Association between inflammation markers and all-cause mortality in critical ill patients with atrial fibrillation: Analysis of the Multi-Parameter Intelligent Monitoring in Intensive Care (MIMIC-IV) database.

Background: Inflammation is related to cardiovascular disease. Among the many inflammatory markers, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and systemic immune-inflammatory index (SII) were considered as novel predictors for atherosclerosis outcomes. We aimed to investigate the impact of these inflammatory markers on the prognosis of patients with atrial fibrillation (AF). Methods: We obtained data on AF patients from the Medical Information Mart for Intensive Care (MIMIC)-IV database. These patients were classified into two groups based on their survival status within 30 days. Then, they were divided into three groups based on the tertile of baseline NLR, PLR, and SII, respectively. We comprehensively explored the relationship between those inflammatory indicators and all-cause mortality in patients with AF by Kaplan-Meier analysis, multivariate Cox regression analysis, receiver operating characteristic (ROC) analyses, restricted cubic spline regression (RCS), and subgroup analysis. Results: A total of 4562 patients with AF were included. Statistically significant differences were found between survivor and non-survivor groups for NLR, PLR and SII. Patients in the high tertile of the NLR had a higher mortality rate than those in the low and intermediate tertiles, as did patients in the PLR and the SII. NLR, PLR and SII were independently associated with increased risk of all-cause mortality. RCS showed that the 30-day and 365-day risk of death were linearly associated with increases in NLR, PLR, and SII, respectively. Conclusion: NLR, PLR, and SII have the potential to be used as indicators for stratifying the risk of mortality in critically ill patients with AF.

Multi-omics analysis identifies potential mechanisms by which high glucose accelerates macrophage foaming.

Atherosclerotic morbidity is significantly higher in the diabetic population. Hyperglycemia, a typical feature of diabetes, has been proven to accelerate foam cell formation. However, the molecular mechanisms behind this process remain unclear. In this study, LPS and IFN-γ were used to convert THP-1-derived macrophages into M1 macrophages, which were then activated with ox-LDL in either high glucose or normal condition. We identified lipids within macrophages by Oil red O staining and total cholesterol detection. The genes involved in lipid absorption, efflux, inflammation, and metabolism were analyzed using qRT-PCR. The mechanisms of high glucose-induced foam cell formation were further investigated through metabolomics and transcriptomics analysis. We discovered that high glucose speed up lipid accumulation in macrophages (both lipid droplets and total cholesterol increased), diminished lipid efflux (ABCG1 down-regulation), and aggravated inflammation (IL1B and TNF up-regulation). Following multi-omics analysis, it was determined that glucose altered the metabolic and transcriptional profiles of macrophages, identifying 392 differently expressed metabolites and 293 differentially expressed genes, respectively. Joint pathway analysis suggested that glucose predominantly disrupted the glycerolipid, glycerophospholipid, and arachidonic acid metabolic pathways in macrophages. High glucose in the glyceride metabolic pathway, for instance, suppressed the transcription of triglyceride hydrolase (LIPG and LPL), causing cells to deposit excess triglycerides into lipid droplets and encouraging foam cell formation. More importantly, high glucose triggered the accumulation of pro-atherosclerotic lipids (7-ketocholesterol, lysophosphatidylcholine, and glycerophosphatidylcholine). In conclusion, this work elucidated mechanisms of glucose-induced foam cell formation via a multi-omics approach.

HDAC3 Impairs Cardiac Function in Chronic Heart Failure Rats via Mediating MicroRNA-26b-3p to Target High Mobility Group AT-Hook 2.

