The adipose-neural axis is involved in epicardial adipose tissue-related cardiac arrhythmias.

Dysfunction of the sympathetic nervous system and increased epicardial adipose tissue (EAT) have been independently associated with the occurrence of cardiac arrhythmia. However, their exact roles in triggering arrhythmia remain elusive. Here, using an in vitro coculture system with sympathetic neurons, cardiomyocytes, and adipocytes, we show that adipocyte-derived leptin activates sympathetic neurons and increases the release of neuropeptide Y (NPY), which in turn triggers arrhythmia in cardiomyocytes by interacting with the Y1 receptor (Y1R) and subsequently enhancing the activity of the Na+/Ca2+ exchanger (NCX) and calcium/calmodulin-dependent protein kinase II (CaMKII). The arrhythmic phenotype can be partially blocked by a leptin neutralizing antibody or an inhibitor of Y1R, NCX, or CaMKII. Moreover, increased EAT thickness and leptin/NPY blood levels are detected in atrial fibrillation patients compared with the control group. Our study provides robust evidence that the adipose-neural axis contributes to arrhythmogenesis and represents a potential target for treating arrhythmia.

Coronary Sinus Metabolite 12,13-diHOME Is a Novel Biomarker for Left Atrial Remodeling in Patients With Atrial Fibrillation.

BACKGROUND: 12,13-dihydroxy-9Z-octadecenoic acid (12,13-diHOME) has shown potential in protecting against heart disease, but its relationship with atrial fibrillation (AF) remains unknown. METHODS: Coronary sinus (CS) and femoral vein blood samplings were synchronously collected from AF and non-AF subjects (paroxysmal supraventricular tachycardia or idiopathic premature ventricular complexes) who underwent catheter ablation. First, untargeted metabolomic profiling was performed in a discovery cohort (including 12 AF and 12 non-AF subjects) to identify the most promising CS or femoral vein metabolite. Then, the selected metabolite was further measured in a validation cohort (including 119 AF and 103 non-AF subjects) to confirm its relationship with left atrium remodeling and 1-year postablation recurrence of AF. Finally, the biological function of the selected metabolite was validated in a rapid-paced cultured HL-1 atrial cardiomyocytes model. RESULTS: Metabolomic analysis identified CS 12,13-diHOME as the most pronounced change metabolite correlated with left atrium remodeling in the discovery cohort. In the validation cohort, CS 12,13-diHOME was significantly lower in patients with AF than non-AF controls (84.32±20.13 versus 96.24±23.56 pg/mL; P<0.01), and associated with worse structural, functional, and electrical remodeling of left atrium. Multivariable regression analyses further demonstrated that decreased CS 12,13-diHOME was an independent predictor of 1-year postablation recurrence of AF (odds ratio, 0.754 [95% CI, 0.648-0.920]; P=0.005). Biological function validations showed that 12,13-diHOME treatment significantly protect the cell viability, improved the expression of MHC (myosin heavy chain) and Cav1.2 (L-type calcium channel α1c), and attenuated mitochondrial damage in the rapid-paced cultured HL-1 cardiomyocytes model. CONCLUSIONS: CS metabolite 12,13-diHOME is decreased in patients with AF and can serve as a novel biomarker for left atrium remodeling.

Redistribution of adipose tissue is associated with left atrial remodeling and dysfunction in patients with atrial fibrillation.

