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BACKGROUND: Leadless pacemakers are a recent technological advancement. It has many advantages, but there are still a few serious complications. CASE PRESENTATION: This article reports the case of a patient with an endocardial tear and dissection caused by contact with the tip of the Micra cup during surgery and summarises the relevant data. CONCLUSIONS: This case report details the occurrence and management of the incident and provides some guidance for future clinical management.
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Marcapaso Artificial , Humanos , Resultado del Tratamiento , Diseño de EquipoRESUMEN
OBJECTIVE: Previous studies have reported that renal denervation (RDN) prevents the occurrence of atrial fibrillation (AF) related to obstructive sleep apnea (OSA). However, the effect of RDN on chronic OSA (COSA)-induced AF is still unclear. METHODS: Healthy beagle dogs were randomized into the OSA group (sham RDN + OSA), OSA-RDN group (RDN + OSA), and CON group (sham RDN + sham OSA). The COSA model was built via repeated apnea and ventilation rounds for 4 h each day lasting 12 weeks, and RDN was employed after 8 weeks of modeling. All dogs were implanted Reveal LINQ™ to detect spontaneous AF and AF burden. Circulating levels of norepinephrine, angiotensin II, and interleukin-6 were determined at baseline and end of the study. In addition, measurements of the left stellate ganglion, AF inducibility, and effective refractory period were conducted. The bilateral renal artery and cortex, left stellate ganglion, and left atrial tissues were collected for molecular analysis. RESULTS: Of 18 beagles, 6 were randomized to each of the groups described above. RDN remarkably attenuated ERP prolongation and AF episodes and duration. RDN markedly suppressed the LSG hyperactivity and atrial sympathetic innervation, decreased the serum concentrations of Ang II and IL-6, further inhibited fibroblast-to-myofibroblast transformation via the TGF-ß1/Smad2/3/α-SMA pathway, and reduced the expression of MMP-9, thus decreasing OSA-induced AF. CONCLUSIONS: RDN may reduce AF by inhibiting sympathetic hyperactivity and AF in a COSA model.
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Fibrilación Atrial , Apnea Obstructiva del Sueño , Animales , Perros , Atrios Cardíacos/patología , Riñón , Desnervación , FibrosisRESUMEN
BACKGROUND: Obstructive sleep apnea (OSA) is significantly associated with a higher risk of ventricular arrhythmia (VA). QT, the Tp-e/QT ratio, and QT dispersion (QTd) are used to evaluate myocardial repolarization and are highly correlated with VA. The aim was to evaluate the predictive value of the Tp-e/QT ratio and other electrocardiogram (ECG) parameters for nocturnal premature ventricular contractions (PVCs) in patients with OSA. METHODS: We retrospectively analyzed data from patients with OSA and conducted a 1:1 matched cohort study. Patients diagnosed with OSA who met our criteria for the PVC group, and sex- and age-matched patients with OSA who met our criteria for the control group were enrolled in the study. The Tp-e, Tp-e/QT ratio, corrected QT interval (QTc), corrected Tp-e interval (Tp-ec), and QTd were measured, calculated and analyzed. RESULTS: Patients in the PVC group (n = 31) showed a greater Tp-e, Tp-ec, QTc, Tp-e/QT ratio, and QTd than patients in the control group (n = 31). In the univariate binary logistic regression analysis, higher Tp-ec (OR: 1.025; P = 0.042), QTc (OR: 1.014; P = 0.036), Tp-e/QT ratio (OR: 1.675; P < 0.001), and QTd (OR: 1.052; P = 0.012) values were all significantly associated with nocturnal PVCs. In multivariate analysis and receiver operating characteristic analysis, a higher Tp-e/QT ratio (OR: 2.168; 95% CI: 0.762-0.952; P < 0.001) was an independent predictor of nocturnal PVCs. CONCLUSIONS: The QTc, Tp-e/QT ratio, and QTd in patients with OSA with nocturnal PVCs were significantly increased compared with those in patients without nocturnal PVCs. A prolonged Tp-e/QT ratio was an independent predictor of nocturnal PVCs in patients with OSA.
