Men with nonobstructive coronary disease have higher burden of ischemic heart disease detected by cardiopulmonary exercise test.

BACKGROUND: Nonobstructive coronary artery disease (NOCAD), characterized by the presence of myocardial ischemic symptoms and signs without obstructive coronaries, is a common clinical condition, but it is less well understood. Few studies have analyzed the gender differences in inducible myocardial ischemia assessed by cardiopulmonary exercise test (CPET) in NOCAD. METHODS: We conducted a study of 289 NOCAD patients (mean age 60, 56% women) with ischemic symptoms and confirmed ⫹50% coronaries stenoses by coronary angiography who underwent symptom-limited CPET. We assessed ischemic response using predicted % peak VO2 , O2 pulse trajectory, and exercise ECG test. RESULTS: Men with NOCAD had significantly lower predicted % peak VO2 (62% vs. 73%), higher proportions of flattening pattern (16% vs. 2%), and downward patterns of O2 pulse trajectory (2% vs. 0%) (p < .0001) compared with women. In contrast, women with NOCAD had a higher prevalence of shallow patterns of O2 pulse trajectory (21% vs. 6%, p < .0001). Men with NOCAD had a higher risk ischemic profile (medium risk: 63% vs. 54%, high risk: 18% vs. 4%, p < .0001). After adjustment, men with NOCAD had significantly lower predicted % peak VO2 (ß -27.4, 95% CI -30.74 to -24.07), higher risk for abnormal O2 pulse trajectories (OR 4.21, 95% CI 1.93 to 9.19), and myocardial ischemia risk per CPET parameters (OR 3.14, 95% CI 1.78 to 5.54) (p < .0001). CONCLUSION: Men with NOCAD had a higher risk profile for ischemic heart disease per CPET. Therefore, they should receive rigorous management and follow-up to prevent cardiovascular events.

Implementing case-based collaborative learning curriculum via webinar in internal medicine residency training: A single-center experience.

This study aimed to investigate the effects of the Case-based collaborative learning (CBCL) curriculum in webinar format on internal medicine residents' knowledge covering cardiologic topics and their attitudes toward the CBCL teaching module. CBCL is a novel small-group approach, that incorporates elements of problem-based learning and case-based learning, and it has shown to improve medical students' knowledge mastery. However, few studies have explored its applicability for internal medicine residents, especially in the webinar format. This prospective cohort study included internal medicine residents in a residency program in Beijing, China. Eight CBCL sessions in webinar format covering cardiologic topics were delivered to them from February to April 2020. Pre-session reading materials included textbook and guidelines published by the academic societies. Multiple-choice questions were delivered to assess participants' knowledge before and after the sessions. Changes in participants' knowledge were determined using the paired t test to compare mean values. In addition, surveys based on 5-point Likert scale scores assessed satisfaction at the end of the second and eighth sessions. The Wilcoxon signed-rank test was used to identify any potential satisfaction improvement. In total, 9 internal medicine residents participated in the study, of whom 33.3% were male, and the overall rate of participation in CBCL sessions in webinar format was 94.4%. The mean scores of 50 multiple-choice questions were 68.0 ± 12.3 and 75.1 ± 9.9 in the pre- and post-curriculum assessments (P = .029). In the first survey performed at the second week, 5 (55.6%) residents chose "like" or "extremely like" in overall satisfaction, "neutral" by 3 (33.3%) residents and "dislike" by 1 (11.1%) resident. In the second survey, only 1 (11.1%) resident selected a neutral reply in satisfactory assessment, and the other 8 (88.9%) residents selected either "like" or "extremely like" choices. Compared with the results of the first survey, the overall satisfaction rate significantly improved (P = .031). Implementing the CBCL sessions in webinar format for cardiology residents was resulted in the improved knowledge mastery and a high acceptance rate.

Coronary stenosis is a risk marker for impaired cardiac function on cardiopulmonary exercise test.

