RESUMO

OBJECTIVE: To investigate the effect of pulmonary vein antrum enlargement combined with left atrial roof cryoballoon ablation in patients with persistent atrial fibrillation (PeAF) by analyzing the relationship between left atrial isolation area surface area (ISA) and early postoperative recurrence. METHODS: 93 patients with PeAF were classified into recurrence and non-recurrence groups according to the results of the 1-year follow-up. Three-dimensional electroanatomical labeling map was constructed and merged with that of the left atrial pulmonary vein CTA, and the ISA and the left atrial surface area (LASA) were measured and analyzed to determine the relationship between ISA/LASA in relation to early postoperative recurrence. RESULTS: 93 patients were included and followed up for 1 year with AF-free recurrence rate of 75.3%. The ISA of the recurrence group was lower than that of the non-recurrence group. Left atrial internal diameter (LAD), left common pulmonary vein, the ISA, the ISA/LASA and early-term recurrence had statistical significance in both groups. The factors that significantly predicted early-term recurrence were left common pulmonary vein and the ISA/LASA. ISA/LASA (HR 0, 95% CI 0-0.005, P = 0.008) and left common pulmonary vein trunk (HR 7.754, 95% CI 2.256-25.651, P = 0.001) were the independent risk factors for early recurrence. ROC curve analysis showed that ISA/LASA predicted the best early recurrence after operation with a cut-off value of 15.2%. CONCLUSION: A greater ISA/LASA reduces early recurrence after cryoablation in patients with PeAF. An ISA/LASA of 15.2% may be the best cut-off value for predicting early recurrence after cryoablation for PeAF.

Assuntos

Fibrilação Atrial , Criocirurgia , Átrios do Coração , Veias Pulmonares , Recidiva , Humanos , Fibrilação Atrial/cirurgia , Fibrilação Atrial/fisiopatologia , Masculino , Feminino , Pessoa de Meia-Idade , Criocirurgia/métodos , Criocirurgia/efeitos adversos , Átrios do Coração/cirurgia , Átrios do Coração/diagnóstico por imagem , Átrios do Coração/fisiopatologia , Veias Pulmonares/cirurgia , Idoso , Ablação por Cateter/métodos , Ablação por Cateter/efeitos adversos , Resultado do Tratamento

RESUMO

BACKGROUND AND AIMS: Evidence is increasingly suggesting that shift work is a risk factor for cardiometabolic disease. However, the causal relationship between shift work and cardiometabolic disease is not yet fully understood. In this study, we employed two-sample Mendelian randomization (MR) to investigate the causal relationship between shift work and the risk of cardiometabolic outcomes. METHODS AND RESULTS: Genome-wide association study (GWAS) statistics for shift work were obtained from the UK Biobank. Mendelian randomization analyses were conducted to explore the causal effects of shift work on cardiometabolic outcomes, using single-nucleotide polymorphisms (SNPs) as instrumental variables. The results suggested a causal effect between shift work and body mass index, body fat percentage, triglycerides, high-density lipoprotein, type 2 diabetes, hypertension, and cardiorespiratory fitness. After correcting for multiple tests, only body mass index and high-density lipoprotein showed significant associations. No causal effects were found between shift work and overweight, obesity, total cholesterol, low-density lipoprotein, fasting glucose, 2-h glucose, fasting insulin, coronary artery disease, myocardial infarction, heart failure, atrial fibrillation, or ischemic stroke. CONCLUSION: This MR study provides genetic evidence for a suggestive causal link between shift work and certain cardiometabolic outcomes. Our research may have the significance of providing insight into public hygiene to improve the understanding of shift work and cardiometabolic disease risk. Further experimental studies are needed to confirm our findings.

RESUMO

The E-twenty-six variant 1 (ETV1)-dependent transcriptome plays an important role in atrial electrical and structural remodelling and the occurrence of atrial fibrillation (AF), but the underlying mechanism of ETV1 in AF is unclear. In this study, cardiomyocyte-specific ETV1 knockout (ETV1f/fMyHCCre/+, ETV1-CKO) mice were constructed to observe the susceptibility to AF and the underlying mechanism in AF associated with ETV1-CKO mice. AF susceptibility was examined by intraesophageal burst pacing, induction of AF was increased obviously in ETV1-CKO mice than WT mice. Electrophysiology experiments indicated shortened APD50 and APD90, increased incidence of DADs, decreased density of ICa,L in ETV1-CKO mice. There was no difference in VINACT,1/2 and VACT,1/2, but a significantly longer duration of the recovery time after inactivation in the ETV1-CKO mice. The recording of intracellular Ca2+ showed that there was significantly increased in the frequency of calcium spark, Ca2+ transient amplitude, and proportion of SCaEs in ETV1-CKO mice. Reduction of Cav1.2 rather than NCX1 and SERCA2a, increase RyR2, p-RyR2 and CaMKII was reflected in ETV1-CKO group. This study demonstrates that the increase in calcium spark and SCaEs corresponding to Ca2+ transient amplitude may trigger DAD in membrane potential in ETV1-CKO mice, thereby increasing the risk of AF.