BACKGROUND: Histone deacetylase 3 (HDAC3) has been studied in chronic heart failure (CHF), while the regulatory mechanism of HDAC3 on the development of CHF in regulating microRNA (miR)-26b-3p/high mobility group AT-hook 2 (HMGA2) axis has not been extensively investigated. This study aimed to probe the effects of HDAC3, miR-26b-3p and HMGA2 on CHF. METHODS: CHF rat models were established using aortic coarctation. HDAC3, miR-26b-3p and HMGA2 levels in CHF rats were examined. Thereafter, the CHF rats were injected with relative oligonucleotides and plasmids of HDAC3, miR-26b-3p and HMGA2 to detect the cardiac function, inflammatory reaction, myocardial tissue pathological changes, and cardiomyocyte apoptosis. The binding relationship between miR-26b-3p and HMGA2 and the interaction between HDAC3 and miR-26b-3p were validated. RESULTS: HDAC3 and HMGA2 were elevated, while miR-26b-3p was decreased in CHF rats. The reduced HDAC3 or HMGA2 or enriched miR-26b-3p attenuated cardiac dysfunction, inflammatory reaction, myocardial tissue pathological changes and cardiomyocyte apoptosis in CHF rats, while the reduction of miR-26b-3p exerted the opposite effects. Furthermore, the inhibition of the miR-26b-3p or elevation of HMGA2 reversed the effect of reduced HDAC3 on mitigating CHF progression. Mechanically, miR-26b-3p targeted HMGA2 and HDAC3 bound to miR-26-3p. CONCLUSION: Downregulation of HDAC3 relieves cardiac function in CHF rats via mediating miR-26b-3p/HMGA2 axis. This study provides novel theory references and a distinct direction for the therapy strategies of CHF.

Integrated analysis of miRNA-mRNA regulatory network and functional verification of miR-338-3p in coronary heart disease.

Coronary heart disease is a cardiovascular disease with high morbidity and mortality. Although great progress has been made in treatment, the prognosis is still very poor. Therefore, this project aims to screen potential diagnostic markers and therapeutic targets related to the progression of coronary heart disease. A total of 94 overlapping differentially expressed mRNAs and 70 differentially expressed miRNAs were identified from GSE20681, GSE12288, GSE49823, and GSE105449. Through a series of bioinformatics methods and experiment, we obtained 5 core miRNA-mRNA regulatory pairs, and selected miR-338-3p/RPS23 for functional analysis. Moreover, we found that RPS23 directly targets miR-338-3p by dual luciferase assay, western, and qPCR. And the expression of miR-338-3p and RPS23 is negatively correlated. The AUC value of miR-338-3p is 0.847. Downregulation of miR-338-3p can significantly inhibit the proliferation and migration of HUVEC. On the contrary, overexpression of miR-338-3p promoted the proliferation and migration of HUVEC. In addition, the interference of RPS23 expression can reverse the regulation of miR-338-3p on HUVEC proliferation. In conclusion, miR-338-3p/RPS23 may be involved in the progression of coronary heart disease, and miR-338-3p may be a diagnostic biomarker and therapeutic target for coronary heart disease.

Clinical Efficacy of Catheter Ablation in the Treatment of Vasovagal Syncope.

Catheter ablation of ganglionated plexi (GPs) performed as cardioneuroablation in the left atrium (LA) has been reported previously as a treatment for vasovagal syncope (VVS). However, the efficacy and safety of catheter ablation in the treatment of VVS remains unclear. The objective of this study is to explore the efficacy and safety of catheter ablation in the treatment of VVS and to compare the different ganglion-mapping methods for prognostic effects. A total of 108 patients with refractory VVS who underwent catheter ablation were retrospectively enrolled. Patients preferred to use high-frequency stimulation (HFS) (n = 66), and anatomic landmark (n = 42) targeting is used when HFS failed to induce a positive reaction. The efficacy of the treatment is evaluated by comparing the location and probability of the intraoperative vagal reflex, the remission rate of postoperative syncope symptoms, and the rate of negative head-up tilt (HUT) results. Adverse events are analyzed, and safety is evaluated. After follow-up for 8 (5, 15) months, both HFS mapping and anatomical ablation can effectively improve the syncope symptoms in VVS patients, and 83.7% of patients no longer experienced syncope (<0.001). Both approaches to catheter ablation in the treatment of VVS effectively inhibit the recurrence of VVS; they are safe and effective. Therefore, catheter ablation can be used as a treatment option for patients with symptomatic VVS.

Kinetic optimization of odor adsorption with acetate fiber cloth prepared from waste cigarette filter.