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Apnea Obstructiva del Sueño , Complejos Prematuros Ventriculares , Humanos , Complejos Prematuros Ventriculares/diagnóstico , Estudios Retrospectivos , Estudios de Cohortes , Electrocardiografía , Apnea Obstructiva del Sueño/diagnósticoRESUMEN
The aim of this study was to investigate the effect of nucleotide-binding oligomerization domain (NOD)-like receptor family CARD domain containing 5 (NLRC5) in cardiac hypertrophy, and to explore the mechanism implicated in this effect Cardiac hypertrophy was induced in neonatal rat cardiac myocytes using 1 µM of angiotensin II (Ang II) for 12, 24 and 48 h. Overexpression of NLRC5 was induced in H9C2 cells, and the NLRC5 + Ang II-treated cells were exposed to SC9 and 3-methyladenine (3MA). An immunofluorescence assay was used for α-actinin staining, and quantitative real-time reverse transcriptase-polymerase chain reaction (qRT-PCR) was performed for NLRC5, atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) determination. Western blot analysis was applied to measure the levels of NLRC5, microtubule-associated protein 1A/1B-light chain 3 type I (LC3I), LC3II, sequestosome 1 (p62), protein kinase B (AKT), phosphorylated Akt (pAKT), mammalian target of rapamycin (mTOR) and phosphorylated mTOR (pmTOR). The level of NLRC5 was significantly decreased after Ang II treatment in cardiomyocytes, but the levels of ANP and BNP were increased. Overexpression of NLRC5 reduced the cell size, downregulated the levels of ANP and BNP, increased LC3II / LC3I, but decreased p62 in Ang II-induced cardiomyocyte hypertrophy. In addition, the results from Western blot showed that overexpression of NLRC5 distinctly decreased the ratios of pAKT/AKT and pmTOR/mTOR in cardiomyocyte hypertrophy. SC79 and 3MA significantly downregulated the ratio of LC3I/LC3II but increased the level of p62 in NLRC5 + Ang II-treated cells. These results provide a possible novel therapeutic strategy for cardiac hypertrophy that might be useful in a clinical setting.
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Autofagia/efectos de los fármacos , Cardiomegalia/metabolismo , Proteínas NLR/farmacología , Serina-Treonina Quinasas TOR/efectos de los fármacos , Angiotensina II/farmacología , Animales , Autofagia/fisiología , Miocitos Cardíacos/metabolismo , Proteínas NLR/metabolismo , Proteínas Proto-Oncogénicas c-akt/efectos de los fármacos , Proteínas Proto-Oncogénicas c-akt/metabolismo , RatasRESUMEN
NEW FINDINGS: What is the central question of this study? Do autoantibodies to the M2 muscarinic receptor (M2R-AAbs) have the potential to facilitate specific sustained tachyarrhythmias in the presence of thyroxine (T4 ) in rabbits? What is the main finding and its importance? The M2R-AAb and T4 jointly destabilized the electrophysiological properties, thus promoting the occurrence of atrial and sinus tachyarrhythmias in rabbits. These findings provide a practical basis for understanding the pathophysiological role of M2R-AAb alone and with T4 in arrhythmia induction and might provide an innovative option for treatment of Graves' disease with rhythm disturbance. ABSTRACT: Activating autoantibodies toward the ß1/2 -adrenergic receptors (ß1/2AR-AAbs) and M2 muscarinic receptor (M2R-AAbs) are present in a high proportion of patients with Graves' disease. We previously demonstrated that ß1/2AR-AAbs with or without the presence of M2R-AAbs in combination with excessive thyroxine (T4 ) increased the induction of sustained tachyarrhythmias in an autoimmune rabbit model. However, the separate role of M2R-AAbs and their interaction with T4 are not clear. The aim of this study was to investigate the impact of M2R-AAbs and T4 on the induction of cardiac arrhythmias in a similar rabbit model. Ten New Zealand White rabbits were randomly divided into two groups. In group A (n = 6), the rabbits were immunized with the second extracellular loop peptide of M2R and subjected to 2 weeks of T4 treatment. In group B (n = 4), the rabbits were treated only with T4 for 2 weeks. After induction of general anaesthesia, rabbits were subjected to an electrophysiological study at 0 (pre-immune), 6 (post-immune) and 8 weeks (post-immune+T4 treatment) in group A and at 0 (baseline) and 8 weeks (T4 treatment) in group B. Each rabbit served as its own control. In group A, high levels and activity of M2R-AAbs were detected in all immunized animals. Thyroxine in combination with immunization significantly increased induction of sustained sinus tachycardia and atrial fibrillation in comparison to the pre-immune state. In group B, T4 predominantly induced sustained sinus tachycardia. This study demonstrated that M2R-AAbs and T4 jointly increased the susceptibility to both sinus and atrial tachyarrhythmias. The data supported the pathophysiological role of M2R-AAbs in hyperthyroidism-associated supraventricular tachyarrhythmias.
