blood concentrations of alpha-carotene, trans-beta-carotene and lycopene are associated with beneficial changes in HRV in the general population. Daily intake of fruit and vegetables may be beneficial to increase blood carotenoid status and further prevent autonomic dysfunction.
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Enfermedades Cardiovasculares , beta Caroteno , Adulto , Carotenoides , Estudios Transversales , Frecuencia Cardíaca , Humanos , LicopenoRESUMEN
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.
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BACKGROUND: Recent basic studies demonstrate that the lung is a primary organ of platelet biogenesis. However, whether the pathophysiological state of the lung affect the platelets is little known. We aim to investigate the incidence of thrombocytopenia in patients with pulmonary infection (PIN) and risk factors associated with pulmonary thrombocytopenia. METHODS: In total, 11,941 patients with pulmonary infection (PIN) were enrolled, and patients with other three infectious diseases were collected as controls. The incidence of thrombocytopenia was compared, and the risk factors associated with thrombocytopenia in PIN patients were investigated by multivariate analysis. To explore the mechanism of thrombocytopenia, hypoxic model was constructed. Blood platelet counts from the angular vein (PLTs), left ventricle (PLTpost) and right ventricle (PLTpre) were determined. Megakaryocytes identified by anti-CD41 antibody were detected through flow cytometry and immunofluorescence. RESULTS: The incidence of thrombocytopenia in PIN was higher than that in other three infectious diseases (9.8% vs. 6.4% ~ 5.0%, P < 0.001). Low arterial oxygen partial pressure (PaO2) was an important risk factor for thrombocytopenia (OR = 0.88; P < 0.001). In a hypoxic mouse model, PLTs decreased (518.38 ± 127.92 vs 840.75 ± 77.30, P < 0.05), which showed that low PaO2 induced thrombocytopenia. The difference between the PLTpost and PLTpre (∆PLTpost-pre), representing the production of platelets in the lungs, was significantly attenuated in hypoxic mice when compared with normoxic mice (F = 25.47, P < 0.05). Additionally, proportions of CD41-positive megakaryocytes in the lungs, marrow, spleen all decreased in hypoxic mice. CONCLUSION: There is a high incidence for thrombocytopenia in PIN patients. Low PaO2-induced thrombocytopenia is associated with impaired generation of platelet in the lungs.
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Oxígeno/sangre , Recuento de Plaquetas , Neumonía/fisiopatología , Trombocitopenia/fisiopatología , Adulto , Anciano , Anciano de 80 o más Años , Animales , Modelos Animales de Enfermedad , Femenino , Citometría de Flujo , Técnica del Anticuerpo Fluorescente , Humanos , Hipoxia/fisiopatología , Modelos Logísticos , Masculino , Megacariocitos/patología , Ratones , Ratones Endogámicos C57BL , Persona de Mediana Edad , Presión Parcial , Neumonía/sangre , Trombocitopenia/sangreRESUMEN
The human leukocyte antigen F-associated transcript 10 (FAT10) is a member of the small ubiquitin-like protein family that binds to its target proteins and subjects them to degradation by the ubiquitin-proteasome system (UPS). In the heart, FAT10 plays a cardioprotective role and affects predisposition to cardiac arrhythmias after myocardial ischemia (MI). However, whether and how FAT10 influences cardiac arrhythmias is unknown. We investigated the role of FAT10 in regulating the sodium channel Nav1.5, a major regulator of cardiac arrhythmias. Fat10 was conditionally deleted in cardiac myocytes using Myh6-Cre and Fat10F/F mice (cFat10-/-). Compared with their wild-type littermates, cFat10-/- mice showed prolonged RR, PR, and corrected QT (QTc) intervals, were more likely to develop ventricular arrhythmia, and had increased mortality after MI. Patch-clamp studies showed that the peak Na+ current was reduced, and the late Na+ current was significantly augmented, resulting in a decreased action potential amplitude and delayed depolarization. Immunoblot and immunofluorescence analyses showed that the expression of the membrane protein Nav1.5 was decreased. Coimmunoprecipitation experiments demonstrated that FAT10 stabilized Nav1.5 expression by antagonizing Nav1.5 ubiquitination and degradation. Specifically, FAT10 bound to the lysine residues in the C-terminal fragments of Nav1.5 and decreased the binding of Nav1.5 to the Nedd4-2 protein, a ubiquitin E3 ligase, preventing degradation of the Nav1.5 protein. Collectively, our findings showed that deletion of the Fat10 in cardiac myocytes led to increased cardiac arrhythmias and increased mortality after MI. Thus, FAT10 protects against ischemia-induced ventricular arrhythmia by binding to Nav1.5 and preventing its Neddylation and degradation by the UPS after MI.