BACKGROUND: Cardiac function varies in different ways in ischemic heart disease (IHD). We aimed to evaluate the characteristics of cardiac function on cardiopulmonary exercise test (CPET) in IHD with different coronary stenoses. METHODS: Totally 614 patients with IHD were divided into non-obstructive coronary artery disease (NOCAD) (stenosis < 50%), obstructive coronary artery disease (OCAD) (stenosis 50-90%) and severe OCAD ( stenosis > 90%) according to the coronary angiography. And 101 healthy volunteers as controls. All participants performed CPET to assess cardiac function by oxygen uptake (VO2), estimated cardiac output (CO), and heart rate (HR). RESULTS: Generally, the values of VO2, CO, and HR in IHD were significantly lower than in healthy volunteers. Among 289 NOCAD, 132 OCAD, and 193 severe OCAD, significantly decreased values of VO2, CO, HR were observed (VO2 peak: 16.01 ± 4.11 vs. 15.66 ± 4.14 vs. 13.33 ± 3.4 mL/min/kg; CO: 6.96 ± 2.34 vs. 6.87 ± 2.37 vs. 6.05 ± 1.79 L/min; HR: 126.44 ± 20.53 vs. 115.15 ± 18.78 vs. 109.07 ± 16.23 bpm, P < 0.05). NOCAD had significantly lower VO2 at anaerobic threshold (-1.35, 95%CI -2.16 - -0.54) and VO2 peak (-2.05, 95%CI -3.18 - -0.93) compared with healthy volunteers after adjustment. All IHD patients were associated with low stroke volume and inefficient gas exchange (P < 0.05). CONCLUSION: IHD with increasing atherosclerotic burdens were associated with impaired cardiac output and chronotropic response on CPET. NOCAD should be given more early prevention and rigorous follow-up.

COL8A1 Promotes NSCLC Progression Through IFIT1/IFIT3-Mediated EGFR Activation.

Activation of EGFR is a major risk factor for non-small cell lung cancer (NSCLC). Understanding the molecular events promoting EGFR activation can help us gain more insights into the progression of NSCLC. In this study, we demonstrate that collagen type VIII alpha 1 chain (COL8A1), an extracellular matrix component, was overexpressed in NSCLC. In NSCLC cells, knockdown of COL8A1 suppressed cell growth, cycle progression, and migration, and induced cell apoptosis. While COL8A1 overexpression promoted cell proliferation and inhibited cell apoptosis. In addition, we found that COL8A1 depletion reduced interferon response signaling and downregulated (IFIT1) and interferon-induced proteins with tetratricopeptide repeats 3 (IFIT3). Moreover, we indicated that COL8A1 could upregulate IFIT1 and IFIT3 mediated EGFR activation in vitro and in vivo. Lastly, there was a positive correlation among COL8A1, IFIT1, and IFIT3 expression, and EGFR activity in patients with NSCLC. Overall, our data demonstrate that COL8A1 contributes to NSCLC proliferation and invasion through EGFR activation, dependent on IFIT1 and IFIT3 expression.

Report of a patient with refractory atrial tachycardia whose heart rate was controlled using ivabradine.

Ivabradine is an effective treatment for focal atrial tachycardia. However, it may also be effective for re-entrant atrial arrhythmia. An 85-year-old woman with a history of underlying ischaemic cardiomyopathy complained of worsening symptoms of heart failure because of rapid atrial tachycardia that was resistant to several rate-controlling drugs, but responded well to ivabradine. An electrophysiology study demonstrated a roof-dependent macro-re-entrant tachycardia of the left atrium. Linear ablation of the left atrial roof resulted in termination of the tachycardia. Thus, ivabradine can be an effective treatment for re-entrant atrial tachycardia.

Time of the low-level cardiopulmonary exercise test does not affect the evaluation of acute myocardial infarction in stable status.

Introduction: Cardiopulmonary exercise test (CPET) provides the means to evaluate the cardiopulmonary function and guide cardiac rehabilitation. The performance of acute myocardial infarction (AMI) patients at different times is different on CPET. Materials and methods: This was a cross-sectional study. Patients diagnosed as AMI in stable status were included and performed the low- level CPET (RAMP 10W). CPET variables at different times were compared among four groups. Results: Sixty and one patients with AMI conducted the low-level CPET from 3 to 15 days after AMI. Patients were stratified according to quartiles of CPET's time: 5 in 3-6 days group, 34 in 7-9 days group, 14 in 10-12 days group, 8 in 13-15 days group. Only VO2/HR at rest showed statistically different among the four groups.VO2/HR at rest in 3-6 days group and 10-12 days group were higher than in 13-15 days group (3.4 ± 0.85, 3.18 ± 0.78 vs. 2.50 ± 0.49 ml/beat, p < 0.05). Patients with complete revascularization had higher peak heart rate and blood pressure product and peak breathing reserve (BR), and lower Borg score compared with incomplete revascularization. And patients with LVEF >50% had higher peak BR compared with LVEF 40-50%. Conclusion: It was safe and efficient to conduct the low-level CPET in stable AMI patients 3 days after onset. Time was not an effector on cardiopulmonary function and exercise capacity and prognosis in AMI during CPET. Complete revascularization and normal LVEF should be good for exercise test in AMI.