Assuntos

Fibrilação Atrial , Cálcio , Átrios do Coração , Camundongos Knockout , Miócitos Cardíacos , Fatores de Transcrição , Animais , Miócitos Cardíacos/metabolismo , Camundongos , Fibrilação Atrial/metabolismo , Fibrilação Atrial/genética , Cálcio/metabolismo , Átrios do Coração/metabolismo , Fatores de Transcrição/metabolismo , Fatores de Transcrição/genética , Proteínas de Ligação a DNA/metabolismo , Proteínas de Ligação a DNA/genética , Sinalização do Cálcio , Potenciais de Ação , Potenciais da Membrana , Masculino

RESUMO

Background: Acral persistent papular mucinosis (APPM) is a rare idiopathic subtype of localized lichen myxedematosus. To date, there have been less than 41 APPM cases reported worldwide, however, almost all patients were older than 18 years of age. A 7-year-old child was first reported in this paper. Case Description: A 7-year-old boy was admitted to our hospital with a solitary skin-colored papule on the radial side of the middle segment of his right index finger. The patient wanted to know the exact diagnosis and remove it because the flexion movement of the middle segment had been affected. Thus, a surgery was performed. Histopathological examination of a biopsy specimen obtained from the papule on the radial side of the middle segment of his right index finger showed a focal and well-circumscribed deposit of mucin in the papillary and middermis. The deposit never extended deeply into the reticular dermis. Mucin spared a subepidermal area in the papillary dermis. Alcian blue stains can highlight the mucin. The papule was histologically diagnosed as an APPM and excised surgically. The wound gradually healed after the operation, and no obvious recurrence, scar or other discomfort was observed during follow-up so far. Conclusions: To the best of our knowledge, this is the rare case of a child APPM presenting as a solitary papule affecting the flexion movement of the middle segment. Since it is a rare disease, we report this case to contribute to future research on the diagnosis and pathogenesis of APPM.

RESUMO

We describe a case of necrotizing fasciitis in the United Kingdom in which Pseudomonas guariconensis was isolated from multiple blood culture and tissue samples. The organism carried a Verona integron-encoded metallo-ß-lactamase gene and evidence of decreased susceptibility to ß-lactam antimicrobial agents. Clinicians should use caution when treating infection caused by this rare pathogen.

Assuntos

Fasciite Necrosante , Infecções por Pseudomonas , Humanos , Pseudomonas aeruginosa/genética , Infecções por Pseudomonas/diagnóstico , Infecções por Pseudomonas/tratamento farmacológico , Infecções por Pseudomonas/epidemiologia , Fasciite Necrosante/diagnóstico , Fasciite Necrosante/tratamento farmacológico , Fasciite Necrosante/epidemiologia , beta-Lactamases/genética , beta-Lactamases/metabolismo , Antibacterianos/uso terapêutico , Integrons , Reino Unido/epidemiologia , Testes de Sensibilidade Microbiana

RESUMO

BACKGROUND: Using self-expanding metal stents (SEMS) and decompression tubes (DT) as a bridge-to-surgery (BTS) treatment may avoid emergency operations for patients with colorectal cancer-caused obstructions. This study aimed to evaluate the efficacy and safety of the two approaches. METHODS: We systematically retrieved literature from January 1, 2000, to May 30, 2023, from the PubMed, Embase, Web of Science, SinoMed, Wanfang Data, Chinese National Knowledge Infrastructure, and Cochrane Central Register of Clinical Trials databases. Randomized controlled trials (RCTs) or cohort studies of SEMS versus DT as BTS in colorectal cancer obstruction were selected. Risks of bias were assessed for RCTs and cohort studies using the Cochrane Risk of Bias tool version 2 and Risk of Bias in Nonrandomized Studies of Interventions. Certainty of evidence was determined using the Graded Recommendation Assessment. Odds ratio (OR), mean difference (MD), and 95% confidence interval (95% CI) were used to analyze measurement data. RESULTS: We included eight RCTs and eighteen cohort studies involving 2,061 patients (SEMS, 1,044; DT, 1,017). Pooled RCT and cohort data indicated the SEMS group had a significantly higher clinical success rate than the DT group (OR = 1.99, 95% CI 1.04, 3.81, P = 0.04), but no significant difference regarding technical success (OR = 1.29, 95% CI 0.56, 2.96, P = 0.55). SEMS had a shorter postoperative length of hospital stays (MD = - 4.47, 95% CI - 6.26, - 2.69, P < 0.00001), a lower rates of operation-related abdominal pain (OR = 0.16, 95% CI 0.05, 0.50, P = 0.002), intraoperative bleeding (MD = - 37.67, 95% CI - 62.73, - 12.60, P = 0.003), stoma creation (OR = 0.41, 95% CI 0.23, 0.73, P = 0.002) and long-term tumor recurrence rate than DT (OR = 0.47, 95% CI 0.22, 0.99, P = 0.05). CONCLUSION: SEMS and DT are both safe as BTS to avoid emergency surgery for patients with colorectal cancer obstruction. SEMS is preferable because of higher clinical success rates, lower rates of operation-related abdominal pain, intraoperative bleeding, stoma creation, and long-term tumor recurrence, as well as a shorter postoperative length of hospital stays. Trial registration CRD42022365951 .