Odor pollution with NH3 as major contributor is a notorious issue that strongly influences our living environment. NH3 removal with acetate fiber cloth (AFC) prepared from waste cigarette filter is an economic feasible approach for simultaneous solid wastes disposal. Herein, waste cigarette filter was used to prepare AFC through hot-pressing approach, which was convinced to have good adsorption efficiency on NH3 due to large specific surface area. Effects of hot-pressing temperature, pressure and pressing time on AFC mechanical property and NH3 adsorption efficiencies were optimized by response surface method. As results, hot-pressing treatment improved the specific surface area of AFC to 9.530 m2/g, and thus enhanced NH3 adsorption efficiency to 68.73 % under hot-pressing temperature of 146 °C, pressure of 12.5 kPa and pressing time of 33 min. While the optimal tensile strength of AFC was obtained as 90.43 N under hot-pressing temperature of 140 °C, pressure of 15.0 kPa and pressing time of 30 min. The work provided an economic feasible approach for waste cigarette filter recycling and odor control.

Acute Myocardial Infarction and Concomitant Acute Intracranial Hemorrhage: Clinical Characteristics and Outcomes.

This study aimed to evaluate the demographic and clinical characteristics, treatments and outcomes of concomitant acute myocardial infarction (AMI) and acute intracranial hemorrhage (ICH). All patients diagnosed with concomitant AMI and acute ICH admitted to our institution were included retrospectively. The patient demographics, clinical characteristics, neuroimaging and treatment approaches were analyzed, and the outcomes of interest included disability as defined by the modified Rankin Scale (mRS) score and all-cause mortality within 1 year of follow-up. Of a total of 4972 patients with AMI, 8 patients (0.2%) with concomitant acute ICH were recruited for the study, including ST-segment elevation myocardial infarction (STEMI, 5 cases) and non-STEMI (3 cases). New-onset acute ICH in 4 of the 5 patients (80%) occurred within 24 hours after the AMI event, and all these patients had a sudden decrease in the level of consciousness, with an average decrease of 4.6 on the Glasgow Coma Scale. All 5 out of 8 patients had irregular shapes and uncommon sites of hematoma presentation documented on CT scans. Unfortunately, 2 patients died from a progression of ICH within 1 week, and 2 of the 6 survivors had poor functional outcomes (mRS ≥3) at the 1-year follow-up. Concomitant acute ICH and AMI are rare complications displaying unique iconography. Acute ICH caused serious prejudice in AMI with higher mortality and poor functional outcomes, and cardiac catheterization without the administration of antithrombotic or antiplatelet agents was feasible for patients who had unstable hemodynamics or STEMI.

LncRNA SOX2OT facilitates LPS-induced inflammatory injury by regulating intercellular adhesion molecule 1 (ICAM1) via sponging miR-215-5p.

AIM: Long non-coding RNA SOX2 overlapping transcript (SOX2OT) is closely related to heart failure and myocardial damage. We attempted to investigate its role in endotoxin lipopolysaccharide (LPS) injury in cardiomyocytes. MATERIALS & METHODS: Cell viability, apoptosis rate, and levels of pro-inflammatory cytokines and apoptosis- and oxidative stress-related proteins were measured by MTS assay kit, flow cytometry, western blotting, and commercial kits. Physical interactions were confirmed by dual-luciferase report assay and RNA immunoprecipitation assay. RESULTS: Silencing SOX2OT and reinforcing miRNA (miR)-215-5p protected human AC16 cardiomyocytes from LPS-induced oxidative and inflammatory injuries by inhibiting intercellular adhesion molecule 1 (ICAM1). SOX2OT directly interacted with miR-215-5p, and miR-215-5p could target ICAM1. CONCLUSION: Inhibiting SOX2OT/miR-215-5p/ICAM1 axis might be a possible approach to treat myocardial damage. LAY ABSTRACT: Lipopolysaccharide (LPS) is an endotoxin from some bacteria including Escherichia coli, and it can cause inflammation in different tissues/cells including myocardia/cardiomyocytes, resulting in diseases such as myocarditis, cardiomyopathy, and cardiac hypertrophy. The underlying mechanism was not completely clarified, but known to include the dysregulation of non-coding RNAs. Herein, we demonstrated the biological role of long non-coding RNA SOX2 overlapping transcript (SOX2OT) in LPS-infected cardiomyocytes. Eventually, we found that inhibiting the expression of SOX2OT could mitigate LPS-induced a series of injuries in human cardiomyocytes, and SOX2OT interacts with a microRNA named as miR-215-5p. Besides, restoring miR-215-5p elicited similar effects to SOX2OT knockdown. Collectively, we concluded that SOX2OT binding to miR-215-5p might protect cardiomyocytes from LPS infection through regulating an important protein named ICAM1. This study suggested SOX2OT/miR-215-5p might be novel potential treatment targets in bacterial infection-related myocardial damages.