Objective: Adipose tissue is recognized as a crucial regulator of atrial fibrillation (AF). However, the effect of epicardial adipose tissue (EAT) on the pathophysiology of AF might be different from that of other adipose tissues. The purpose of this study was to explore the distribution features of different adipose tissues in AF patients and their relationships with left atrial (LA) remodeling and function. Methods: A total of 205 participants (including 112 AF and 93 non-AF patients) were recruited. Color doppler ultrasound was used to measure the thickness of subcutaneous, extraperitoneal, and intra-abdominal adipose tissue. Cardiac CT scan was performed to measure the mean thickness of EAT surrounding the whole heart (total-EAT) and specific regions, including left atrium (LA-EAT), left ventricle, right ventricle, interventricular groove, and atrioventricular groove. LA anatomical remodeling and function were measured by echocardiography, while electrical remodeling was evaluated by P-wave duration and dispersion using Electrocardiography (obtained after cardioversion or ablation in AF patients). Relationship between the thickness of different adipose tissues and LA remodeling and function was analyzed. Results: The thickness of subcutaneous, extraperitoneal, and intra-abdominal adipose tissue was similar between AF and non-AF patients, and had no or only weak association with LA remodeling and dysfunction. However, compared to non-AF participants, total-EAT thickness significantly increased in both paroxysmal and persistent AF patients (non-AF vs. paroxysmal AF vs. persistent AF: 6.31 ± 0.63 mm vs. 6.76 ± 0.79 mm vs. 7.01 ± 1.18 mm, P < 0.001), which was positively correlated with the LA size and P-wave duration and dispersion, and negatively correlated with LA ejection fraction and peak strain rate. More interestingly, EAT thickness in AF patients did not increase uniformly in different regions of the heart. Compared to EAT surrounding the other regions, LA-EAT was found to accumulate more greatly, and had a closer relationship to LA remodeling and dysfunction. Multivariate logistic regression analysis also showed that LA-EAT was significantly correlated with the presence of AF (OR = 4.781; 95% CI 2.589-8.831, P < 0.001). Conclusion: Rather than other adipose tissues, accumulation and redistribution of EAT, especially surrounding the LA, is associated with LA remodeling and dysfunction in AF patients.

Implications of the COVID-19 pandemic for urban informal housing and planning interventions: Evidence from Singapore.

The outbreak of the COVID-19 pandemic revealed the crucial role of social distancing and hygiene practices in reducing virus transmission and thus revealed the high risk of infection in urban informal housing. Through an empirical study of Singapore's infectious situation and antiepidemic measures, this paper shows that the number of infected migrant workers living in dormitories was three hundred times greater than the number of infected local urban residents, not only because of the migrants' 'vulnerable' position but also because their living conditions fostered widespread transmission of the virus. The dwelling conditions of migrant dormitories, such as overcrowded living spaces, widely shared sanitation facilities, and poor hygiene practices, present great challenges to standard prevention strategies and control measures. Adverse health impacts resulting from the lockdown of dormitories during the COVID-19 pandemic suggest the importance of planning intervention in the dwelling conditions of informal housing, and indicate a need for the governments' active reforms of building codes and health care systems to promote the health of disadvantaged groups and then create more inclusive and healthy cities for all the society.

The feasibility and safety of a simple method for coronary sinus blood sampling during catheter ablation of arrhythmias.

Background: Coronary sinus (CS) blood sampling gives an insight into the localized pathophysiology of heart diseases. However, additional specifically-designed or modified catheters were needed in most previous studies, making the convenience of clinical application unsatisfactory. This study aimed to introduce a simple method for CS blood sampling without using additional catheters during catheter ablation (CA) of arrhythmias, and to investigate its feasibility and safety. Methods: A total of 119 patients undergoing CA were prospectively enrolled, including 25 with paroxysmal supraventricular tachycardia (PSVT), 30 with premature ventricular complexes (PVC), and 64 with atrial fibrillation (AF). Cannulation and sampling of CS was performed via the femoral vein using a conventional 8F SR0TM or 8.5F SL1TM introducer sheath (St. Jude Medical) guided by a 6F steerable diagnostic catheter (St. Jude Medical). The success rate and any suspicious complications were recorded. Untargeted liquid chromatograph-mass spectrometer (LC-MS)-based metabonomics of CS samples versus peripheral venous samples were also performed. Results: CS blood samples were successfully collected from 114 patients, with an overall success rate of 95.8%. Among patients with different arrhythmias, the success rates were similar, with 96.0% in PSVT, 96.7% in PVC, and 95.3% in AF (P=0.223). Adverse events occurred in four (3.4%) patients, including two patients with occasional atrial ectopic beats without causing any discomfort, and two patients with new-onset paroxysmal AF lasting for about 2 min. No serious complications were noted. Metabonomics analysis showed that CS samples provided a number of different metabolites (93 in PVST, 217 in PVC, and 109 in AF) versus peripheral samples. Conclusions: Our method for CS blood sampling during CA is feasible and safe, and can provide useful cardiometabolic information that is significantly different from a peripheral sample.

Ginsenoside Rb1 attenuates age-associated vascular impairment by modulating the Gas6 pathway.