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Arritmias Cardíacas/genética , Isquemia Miocárdica/genética , Ubiquitina-Proteína Ligasas Nedd4/metabolismo , Ubiquitinas/metabolismo , Arritmias Cardíacas/patología , Humanos , Isquemia Miocárdica/patología , Procesamiento Proteico-PostraduccionalRESUMEN
Nifekalant has been used in the treatment of atrial arrhythmia recently. However, there is no consensus on the preferable nifekalant dose to treat atrial fibrillation (AF). The purpose of this study was to explore efficacy and safety of different doses of nifekalant in the cardioversion of persistent AF. The study was a single-centre, randomized controlled trial. All subjects received nifekalant or placebo intravenously, and the nifekalant was given at the dosage of 0.3, 0.4 or 0.5 mg/kg. Primary efficacy end-point: compared with 0.3 mg group, the rate of cardioversion to sinus rhythm from AF in 0.4 and 0.5 mg group was higher. The 0.4 and 0.5 mg/kg doses were associated with a similar magnitude of efficacy (P > .05). Secondary efficacy end-point: termination rates of AF in the group of 0.4 mg and 0.5 mg were higher than 0.3 mg. Primary safety end-point: the rate of Torsades de Pointes or ventricular fibrillation was numerically lower in the 0.4 mg group than 0.5 mg group (P = .02). Secondary safety end-point: The rates of the majority of other common drug-related adverse events in the group of 0.5 and 0.4 mg were higher than the 0.3 mg group. A 0.4 mg/kg dose of intravenous nifekalant may be recommended during the radiofrequency ablation for persistent AF considering the benefit-risk profile.
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Antiarrítmicos/uso terapéutico , Fibrilación Atrial/tratamiento farmacológico , Cardioversión Eléctrica , Pirimidinonas/uso terapéutico , Ablación por Radiofrecuencia , Anciano , Electrocardiografía/efectos de los fármacos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pirimidinonas/efectos adversosRESUMEN
BACKGROUND: The direct relationship between inflammation and depression in patients with diabetes is still unclear. We examined the association between serum C-reactive protein (CRP) levels and the high prevalence of depression in populations (aged ≥49 years) with and without type 2 diabetes. METHODS: Cross-sectional and longitudinal data from 3895 participants obtained from The Irish Longitudinal Study on Ageing (TILDA) were analyzed to determine the association between serum CRP levels and depression, accounting for relevant confounding factors. RESULTS: Multivariable analyses showed a positive association between serum CRP and depression score, independent of age and gender, BMI, marital status, education, smoking status, alcohol drinking status, systolic BP, diastolic BP, physical activity, self-reported CVDs and laboratory measurements in subjects with diabetes mellitus (coefficient = 0.179, P<0.001) but not in subjects without diabetes mellitus (coefficient = 0.011, P = 0.495). Higher serum CRP levels were associated with an increased risk of depressive symptoms in subjects with diabetes mellitus (OR = 1.301, 95% CI 1.012-1.799, P = 0.011) but not in subjects without diabetes mellitus (OR = 1.004, 95% CI 0.992-1.013, P = 0.344) after adjusting for these same confounding factors. After a follow-up of 4 years, higher serum CRP levels were significantly associated with a higher possibility of depression events in subjects with diabetes mellitus. LIMITATIONS: Time-varying confounding factors may interfere with our results. CONCLUSION: We observed a significant positive association between serum CRP levels and the prevalence of depressive symptoms in a middle-aged and elderly population with diabetes after adjustment for a range of lifestyle factors.