Sex differences in global disability-adjusted life years due to ischemic stroke: findings from global burden of diseases study 2019.

To investigate the sex differences in disability-adjusted life years (DALYs) due to ischemic stroke (IS) by year, location and age. We extracted sex-specific data on DALYs number, age-standardized DALYs rate (ASDR) and all-age DALYs rate of IS by year, location and age from the Global Burden of Diseases study 2019. The estimated annual percentage changes (EAPC) were calculated to evaluate the temporal trend of ASDR. For both sexes, although the ASDR of IS slightly decreased from 1990 to 2019, there has been an 60.3% increase in DALYs number worldwide. Sex difference in DALYs number (men minus women) decreased from - 2.83 million in 1990 to 0.14 million in 2019, while the men to women's ASDR ratio slightly increased from 1.10 in 1990 to 1.21 in 2019. The sex differences in IS DALYs showed remarkable regional variation. The largest sex differences in DALYs number and ASDR were in China and Vietnam. Middle-aged men had a higher IS DALYs than their age-matched counterparts. High systolic blood pressure accounted for the highest DALYs number in 2019, but the top three attributable risk factors that had the greatest sex differences were tobacco, dietary risk, and alcohol use. Sex differences in IS DALYs varied by year, location and age, mostly attributed to the disproportion of cardiovascular risk factors between sexes. Considering the population growth and aging, it is necessary to monitor the sex difference in IS DALYs in different populations and thus provide evidence for local administration to improve current preventive and management strategies of IS.

Ferroptosis-Specific Inhibitor Ferrostatin-1 Relieves H2O2-Induced Redox Imbalance in Primary Cardiomyocytes through the Nrf2/ARE Pathway.

OBJECTIVE: Ischemic heart disease (IHD) has always been the focus of attention of many researchers in cardiovascular disease, and its pathogenesis is also very complicated. Ferroptosis may be involved in the occurrence and development of IHD. METHODS: First, primary cardiomyocytes were treated with H2O2 to simulate the IHD in vitro model. After pretreatment with different concentrations of ferrostatin-1, cell survival rate was detected by MTT method, cell apoptosis was detected by TUNEL staining and flow cytometry, and the expression of oxidative stress, ferroptosis, and related molecules of Nrf2/ARE pathway was detected by Western blotting (WB) and quantitative real-time polymerase chain reaction (qRT-PCR). RESULTS: The mortality of primary cardiomyocytes in the H2O2 group was obviously increased. Ferrostatin-1 treatment can effectively inhibit cell death, improve antioxidant enzyme activity, inhibit the expression of ferroptosis-related molecules, and activate Nrf2/ARE pathway expression. CONCLUSION: Ferroptosis-specific inhibitor ferrostatin-1 relieves H2O2-induced redox imbalance in primary cardiomyocytes through the Nrf2/ARE pathway, inhibits ferroptosis, and thereby slows cardiomyocyte death.

Refinement of CHADS2 and CHA2DS2-VASc scores predict left atrial thrombus or spontaneous echo contrast in nonvalvular atrial fibrillation patients.

OBJECTIVE: To investigate the risk factors of left atrial thrombus (LAT)/spontaneous echo contrast (SEC) in patients with nonvalvular atrial fibrillation (AF). METHODS: This retrospective study analysed the data from consecutive patients with nonvalvular AF that underwent transoesophageal echocardiography. Logistic regression analysis was performed to identify risk factors of LAT/SEC. Receiver operating characteristic curve analysis was undertaken compare the new scales with CHADS2 and CHA2DS2-VASc scores. RESULTS: A total of 558 patients with AF were included in the study. LAT/SEC was detected in 137 (24.6%) patients. The independent risk factors of LAT/SEC beyond CHADS2 or CHA2DS2-VASc scores included non-paroxysmal AF and left atrial diameter >37.5 mm. These two variables were added into the CHADS2 or CHA2DS2-VASc score to build new scales. Areas under the curve for the new scales based on CHADS2 and CHA2DS2-VASc scores were significantly higher than the CHADS2 or CHA2DS2-VASc score both in the overall study cohort and in patients at a high risk of thromboembolism. CONCLUSIONS: Non-paroxysmal AF and increased left atrial diameter beyond the CHADS2 or CHA2DS2-VASc score were independent risk factors of LAT/SEC and may help to improve the current risk stratification, especially for patients with nonvalvular AF at a high risk of thromboembolism.