CONTEXT: Ginsenoside Rb1 (Rb1) exerts many beneficial effects and protects against cardiovascular disease. OBJECTIVE: To investigate whether Rb1 could attenuate age-related vascular impairment and identify the mechanism. MATERIALS AND METHODS: Female C57BL/6J mice aged 2 and 18 months, randomly assigned to Young, Young + 20 mg/kg Rb1, Old + vehicle, Old + 10 mg/kg Rb1 and Old + 20 mg/kg Rb1 groups, were daily intraperitoneal injected with vehicle or Rb1 for 3 months. The thoracic aorta segments were used to inspect the endothelium-dependent vasorelaxation. Left thoracic aorta tissues were collected for histological or molecular expression analyses, including ageing-related proteins, markers relevant to calcification and fibrosis, and expression of Gas6/Axl. RESULTS: We found that in Old + vehicle group, the expression of senescence proteins and cellular adhesion molecules were significantly increased, with worse endothelium-dependent thoracic aorta relaxation (58.35% ± 2.50%) than in Young group (88.84% ± 1.20%). However, Rb1 treatment significantly decreased the expression levels of these proteins and preserved endothelium-dependent relaxation in aged mice. Moreover, Rb1 treatment also reduced calcium deposition, collagen deposition, and the protein expression levels of collagen I and collagen III in aged mice. Furthermore, we found that the downregulation of Gas6 protein expression by 41.72% and mRNA expression by 52.73% in aged mice compared with young mice was abrogated by Rb1 treatment. But there was no significant difference on Axl expression among the groups. CONCLUSIONS: Our study confirms that Rb1 could ameliorate vascular injury, suggesting that Rb1 might be a potential anti-ageing related vascular impairment agent.

Atrial fibrillation increases inpatient and 4-year all-cause mortality in critically ill patients with liver cirrhosis.

BACKGROUND: The association between atrial fibrillation (AF) and cirrhosis is unclear. Therefore, the aim of the present study was to determine the association between AF and short-term and 4-year mortality in critically ill patients with cirrhosis using a large database. METHODS: The Medical Information Mart for Intensive Care III (MIMIC III) database was used to identify patients with cirrhosis hospitalized in an intensive care unit from 2001 to 2012. Demographic and clinical data were extracted from the database. Clinical data and demographic information were collected for each patient in our study. Kaplan-Meier analysis and multivariate Cox regression models were performed to examine the relation between atrial fibrillation and in-hospital and 4-year all-cause mortality. RESULTS: A total of 1,481 patients (mean age: 58 years, 68% male) with liver cirrhosis were included in the analysis, and the prevalence of AF was 14.18%. The inpatient all-cause mortality rate was 26.6%, and patients who died in hospital had a significantly higher rate of AF (21.57% vs. 11.50%, P<0.001). Multivariate Cox regression analysis indicated that AF was significantly associated with inpatient all-cause mortality [hazard ratio (HR): 1.52, 95% confidence interval (CI): 1.19-1.95, P<0.001], and 4-year all-cause mortality (HR: 1.55, 95% CI: 1.12-2.13, P=0.008). Kaplan-Meier survival analysis showed that patients with AF had a significantly higher inpatient and 4-year all-cause mortality. CONCLUSIONS: Critically ill patients with liver cirrhosis have a high rate of AF, and the presence of AF is an independent risk factor for inpatient and 4-year all-cause mortality.

Adaptive Spatio-Temporal Graph Enhanced Vision-Language Representation for Video QA.

Vision-language research has become very popular, which focuses on understanding of visual contents, language semantics and relationships between them. Video question answering (Video QA) is one of the typical tasks. Recently, several BERT style pre-training methods have been proposed and shown effectiveness on various vision-language tasks. In this work, we leverage the successful vision-language transformer structure to solve the Video QA problem. However, we do not pre-train it with any video data, because video pre-training requires massive computing resources and is hard to perform with only a few GPUs. Instead, our work aims to leverage image-language pre-training to help with video-language modeling, by sharing a common module design. We further introduce an adaptive spatio-temporal graph to enhance the vision-language representation learning. That is, we adaptively refine the spatio-temporal tubes of salient objects according to their spatio-temporal relations learned through a hierarchical graph convolution process. Finally, we can obtain a number of fine-grained tube-level video object representations, as the visual inputs of the vision-language transformer module. Experiments on three widely used Video QA datasets show that our model achieves the new state-of-the-art results.

Ginsenoside Rb1 Protects Human Umbilical Vein Endothelial Cells against High Glucose-Induced Mitochondria-Related Apoptosis through Activating SIRT3 Signalling Pathway.