Assuntos

Neoplasias Colorretais , Obstrução Intestinal , Humanos , Neoplasias Colorretais/complicações , Neoplasias Colorretais/cirurgia , Recidiva Local de Neoplasia/complicações , Obstrução Intestinal/etiologia , Obstrução Intestinal/cirurgia , Stents , Dor Abdominal , Descompressão/efeitos adversos

RESUMO

OBJECTIVE: to retrospectively investigate the efficacy and safety of the application of 28 mm cryoballoon for pulmonary vein electrical isolation (PVI) combined with top left atrial linear ablation and pulmonary vein vestibular expansion ablation for persistent atrial fibrillation. METHODS: From July 2016 to December 2020, 413 patients diagnosed with persistent atrial fibrillation were evaluated, including 230 (55.7%) in the PVI group (PVI only) and 183 (44.3%) in the PVIPLUS group (PVI plus ablation of the left atrial apex and pulmonary vein vestibule). The safety and efficacy of the two groups were retrospectively analyzed. RESULTS: The AF/AT/AFL-free survival rates at 6, 12, 18, 24 and 30 months after procedure was 86.6%, 72.6%, 70.0%, 61.1% and 56.3% in the PVI group and 94.5%, 87.0%, 84.1%, 75.0% and 67.9% in the PVIPLUS group, respectively. At 30 months after procedure, the AF/AT/AFL-free survival rate was significantly higher in the PVIPLUS group than in the PVI group (P = 0.036; HR:0.63; 95% CI:0.42 to 0.95). CONCLUSION: The application of 28-mm cryoballoon for pulmonary vein electrical isolation combined with linear ablation of the left atrial apex and expanded ablation of the pulmonary vein vestibule improves the outcome of persistent atrial fibrillation.

Assuntos

Fibrilação Atrial , Ablação por Cateter , Criocirurgia , Veias Pulmonares , Humanos , Fibrilação Atrial/cirurgia , Veias Pulmonares/cirurgia , Estudos Retrospectivos , Criocirurgia/métodos , Resultado do Tratamento , Ablação por Cateter/métodos , Recidiva

RESUMO

INTRODUCTION AND OBJECTIVES: Pulmonary vein isolation (PVI) technique has become the cornerstone of atrial fibrillation (AF) catheter ablation. The objective of this study was to assess the efficacy and safety of extended antrum ablation based on electrophysiological substrate mapping plus PVI in AF patients who underwent cryoballoon ablation. METHODS: In this observational study, a total of 121 paroxysmal AF patients and 80 persistent AF patients who did not achieve the procedure endpoint after cryoballoon ablation received extra extended antrum ablation (EAA) based on electrophysiological substrate mapping via radiofrequency ablation (EAA group). As a control group (PVI group), among paroxysmal AF and persistent AF patients, we conducted a propensity score-matched cohort, in whom only PVI was completed. RESULTS: The average follow-up time was 15.27±7.34 months. Compared with PVI group, paroxysmal AF patients in the EAA group had a significantly higher rate of AF-free survival (90.1% vs. 80.2%, p=0.027) and AF, atrial flutter, or atrial tachycardia (AFLAT) -free rate survival (89.3% vs. 79.3%, p=0.031). Persistent AF patients in the EAA group also had a significantly higher rate of AF-free survival (90.0% vs. 75.0%, p=0.016) and AFLAT-free survival (88.8% vs. 75.0%, p=0.029) than PVI group. Complication rates did not significantly differ between both groups, in either paroxysmal AF or persistent AF patients. CONCLUSION: Our findings demonstrate that extra extended antrum ablation based on electrophysiological substrate mapping is effective and safe. Moreover, the strategy can improve the outcome of AF cryoablation.