Responses of nitrous oxide fluxes to autumn freeze-thaw cycles in permafrost peatlands of the Da Xing'an Mountains, Northeast China.

Climate warming has intensified changes of permafrost freeze-thaw process and postponed the starting period of soil freezing, which significantly affected the processes of N2O production and emission from the soils. However, responses of soil N2O fluxes to freeze-thaw cycles (FTCS) during autumn freezing period in permafrost peatlands in field remain unclear. Therefore, the static chamber-GC techniques were used to explore the effects of autumn FTCS on N2O fluxes in the three permafrost peatlands [Calamagrostis angustifolia peatland (CA), Larix gmelini-Sphagnum swamp (LS), and Eriophorum vaginatum peatland (EV)] in Da Xing'an Mountains, Northeast China, from September to November 2019. The response peaks of N2O fluxes to autumn FTCS in CA (29.22 ± 14.90 µg m-2 h-1) and EV (19.70 ± 7.26 µg m-2 h-1) occurred in the autumn FTCS prophase, whereas LS (11.33 ± 0.90 µg m-2 h-1) appeared in the autumn FTCS metaphase. CA (394.90 µg m-2) and EV (497.82 µg m-2) acted as a N2O source, and LS (- 1321.43 µg m-2) was a N2O sink. The effects of autumn FTCS on N2O fluxes were significantly different (p < 0.001) in the three permafrost peatlands. N2O emissions during autumn FTCS were mainly driven by soil NH4+-N0-50 cm, DOC30-40 cm and 40-50 cm content and soil NO3--N0-50 cm content. The results implied that autumn FTCS could stimulate soil N2O emissions in permafrost peatlands and confirmed the important contribution of N2O emissions during autumn FTCS to annual nitrogen budget. This study could improve the accuracy of regional estimates of annual nitrogen budget.

The Comparison of Long-Term Outcome Between Patients with Single and Multiple Coronary Chronic Total Occlusions After Percutaneous Coronary Intervention.

BACKGROUND: Rapid advancements in percutaneous coronary intervention (PCI) have improved the outcome of chronic coronary total occlusions (CTOs); however, data regarding the difference in long-term outcomes in stable coronary artery disease (CAD) patients with single and multiple CTOs who underwent PCI are scarce. This study aimed to compare the long-term outcomes of patients with multiple CTOs and single CTO after PCI. METHODS: This study cohort included stable CAD patients who were diagnosed with CTO and treated with PCI from a single center. The primary endpoint was all-cause death. RESULTS: We retrospectively reviewed 670 consecutive patients with CTO-PCI. Among them, 539 patients had a single CTO, and 131 (19.7%) patients had multiple (at least two) CTOs. CTO revascularization was achieved in 470 (70.1%) patients. After a median follow-up duration of 33.7 months, the cumulative all-cause mortality (p = 0.037) and cardiac mortality (p = 0.003) were higher in patients with multiple CTOs than in those with a single CTO. In the multivariable model, multiple CTOs and left ventricular ejection fraction (LVEF) less than 40% were independent predictors for cardiac death (adjusted hazard ratio (HR) 2.53; P = 0.013 and adjusted HR 3.95; P < 0.001), while age older than 65 and LVEF less than 40% were independent predictors for all-cause death in CTO-PCI patients (adjusted hazard ratio (HR) 1.84; P = 0.035 and adjusted HR 2.54; P = 0.001). CONCLUSION: In CTO-PCI patients, long-term survival was associated with multiple CTOs, age and LVEF, but not with CTO revascularization.

