Corilagin inhibits angiotensin II-induced atrial fibrosis and fibrillation in mice through the PI3K-Akt pathway.

Objectives: Corilagin (Cor) is reported as beiing hepatoprotective, anti-inflammatory, antibacterial, and anti-oxidant, while the effect on atrial fibrosis remains unknown. Therefore, we investigated the protective effect of Cor in angiotensin II (Ang II)-induced atrial fibrosis and atrial fibrillation (AF). Materials and Methods: C57BL/6 mice (male, 8-10 weeks, n = 40) were subcutaneously infused either with saline or Ang II (2.0 mg/kg/day) and Cor (30 mg/kg) intraperitoneally injected 2 hr before Ang II infusion for 4 weeks. Mice were grouped into the control group (n=8), Cor group (n=8), Ang II group (n=8), and Ang II + Cor group (n=8). Morphological, histological, and biochemical examinations were performed. In vivo, transesophageal burst pacing was used to generate AF. Results: Cor treatment markedly reduced Ang II-induced AF development in mice. Ang II + Cor therapy potentially decreased the atrial fibrotic area. It significantly decreased the increase in smooth muscle alpha-actin (α-SMA), CTGF, Collagen I, and Collagen III expressions brought on by Ang II treatment. Moreover, Ang II + Cor treatment remarkably decreased the malondialdehyde (MDA) content, whereas superoxide dismutase (SOD) and catalase (CAT) activities were potentially increased (all, P<0.001). In addition, Ang II + Cor significantly reduced Ang II-induced interleukin 1 beta (IL-1ß), interleukin 6 (IL-6), and tumor necrosis factor-alpha (TNF-α) concentrations in atrial tissues. Furthermore, Cor significantly inhibited Ang II-induced p-PI3K, p-Akt, and NF-κB p-p65 protein expression in atrial tissues. Conclusion: Our data speculated that Cor could have a protective effect against Ang II-induced atrial fibrosis and AF via down-regulation of the PI3K-Akt pathway.

The Study of Endothelial-Mesenchymal Transition in an Atrial Fibrillation Rat Model.

Background: Activated fibroblasts are reported partly of endothelial origin, derived through endothelial-mesenchymal transition (EndMT). Few studies have investigated EndMT in atrial fibrillation (AF), which may have a potential effect on cardiac fibrosis. Objective: To investigate whether EndMT occurs in an animal model of AF. Methods: A total of 80 Sprague‒Dawley rats (8 weeks, male, 200-250 g) were randomly divided into two groups: the control group and the AF group (n = 40 in each group). Rats in the AF group received a daily intravenous injection of acetylcholine-calcium chloride for seven days to establish an AF model, and rats in the control rats were injected with saline in the same way. At different time points (Day 3, Day 5, Day 7, Day 9, Day 11, Day 13, Day 15, and Day 17), we observed changes in EndMT-related indexes (CD31, VE-cadherin, FSP-1, TGF-ß1 and collagen) and HIF-1α in the rat atria of two groups, as well as immunofluorescence co-expression of CD31/FSP-1 and VE-cadherin/FSP-1 in the endocardial endocardium of the atria. Results: In the AF group, atrial EndMT was observed and enhanced with time. Compared with the control group, the levels of CD31 and VE-cadherin in the AF group decreased, while mesenchymal marker (FSP-1) and EndMT inducer (TGF-ß1) were dynamically increased after Day 3. The co-expression of CD31/FSP-1 and VE-cadherin/FSP-1 was observed from Day 3 to the end of observation time Day 17 by immunofluorescence in AF rat hearts, indicating the existence of EndMT. In addition, the level of HIF-1α in the hearts of AF rats was increased. Conclusion: As far as we know, this is the first study to explore the dynamic process of EndMT in an AF rat model. The presence of EndMT was verified in the atria of the AF rat model, and Day 7-Day 17 was the best observation time point for the model. This may lead to a better understanding of the pathological changes and mechanisms in AF with a short modeling cycle.

Analysis of competing risks of cardiovascular death in patients with hepatocellular carcinoma: A population-based study.