RESUMO

BACKGROUND: Anticoagulation is important for extracorporeal membrane oxygenation (ECMO). Heparin is widely used; however, in some cases, it is not suitable for patients. Bivalirudin has been recently proposed for ECMO patients, and there is no evidence regarding its effectiveness and safety. OBJECTIVE: We aimed to systematically review the effectiveness and safety of bivalirudin in ECMO patients. STUDY DESIGN AND METHODS: PubMed, Web of Science, Cochrane Library, and EMBASE were searched to find relevant research on the use of bivalirudin versus heparin for anticoagulation in ECMO patients. Outcomes included in-hospital mortality, ECMO duration, major bleeding events, thrombosis events and circuit intervention events. Types of studies included randomized control trials (RCTs), cohort studies, and case-control studies. Case reports, studies lacking comparison with heparin, and where patients transitioned between heparin and bivalirudin, were excluded. Publication bias was evaluated when the number of included studies was more than ten. Sensitivity analysis was performed to examine the stability of the results. RESULTS: Ten articles were selected, and nine articles were included in the meta-analysis. The results of the meta-analysis showed hospital mortality [OR = 0.65, 95%CI (0.44, 0.95), P = 0.03] and thrombosis events decreased (OR = 0.55, 95%CI [0.37, 0.83], P = 0.004) in bivalirudin group compared with heparin in adult patients. Major bleeding events (OR = 0.66, 95%CI [0.17, 2.55], P = 0.55), ECMO duration (MD = 18.92, 95%CI [-29.33, 67.17], P = 0.44) and circuit intervention events (OR = 1.67, 95%CI [0.54, 5.18], P = 0.37) in the bivalirudin group was not statistically significant compared with the heparin group. CONCLUSION: Bivalirudin may provide survival benefits and reduce thrombosis in adult patients on ECMO compared with heparin. There is no difference in treating major bleeding events between bivalirudin and heparin group. However, because all included studies were retrospective observational studies, the evidence level of this systematic review is low and heterogeneity could not be avoided. More high-quality clinical studies are urgently needed to confirm these benefits.

Assuntos

Oxigenação por Membrana Extracorpórea , Adulto , Anticoagulantes/uso terapêutico , Oxigenação por Membrana Extracorpórea/métodos , Heparina/uso terapêutico , Hirudinas , Humanos , Fragmentos de Peptídeos/uso terapêutico , Proteínas Recombinantes/efeitos adversos

RESUMO

A novel Gram-stain-negative, aerobic strain, designated Y22T, was isolated from peanut field soil in Laoshan Mountain in China. Cells of strain Y22T were rod-shaped and motile by a single flagellum. The strain was found to be oxidase- and catalase-positive. 16S rRNA gene sequence based on phylogenetic analysis indicated that strain Y22T belonged to the genus Pseudomonas, and showed the highest 16S rRNA gene sequence similarity of 99.0% to Pseudomonas pelagia JCM 15562T, followed by Pseudomonas salina JCM 19469T (98.4%), Pseudomonas sabulinigri JCM 14963T (97.9%), Pseudomonas bauzanensis CGMCC 1.9095T (97.6%) and Pseudomonas litoralis KCTC23093T (97.5%). The phylogenetic analysis based on multilocus sequence analyses with concatenated 16S rRNA, gyrB, rpoD and rpoB genes indicated that strain Y22T belonged to Pseudomonas pertucinogena lineage. The average nucleotide identity scores between strain Y22T and closely related species were 74.6-82.8%, and the Genome-to-Genome Distance Calculator scores were 16.4-44.9%. The predominant cellular fatty acids of strain Y22T were C18:1ω7c (29.6%), C17:0 cyclo (17.5%) and summed feature 3 (C16:1ω7c and/or C16:1ω6c) (17.4%). The genomic DNA G+C content was 57.9 mol%. On the basis of phenotypic characteristics, phylogenetic analyses and in silico DNA-DNA relatedness, a novel species, Pseudomonas laoshanensis sp. nov. is proposed. The type strain is Y22T (= JCM 32580T = KCTC 62385T = CGMCC 1.16552T).