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Fibrilación Atrial , Animales , Conejos , Autoanticuerpos , Colinérgicos , Receptores Adrenérgicos beta 1 , Taquicardia Sinusal , Hormonas TiroideasRESUMEN
NEW FINDINGS: What is the central question of this study? Is there a causal relationship between gonadotrophin-releasing hormone (GnRH) receptor-activating autoantibodies and polycystic ovary syndrome (PCOS)? What is the main finding and its importance? Induction of GnRH receptor-activating autoantibodies in rats resulted in increased luteinizing hormone pulsatility and testosterone concentrations, disrupted oestrous cycles, increased atretic follicles, and activation of insulin signalling in the pituitary and ovary. These changes replicate those seen in humans with PCOS, suggesting that GnRH receptor-activating autoantibodies might be involved in the pathogenesis of PCOS. ABSTRACT: Gonadotrophin-releasing hormone receptor-activating autoantibodies (GnRHR-AAb) are associated with polycystic ovary syndrome (PCOS). In the present study, we examined the impact of GnRHR-AAb on reproductive function in GnRHR-immunized female rats. All immunized rats produced high titres of GnRHR-AAb targeting a dominant epitope located in the central region of the second extracellular loop of the GnRHR. Increased pulsatile luteinizing hormone secretion and testosterone concentrations were found in immunized rats. These rats exhibited disrupted oestrous cycles, increased ovarian follicular atresia, and activation of insulin signalling in the pituitary and ovary, as indicated by increased mRNA expressions of insulin receptor substrate, phosphatidylinositol 3-kinase and glucose transporter 1. No significant changes in inflammatory cytokines were detected in the ovarian tissue. These features mimic those observed in humans with PCOS. Our findings support the concept that chronic stimulation of the GnRHR by GnRHR-AAb, with an associated increase in pituitary luteinizing hormone secretion and ovarian androgen overproduction, might represent a new aetiological mechanism for PCOS.
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Síndrome del Ovario Poliquístico , Animales , Autoanticuerpos , Femenino , Atresia Folicular , Hormona Liberadora de Gonadotropina , Hormona Luteinizante , Síndrome del Ovario Poliquístico/metabolismo , Ratas , Receptores LHRHRESUMEN
BACKGROUND: Obstructive sleep apnoea (OSA) is closely related to atrial fibrillation (AF), and OSA-induced atrial structural remodelling is the basis of AF maintenance. However, the process of atrial structural remodelling during the progression of acute OSA to chronic OSA is still unclear. OBJECTIVE: To investigate changes in the atrial myocardium in acute sleep apnoea (6 h) and chronic sleep apnoea (12 weeks) by echocardiography, atrial myocardium morphology analysis, PAS staining, TUNEL staining, Masson's trichrome staining and analyses of ultrastructural changes. METHODS: Eighteen adult beagle dogs under general anaesthesia were used to establish an OSA model. The animals were divided into the control group, acute OSA group and chronic OSA group, and there were six animals in each group. Cardiac ultrasounds of dogs from the three groups were examined. Left and right atrial muscle tissues were taken for HE staining, PAS staining, TUNEL staining, Masson's trichrome staining and transmission electron microscopy. RESULTS: In the acute OSA model, the left atrial diameter of the dogs began to increase 3 h after ventilation, and this difference was more obvious at 6 h. The morphology of the myocardial cells did not change significantly, but mitochondrial swelling was observed in some atrial myocytes at 3 h. In the chronic OSA model, the left atrial diameter gradually increased, the volume of the right and left atria increased, the glycogen and collagen volume fractions and apoptosis ratio were significantly increased in atrial myocytes, mitochondria swelling and lengthening occurred in some atrial myocytes, the matrix became lighter, the mitochondrial ridge density decreased and the myofilament arrangement was disordered. The disc was distorted and not continuous, and there was some cardiomyocyte necrosis. CONCLUSION: With the prolongation of apnoea, the atrium gradually enlarges, myocardial cells become disordered, glycogen aggregates, the number of necrotic cells increases, fibrosis worsens, mitochondrial abnormalities occur and the arrangement of the discs are disordered, providing a basis for the maintenance of AF.