Clinical data has shown that cardiovascular diseases (CVDs) have emerged as a prominent cause of mortality in individuals with hepatocellular carcinoma (HCC). This research aimed to reveal the comorbid effects of CVDs in patients with HCC. The cardiovascular mortality of patients diagnosed with HCC between 2000 and 2014 was compared to that of the general US population. Standardized mortality ratios were calculated to quantify the relative risk of cardiovascular mortality in HCC patients. The cumulative incidence of cardiovascular death (CVD) was estimated using Fine-Gray testing, and independent risk factors for CVD were determined using competing risk models. The results were analyzed using the Kaplan-Meier analysis. The overall SMR for CVD in HCC patients was 11.15 (95% CI: 10.99-11.32). The risk of CVD was significantly higher in patients aged < 55 years (SMR: 56.19 [95% CI: 54.97-57.44]) compared to those aged ≥ 75 years (SMR: 1.86 [95% CI: 1.75-1.97]). This study suggests that patients with HCC are at significant risk of developing CVD. Competing risk analyses indicated that age, grade, tumor size, surveillance, epidemiology, and end results stage, and surgical status were independent risk factors for CVD in patients with HCC. Therefore, patients with HCC require enhanced preventive screening and management of CVDs during and after treatment to improve patient survival.

Salidroside attenuates atrial fibrosis and atrial fibrillation vulnerability induced by angiotensin-II through inhibition of LOXL2-TGF-ß1-Smad2/3 pathway.

Aims and objectives: Salidroside (SAL), an active component isolated from the Chinese plant Rose Rhodiola, has anti-inflammatory, antioxidant, anti-cancer, neuroprotective, and renal protective properties. Atrial fibrosis developed due to angiotensin II (Ang II) plays a crucial function in developing atrial fibrillation (AF). This research investigates the involvement of SAL in AF, its vulnerability to AF, and Ang II-induced inflammatory atrial fibrosis. Methods: Ang II (2 mg/kg/day) was infused underneath the skin into male C57BL/6 mice (8-10 weeks old, n = 40) for four weeks to create the AF model. SAL (50 mg/kg/day) was given intraperitoneally once per day for 28 days. Analyses of morphology, histology, and biochemical were carried out. Transesophageal burst pacing was used in vivo to induce AF. Results: Ang II injection increased mice's heart rate and systolic blood pressure (SBP), whereas SAL treatment was significantly reduced. Ang II infusion increased left atrial diameter (LAD) in mice, which was attenuated after SAL treatment. SAL alone did not affect AF inducibility, but SAL therapy markedly decreased Ang II-induced AF inducibility. Additionally, the expression levels of interleukin-1 beta (IL-1ß), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) were inhibited with SAL therapy in mice. Compared to the Ang II group, Ang II infusion raised malondialdehyde (MDA) levels and reduced superoxide dismutase (SOD) and catalase (CAT) activity, but SAL therapy altered all of these effects. SAL treatment significantly reduced LOXL2, TGF-ß1, p-Smad2 and p-Smad3 protein expression than the Ang II group mice. Conclusion: SAL inhibits atrial fibrosis and potentially attenuates increased susceptibility to AF by suppressing the LOXL2-TGF-ß1-Smad2/3 pathway.

Stachydrine ameliorates hypoxia reoxygenation injury of cardiomyocyte via enhancing SIRT1-Nrf2 pathway.

BACKGROUND: Hypoxia/reoxygenation (H/R)-induced cardiomyocyte cell apoptosis is critical in developing myocardial infarction. Stachydrine (STA), an active constituent of Leonurus heterophyllus sweet, could have a protective effect on myocardial H/R injury, which remains unexplored. Therefore, the study aimed to investigate the protective effects and mechanisms of STA on H/R injury of cardiomyocytes. METHODS: Rat cardiomyocyte H9c2 cells underwent H/R (hypoxia for 4 h and reoxygenation for 12 h). Cells were pretreated with STA (50 µM) 2 h before H/R. Cardiomyocyte injury was evaluated by CCK-8 assay and lactate dehydrogenase (LDH) release. Apoptosis was assessed by TUNEL staining and caspase-3 activity. Oxidative stress was assessed by lipid oxidation product MDA and a ROS-scavenging enzyme SOD in culture media. Western blot was performed to measure the protein expressions of SIRT1, Nrf2, and heme oxygenase-1 (HO-1). RESULTS: STA reversed the decrease in cell viability and increased LDH release in H9c2 cells with the H/R insult. STA significantly suppressed oxidative stress, reduced MDA content, and increased SOD activity in H9c2 cells exposed to H/R. STA reduced apoptosis in H9c2 cells exposed to H/R, as evidenced by the reduced TUNEL positive cells and caspase-3 activity. In addition, STA enhanced SIRT1, Nrf2, and HO-1 protein expression in H/R-stimulated H9c2 cells. SIRT1 and Nrf2 involved the protective effect of STA in H/R-exposed H9c2 cells, as the changes in cell viability and caspase-3 activity by STA can be reversed by SIRT1 inhibitor EX-527 or Nrf2 siRNA. CONCLUSIONS: Our data speculated that STA protects H/R injury and inhibits oxidative stress and apoptosis in cardiomyocytes by activation of the SIRT1-Nrf2 pathway.