Assuntos

Filogenia , Pseudomonas/classificação , Microbiologia do Solo , Arachis , China , Genes Bacterianos/genética , Pseudomonas/genética , RNA Ribossômico 16S/genética , Especificidade da Espécie

RESUMO

BACKGROUND: In this study, we investigated the effect of forskolin (FSK, a selective adenylate cyclase agonist) on the automatic diastolic depolarization of sinus node cells (SNC) with hypoxia/reoxygenation (H/R) injury. METHODS: The SNC of the newborn rat was randomly assigned into the control group, the H/R (H/R injury) group, or the H/R + FSK (H/R injury + FSK treatment) group. Patch-clamp was performed to record the action potential and electrophysiological changes. The cellular distribution of intracellular calcium concentration was analyzed by fluorescence staining. RESULTS: Compared with the control cells, spontaneous pulsation frequency (SPF) and diastolic depolarization rate (DDR) of H/R cells were reduced from 244.3 ± 10.6 times/min and 108.7 ± 7.8 mV/s to 130.5 ± 7.6 times/min and 53.4 ± 6.5 mV/s, respectively. FSK significantly increased SPF and DDR of H/R cells to 208.3 ± 8.3 times/min and 93.2 ± 8.9 mV/s (n = 15, both p < 0.01), respectively. H/R reduced the current densities of If, ICa,T and inward INCX, which were significantly increased by 10 µM FSK treatment (n = 15, p < 0.01). Furthermore, reduced expression of HCN4 and NCX1.1 channel protein were significantly increased by FSK. Inhibitor studies showed that both SQ22536 (a selective adenylate cyclase inhibitor) and H89 (a selective protein kinases A [PKA] inhibitor) blocked the effects of FSK on SPF and DDR. CONCLUSIONS: H/R causes pacemaker dysfunction in newborn rat sinoatrial node cells leading to divergence of the DD and the slow of spontaneous APs, which change can be dramatically reversed by FSK through increasing INCX and If current in H/R injury.

Assuntos

Potenciais de Ação/efeitos dos fármacos , Cálcio/metabolismo , Colforsina/farmacologia , Nó Sinoatrial/efeitos dos fármacos , Adenilil Ciclases/efeitos dos fármacos , Adenilil Ciclases/metabolismo , Animais , Animais Recém-Nascidos , Hipóxia Celular/efeitos dos fármacos , Células Cultivadas , Feminino , Masculino , Ratos , Ratos Wistar , Nó Sinoatrial/metabolismo

RESUMO

OBJECTIVE: The spontaneous action potential of isolated sinoatrial node (SAN) cells is regulated by a coupled-clock system of two clocks: the calcium clock and membrane clock. However, it remains unclear whether calcium clock inhibitors have a direct effect on the membrane clock. The purpose of this study was to investigate the direct effect of cyclopiazonic acid (CPA), a selective calcium clock inhibitor, on the function of the membrane clock of SAN cells. METHODS: at SAN cells were isolated by trypsinization and identified based on morphology and electrophysiology. If and HCN currents were recorded via patch clamp technique. The expression of the HCN channel protein was determined by Western blotting analysis. RESULTS: The diastolic depolarization rate of spontaneous action potentials and the current densities of If were reduced by exposure to 10 µM CPA. The inhibitory effect of CPA was concentration-dependent with an IC50 value of 16.3 µM and a Hill coefficient of 0.98. The effect of CPA on If current was also time-dependent, and the If current amplitude was partially restored after washout. Furthermore, the steady-state activation curve of the If current was shifted to a negative potential, indicating that channel activation slowed down. Finally, the protein expression of HCN4 in HEK293 cells was markedly downregulated by CPA. CONCLUSIONS: These results indicate that the direct inhibition effect of CPA on the If current in SAN cells is both concentration- and time-dependent. The underlying mechanisms may involve slowing down steady-state activation and the downregulation of pacemaker channel protein expression.

Assuntos

Nó Sinoatrial , Potenciais de Ação , Cálcio , Células HEK293 , Humanos , Indóis/farmacologia

RESUMO

There is little research that focuses on the relationship between the gut, metabolism, nutritional support and COVID-19. As a group of Chinese physicians, nutritionists and scientists working on the frontline treating COVID-19 patients, we aim to integrate our experiences and the current clinical evidence to address this pressing issue in this article. Based on our clinical observations and available evidence, we recommend the following practice. Firstly, the Nutritional Risk Screening 2002 tool should be used routinely and periodically; for patients with a score ≥3, oral nutritional supplements should be given immediately. Secondly, for patients receiving the antiviral agents lopinavir/ritonavir, gastrointestinal side effects should be monitored for and timely intervention provided. Thirdly, for feeding, the enteral route should be the first choice. In patients undergoing mechanical ventilation, establishing a jejunal route as early as possible can guarantee the feeding target being achieved if gastric dilatation occurs. Fourthly, we suggest a permissive underfeeding strategy for severe/critical patients admitted to the intensive care unit during the first week of admission, with the energy target no more than 20 kcal/kg/day (for those on mechanical ventilation, this target may be lowered to 10-15 kcal/kg/day) and the protein target around 1.0-1.2 g/kg/day. If the inflammatory condition is significantly alleviated, the energy target may be gradually increased to 25-30 kcal/kg/day and the protein target to 1.2-1.5 g/kg/day. Fifthly, supplemental parenteral nutrition should be used with caution. Lastly, omega-3 fatty acids may be used as immunoregulators, intravenous administration of omega-3 fatty emulsion (10 g/day) at an early stage may help to reduce the inflammatory reaction.