NT Pro-BNP can be used as a risk predictor of clinical atrial fibrillation with or without left atrial enlargement.

BACKGROUND: NT Pro-BNP is a blood marker secreted by cardiomyocytes. Myocardial stretch is the main factor to stimulate NT Pro-BNP secretion in cardiomyocytes. NT Pro-BNP is an important risk factor for cardiac dysfunction, stroke, and pulmonary embolism. So does atrial myocyte stretching occur when patients have atrial fibrillation (AF)? Whether atrial muscle stretch induced by AF leads to increased NT Pro-BNP remains unclear. The purpose of this study is to investigate the relationship between NT Pro-BNP and AF. HYPOTHESIS: AF can cause changes in myocardial tension. Changes in myocardial tension may lead to increased secretion of NT Pro-BNP. We hypothesize that NT Pro-BNP may increase in AF with or without LAD enlargement. METHODS: This clinical study is an observational study and has been approved by the Ethics Committee of the First Affiliated Hospital of Xi'an Jiaotong University. Ethical approval documents is attached. The study retrospectively reviewed 1345 patients with and without AF. After excluding 102 patients who were not eligible, the final total sample size was 1243 cases: AF group 679 patients (378, 55.7% males) and non-AF group 564 patients (287, 50.8% males). NT Pro-BNP was observed in AF group and non-AF group with or without LAD. After adjusting for age, gender, BMI, left atrial diameter, hypertension, diabetes, coronary heart disease, and cerebral infarction, NT Pro-BNP remains statistically significant with AF. CONCLUSION: NT Pro-BNP can be used as a risk predictor of AF with or without left atrial enlargement.

In-hospital and one-year outcomes in cancer patients receiving percutaneous coronary intervention for acute myocardial infarction: A real-world study.

Background: Cancer and ischemic heart disease are the leading causes of mortality. The optimal management for patients with concomitant acute myocardial infarction (AMI) and cancer remains challenging. Objective: To evaluate in-hospital and 1-year adverse outcomes in cancer patients receiving percutaneous coronary intervention (PCI) to treat AMI. Methods: This was a single-center, retrospective cohort study, patients with cancer admitted to The First Affiliated Hospital of Xi'an Jiaotong University for AMI and discharged between January 2015 and June 2020 were analyzed. The outcomes were all-cause mortality at 1-year follow up and incidence of in-hospital adverse events, including arrhythmias, heart failure, major bleeding, stroke, and all-cause death. Results: A total of 119 patients were included, of these, 68 (57.1%) received PCI (PCI group) and 51 (42.9%) did not (non-PCI group). Patients in the PCI group had a lower incidence of in-hospital arrhythmias (22.1 vs. 39.2%; p = 0.042), major bleeding (2.9 vs. 15.7%; p = 0.013), and all-cause mortality (1.5 vs. 11.8%; p = 0.018) than those in non-PCI group. On 1-year follow-up, the PCI group had a lower all-cause mortality than the non-PCI group (log-rank test = 14.65; p < 0.001). Multivariable Cox regression showed that PCI is an independent protective factor (adjusted HR = 0.503 [0.243-0.947], p = 0.045) for cancer patients who have concomitant AMI. Conclusion: Cancer patients receiving PCI for AMI had a lower risk of in-hospital adverse events and mortality as well as 1-year all-cause mortality compared to those who refused PCI. Our study therefore supports the use of PCI to improve prognosis of this selected group of patients.

Periostin contributes to the adventitial remodeling of atherosclerosis by activating adventitial fibroblasts.