Safety and Efficacy of Cryoballoon Pulmonary Vein Isolation and Left Atrial Appendage Closure Combined Procedure and Half-Dose Rivaroxaban After Operation in Elderly Patients with Atrial Fibrillation.

Background: To investigate the safety and effectiveness of cryo-balloon pulmonary vein isolation (PVI) and left atrial appendage closure (LAAC) combined procedure and half-dose rivaroxaban after operation in elderly patients with atrial fibrillation (AF). Patients and Methods: A total of 203 AF patients presented for cryo-balloon PVI, and LAAC combined procedure was included from 2019 to 2021. Postoperative patients were anticoagulated with rivaroxaban with/without clopidogrel for 60 days, with oral rivaroxaban of 10 mg in the elderly group and 20 mg in the non-elderly group. Patients with AF ≥80 and <80 years were considered elderly and non-elderly groups, respectively. Scheduled follow-ups and transesophageal echocardiography were used to assess peri- and post-procedural safety and effectiveness. Results: A total of 203 patients underwent the combined procedure, 83 in the elderly and 120 in the non-elderly groups. All patients successfully obtained PVI and satisfactory LAAC. During the perioperative period, one patient had puncture complications in the elderly group and one with thrombosis in the non-elderly group. Oral rivaroxaban was administered to 83.2% and 75% of patients in the elderly and non-elderly groups, respectively, and rivaroxaban was combined with clopidogrel anticoagulation in the remaining patients. The annual rates of composite clinical events were 8.4% and 9.2% in the elderly and non-elderly groups, respectively, with no statistically significant difference. Patients in both groups had complete sealing, and there was no displacement of devices, death and peripheral arterial thrombosis. Recurrence of AF occurred in 25 and 32 patients in the elderly and non-elderly groups, respectively, with no statistically significant difference. Besides, the two groups had no statistically significant difference in cerebral infarction/transient ischemic attack and device-related thrombosis (p > 0.05). Conclusion: This study suggests that cryo-balloon PVI and LAAC combined procedure and half-dose rivaroxaban after the operation is safe and effective in treating elderly patients with AF.

Machine learning algorithms identify target genes and the molecular mechanism of matrine against diffuse large B-cell lymphoma.

BACKGROUND: Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin's lymphoma worldwide. Novel treatment strategies are still needed for refractory or relapsed DLBCL. OBJECTIVE: The present study aimed to systematically explore the potential targets and molecular mechanisms of matrine in the treatment of DLBCL. METHODS: Potential matrine targets were collected from multiple platforms. Microarray data and clinical characteristics of DLBCL were downloaded from publicly available databases. Differential expression analysis and weighted gene co-expression network analysis (WGCNA) were applied to identify the hub genes of DLBCL using R software. Then, the shared target genes between matrine and DLBCL were identified as the potential targets of matrine against DLBCL. The least absolute shrinkage and selection operator (LASSO) algorithm was used to determine the final core target genes, which were further verified by molecular docking simulation and receiver operating characteristic (ROC) curve analysis. Functional analysis was also performed to elucidate the potential mechanisms. RESULTS: A total of 222 matrine target genes and 1269 DLBCL hub genes were obtained through multiple databases and machine learning algorithms, respectively. From the nine shared target genes of matrine and DLBCL, five final core target genes, including CTSL, NR1H2, PDPK1, MDM2, and JAK3, were identified. Molecular docking showed that the binding of matrine to the core genes was stable. ROC curves also suggested close associations between the core genes and DLBCL. Additionally, functional analysis showed that the therapeutic effect of matrine against DLBCL may be related to the PI3K-Akt signaling pathway. CONCLUSION: Matrine may target five genes and the PI3K-Akt signaling pathway in DLBCL treatment.

2023 Chinese expert consensus on the impact of COVID-19 on the management of cardiovascular diseases.

The primary site of infection in COVID-19 exhibit is the respiratory system, but multiple organ systems could be affected. The virus could directly invade cardiomyocytes. Alternatively, cytokine storm could lead to myocardial injury. More importantly, the management of existing cardiovascular diseases must be re-examined in COVID-19 due to, for example, interaction between antiviral agents and with a wide variety of pharmacological agents. The Branch of Cardiovascular Physicians of Chinese Medical Doctor Association organized a panel of experts in cardiovascular and related fields to discuss this important issue, and formulated the "2023 Chinese Expert Consensus on the Impact of COVID-19 on the Management of Cardiovascular Diseases." The Consensus was drafted on the basis of systematic review of existing evidence and diagnosis and treatment experience, and covers three major aspects: myocardial injury caused by COVID-10 and COVID-19 vaccine, the impact of COVID-19 on patients with cardiovascular disease, and the impact of COVID-19 on the cardiovascular system of healthy people, and rehabilitation guidance recommendations. The Consensus involves 11 core clinical issues, including incidence, pathogenesis, clinical manifestations, treatment strategies, prognosis, and rehabilitation. It is our hope that this Consensus will provide a practical guidance to cardiologists in the management of cardiovascular diseases in the new era of COVID-19 pandemic.