RESUMO

BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) has a poor prognosis that has not significantly improved in the past several decades. A prognostic-related signature was needed. METHODS: The Cancer Genome Atlas and GSE41613 databases were downloaded as a training and validation set, respectively. We identified 12 genes that demonstrated progression and prognostic value, and then, a gene signature was constructed. RESULTS: This classification could reflect distinct characteristics, phenotypically and molecularly, among HNSCC tumors. It could stratify patients with significantly different survival rates (median survival: 2083 days vs 927 days; P = 3.85E-08) in the training cohort and validation cohort (P = 0.007) and was significantly involved in immune/inflammatory response and tumor progression processes. CONCLUSIONS: This bioinformatics-based signature suggested the presence of two distinct populations of patients with HNSCC with distinguishable phenotypic characteristics and clinical outcomes and might provide insight for new types of immune therapy.

Assuntos

Carcinoma de Células Escamosas/genética , Perfilação da Expressão Gênica , Neoplasias de Cabeça e Pescoço/genética , Linfócitos B/metabolismo , Biomarcadores/metabolismo , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/mortalidade , Biologia Computacional , Conjuntos de Dados como Assunto , Células Dendríticas/metabolismo , Feminino , Regulação Neoplásica da Expressão Gênica , Neoplasias de Cabeça e Pescoço/metabolismo , Neoplasias de Cabeça e Pescoço/mortalidade , Humanos , Masculino , Análise Multivariada , Fenótipo , Prognóstico , Linfócitos T/metabolismo

RESUMO

AIM: We aimed to study the effect of allocryptopine (All) on the late sodium current (INa,Late) of atrial myocytes in spontaneously hypertensive rats (SHR). METHODS: The enzyme digestion method was used to separate single atrial myocytes from SHR and Wistar-Kyoto (WKY) rats. INa,Late was recorded using the patch-clamp technique, and the effect of All was evaluated on the current. RESULTS: Compared with WKY rat cells, an increase in the INa,Late current in SHR myocytes was found. After treatment with 30 µM All, the current densities were markedly decreased; the ratio of INa,Late/INa,peak of SHR was reduced by 30 µM All. All reduced INa,Late by alleviating inactivation of the channel and increasing the window current of the sodium channel. Furthermore, INa,Late densities of three SCN5A mutations declined substantially with 30 µM All in a concentration-dependent manner. CONCLUSIONS: The results clearly show that an increase in INa,Late in SHR atrial myocytes was inhibited by All derived from Chinese herbal medicine.

Assuntos

Antiarrítmicos/farmacologia , Fibrilação Atrial/prevenção & controle , Alcaloides de Berberina/farmacologia , Átrios do Coração/efeitos dos fármacos , Hipertensão/tratamento farmacológico , Miócitos Cardíacos/efeitos dos fármacos , Canal de Sódio Disparado por Voltagem NAV1.5/efeitos dos fármacos , Sódio/metabolismo , Potenciais de Ação , Animais , Fibrilação Atrial/etiologia , Fibrilação Atrial/metabolismo , Fibrilação Atrial/fisiopatologia , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Células HEK293 , Átrios do Coração/metabolismo , Frequência Cardíaca , Humanos , Hipertensão/complicações , Hipertensão/metabolismo , Hipertensão/fisiopatologia , Masculino , Mutação , Miócitos Cardíacos/metabolismo , Canal de Sódio Disparado por Voltagem NAV1.5/genética , Canal de Sódio Disparado por Voltagem NAV1.5/metabolismo , Ratos Endogâmicos SHR , Ratos Endogâmicos WKY , Fatores de Tempo

RESUMO

Background: The purpose of the study was to compare the differences of the subjective satisfaction of the donor site morbidity between the free radial forearm flap (FRFF) and anterolateral thigh flap (ALTF) for tongue reconstruction. Material and Methods: One hundred and nineteen patients underwent FRFF or ALTF reconstruction were retrospectively evaluated by a standardized self-established donor site morbidity questionnaire which included 5 domains, sensibility, movement disabilities, cosmetics, social activities and general impacts on the quality of life. Results: The Cronbach's coefficient alpha of the questionnaire was 0.707. The exploratory factor analysis revealed that the 5 items of the questionnaire might load onto two distinct subscales. Patients with ALTF had higher scores in the sensibility, cosmetics and the composite score (P < 0.05). No significant differences were found in the movement disabilities, social activities and general impacts on the quality of life between the two groups (P > 0.05). Conclusions: ALTF has the advantage of better results of donor site morbidity, such as sensibility and cosmetics, over FRFF