Background and aims: Adventitial remodeling is an important pathological process of atherosclerosis, but cues implicated in adventitial remodeling are far from fully understood. Periostin (POSTN), a matricellular protein, has been demonstrated to have multiple roles in cardiovascular diseases. The aim of the study was to explore the function of POSTN in adventitial remodeling during atherosclerosis. Methods: An atherosclerosis model was constructed based on ApoE-/- mice fed a high-fat and high-cholesterol diet. The expression of POSTN in the adventitia of mouse atherosclerotic vascular specimens was detected by immunohistochemical staining. The roles of POSTN in regulating adventitial fibroblast activation were assessed by cell contractility and activation marker α-smooth muscle actin (α-SMA) expression evaluation in adventitial fibroblasts overexpressing POSTN. In addition, we performed quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting to examine the expression of the proinflammatory chemokines transforming growth factor-ß1 (TGF-ß1) and monocyte chemotactic protein 1 (MCP1), as well as some extracellular matrix (ECM)-related proteins, in POSTN-overexpressing adventitial fibroblasts. Finally, the integrin-related signaling pathway was detected upon POSTN overexpression in adventitial fibroblasts. Results: POSTN was highly expressed in the adventitia of atherosclerotic aortae in the mouse atherosclerosis model and promoted the activation and contraction of adventitial fibroblasts. Meanwhile, POSTN also induced adventitial fibroblasts to express TGF-ß1, monocyte chemotactic protein-1 (MCP1), and ECM-related proteins and activated the phosphorylation of focal adhesion kinase (FAK) and Src. Conclusions: Our results revealed that POSTN is elevated in adventitia during atherosclerosis and contributes to the adventitial remodeling of atherosclerosis by activating adventitial fibroblasts.

Incidence of Arrhythmias and Their Prognostic Value in Patients With Multiple Myeloma.

Background: Arrhythmias are common cardiovascular complications in multiple myeloma (MM) patients and are related to a poor prognosis. Objective: This study aimed to assess the burden of arrhythmias and their prognostic value in patients with MM. Methods: This was a retrospective study of patients with MM between January 2015 and April 2020 at the First Affiliated Hospital of Xi'an Jiaotong University. The incidence of arrhythmia and associated risk factors were evaluated. The relationship between the type of arrhythmia and survival was analyzed. Results: A total of 319 patients with MM were identified, and 48.0% (153/319) had arrhythmias. The most common type of arrhythmia was sinus tachycardia (ST) (15.0%, 48/319), followed by sinus bradycardia (SB) (14.4%, 46/319), premature atrial contractions (PACs) (6.3%, 20/319), conduction disorders (CDs) (6.0%, 19/319), atrial fibrillation (AF) (6.0%, 19/319), premature ventricular contractions (PVCs) (4.4%, 14/319) and paroxysmal supraventricular tachycardia (PSVT) (0.6%, 2/319). The patients with arrhythmias had higher levels of log NT-proBNP and creatinine, greater bortezomib use, and a higher incidence of diabetes than those without arrhythmias (P < 0.05). The all-cause mortality rates of patients without arrhythmias and those with AF, ST, PACs, CDs, SB, and PVCs were 50.6% (84/166), 73.7% (14/19), 60.4% (29/48), 60.0% (12/20), 52.6% (10/19), 34.8% (16/46), and 28.6% (4/14), respectively. In a subgroup analysis of patients experiencing different types of arrhythmias, patients with SB had lower all-cause mortality than patients with AF (P < 0.01). Univariate and multivariate Cox analyses showed that there was a positive statistically significant association between SB and survival (HR: 0.592 [0.352-0.998], P = 0.049) in a subgroup analysis of different arrhythmias. Conclusions: Patients with MM had a heavy arrhythmia burden, and in this study, approximately half of MM patients had arrhythmias. MM patients with SB were associated with lower all-cause mortality than those with AF. SB might be an independent positive factor for prognosis.

Prognostic Potential of Heart Rate and Hypertension in Multiple Myeloma Patients.

Background: The prognosis of patients with multiple myeloma (MM) is variable and partly depends on their cardiovascular status. The presence of arrhythmias can lead to worse outcomes. Therefore, this study aimed to evaluate the potential of heart rate (HR) and hypertension in predicating the outcomes of MM patients. Methods: This study retrospectively enrolled patients with MM between January 1, 2010, and December 31, 2018, at the First Affiliated Hospital of Xi'an Jiaotong University. The endpoint was all-cause mortality. The Pearson's chi-square test was used to assess the association between hypertension and outcomes. Univariate and multivariate Cox proportional hazards models were developed to evaluate the relationship between HR and all-cause mortality. Results: A total of 386 patients were included. The mean HR was 83.8 ± 23.1 beats per minute (bpm). Patients with HR >100 bpm had a higher all-cause mortality (79.4%, 50/63) than those with 60 ≤ HR ≤ 100 bpm (39.9%, 110/276) and <60 bpm (19.1%, 9/47) (p < 0.001). Subgroup analysis based on the International Staging System and sex revealed similar relationships (p < 0.01). When stratified by age, patients with HR >100 bpm had higher all-cause mortality than those with a lower HR when age was <65 years or 65-75 years (p < 0.001) but not >75 years. The proportion of patients with hypertension was 54.7% (211/386). However, hypertension was not associated with all-cause mortality in MM patients (χ2=1.729, p > 0.05). MM patients with HR >100 bpm had the highest all-cause mortality. Conclusions: The prognostic potential of HR may be useful in aiding risk stratification and promoting the management of these patients.