Irisin attenuates angiotensin II-induced atrial fibrillation and atrial fibrosis via LOXL2 and TGFß1/Smad2/3 signaling pathways.

Objectives: Irisin was reported as a cardioprotective and anti-oxidative effector, while the effect on atrial fibrosis is unknown. The current research examined irisin's function in atrial fibrillation (AF); atrial fibrosis brought on by Ang II can be suppressed, thus lessening the risk of developing AF. Materials and Methods: 246 individuals were enrolled in the present case-control study. Chinese AF patients (n=126), 83 of whom were paroxysmal AF (PAF), 43 patients with persistent AF (PeAF), and 120 healthy controls. Saline or Ang II (2.0 mg/kg/day) was subcutaneously injected into healthy male C57BL/6 mice for four weeks. Once daily for four weeks, intraperitoneal injections of exogenous irisin (500 g/kg/day) were administered. Results: In comparison to PAF patients and healthy controls (all P<0.05), PeAF patients had significantly higher rates of heart failure (HF), large left atrial size (LAD), hypertrophic protein B-type natriuretic peptide (BNP), malondialdehyde (MDA), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), C-terminal telopeptide of type I collagen (CTX-I), and transforming growth factor beta-1 (TGF-ß1), while superoxide dismutase (SOD) level was low. Expression of irisin was decreased in AF patients' serum and Ang II-infused mice. Exogenous irisin dramatically reduced apoptosis, atrial fibrosis, atrial inflammation, and the susceptibility to AF caused by Ang II. In the atrial tissue, irisin inhibited Ang II-induced fibroblast transdifferentiation, LOXL2, TGF-ß1, collagen production, and phosphorylation of Smad2/3. Conclusion: The study results speculated that irisin could be a potential AF target, and it inhibited atrial fibrosis and significantly impaired increased AF susceptibility through inactivation of LOXL2 and the TGF-ß/Smad pathway.

Temporary COVID-19 Specialized Hospital: Management Strategies for Public Health Emergencies.

During the coronavirus disease 2019 (COVID-19) outbreak in Shanghai with the Omicron variant in March 2022, locally accessible hospitals and healthcare centres encountered difficulties quickly responding to a demand for hospitals that were rapidly increasing, optimizing clinical results and controlling the infection. In this commentary, we summarize the management strategies of patients in a temporary COVID-19 specialized hospital during the outbreak in Shanghai, China. The present commentary was considered eight characteristics of management system, including general idea, infection prevention team, and efficient time management, and preventive and protective measures management, strategies for the management of infected patients, disinfection management, drug supply management strategies, and medical waste management. Following eight characteristics, the temporary COVID-19 specialized hospital operated effectively for 21 days. A total of 9674 patients were admitted, 7127 cases (73.67%) were cured and discharged, and 36 were transferred to designate hospitals for better treatment. Twenty-five management staff, 1130 medical, nursing staff, 565 logistics staff, and 15 volunteers participated in the temporary COVID-19 specialized hospital, and no infection prevention team member was infected. We speculated that these management strategies could be potential references for public health emergencies.

Echinacoside ameliorates 5-fluorouracil-induced endothelial injury and senescence through SIRT1 activation.

Echinacoside (ECH) is a natural bioactive component with antioxidant, anti-inflammatory, anti-apoptosis, and anti-tumor properties. In the current study, we explore the ECH-mediated protective effect and underlying mechanism of 5-fluorouracil (5-FU)-induced endothelial injury and senescence in the Human umbilical vein endothelial cells (HUVECs). In HUVECs, Cell viability, Apoptosis and Senescence assays evaluated 5-fluorouracil-induced endothelial injury and senescence. Protein expressions were assessed using RT-qPCR and Western blotting. Our results showed that 5-FU-induced endothelial injury and endothelial cell senescence could be improved when treated with ECH in HUVECs. ECH treatment potentially attenuated oxidative stress and ROS production in HUVECs. In addition, the effect of ECH on autophagy markedly reduced the percentage of HUVECs with LC3-II dots and suppressed the Beclin-1 and ATG7 mRNA expression but enhanced the p62 mRNA expression. Besides, ECH treatment significantly increased migrated cells and suppressed the adhesion of THP-1 monocytes in HUVECs. Furthermore, ECH treatment activated the SIRT1 pathway, and its related proteins (SIRT1, p-AMPK and eNOS) expression increased. Nicotinamide (NAM), an inhibitor of SIRT1, significantly attenuated the ECH-induced decrease in the apoptotic rate, increased SA-ß-gal-positive cells and significantly reversed the ECH-induced reduction of endothelial senescence. Our results demonstrated that ECH employed endothelial injury and senescence in HUVECs via activation of the SIRT1 pathway.