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Assuntos

Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Neoplasias da Língua/cirurgia , Retalhos Cirúrgicos , Transplante de Pele/métodos , Carcinoma de Células Escamosas/cirurgia , Sítio Doador de Transplante , Procedimentos de Cirurgia Plástica/métodos , Satisfação do Paciente/estatística & dados numéricos , Medidas de Resultados Relatados pelo Paciente , Estudos Retrospectivos

RESUMO

OBJECTIVE: This study aimed to investigate the effects of transforming growth factor ß1 (TGF ß1) and hepatocyte growth factor (HGF) on the expression of connective tissue growth factor (CTGF) in human atrial fibroblasts, and to explore the relationship of these factors in atrial fibrosis and atrial anatomical remodelling (AAR) of patients with atrial fibrillation (AF). METHODS: Fresh right auricular appendix tissue of 20 patients with rheumatic heart disease undergoing valve replacement surgery was collected during surgeries, 10 patients had sinus rhythm(SR), and 10 patients had chronic atrial fibrillation (CAF). Atrial fibroblasts were then cultured from the tissues with differential attachment technique and treated with either TGFß1 (10 ng/mL) or HGF (100 ng/mL). CTGF mRNA levels were measured by RT-PCR, and CTGF protein content was determined using immunofluorescence and Western blotting assays. RESULTS: CAF group had higher left atrial diameters (LADs) and higher CTGF mRNA expression in atrial fibroblasts compared with SR group. The CTGF protein content in CAF group was higher than that of SR group and positively correlated with LAD and AF duration. After CAF group was treated with TGFß1, CTGF mRNA and protein expression were significantly down-regulated, whereas when treated with HGF, expression was up-regulated compared with SR group. CONCLUSIONS: Increased CTGF expression was associated with enlarged LAD, atrial fibrosis and AAR in patients with AF. TGFß1 and HGF regulate CTGF expression in human atrial fibroblasts with up-regulation of mRNA and down-regulation of protein, therefore, either promote or inhibit atrial fibrosis, which could be related to the incidence and persistence of AF.

Assuntos

Remodelamento Atrial , Fator de Crescimento do Tecido Conjuntivo/metabolismo , Fibroblastos/patologia , Fibrose/etiologia , Fator de Crescimento de Hepatócito/metabolismo , Cardiopatia Reumática/complicações , Fator de Crescimento Transformador beta1/metabolismo , Adulto , Fibrilação Atrial/etiologia , Fibrilação Atrial/metabolismo , Fibrilação Atrial/patologia , Células Cultivadas , Fator de Crescimento do Tecido Conjuntivo/genética , Feminino , Fibroblastos/metabolismo , Fibrose/metabolismo , Fibrose/patologia , Fator de Crescimento de Hepatócito/genética , Humanos , Masculino , Cardiopatia Reumática/metabolismo , Cardiopatia Reumática/patologia , Fator de Crescimento Transformador beta1/genética

RESUMO

Stroke survivors often experience social isolation, which can lead to post­stroke depression (PSD) and post­stroke anxiety (PSA) that can compromise neurogenesis and impede functional recovery following the stroke. The present study aimed to investigate the effects and mechanisms of post­stroke social isolation­mediated PSD and PSA on hippocampal neurogenesis and cognitive function. The effects of the natural antidepressant hyperforin on post­stroke social isolation­mediated PSD and PSA were also investigated. In the present study, a model of PSD and PSA using C57BL/6J male mice was successfully established using middle cerebral artery occlusion combined with post­stroke isolated housing conditions. It was observed that PSD and PSA were more prominent in the isolated mice compared with the pair­housed mice at 14 days post­ischemia (dpi). Mice isolated 3 dpi exhibited decreased transforming growth factor­ß (TGF­ß) levels and impairment of hippocampal neurogenesis and memory function at 14 dpi. Intracerebroventricular administration of recombinant TGF­ß for 7 consecutive days, starting at 7 dpi, restored the reduced hippocampal neurogenesis and memory function induced by social isolation. Furthermore, intranasal administration of hyperforin for 7 consecutive days starting at 7 dpi improved PSD and PSA and promoted hippocampal neurogenesis and memory function in the isolated mice at 14 dpi. The inhibition of TGF­ß with a neutralizing antibody prevented the effects of hyperforin. In conclusion, the results revealed a previously uncharacterized role of hyperforin in improving post­stroke social isolation­induced exaggeration of PSD and PSA and, in turn, promoting hippocampal neurogenesis and cognitive function via TGF­ß.