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Fibrilación Atrial/etiología , Atrios Cardíacos/patología , Apnea Obstructiva del Sueño/complicaciones , Apnea Obstructiva del Sueño/patología , Animales , Modelos Animales de Enfermedad , Progresión de la Enfermedad , PerrosRESUMEN
A Cr(VI)-reducing Mangrovibacter plantisponsor strain, CR1, was isolated from tannery effluent sludge and had quinone respiration characteristics. Its chromate (CrO4 (2-) ) resistance, quinone respiration characteristics, and Cr(VI) reduction efficiencies were evaluated in detail. Strain CR1 exhibited a high Cr(VI) resistance with a minimal inhibitory concentration (MIC) of 32 mM in LB medium, and its quinone respiration could occur when an electron donor and strain CR1 both existed in the reaction system. Cr(VI) reduction by strain CR1 was significantly enhanced by a factor of 0.4-4.3 with five different quinone compounds: anthraquinone-2,7-disulfonate, anthraquinone-1-sulfonate, anthraquinone-2-sulfonate (AQS), anthraquinone-2,6-disulfonate, and anthraquinone-1,5-disulfonate. AQS was the best electron shuttle among them, and the greatest enhancement to the Cr(VI) bio-reduction was achieved with 0.96 mM AQS. The correlation between the reaction constant k (mg Cr(VI) g(-1) dry cell weight H(-1) ) and thermodynamic temperature T (K) was expressed as an Arrhenius equation lnk=-7662.9/T+27.931(R2=0.9486); the activation energy Ea was 63.71 kJ mol(-1) , and the pre-exponential factor A was 1.35 × 10(12) mg Cr(VI) g(-1) dry cell weight H(-1) . During the Cr(VI) reduction process, the pH tended to become neutral, and the oxidation-reduction potential decreased to -440 mV. The efficient reduction of Cr(VI) mediated by a quinone respiration strain shows potential for the rapid anaerobic removal of Cr(VI).
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Benzoquinonas/metabolismo , Cromo/aislamiento & purificación , Cromo/metabolismo , Enterobacteriaceae/metabolismo , Contaminantes Ambientales/aislamiento & purificación , Contaminantes Ambientales/metabolismo , Benzoquinonas/farmacología , Biodegradación Ambiental , Enterobacteriaceae/efectos de los fármacos , Concentración de Iones de Hidrógeno , Oxidación-Reducción/efectos de los fármacos , TemperaturaRESUMEN
Electrochemical oxidation of Acid Red 3R (AR3R) was investigated with the new catalyst of iron phosphomolybdate (FePMo12) supported on modified molecular sieves type 4 Å (4A) as packing materials in the reactor. The results of the Fourier transform infrared spectroscopy and X-ray diffraction indicated that the heteropolyanion had a Keggin structure. The optimal conditions for decolorization of simulated AR3R wastewater were as follows: current density 35 mA/cm², initial pH 4.0, airflow 0.08 m³/hour and inter-electrode distance 3.0 cm. With the addition of NaCl to the system, the decolorization efficiency increased. But Na2SO4had a negative effect on the decolorization efficiency, which was attributed to the negative salt effect. The degradation mechanisms of AR3R were also discussed in detail.
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Eritrosina/química , Colorantes Fluorescentes/química , Molibdeno/química , Ácidos Fosfóricos/química , Contaminantes Químicos del Agua/química , Técnicas Electroquímicas , Hierro/química , Oxidación-Reducción , Espectroscopía Infrarroja por Transformada de Fourier , Aguas Residuales/análisis , Difracción de Rayos XRESUMEN
In this paper, the effect of NaCl and Na2SO4 on the biodecolourization of reactive brilliant red K-2BP by a Halomonas sp. GYW (EF188281) was investigated in details. The decolourisation efficiency and the oxidation-reduction potential (ORP) change were explored during the decolourization process. The results from sequencing batch tests showed that Na2SO4 influenced the decolourization efficiency more slightly than NaCl in different synthetic dye solutions with different mixtures of Na2SO4 and NaCl. In the dye solutions with the same salt concentration or the same Na+ concentration, high Na2SO4 concentration did not inhibit the decolourization process and even stimulated the decolourization efficiency of reactive brilliant red K-2BP. Compared to NaCl system, the addition of Na2SO4 increased the ORP values about 35 mV, which agreed with the theoretic analysis of Gibbs function. This study improved our knowledge of azo dye decolourization under high salinity conditions and provided efficient option for the treatment of azo dye wastewater.
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Background: Coronary slow flow phenomenon (CSFP) is a phenomenon in which distal vascular perfusion is delayed on angiography, but coronary arteries are not significantly narrowed and there is no other organic cardiac disease. Patients with CSFP may be repeatedly readmitted to the hospital because of chest pain or other symptoms of precordial discomfort, and there is a risk of adverse events. In order to investigate the risk factors affecting the readmission of CSFP patients, a prediction model was constructed with the aim of identifying patients at risk of readmission at an early stage and providing a reference for further clinical intervention. Methods: In this study, we collected clinical data from 397 CSFP patients between June 2021 and January 2023 in Xinjiang Medical University Hospital. Telephone follow-up clarified whether the patients were readmitted to the hospital. A predictive model for readmission of CSFP patients was constructed using multifactorial logistic regression. Nomogram was used to visualize the model and bootstrap was used to internally validate the model. ROC, DCA and Calibration curve were plotted to evaluate the calibration and discriminative ability of the column line graphs, respectively. Calibration and resolution of the column line graphs, respectively. Results: A total of 34 of 397 CSFP patients experienced readmission. Smoking history, creatine kinase isoenzyme-MB, total cholesterol, and left ventricular ejection fraction were the predictors of readmission in patients with CSFP. The area under the curve of the Nomogram model was 0.87, which indicated that the model had good predictive ability and differentiation, and the DCA and Calibration curves also indicated that the model had good consistency and was clinically useful. Conclusion: A readmission prediction model for patients with CSFP may facilitate early identification of patients at potential risk for readmission and timely interventional therapy to improve patient prognosis.