ANGPTL4 suppresses the profibrogenic functions of atrial fibroblasts induced by angiotensin II by up-regulating PPARγ.

Objectives: The present study's objective was to investigate the association between angiopoietin-like 4 (ANGPTL4) levels and the prognosis of Atrial fibrillation (AF), the causative effect in angiotensin II- (Ang II) induced AF, and its underlying mechanisms. Materials and Methods: Baseline serum ANGPTL-4 concentrations were measured in 130 patients with AF. Rat atrial fibroblasts were isolated from 14-day-old SD rats and transfected with Ang II treatment. Transfected cells were divided into: The control group, ANGPTL4-OE group, Ang II group, and Ang II+ANGPTL4-OE group. Transfected cells were used to analyze fibroblasts' proliferation, migration, and collagen production at the cellular level. RT-qPCR and western blotting evaluated the ANGPTL4-targeted gene and PPARγ-Akt pathway. Results: In patients with AF, serum ANGPTL4 concentrations decreased significantly compared with the healthy group. ANGPTL4 mRNA and protein expressions were significantly down-regulated in Ang II-induced cardiac fibroblasts. ANGPTL4 overexpression potentially attenuated Ang IIinduced fibroblast proliferation, migration, and collagen production in atrial tissue. ANGPTL4 inhibited the signaling proteins, such as PPARγ, α-SMA, and Akt. Conclusion: Our experimental data speculate that ANGPTL4 is a key factor in regulating AF progression. Therefore, increasing ANGPTL4 expression could be an effective strategy for AF treatment.

The neutrophil-lymphocyte ratio to predict poor prognosis of critical acute myocardial infarction patients: a retrospective cohort study.

Introduction: Inflammation is closely related to adverse outcomes of acute myocardial infarction (AMI). This study aimed to evaluate whether neutrophil-lymphocyte ratio (NLR) can predict poor prognosis of critical AMI patients. Materials and methods: We designed a retrospective cohort study and extracted AMI patients from the "Medical Information Mart for Intensive Care-III" database. The primary outcome was 1-year all-cause mortality. The secondary outcomes were 90-day and in-hospital all-cause mortalities, and acute kidney injury (AKI) incidence. The optimal cut-offs of NLR were picked by X-tile software according to the 1-year mortality and patient groups were created: low-NLR (< 4.8), high-NLR (4.8 - 21.1), and very high-NLR (> 21.1). Cox and modified Poisson regression models were used to evaluate the effect of NLR on outcomes in critically AMI patients. Results: Finally, 782 critical AMI patients were enrolled in this study, and the 1-year mortality was 32% (249/782). The high- and very high-NLR groups had a higher incidence of outcomes than the low-NLR group (P < 0.05). The multivariate regression analyses found that the high- and very high-NLR groups had a higher risk of 1-year mortality (Hazard ratio (HR) = 1.59, 95% CI: 1.12 to 2.24, P = 0.009 and HR = 1.73, 95% CI: 1.09 to 2.73, P = 0.020), 90-day mortality (HR = 1.69, 95% CI: 1.13 to 2.54, P = 0.011 and HR = 1.90, 95% CI: 1.13 to 3.20, P = 0.016), in-hospital mortality (Relative risk (RR) = 1.77, 95% CI: 1.14 to 2.74, P = 0.010 and RR = 2.10, 95% CI: 1.23 to 3.58, P = 0.007), and AKI incidence (RR = 1.44, 95% CI: 1.06 to 1.95, P = 0.018 and RR = 1.34, 95% CI: 0.87 to 2.07, P = 0.180) compared with low-NLR group. NLR retained stable predictive ability in sensitivity analyses. Conclusion: Baseline NLR is an independent risk factor for 1-year mortality, 90-day mortality, in-hospital mortality, and AKI incidence in AMI patients.

Interleukin-11 Is Elevated in Patients with Atrial Fibrillation, Correlates with Serum Fibrosis Markers, and Represents a Therapeutic Target for Atrial Fibrosis.