Assuntos

Ansiedade/tratamento farmacológico , Ansiedade/etiologia , Depressão/tratamento farmacológico , Depressão/etiologia , Floroglucinol/análogos & derivados , Isolamento Social , Acidente Vascular Cerebral/complicações , Terpenos/uso terapêutico , Fator de Crescimento Transformador beta/metabolismo , Animais , Ansiedade/fisiopatologia , Comportamento Animal , Isquemia Encefálica/tratamento farmacológico , Isquemia Encefálica/patologia , Isquemia Encefálica/fisiopatologia , Depressão/fisiopatologia , Hipocampo/patologia , Hipocampo/fisiopatologia , Masculino , Camundongos Endogâmicos C57BL , Neurogênese/efeitos dos fármacos , Floroglucinol/farmacologia , Floroglucinol/uso terapêutico , Proteínas Recombinantes/farmacologia , Proteínas Recombinantes/uso terapêutico , Recuperação de Função Fisiológica/efeitos dos fármacos , Acidente Vascular Cerebral/tratamento farmacológico , Acidente Vascular Cerebral/metabolismo , Terpenos/farmacologia , Fator de Crescimento Transformador beta/farmacologia , Fator de Crescimento Transformador beta/uso terapêutico

RESUMO

Aim: We investigated the underlying mechanisms in atrial fibrillation (AF) associated with R33Q mutation and Ca2+-triggered activity. Methods and Results: We examined AF susceptibility with intraesophageal burst pacing in the sarcoplasmic reticulum (SR) Ca2+ leak model calsequestrin 2 R33Q (Casq2R33Q/R33Q) mice. Atrial trigger appeared in R33Q mice but not WT mice (17.24%, 5/29 vs. 0.00%, 0/32, P < 0.05). AF was induced by 25 Hz pacing in R33Q mice (48.27%, 14/29 vs. 6.25%, 2/32, P < 0.01). The mice were given 1.5 mg/kg isoproterenol (Iso), and the incidences of AF increased (65.51%, 19/29 vs. 9.21%, 3/32, P < 0.01). Electrophysiology experiments and the recording of intracellular Ca2+ indicated significant increases in the Ca2+ sparks (5.24 ± 0.75 100 µM-1.s-1 vs. 0.29 ± 0.04 100 µM-1.s-1, n = 20, P < 0.05), intracellular free Ca2+ (0.238 ± 0.009 µM vs. 0.172 ± 0.006 µM, n = 20, P < 0.05), Ca2+ wave (11.74% vs. 2.24%, n = 20, P < 0.05), transient inward current (ITi) (-0.56 ± 0.02 pA/pF vs. -0.42 ± 0.01 pA/pF, n = 10, P < 0.05), and oscillation in membrane potentials (10.71%, 3/28 vs. 4.16%, 1/24, P < 0.05) in the R33Q group, but there was no significant difference in the L-type calcium current. These effects were enhanced by Iso, and the inhibition of calmodulin-dependent protein kinase II (CaMKII) by 1 µM KN93 reversed the effects of Iso on Ca2+ sparks (5.01 ± 0.66 100 µm-1.s-1 vs. 11.33 ± 1.63 100 µm-1.s-1, P < 0.05), intracellular Ca2+ (0.245 ± 0.005 µM vs. 0.324 ± 0.008 µM, P < 0.05), Ca2+ wave (12.35% vs. 17.83%, P < 0.05), ITi (-0.61 ± 0.02 pA/pF vs. -0.78 ± 0.03 pA/pF, n = 10, P < 0.05), and oscillation in membrane potential (17.85% 5/28 vs. 32.17% 9/28, P < 0.05). The reduction of ryanodine receptor 2 (RyR2) stable subunits (Casq2, triadin, and junctin) rather than RYR2 and the increase in CaMKII, phosphor-CaMKII, phosphor-RyR2 (Ser 2814), SERCA, and NCX1.1 was reflected in the R33Q group. Conclusion: This study demonstrates that the increase in spontaneous calcium elevations corresponding to ITi that may trigger the oscillation in membrane potentials in the R33Q group, thereby increasing the risk of AF. The occurrence of spontaneous calcium elevations in R33Q atrial myocytes is due to the dysfunction of RyR2 stable subunits, CaMKII hyperactivity, and CaMKII-mediated RyR phosphorylation. An effective therapeutic strategy to intervene in Ca2+-induced AF associated with the R33Q mutation may be through CaMKII inhibition.