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Glycosaminoglycan (GAG) lyases are important tools for investigating the structure of GAGs and preparing low-molecular-weight GAGs. The PL35 family, a recently established polysaccharide lyase family, should be further investigated. In this study, we discovered a new GAG lyase, CHa1, which belongs to the PL35 family. When expressed heterologously in Escherichia coli (BL21), CHa1 exhibited high expression levels and solubility. The optimal activity was observed in Tris-HCl buffer (pH 7.0) or sodium phosphate buffer (pH 8.0) at 30 °C. The specific activities towards HA, CSA, CSC, CSD, CSE, and HS were 3.81, 13.03, 36.47, 18.46, 6.46, and 0.50 U/mg protein, respectively. CHa1 digests substrate chains randomly that acting as an endolytic lyase and shows a significant preference for GlcA-containing structures, prefers larger oligosaccharides (≥UDP8) and can generate a series of oligosaccharides composed mainly of the A unit when digesting CSA. These oligosaccharides include ΔC-A, ΔC-A-A, ΔC-A-A-A, ΔC-A-A-A-A, and ΔC-A-A-A-A-A. The residues Tyr257 and His421 play crucial roles in the catalytic process, and Ser211, Asn212, Asn213, Trp214, Gln216, Lys360, Arg460 and Gln462 may participate in the binding process of CHa1. This study on CHa1 contributes to our understanding of the PL35 family and provides valuable tools for investigating the structure of GAGs.
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Polisacárido Liasas , Polisacárido Liasas/química , Polisacárido Liasas/metabolismo , Polisacárido Liasas/genética , Especificidad por Sustrato , Acetilgalactosamina/química , Acetilgalactosamina/metabolismo , Escherichia coli/genética , Glicosaminoglicanos/metabolismo , Glicosaminoglicanos/química , Secuencia de Aminoácidos , Oligosacáridos/química , Oligosacáridos/metabolismoRESUMEN
BACKGROUND: The incidence of heart failure (HF) presents an escalating trend annually, second only to cancer. Few literatures are available regarding on the role of paraoxonase 2 (PON2) in HF so far despite the protective role of PON2 in cardiovascular diseases. METHODS: PON2 expression in AC16 cells was examined with reverse transcriptase-quantitative polymerase chain reaction and western blot following angiotensin II (Ang II) challenging. After PON2 elevation, 2, 7-dichlorofluorescein diacetate assay estimated reactive oxygen species content, related kits appraised oxidative stress, enzyme-linked immunosorbent assay evaluated inflammatory levels, and Western blot was applied to the analysis of apoptosis levels. Research on cytoskeleton was conducted by immunofluorescence (IF), and Western blot analysis of the expressions of hypertrophy-related proteins was performed. BioGRID and GeneMania databases were used to analyze the relationship between PON2 and Calnexin (CANX), which was corroborated by co-immunoprecipitation experiment. Subsequently, PON2 and CANX were simultaneously overexpressed in AC16 cells induced by Ang II to further figure out the mechanism. RESULTS: PON2 expression was depleted in Ang II-induced AC16 cells. PON2 might mediate CANX/NOX4 signaling to inhibit oxidation, inflammatory, hypertrophy, and damage in Ang II-induced AC16 cells. CONCLUSION: PON2 can ease Ang II-induced cardiomyocyte injury via targeting CANX/NOX4 signaling.