INTRODUCTION: Inflammatory cytokines are closely associated with developing cardiac fibrosis. This research aimed to explore the significant role of IL-11 in atrial fibrosis progression and potential therapeutic targets. METHODS: 207 AF patients and 160 healthy subjects were included in the case-control study. Blood samples were analyzed for the level of IL-11 by enzyme-linked immunosorbent assay (ELISA). Angiotensin II (Ang II)-treated fibrosis mouse models were generated, and expression of IL-11 mRNA and protein was detected by RT-qPCR and Western blot. IL-11 antagonist was used to evaluating atrial fibrosis-related markers. RESULTS: The persistent atrial fibrillation patients (n = 76) had significantly larger left atrial size, higher serum levels of hypertrophic protein BNP, proinflammatory cytokine high-sensitivity C-reactive protein (hs-CRP), and interleukin-6 (IL-6) compared to paroxysmal atrial fibrillation patients (n = 131), and healthy subjects (all p < 0.05). Pearson correlation analysis revealed significant positive correlation between serum IL-11 and cardiac fibrosis markers BNP (r = 0.394, p < 0.001), CTX-I (r = 0.418, p < 0.001), PICP (r = 0.306, p < 0.001), PIIINP (r = 0.335, p < 0.001), and TGF-ß1 (r = 0.273, p < 0.001). In the fibrosis mouse model, Ang II infusion significantly upregulated IL-11 mRNA and protein expression in the left atrium of mice (p < 0.05), as well as staining intensity of Masson trichrome, the intensity of α-SMA, and it increased mRNA expression of collagen I and III in atrial tissue. IL-11 antagonist treatment significantly attenuated Masson trichrome, number of α-SMA-positive myofibroblasts in atrial tissue. Also, it significantly reduced the p-ERK1/2 in atrial tissue of mice infused with Ang II (p < 0.05). CONCLUSIONS: IL-11 is upregulated in the serum of AF patients, and IL-11 inhibitor significantly inhibited Ang II-induced atrial fibrosis, a key pathological feature of AF. Therefore, IL-11 could be a potential therapeutic target for AF.

[Clinical analysis of severe/critical 2019 novel coronavirus Omicron variant infection combined with atrial fibrillation].

OBJECTIVE: To investigate the clinical characteristics and prognosis of coronavirus disease 2019 (COVID-19) patients with Omicron variant combined with atrial fibrillation (AF). METHODS: From March 23, 2022 to May 15, 2022, 2 675 aged ≥ 50 years old COVID-19 patients with AF were admitted to Zhoupu Hospital, the designated hospital for COVID-19 in Shanghai. Patients were divided into mild symptoms group, normal group, and serious/critical group according to the symptoms. The clinical data, imaging examination and laboratory results and prognosis of the three group patients were compared. RESULTS: The median age of 2 675 COVID-19 patients was 69.0 (60.0, 81.0) years old, the incidence of AF was 5.05% (135/2 675), the age range of AF patients were from 55 to 101 years old, with a median age of 84.0 (74.0, 89.0), and the number of mild symptoms, normal, serious/critical patients were 68, 30, 37, respectively, including 9 of serious and 28 of critical patients. In the serious/critical patients, aged 55-75 years old accounted for 43.2%, the rate of 2019 novel coronavirus vaccination was 32.4%. The identified new-onset AF was the highest among the three groups, but the rate of persistent AF was the highest in the mild symptoms group (58.8%). The severe/critical group complicated with fever (29.7%), hepatic insufficiency (13.5%), renal insufficiency (46.0%), type 2 diabetes (46.0%), and heart failure were higher in NYHA classification [compared with the mild symptoms and normal group (score): 1.8±1.1 vs. 1.1±0.8, 1.2±0.7, respectively, all P < 0.05]. In term of laboratory examinations, C-reactive protein (CRP), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) levels were significantly higher in serious/critical patients compared to the mild symptoms and normal groups [CRP (mg/L): 27.2 (6.0, 60.8) vs. 7.6 (3.1, 19.3), 12.8 (4.9, 26.3), ALT (U/L): 31.3±15.4 vs. 15.4±9.3, 19.3±11.7, AST (U/L): 78.0±21.7 vs. 34.7±15.6, 38.1±24.4, all P < 0.05]. The hemoglobin (Hb) and albumin (ALB) levels were significantly lower than those in the mild symptoms and normal groups [Hb (g/L): 105.3±22.5 vs. 125.8±25.4, 123.0±20.4, ALB (g/L): 33.7±6.0 vs. 39.0±5.5 and 39.6±13.1, all P < 0.05]. In addition, MB isoenzyme of creatine kinase (CK-MB) was significantly higher in the serious/critical group than that in the mild symptoms group [µg/L: 2.5 (1.5, 3.4) vs. 2.2 (1.2, 2.8), P < 0.05]. In terms of the treatment, the percentage of antiplatelet agents and low-molecular heparin ratio compared among the three groups were statistically significant, with the serious/critical group using the lowest percentage of antiplatelet agents (27.0%) and a higher percentage of low-molecular heparin usage than that in mild symptoms group [81.1% (30/37) vs. 51.5% (35/68), P < 0.05]. In terms of prognosis, the mortality of patients with AF was 18.5% (25/135), all of whom were critical ill, including 32.0% (8/25) with cerebral embolism, pulmonary embolism and cerebral hemorrhage. Among them, 40.0% (10/25) died of multiple organ failure (40.0% combined with gastrointestinal hemorrhage), 20.0% (5/25) died of heart failure, and 12.0% (3/25) died of respiratory failure; while there were no death cases recorded in the mild symptoms, normal group and 9 serious patients. CONCLUSIONS: The serious/critical patients infected with COVID-19 Omicron variant with AF, have a worse prognosis and high mortality. Multiple organ failure, heart failure, sudden cardiac death, respiratory failure and embolic disease are the major causes of death.