OBJECTIVE: To investigate whether ginsenoside Rb1 (Rb1) can protect human umbilical vein endothelial cells (HUVECs) against high glucose-induced apoptosis and examine the underlying mechanism. METHODS: HUVECs were divided into 5 groups: control group (5.5 mmol/L glucose), high glucose (HG, 40 mmol/L) treatment group, Rb1 (50 µ mol/L) treatment group, Rb1 plus HG treatment group, and Rb1 and 3-(1H-1,2,3-triazol-4-yl) pyridine (3-TYP, 16 µ mol/L) plus HG treatment group. Cell viability was evaluated by cell counting kit-8 assay. Mitochondrial and intracellular reactive oxygen species were detected by MitoSox Red mitochondrial superoxide indicator and dichloro-dihydro-fluorescein diacetate assay, respectively. Annexin V/propidium iodide staining and fluorescent dye staining were used to measure the apoptosis and the mitochondrial membrane potential of HUVECs, respectively. The protein expressions of apoptosis-related proteins [Bcl-2, Bax, cleaved caspase-3 and cytochrome c (Cyt-c)], mitochondrial biogenesis-related proteins [proliferator-activated receptor gamma coactivator 1-alpha, nuclear respiratory factor-1 and mitochondrial transcription factor A)], acetylation levels of forkhead box O3a and SOD2, and sirtuin-3 (SIRT3) signalling pathway were measured by immunoblotting and immunoprecipitation. RESULTS: Rb1 ameliorated survival in cells in which apoptosis was induced by high glucose (P<0.05 or P<0.01). Upon the addition of Rb1, mitochondrial and intracellular reactive oxygen species generation and malondialdehyde levels were decreased (P<0.01), while the activities of antioxidant enzymes were increased (P<0.05 or P<0.01). Rb1 preserved the mitochondrial membrane potential and reduced the release of Cyt-c from the mitochondria into the cytosol (P<0.01). In addition, Rb1 upregulated mitochondrial biogenesis-associated proteins (P<0.01). Notably, the cytoprotective effects of Rb1 were correlated with SIRT3 signalling pathway activation (P<0.01). The effect of Rb1 against high glucose-induced mitochondria-related apoptosis was restrained by 3-TYP (P<0.05 or P<0.01). CONCLUSION: Rb1 could protect HUVECs from high glucose-induced apoptosis by promoting mitochondrial function and suppressing oxidative stress through the SIRT3 signalling pathway.

Serum lipoprotein(a) and risk of periprocedural myocardial injury in patients undergoing percutaneous coronary intervention.

Recent studies and guidelines have indicated that lipoprotein(a) [Lp(a)]was an independent risk factor of arteriosclerotic cardiovascular disease (ASCVD). This study aimed to determine the relationship between serum Lp(a) levels and the risk of periprocedural myocardial injury following percutaneous coronary intervention (PCI) in coronary heartdisease (CHD) patients. This study enrolled 528 nonacute myocardial infarction (AMI) coronary heart disease (CHD) patients who successfully underwent PCI. Fasting serum lipids including Lp(a) were tested before PCI. High-sensitivity cardiac troponin I (hs-cTnI) was tested before PCI and 24 h after PCI. Univariate and multivariate logistic regression analyses were used to determine the relationship between preprocedural Lp(a) levels and postprocedural cTnI elevation from 1 × upper limit of normal (ULN) to 70 × ULN. As a continuous variable, multivariate analyses adjusting for conventional covariates and other serum lipids revealed that increased Lp(a) levels were independently associated with the risk of elevated postprocedural cTnI values above 1 × ULN (odds ratio [OR] per log-unit higher: 1.31, 95% confidence interval [CI]: 1.02-1.68, P = 0.033], 5 × ULN (OR: 1.25, 95%CI: 1.02-1.53, P = 0.032), 10 × ULN (OR: 1.48, 95%CI: 1.18-1.86, P = 0.001) and 15 × ULN (OR: 1.28, 95%CI: 1.01-1.61, P = 0.038). As a categorical variable, Lp(a) > 300 mg/L was an independent risk factor of postproceduralc TnI≥1 × ULN (OR 2.17, 95%CI 1.12-4.21, P = 0.022), ≥5 × ULN (OR 1.82, 95%CI 1.12-2.97, P = 0.017) and ≥10 × ULN (OR 2.17, 95%CI 1.33-3.54, P = 0.002). Therefore, it could be concluded that elevated preprocedural Lp(a) levels were associated with the risk of PCI-related myocardial injury in non-AMI CHD patients.