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Angiotensina II , Arildialquilfosfatasa , Calnexina , Miocitos Cardíacos , NADPH Oxidasa 4 , Humanos , Angiotensina II/farmacología , Arildialquilfosfatasa/metabolismo , Calnexina/metabolismo , Hipertrofia/metabolismo , Miocitos Cardíacos/metabolismo , NADPH Oxidasa 4/metabolismo , Transducción de SeñalRESUMEN
Background: Recent studies have demonstrated that antiadrenergic autoantibodies are involved in the pathophysiology of postural orthostatic tachycardia syndrome (POTS). Objective: The purpose of this study was to test the hypothesis that transcutaneous low-level tragus stimulation (LLTS) ameliorates autoantibody-induced autonomic dysfunction and inflammation in a rabbit model of autoimmune POTS. Methods: Six New Zealand white rabbits were co-immunized with peptides from the α1-adrenergic and ß1-adrenergic receptors to produce sympathomimetic antibodies. The tilt test was performed on conscious rabbits before immunization, 6 weeks after immunization, and 10 weeks after immunization with 4-week daily LLTS treatment. Each rabbit served as its own control. Results: An enhanced postural heart rate increase in the absence of significant change in blood pressure was observed in immunized rabbits, confirming our previous report. Power spectral analysis of heart rate variability during the tilt test showed a predominance of sympathetic over parasympathetic activity in immunized rabbits as reflected by markedly increased low-frequency power, decreased high-frequency power, and increased low-to-high-frequency ratio. Serum inflammatory cytokines were also significantly increased in immunized rabbits. LLTS suppressed the postural tachycardia, improved the sympathovagal balance with increased acetylcholine secretion, and attenuated the inflammatory cytokine expression. Antibody production and activity were confirmed with in vitro assays, and no antibody suppression by LLTS was found in this short-term study. Conclusion: LLTS improves cardiac autonomic imbalance and inflammation in a rabbit model of autoantibody-induced hyperadrenergic POTS, suggesting that LLTS may be used as a novel neuromodulation therapy for POTS.
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PURPOSE: Previous studies demonstrated M2 muscarinic acetylcholine receptor-activating autoantibodies (M2R-AAb) were present in some patients with postural tachycardia syndrome (POTS). This study examines how these autoantibodies might contribute to the pathophysiology of POTS, and whether low-level tragus stimulation (LLTS) can ameliorate autoantibody-mediated autonomic dysregulation in the rabbit. METHODS: Five New Zealand white rabbits were immunized with a M2R second extracellular loop peptide to produce cholinomimetic M2R-AAb. Tilt test and infusion studies were performed on conscious rabbits before immunization, 6 weeks after immunization, and 8 weeks after immunization with 2-week daily LLTS treatment. Each rabbit served as its own control. RESULTS: Compared to preimmune state, an enhanced heart rate increase and decreased parasympathetic activity upon tilting were observed in immunized rabbits. Furthermore, these rabbits demonstrated an attenuated heart rate-slowing response to infusion of the M2R orthosteric agonist arecaidine propargyl ester (APE), suggesting an inhibitory allosteric effect of M2R-AAb. There was also a significant increase in serum inflammatory cytokines in immunized rabbits. LLTS treatment suppressed the postural tachycardia, improved the sympathovagal balance with increased acetylcholine secretion, reduced the levels of inflammatory cytokines, and reversed the attenuated heart rate response to APE in immunized rabbits. No suppression of M2R-AAb expression by LLTS was found during this short-term study period. Receptor-modulating activity of M2R-AAb produced in immunized rabbits was confirmed with in vitro bioassay. CONCLUSIONS: Autoantibody inhibition of cholinergic ligand activity may be involved in the development of cardiovagal dysfunction and inflammation associated with POTS, both of which can be improved by vagal stimulation.
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Hominidae , Síndrome de Taquicardia Postural Ortostática , Estimulación del Nervio Vago , Conejos , Animales , Autoanticuerpos/metabolismo , Síndrome de Taquicardia Postural Ortostática/terapia , Inflamación , Hominidae/metabolismo , Nervio Vago/metabolismoRESUMEN
Objective: This study aimed to identify a newly identified target involved in atrial fibrillation (AF) linked to chronic obstructive sleep apnea (COSA) through an integrative analysis of transcriptome and proteome. Methods: Fifteen beagle canines were randomly assigned to three groups: control (CON), obstructive sleep apnea (OSA), and OSA with superior left ganglionated plexi ablation (OSA+GP). A COSA model was established by intermittently obstructing the endotracheal cannula during exhalation for 12 weeks. Left parasternal thoracotomy through the fourth intercostal space allowed for superior left ganglionated plexi (SLGP) ablation. In vivo open-chest electrophysiological programmed stimulation was performed to assess AF inducibility. Histological, transcriptomic, and proteomic analyses were conducted on atrial samples. Results: After 12 weeks, the OSA group exhibited increased AF inducibility and longer AF durations compared to the CON group. Integrated transcriptomic and proteomic analyses identified 2422 differentially expressed genes (DEGs) and 1194 differentially expressed proteins (DEPs) between OSA and CON groups, as well as between OSA+GP and OSA groups (1850 DEGs and 1418 DEPs). The analysis revealed that differentially regulated DEGs were primarily enriched in mitochondrial biological processes in the CON-vs.-OSA and OSA-vs.-GP comparisons. Notably, the key regulatory molecule GSTZ1 was activated in OSA and inhibited by GP ablation. Conclusion: These findings suggest that GSTZ1 may play a pivotal role in mitochondrial damage, triggering AF substrate formation, and increasing susceptibility to AF in the context of COSA.