Inhibition of FABP4 attenuates cardiac fibrosis through inhibition of NLRP3 inflammasome activation.

Objectives: Cardiac fibrosis is a key biological process of cardiac remodeling and heart failure. Fatty acid-binding protein 4 (FABP4) is a lipid-binding protein that can regulate glucose and lipid homeostasis, and its expression was elevated in heart failure. However, whether FABP4 is involved in cardiac fibrosis remains unknown. Materials and Methods: The cardiac fibrosis model was established in male C57BL/6 mice with subcutaneously infused angiotensin II (Ang-II) (2.8 mg/kg/day) for 4 weeks. DMSO or FABP4 inhibitor BMS309403 (50 mg/kg/day) was intraperitoneally injected for 4 weeks. Ang II-infused mice, FABP4 inhibitor (BMS309403) injected mice, and ventricular tissue were used for morphological studies, and histological and biochemical analyses (FABP4 protein composition and expression). Results: Ang II infusion increased FABP4 mRNA and protein expression in the mouse ventricular tissue. After treatment with FABP4 inhibitor BMS309403 for 4 weeks, mice showed improved cardiac structure and function as detected by echocardiography. BMS309403 suppressed cardiac and systemic inflammatory response, reduced collagen deposition, and mRNA expression of collagen type I (COL1A1) and collagen type III (COL3A1) in Ang II-infused mice. BMS309403 also reduced the number of α-smooth muscle actin (α-SMA)+cells and decreased the mRNA expression of α-SMA, matrix metalloproteinases-2 (MMP-2), MMP-9, and transforming growth factor-ß (TGFß) in ventricular tissue. Conclusion: The inhibitory effect of BMS309403 on cardiac fibrosis might be associated with inhibition of NLRP3 inflammasome activation, which Ang II activated. Thus, our data speculated that inhibition of FABP4 could significantly induce cardiac fibrosis.

LOXL2 silencing suppresses angiotensin II-induced cardiac hypertrophy through the EMT process and TGF-ß1/Smad3/NF-κB pathway.

Objectives: Atrial fibrillation (AF) is a common arrhythmia with atrial myocyte hypertrophy linked with stroke, heart failure, and increased mortality. Lysyl oxidase-like 2 (LOXL2) involves the cross-linking of collagen in the extracellular matrix (ECM). In the present study, we investigated the roles and underlying mechanisms of LOXL2 on cardiomyocyte hypertrophy. Materials and Methods: The expression of LOXL2 mRNA and protein were detected in angiotensin II (Ang II) treated rat cardiomyocytes H9c2 by RT-qPCR and western blot. Small interfering RNA (siRNA) mediated LOXL2 gene silencing was used to evaluate cardiac hypertrophy and related markers. Also, the protein expression of EMT markers and Smad3/NF-κB pathway was determined by western blot. Results: Ang II significantly increased mRNA and protein expressions of LOXL2 and increased mRNA levels of myocardial hypertrophy markers, including ANP, BNP, and ß-MHC in H9c2 cells. Silencing of LOXL2 significantly suppressed Ang II-induced hypertrophy and reversed the increase in ANP, BNP, and ß-MHC mRNA levels. Also, EMT markers' expressions, as evidenced by increased E-cadherin and decreased vimentin, α-smooth muscle actin (α-SMA), fibroblast-specific protein (FSP), and collagen 1A1. Mechanistically, we found that LOXL2 silencing suppressed protein expressions of TGF-ß1, p-Smad3, and p-NF-κB in Ang II-stimulated H9c2 cells. LOXL2 silencing also attenuated Ang II-induced increased expression and content of proinflammatory cytokines IL-1ß (H) and TNF-α. Conclusion: Our data speculated that LOXL2 might be a potential contributing factor to Ang II-induced cardiac hypertrophy, and TGF-ß1/Smad3/NF-κB is involved in a signal axis and might be a potential strategy in treating cardiac hypertrophy.