Aerobic exercise improves cardiac function in rats with chronic heart failure through inhibition of the long non-coding RNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1).

BACKGROUND: To explore the beneficial effects and underlying mechanisms of aerobic exercise on chronic heart failure (CHF). METHODS: A CHF rat model was induced via left anterior descending coronary artery ligation. Four weeks post-surgery, CHF rats received aerobic exercise training over an 8-week period and cardiac function indexes including xxx were analyzed. To investigate the mechanisms involved in the aerobic exercise-induced benefits on CHF, overexpression of the long non-coding RNA MALAT1 was examined both in vivo and in vitro. Furthermore, the interaction between MALAT1 and the microRNA miR-150-5p and the downstream PI3K/Akt signaling pathway was investigated. RESULTS: Compared to the control group, the CHF rats showed evidence of left ventricular dysfunction including aggravated cardiac function indexes and lung to body weight ratio. The Masson staining demonstrated a significant degree of blue-stained fibrotic myocardial tissue in CHF rats compared to control rats. Furthermore, the levels of collagen I and collagen II were also markedly increased in CHF rats. Aerobic exercise improved cardiac function and left ventricular remodeling in rats with CHF. There was a significant reduction in the levels of the reactive oxygen species (ROS), inflammatory cytokines including TNF-α, IL-6, and IL-1ß, and inflammatory mediums containing the matrix metalloproteinases (MMPs) MMP-2 and MMP-9. Moreover, CHF rats receiving aerobic exercise showed decreased myocardial apoptosis and increased expression of autophagy-related proteins including beclin-1 and LC3B-II. Overexpression of the lncRNA MALAT1 eliminated all the beneficial effects related to aerobic exercise in CHF rats. Subsequent investigations demonstrated that miR-150-5p expression was up-regulated in CHF-Tr rats and down-regulated in CHF-Tr-MALAT1 rats. Furthermore, the downstream PI3K/Akt signaling pathway was re-activated in CHF-Tr-MALAT1 rats. In vitro experiments revealed that overexpression of MALAT1 reduced the miR-150-5p levels, resulting in increased cellular apoptosis and less autophagy. In addition, overexpression of MALAT1 suppressed the downstream PI3K/Akt signaling pathway. Restoring miR-150-5p level with a miR-150-5p mimic decreased the cellular apoptosis and increased autophagy, and the downstream PI3K/Akt signaling pathway was re-activated. CONCLUSIONS: Aerobic exercise improved cardiac function through inhibition of the lncRNA MALAT1 in CHF, and the potential mechanisms may be mediated via the miR-150-5p/PI3K/Akt signaling pathway.

Isolation of probiotics and their effects on growth, antioxidant and non-specific immunity of sea cucumber Apostichopus japonicus.

Probiotics play vital roles in controlling diseases, enhancing specific and non-specific immunity and stimulating growth in the aquaculture industry. However, the effect of fermentation of feed by probiotics on the immune ability of sea cucumber has not been reported to date. Here, three candidate probiotic strains (Bacillus species) were isolated from the culture seawater and sediment of sea cucumber, and fishmeal and scallop mantle fermented by the candidate probiotic strains were used to feed sea cucumber. The results showed that the free amino acid and small peptide contents of the fishmeal and scallop mantle were significantly increased after fermentation for 72 h. However, the weight gain (WG) and specific growth rate (SGR) of sea cucumber showed no significant differences among the fermented fishmeal, fermented scallop mantle and control groups. Scallop mantle fermented by the three candidate probiotics could increase the coelomocyte number and respiratory burst activity. The immune-related enzymatic activity was increased after consuming the fermented fishmeal and scallop mantle, while the activity of antioxidant enzymes was reduced. The expression levels of immune- and antioxidant-related genes were changed after consuming the fermented fishmeal and scallop mantle. Taken together, our results suggest that probiotics could increase the immunocompetence of sea cucumber, and fermented scallop mantle might be a potential substitute for fishmeal during feed preparation. Our results lay a foundation for further understanding the relationship between probiotics and the non-specific immunity of sea cucumber.

Familial dilated cardiomyopathy with a novel LMNA mutation (p.R429C): a case report.