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To assess pacing and electrophysiological parameters, as well as mid-term outcomes, among patients undergoing His bundle pacing (HBP) guided by KODEX-EPD (a novel mapping system). Consecutive patients undergoing conduction system pacing (CSP) for bradycardia indications were evaluated. Procedural and fluoroscopic times and pacing characteristics were compared between conventional fluoroscopy (the standard group, N = 20 cases) and KODEX-EPD mapping system guided group (the KODEX group, N = 20cases) at CSP implantation and all patients were followed at 6-month. HBP was achieved in all patients (the standard group 20/20 and the KODEX group 20/20). There was no difference in the mean procedure time between the two groups (63.7 ± 9.3 vs. 78.2 ± 25.1 min, p = 0.33). Compared with the standard group, the KODEX group significantly reduced the intraoperative X-ray exposure time (3.8 ± 0.5 vs. 19.3 ± 5.1 min, p < 0.05) and X-ray dose (23.6 ± 5.4 vs. 120.2 ± 38.3 mGy, p < 0.05). There were no significant differences in atrial impedance (643.0 ± 98.8 vs. 591.5 ± 92.1 Ω, p = 0.09), atrial sensing (2.9 ± 0.8 vs. 2.5 ± 0.8 mV, p = 0.08), ventricular sensing (12.8 ± 2.4 vs. 13.3 ± 3.3 mV, p = 0.63),atrial pacing threshold (1.0 ± 0.2 vs. 1.0 ± 0.1 V/0.4 ms, p = 0.81) and ventricular pacing threshold (1.0 ± 0.2 vs. 0.9 ± 0.1 V/0.4 ms, p = 0.63) between two groups, There were statistical differences in ventricular impedance (640.0 ± 80.3 vs. 702.0 ± 86.1 Ω, p < 0.05). There was no statistical significance in pacing parameters between the two groups at 6 months after procedure (p > 0.05). During the 6-months follow-up period, no adverse events occurred in the two groups. It can be concluded that KODEX-EPD can safely guide His bundle branch pacing lead implantation with reduced fluoroscopic time and dose without lengthening the procedure time.
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Fibrilación Atrial , Marcapaso Artificial , Humanos , Estudios Prospectivos , Fascículo Atrioventricular , Estimulación Cardíaca Artificial/métodos , Estudios de Factibilidad , Fibrilación Atrial/etiología , Trastorno del Sistema de Conducción Cardíaco , Resultado del Tratamiento , Electrocardiografía/métodosRESUMEN
To evaluate the feasibility of cryoballoon (CB) ablation of atrial fibrillation (AF) under the guidance of a new three-dimensional (3D) mapping system KODEX-EPD. 40 patients scheduled for CB ablation of AF in the first affiliated Hospital of Xinjiang Medical University from August 2021 to July 2022 were randomly divided into two groups: KODEX-EPD 3D mapping system guidance group (KODEX group, n = 20) and conventional two-dimensional perspective group (standard group, n = 20). The ablation time, operation time, fluoroscopy time, fluoroscopy dose, contrast agent dosage and follow-up data were compared between the two groups. Besides, the feasibility and accuracy of the dielectric sensing system in evaluating pulmonary vein (PV) occlusion in patients with AF during CB ablation were verified. All pulmonary veins were being isolated. The ablation time (36.40 ± 6.72 min vs 35.15 ± 6.29 min, P > 0.05) and the operation time (64.20 ± 11.82 min vs 66.00 ± 13.18 min, P > 0.05) were not statistically different in the two groups. The standard group has longer fluoroscopy time, dose and contrast medium dosage. There were significant differences in fluoroscopy time (532.30 ± 72.83 s vs 676.25 ± 269.33 s, P < 0.05), fluoroscopy dose (110.00 ± 28.64 mGy vs 144.68 ± 66.66 mGy, P < 0.05), and contrast medium dosage (71.90 ± 5.97 ml vs 76.05 ± 5.93 ml, P < 0.05) between the two groups. The learning curves of the first 5 patients and the last 15 patients in the KODEX group were compared. There was no statistical difference in the ablation time (36.80 ± 8.56 min vs 36.27 ± 6.34 min, P > 0.05) or the operation time (69.00 ± 5.00 min vs 62.60 ± 13.10 min, P > 0.05); however, compared to the first 5 patients, fluoroscopy time (587.40 ± 38.34 s vs 513.93 ± 73.02 s, P < 0.05), fluoroscopy dose (147.85 ± 35.19 mGy vs 97.39 ± 8.80 mGy, P < 0.05) and contrast medium dosage (79.60 ± 1.14 ml vs 69.33 ± 4.45 ml, P < 0.05) were significantly decreased. Using pulmonary venography as the gold standard, the sensitivity, specificity of the completely occlusion in KODEX group was 93.6% (95% CI 85-97.6%) and 69.6% (95% CI 54-81.8%); and the sensitivity, specificity of the small leak in KODEX group was 93.1% (95% CI 82.4-97.8%) and 82.0% (95% CI 65.9-91.9%). During an average follow-up of (9.90 ± 1.06) months, there was no statistical difference in arrhythmia recurrence and antiarrhythmic drugs taking after CB ablation between the two groups (P > 0.05). Using the KODEX-EPD system, the CB ablation procedure can correctly evaluate the PV occlusion, and significantly reduce fluoroscopy exposure and contrast medium without significantly increasing the operation time.