Impact of long-term glucose variability on coronary atherosclerosis progression in patients with type 2 diabetes: a 2.3 year follow-up study.

BACKGROUND: Glycemic variability (GV) confers a risk of cardiovascular events. In this study, we aimed to investigate whether long-term GV has an impact on coronary atherosclerosis progression in patients with type 2 diabetes mellitus (T2DM). METHODS: A total of 396 patients with T2DM who had coronary computed tomography angiography and laboratory data available at baseline and for follow-up evaluations [median 2.3 (1.8-3.1) years] were included. Fasting plasma glucose (FPG) was measured every 1-3 months, and HbA1c was measured quarterly. The coefficient of variation (CV) of HbA1c and FPG were calculated as measures of GV. Quantitative assessment of coronary plaques was performed by measuring the annual change and progression rate of total plaque volume (TPV). Significant progression was defined as annual TPV progression ≥ 15%. Multivariable regression analyses were used to assess the effects of GV on atherosclerosis progression. RESULTS: In the 396 patients, the annual change in TPV was 12.35 ± 14.23 mm3, and annual progression rate was 13.36 ± 12.69%. There were 143 (36.11%) patients with significant progression, and they had a significantly higher CV-HbA1c (P < 0.001) and CV-FPG (P < 0.001) than those without significant progression. In multivariable regression analyses, both CV-HbA1c and CV-FPG were independent predictors of annual change in TPV [CV-HbA1c: ß = 0.241 (0.019-0.462), P = 0.034; CV-FPG: ß = 0.265 (0.060-0.465), P = 0.012], annual TPV progression [CV-HbA1c: ß = 0.214 (0.023-0.405), P = 0.029; CV-FPG: ß = 0.218 (0.037-0.399), P = 0.019], and significant atherosclerosis progression [CV-HbA1c: odds ratio [OR] = 1.367 (1.149-1.650), P = 0.010; CV-FPG: OR = 1.321 (1.127-1.634), P = 0.013]. CONCLUSIONS: Long-term GV is associated with accelerated progression of coronary atherosclerosis independent of conventional risk factors in patients with T2DM. Trial registration ClinicalTrials.gov (NCT02587741), October 27, 2015; retrospectively registered.

Ginsenoside Rb1 Ameliorates Age-Related Myocardial Dysfunction by Regulating the NF-[Formula: see text]B Signaling Pathway.

Age-related myocardial dysfunction is a very large healthcare burden. Here, we aimed to investigate whether ginsenoside Rb1 (Rb1) improves age-related myocardial dysfunction and to identify the relevant molecular mechanism. Young mice and aged mice were injected with Rb1 or vehicle for 3 months. Then, their cardiac function was inspected by transthoracic echocardiography. Serum and myocardium tissue were collected from all mice for histological or molecular expression analyses, including aging-related proteins, markers relevant to fibrosis and inflammation, and markers indicating the activation of the nuclear factor-kappa B (NF-[Formula: see text]B) pathway. Compared with the control condition, Rb1 treatment significantly increased the ejection fraction percentage and significantly decreased the internal diameter and volume of the left ventricle at the end-systolic and end-diastolic phases in aged mice. Rb1 treatment reduced collagen deposition and collagen I, collagen III, and transforming growth factor-[Formula: see text]1 protein expression levels in aged hearts. Rb1 also decreased the aging-induced myocardial inflammatory response, as measured by serum or myocardial interleukin-6 and tumor necrosis factor-[Formula: see text] levels. Furthermore, Rb1 treatment in aged mice increased cytoplasmic NF-[Formula: see text]B but decreased nuclear NF-[Formula: see text]B, which indicated the suppression of the NF-[Formula: see text]B signaling pathway by regulating the translocation of NF-[Formula: see text]B. Rb1 could alleviate aging-related myocardial dysfunction by suppressing fibrosis and inflammation, which is potentially associated with regulation of the NF-[Formula: see text]B signaling pathway.

Renin-Angiotensin System Inhibitors for the Prevention of Atrial Fibrillation Recurrence After Ablation　- A Meta-Analysis.