Inhibition of TNFAIP1 ameliorates the oxidative stress and inflammatory injury in myocardial ischemia/reperfusion injury through modulation of Akt/GSK-3ß/Nrf2 pathway.

Tumor necrosis factor α-induced protein 1 (TNFAIP1) has been documented as a vital regulator of apoptosis and oxidative stress under various pathological conditions. However, whether TNFAIP1 plays a role in myocardial ischemia/reperfusion (I/R) injury has not been well investigated. This work aimed to evaluate the possible role of TNFAIP1 in mediating myocardial I/R injury. Firstly, we demonstrated that TNFAIP1 expression was dramatically increased in rat cardiomyocytes following hypoxia/reoxygenation (H/R) in vitro, and in rat myocardial tissues following I/R treatment in vivo. Silencing of TNFAIP1 alleviated H/R-induced apoptosis, oxidative stress and inflammatory response in rat cardiomyocytes in vitro. Moreover, knockdown of TNFAIP1 ameliorated I/R-induced myocardial injury, infarction size, cardiac apoptosis, oxidative stress and inflammatory response in vivo. Further investigation elucidated that knockdown of TNFAIP1 enhanced the activation of nuclear factor erythroid 2-related factor 2 (Nrf2) signaling associated with modulation of the Akt/glycogen synthase kinase-3ß (GSK-3ß) pathway in vitro and in vivo. Inhibition of Akt markedly abrogated TNFAIP1-knockdown-mediated Nrf2 activation in cardiomyocytes following H/R injury. In addition, suppression of Nrf2 significantly diminished TNFAIP1-knockdown-induced cardioprotective effects in H/R-exposed cardiomyocytes. In summary, this work elucidates that inhibition of TNFAIP1 ameliorates myocardial I/R injury by potentiating Nrf2 signaling via the modulation of the Akt/GSK-3ß pathway. Our study highlights a vital role of the TNFAIP1/Akt/GSK-3ß/Nrf2 pathway in mediating myocardial I/R injury and suggests TNFAIP1 as an attractive target for treatment of this disease.

Transient complete atrioventricular block and ST-segment elevation induced by coronary vasospasm due to iatrogenic hyperkalemia: a case report.

BACKGROUND: Hyperkalemia and acute coronary syndrome are not only all responsible for syncope related to complete atrioventricular block, but also share parts of electrocardiogram manifestations. Additionally, they influence each other. CASE PRESENTATION: A 32-year-old Chinese man presented with severe hypokalemia (1.63 mmol/l) at midnight in the emergency room. He developed unexpected rebound hyperkalemia (7.76 mmol/l) after 18 hours of oral and intravenous potassium chloride supplementation at a concentration of about 10 g/day and a rate of 10 mmol/hour. Subsequently, the patient complained of chest discomfort and dyspnea, followed by syncope for several minutes, approximately 2 hours after potassium reduction treatment had been started. The instant electrocardiogram showed complete atrioventricular block and elevated ST segment in the inferolateral leads, which resolved 15 minutes later, before hyperkalemia was corrected. Combined with mild coronary stenosis and negative myocardial injury markers, transient complete atrioventricular block induced by coronary vasospasm due to iatrogenic hyperkalemia was diagnosed. Normal urine potassium excretion, acid-base state, and other examinations made the diagnosis of hypokalemic periodic paralysis possible. CONCLUSIONS: Hyperkalemia may provoke acute coronary syndrome, and early coronary angiography is an effective strategy for identifying the direct cause of acute complete atrioventricular block.