Asunto(s)
Fibrilación Atrial , Ablación por Catéter , Criocirugía , Venas Pulmonares , Humanos , Fibrilación Atrial/diagnóstico por imagen , Fibrilación Atrial/cirugía , Estudios de Factibilidad , Criocirugía/métodos , Medios de Contraste , Venas Pulmonares/diagnóstico por imagen , Venas Pulmonares/cirugía , Ablación por Catéter/métodos , Resultado del Tratamiento , RecurrenciaRESUMEN
PURPOSE: We have recently demonstrated that gonadotrophin-releasing hormone receptor-activating autoantibodies (GnRHR-AAb) are associated with polycystic ovary syndrome (PCOS). The aim of this study was to map the antigenic epitopes of GnRHR-AAb from PCOS patients, and develop retro-inverso peptide inhibitors that specifically target GnRHR-AAb. METHODS: Serum samples from ten GnRHR-AAb-positive PCOS patients and ten GnRHR-AAb-negative healthy controls were tested. Epitope mapping for GnRHR-AAb was performed using a set of 11 overlapping octapeptides spanning the second extracellular loop of GnRHR. Antibody-blocking effect of the designed retro-inverso peptide inhibitors was evaluated in a cell-based bioassay. RESULTS: Two peptide sequences, FSQCVTHC and HCSFSQWW, were found to react with all PCOS sera, but not with control sera. Two retro-inverso peptides that mimic the identified epitopes, d-CHTVCQSF and d-WWQSFSCH, significantly inhibited PCOS serum IgG-induced GnRHR activation. One of these two peptide inhibitors, d-CHTVCQSF, largely suppressed autoantibody-induced GnRHR activation, suggesting that the epitope sequence FSQCVTHC may be a major functional target of GnRHR-AAb. CONCLUSION: We have identified a dominant functional epitope for GnRHR-AAb associated with PCOS, and demonstrated effective blocking of GnRHR-AAb activity with epitope-mimicking retro-inverso peptide inhibitors. These proteolytically stable decoy peptides may have important therapeutic implications in subjects who harbor these autoantibodies.
Asunto(s)
Síndrome del Ovario Poliquístico , Autoanticuerpos , Epítopos , Femenino , Humanos , Péptidos , Receptores LHRHRESUMEN
Actual pharmaceutical wastewater was pretreated with ozone microbubbles and compared with the treatment processes of nitrogen microbubbles, ozone common bubbles, and nitrogen common bubbles. The removal process and performance of suspended solids (SS) and organic compounds were investigated. The results showed that ozone microbubble treatment with strong adsorption-flotation-oxidation effects could enhance SS removal significantly, and the corresponding SS removal efficiency reached 81.67% at 60 min. The SS particle size was reduced, and the negative charge on the SS surface was simultaneously changed into a positive charge. Microbubble ozonation with a strong·OH oxidation effect also significantly enhanced the degradation and removal of organic compounds. The removal efficiency of soluble COD (SCOD) reached 36.60% at 60 min, and the SCOD removal was accelerated after the SS removal. The removal efficiency of UV254 also reached 36.91%. The biodegradability was improved, and the biological toxicity was obviously eliminated. The analysis of three-dimensional fluorescence and GC-MS showed that the macromolecular organic compounds with complex structure could be oxidized and decomposed efficiently with microbubble ozonation, resulting in the aromatic reduction in organic compounds in wastewater. Therefore, microbubble ozonation could be considered as an efficient and feasible pretreatment method for high concentration and refractory pharmaceutical wastewater.