Identification of an Epigenetic Signature for Coronary Heart Disease in Postmenopausal Women's PBMC DNA.

Menopause is accompanied with an increased risk of cardiovascular disease. DNA methylation may have a significant impact on postmenopausal women's development of coronary heart disease. DNA methylation alterations in peripheral blood mononuclear cells (PBMCs) from women with coronary heart disease and healthy controls were detected using the Illumina Infinium MethylationEPIC BeadChip platform in this work. We employed Sangerbox technology and the GO and KEGG databases to further study the pathogenesis of coronary heart disease in postmenopausal women. After that, we used functional epigenetic module analysis and Cytoscape to remove the hub genes from the protein-protein interaction networks. Five genes (FOXA2, PTRD, CREB1, CTNAP2, and FBN2) were the hub genes. Lipid accumulation, endothelial cell failure, inflammatory responses, monocyte recruitment and aggregation, and other critical biological processes were all influenced by these genes. Finally, we employed methylation-specific PCR to demonstrate that FOXA2 was methylated at a high level in postmenopausal women with coronary heart disease. To better understand coronary heart disease in postmenopausal women's molecular mechanisms, our study examine the major factors contributing to the state of DNA methylation modification, which will help discover novel diagnostic tools and treatment options.

Percutaneous Retrieval of Left Atrial Appendage Closure Devices in Patients With Atrial Fibrillation: A Case Report.

Left atrial appendage closure (LAAC) devices can be inadvertently released into unfavorable locations, which may allow them to migrate to a different position within the left atrial appendage or embolize from the heart into the aorta. In such instances, it can be challenging to remove the LAAC device. Here, we present two cases in which patients with atrial fibrillation experienced LAAC device exposure at an inappropriate site because of interventional operator error and device mismatch: (a) the LAAC device was dislodged into the aortic arch and retrieved percutaneously from the femoral artery route, and (b) in the left atrium, which was dislodged into the left atrium and retrieved via atrial transseptal puncture of the femoral vein.

Prediction model based on machine learning for short- and long-term adverse events in left atrial appendage closure.

Background: At present, the prediction of adverse events (AE) had practical significance in clinic and the accuracy of AE prediction model after left atrial appendage closure (LAAC) needed to be improved. To identify a good prediction model based on machine learning for short- and long-term AE after LAAC. Methods: In this study, 869 patients were included from the Department of Cardiovascular Medicine of Shanghai University of Medicine and Health Sciences Affiliated Zhoupu Hospital during 2017 and 2021. Univariate and multivariate analyses were conducted for short-term AE after LAAC to determine possible risk factors related with AE. We compared 8 machine learning algorithms for prediction short-term AE, and XGBoost was found to have the best performance. In addition, Cox-regression was used for long-term AE to find out the risk factors and establish a prediction model. Results: In univariate and multivariate analysis, body mass index (BMI) [odds ratio (OR) =0.91], congestive heart failure, hypertension, age ≥75 years, diabetes, stroke2 attack (CHADS2) score (OR =0.49) and bleeding history or predisposition, labile international normalized ratio (INR), elderly, drug/alcohol usage (BLED) score (OR =1.71) were shown to be significant risk factors for short-term AE. The XGbosst algorithm was used to predict short-term AE based on 15 possible risk factors. For long-term AE, Cox regression was used for the prediction. The CHADS2 score [hazard ratio (HR) =1.43], hypertension (HR =2.18), age more than 75 (HR =0.49), diabetes (HR =0.57), BLED score (HR=0.28), stroke (HR =19.8), hepatopathy (HR =3.97), nephropathy (HR =2.93), INR instability (HR =4.18), drinking (HR =2.67), and drugs (HR =2.36) were significant risk factors for long-term AE. The XGBoost had a good receiver operating characteristic (ROC) curve and area under the curve (AUC) was 0.85. The accuracy of the XGBoost model stayed at nearly 0.95. Conclusions: In short- and long-term AE, CHADS2 score and BLED score were the most obvious risk factors. Several other risk factors also played roles in AE of LAAC. The incidence of long-term AE is under 15% and LAAC is effective and safe. The XGBoost model had good prediction accuracy and ROC curve.