BACKGROUND: Atrial fibrillation (AF) recurrence remains a tricky problem in patients undergoing ablation. This meta-analysis aimed to summarize the current literature to clarify whether renin-angiotensin system inhibitors (RASIs) prevent AF recurrence after ablation.Methods and Results:Relevant studies were searched on Pubmed and EMBASE through December 2019. Pooled relative risk (RR) of AF recurrence was calculated. Subgroup analyses according to study design, race, and follow-up duration were further performed. A total of 15 studies examining 4,300 patients were included, with 3 randomized controlled trials and 12 cohort studies. Overall analysis showed that RASIs significantly reduced AF recurrence after ablation (RR=0.83; 95% confidence interval (CI) 0.70-0.98, P=0.028; I2=68.9%). Subgroup analysis further indicated that positive results were found in randomized controlled trials (RR=0.51, 95% CI 0.37-0.70, P<0.001; I2=4%), studies conducted in Asia (RR=0.59, 95% CI 0.46-0.76, P<0.001; I2=30.7%), and studies with follow-up duration ≥1 year (RR=0.82, 95% CI 0.70-0.95, P=0.01; I2=59.1%); negative results were found in cohort studies, studies conducted in Europe or the USA, and studies with follow-up duration <1 year. CONCLUSIONS: RASIs can potentially prevent AF recurrence after ablation under selected conditions. However, more studies are required to confirm this finding due to the variation in current evidence.

ATP-sensitive potassium channels gene polymorphism rs1799858 affects the risk of macro-/micro-vascular arteriosclerotic event in patients with increased low-density lipoprotein cholesterol levels.

BACKGROUND: Plasma concentration of low-density lipoprotein cholesterol (LDL-C) is causally related to the risk of arteriosclerotic events. Whether ATP-sensitive potassium channels (KATP) genetic variants predict increased LDL-C concentration (≥1.8 mmol/L) and risk of macro-/micro-vascular arteriosclerotic event remain elusive. METHODS: A total of 320 subjects with increased LDL-C concentration (≥1.8 mmol/L) and 320 counterpart subjects (< 1.8 mmol/L) from the South China were enrolled in this study. Three KATP polymorphisms (rs1799858, rs4148671 and rs78148713) were genotyped by the Sequenom MassARRAY system. Binary logistic regression analysis was used to evaluate the association of the 3 KATP variants with increased LDL-C concentration and carotid artery stenosis (CAS) ≥50%. Two-way ANOVA was used to analyze the association of the 3 KATP variants with microalbumin in urine (MAU) and high-sensitivity C-reactive protein (HsCRP) levels. Cox proportional hazards regression analysis was used to retrospectively analyse the association of the optimal variant with the risk of new onset/recurrent acute myocardial infarction (AMI). RESULTS: Among the 3 studied KATP gene single nucleotide polymorphisms (SNPs), only rs1799858 (TT + CT genotype) was associated with elevated risk of LDL-C ≥ 1.8 mmol/L (adjusted OR = 2.25, 95% CI: 1.31-3.85, P = 0.003) and CAS ≥50% (adjusted OR = 2.80, 95% CI: 1.12-6.98, P = 0.028). KATP SNP rs1799858 was also associated with increased MAU (P = 0.013) and HsCRP (P = 0.027) levels. The follow-up for an average of 51.1-months revealed that participants carrying the T-allele (TT + CT) of rs1799858 was associated with high risk of new onset/recurrent AMI (adjusted HR = 2.90, 95% CI: 1.06-7.94, P = 0.038). CONCLUSION: The KATP SNP rs1799858 may be an optimal genetic predisposition marker for increased LDL-C concentration (≥1.8 mmol/L) and its related macro-/micro-vascular arteriosclerotic event risk. The KATP variant rs1799858 was associated with higher risk of macro-/micro-vascular arteriosclerotic events in patients with elevated serum LDL-C levels.

Ginsenoside Rb1 reduces H2O2­induced HUVEC dysfunction by stimulating the sirtuin­1/AMP­activated protein kinase pathway.

Endothelial dysfunction and senescence are closely associated with cardiovascular diseases including atherosclerosis and hypertension. Ginsenoside Rb1 (Rb1), the major active constituent of ginseng, has been investigated intensively because of its anti­obesity and anti­inflammatory effects. In a previous study, hydrogen peroxide (H2O2) was applied to induce human umbilical vein endothelial cell (HUVEC) aging. It was demonstrated that Sirtuin­1 (SIRT1) was activated by Rb1 to protect HUVECs from H2O2­induced senescence. However, the mechanisms are not fully understood. The present study examined the role of AMP­activated protein kinase (AMPK), an energy sensor of cellular metabolism, in the signaling pathway of SIRT1 during H2O2­stimulated HUVEC aging. It was identified that Rb1 restored the H2O2­induced reduction of SIRT1 expression, which was consistent with our previous study, together with the activation of AMPK phosphorylation. Using compound C, an AMPK inhibitor, the role of AMPK in the protective effect of Rb1 against H2O2­induced HUVEC senescence was examined. It was identified that the induction of phosphorylated AMPK by Rb1 markedly increased endothelial nitric oxide synthase expression and nitric oxide production, and suppressed PAI­1 expression, which were abrogated in HUVECs pretreated with compound C. Further experiments demonstrated that nicotinamide, a SIRT1 inhibitor, downregulated the phosphorylation of AMPK and reduced the protective effects of Rb1 against H2O2­induced endothelial aging. Taken together, these results provide new insights into the possible molecular mechanisms by which Rb1 protects against H2O2­induced HUVEC senescence via the SIRT1/AMPK pathway.

Predictive value of P wave terminal force in lead V1 for atrial fibrillation: A meta-analysis.

BACKGROUND: Several studies have explored the association between P wave terminal force in lead V1 (PTFV1) and risk of atrial fibrillation (AF) occurrence, but the results were controversial. This meta-analysis aimed to examine whether abnormal PTFV1 could predict AF occurrence. METHODS: We searched PubMed, Embase, and Cochrane Library databases for articles published before August 25, 2018. Pooled odds ratios (ORs) of AF occurrence were calculated using random-effects models to explore the significance of PTFV1. RESULTS: A total of 12 studies examining 51,372 participants were included, with 9 studies analyzing PTFV1 as a categorical variable and 4 studies analyzing PTFV1 as a continuous variable. As a categorical variable, abnormal PTFV1 (>0.04 mm s) was significantly associated with AF occurrence with a pooled OR of 1.39 (95% confidence interval [CI] 1.08-1.79, p = .01). Subgroup analysis found that ORs of studies in hemodialysis patients (OR = 4.89, 95% CI 2.54-9.90, p < .001) and acute ischemic stroke patients (OR = 1.60, 95% CI 1.14-2.25, p = .007) were higher than general population (OR = 1.15, 95% CI 1.03-1.29, p = .01). Studies from Europe (OR = 1.05, 95% CI 0.91-1.20, p = .51) yielded lower OR of endpoints compared with Asia (OR = 1.89, 95% CI 1.38-2.60, p < .001) and United States (OR = 1.43, 95% CI 1.19-1.72, p < .001). As a continuous variable, PTFV1 was also significantly associated with AF occurrence with a polled OR per 1 standard deviation (SD) change of 1.27 (95% CI 1.02-1.59, p = .03). CONCLUSIONS: PTFV1 was significantly associated with the risk of AF and was considered to be a good predictor of AF occurrence in population with or without cardiovascular diseases.

Intravenous versus intraosseous adrenaline administration in out-of-hospital cardiac arrest: A retrospective cohort study.

BACKGROUND: Adrenaline is an important component in the resuscitation of individuals experiencing out-of-hospital cardiac arrest (OHCA). The 2018 Advanced Cardiac Life Support (ACLS) algorithm gives the option of either intravenous (IV) or intraosseous (IO) routes for adrenaline administration during cardiac arrest. However, the optimal route during prehospital resuscitation remains controversial. This study aims to investigate whether IV and IO routes lead to different outcomes in OHCA patients who received prehospital adrenaline. METHODS: This retrospective analysis included adult patients with OHCA of presumed cardiac origin who had Emergency Medical Services (EMS) CPR, received adrenaline, and were enrolled in the Resuscitation Outcomes Consortium (ROC) Cardiac Epistry version 3 database between 2011 and 2015. We divided the study population into IV and IO groups based on the administration route. Logistic regression analysis was performed to evaluate the association between adrenaline delivery routes and prehospital return of spontaneous circulation (ROSC), survival to hospital discharge, and favorable neurological outcome. RESULTS: Of the 35,733 patients included, 27,758 (77.7%) had adrenaline administered via IV access and 7975 (22.3%) via IO access. With the IO group as a reference in the logistic regression model, the adjusted odds ratios of the IV group for prehospital ROSC, survival and favorable neurological outcome were 1.367 (95%CI, 1.276-1.464), 1.468 (95%CI, 1.264-1.705) and 1.849 (95%CI, 1.526-2.240), respectively. Similar results were found in the propensity score matched population and subgroup analysis. CONCLUSION: Compared with the IO approach, the IV approach appears to be the optimal route for adrenaline administration in advanced life support for OHCA during prehospital resuscitation.

Impact of HbA1c variability on subclinical left ventricular remodeling and dysfunction in patients with type 2 diabetes mellitus.

BACKGROUND: Glycemic instability confers a risk of poor prognosis in patients with type 2 diabetes mellitus (T2DM). This study aimed to investigate whether HbA1c variability provided additional value over mean HbA1c for predicting subclinical left ventricular remodeling and dysfunction in T2DM patients. METHODS: A total of 466 T2DM patients with normal cardiac structure and function were recruited and prospectively followed up for a median of 4.7 y. HbA1c was measured quarterly. The intrapersonal mean and standard deviation (SD) of HbA1c measurements were calculated, and SD-HbA1c was considered as a measure of HbA1c variability. All participants underwent transthoracic echocardiography at baseline and after follow-up. RESULTS: In multivariable regression analyses, SD-HbA1c was independently associated with annualized changes in left ventricular end diastolic diameter, interventricular septum, left ventricular posterior wall, left ventricular mass index, left ventricular ejection fraction, E/e' ratio, and E/A ratio (P < 0.001). Subgroup analysis based on mean HbA1c levels (<7.0%, 7.0-7.5%, and ≥7.5%) further confirmed that SD-HbA1c was associated with most of the above parameters regardless of mean HbA1c levels. CONCLUSION: This study indicates that HbA1c variability adds to the mean value in predicting subclinical left ventricular remodeling and dysfunction in T2DM patients.

Ginsenoside Rb1 Alleviates Oxidative Low-Density Lipoprotein-Induced Vascular Endothelium Senescence via the SIRT1/Beclin-1/Autophagy Axis.

Oxidative low-density lipoprotein (ox-LDL) induces endothelium senescence and promotes atherosclerosis. Ginsenoside Rb1 (gRb1) has been proved to protect human umbilical vein cells (HUVECs), but its effect on ox-LDL-induced endothelium senescence and the underlying mechanism remains unknown. This study is to explore the involvement of the SIRT1/Beclin-1/autophagy axis in the effect of gRb1 on protecting endothelium against ox-LDL-induced senescence. Hyperlipidemia of Sprague Dawley rats was induced by high-fat diet, and gRb1 was intraperitoneal injected. A senescence model of HUVECs induced by ox-LDL was also established. The results showed that gRb1 alleviated hyperlipidemia-induced endothelium senescence and ox-LDL-induced HUVECs senescence. GRb1 also restored the reductions in SIRT1 and autophagy, which were involved in the anti-senescence effects. Beclin-1 acetylation was reduced, and the correlation between SIRT1 and Beclin-1 was increased by gRb1. Results of our study demonstrated the anti-senescence function of gRb1 against hyperlipidemia in the endothelium, and the underlying mechanism involves the SIRT1/Beclin-1/autophagy axis.

Trimetazidine inhibits cardiac fibrosis by reducing reactive oxygen species and downregulating connective tissue growth factor in streptozotocin-induced diabetic rats.

Diabetes may affect myocardial fibrosis through oxidative stress. Trimetazidine (TMZ) is an anti-anginal agent. The present study aimed to determine the modulatory effect of TMZ on reactive oxygen species (ROS) and connective tissue growth factor (CTGF) expression and to evaluate the potential of TMZ to improve diastolic function in streptozotocin (STZ)-induced diabetic rats. After treating STZ-induced diabetic rats with TMZ for 16 weeks, a decrease in malondialdehyde levels, cardiac collagen volume fraction, left ventricular (LV) end-diastolic pressure and protein expression of collagen-I (Col I), Col III and CTGF compared with those in diabetic control rats was observed. In vitro, TMZ inhibited Col I, Col III and CTGF protein expression in cardiac fibroblasts treated with high glucose and decreased intracellular ROS generation and hydroxyproline content in the cell culture medium of cardiac fibroblasts. TMZ markedly improved cardiac fibrosis and diastolic function in diabetic rats. This effect was associated with a reduction in ROS production and CTGF expression in cardiac fibroblasts. The present study suggests that TMZ may be beneficial for protecting the hearts of diabetic patients.