LMNA mutations cause a variety of inherited diseases referred to as laminopathies which are associated with a wide spectrum of disease phenotypes, ranging from skeletal muscle disease, pre-mature ageing, metabolic disorders, and cardiac abnormalities. We present a case of a 14-year-old boy with dilated cardiomyopathy induced by the LMNA mutation (p. R429C) and described its electrocardiogram and imaging features.

Effect of pericardial incision on left ventricular morphology and systolic function in patients during coronary artery bypass grafting.

BACKGROUND: Accurate assessment of left ventricular (LV) systolic function is important after coronary artery bypass grafting (CABG). LV ejection fraction (LVEF) is conventionally used to evaluate LV systolic function; deformation parameters can be used to detect subtle LV systolic dysfunction. It is unclear whether an incised pericardium without sutures during CABG could affect LV morphology and function. We investigated the effect of pericardial incision on LV morphology and systolic function during CABG. METHODS: Intraoperative transesophageal echocardiography was performed in 27 patients during elective off-pump beating heart CABG 5 min before and after pericardial incision. LV longitudinal and mid-cavity transversal diameters, sphericity index, volumes, and LVEF were measured. LV global longitudinal strain (GLS), global circumferential strain (GCS), global radial strain (GRS), and twist obtained by two-dimensional speckle tracking echocardiography were measured simultaneously. RESULTS: LV mid-cavity transversal diameter increased, while the LV sphericity index decreased (P < 0.001) immediately after pericardial incision. The GLS, GCS, and twist significantly decreased, while the GRS notably increased (P < 0.001). The LV volumes and LVEF remained unchanged. CONCLUSIONS: Pericardial incision immediately transformed LV morphology from an ellipsoid to sphere, with decreased longitudinal and circumferential strain and twist, and increased radial strain, while LVEF remained unchanged. This should be considered when evaluating LV systolic function in patients after CABG.

Subclinical left ventricular dysfunction assessed by two-dimensional speckle tracking echocardiography in asymptomatic patients with carotid stenosis.

The relationship between subclinical left ventricular (LV) dysfunction and atherosclerosis may have been underestimated in the past, which might be responsible for the high incidence of premature death in individuals with carotid stenosis. We sought to evaluate the underlying myocardial dysfunction in asymptomatic carotid stenosis patients using speckle tracking echocardiography (STE). Fifty patients with carotid stenosis ≥ 50% and a preserved LV ejection fraction (LVEF), and 45 controls without carotid stenosis who were matched in terms of vascular comorbidities were enrolled. All participants underwent carotid ultrasound and echocardiographic examination. The global LV longitudinal strain (GLS) was measured using STE. Compared with the control group, the e' of the mitral annular velocity and GLS were decreased in asymptomatic carotid stenosis patients (p < 0.05), however, the LVEF was well preserved. Based on a predefined cutoff for subclinical LV systolic dysfunction that was defined at a GLS < - 18%, this dysfunction was detected in 22 patients with carotid stenosis (44%) and in 10 patients in the control group (22%) (p < 0.05). The GLS was negatively correlated with the levels of low-density lipoprotein cholesterol (r = - 0.356, p < 0.05) and triglyceride (r = - 0.396, p < 0.05). In conclusion, LV diastolic and systolic functioning were significantly decreased in patients with asymptomatic carotid stenosis, and dyslipidemia likely contributed to the subclinical LV dysfunction in these patients. Our findings indicated the importance of detecting LV subclinical dysfunction and early intervention in this patient population.

Biomarkers for detecting malignant pleural mesothelioma: Protocol for a reanalysis of published data based on systematic reviews of diagnostic test accuracy.

BACKGROUND: Malignant pleural mesothelioma (MPM) is a highly invasive tumor caused primarily by asbestos exposure. In recent decades, the incidence of MPM has shown an increasing trend, posing a great threat to human health. Although there is currently no effective way to treat MPM, patients can survive for more than 5 years if the tumor is removed early. Several systematic reviews (SRs) have evaluated the diagnostic value of biomarkers for diagnosing MPM. However, no studies have been conducted to analyze the quality of these SRs and it remains unclear which biomarker is the excellent diagnostic test. This study aims to assess the methodological quality of the SRs and reanalyze the published data based on SRs to find the optimal biomarker for the early diagnosis of MPM. METHODS: A systematic search will be performed in PubMed, Embase.com, the Cochrane Library of Systematic Reviews, and Web of Science to identify SRs reporting value of biomarkers for detecting MPM. We will evaluate the risk of bias of the included SRs according to the Assessment of Multiple Systematic Reviews-2 (AMSTAR-2) instrument. Standard pairwise meta-analysis and adjusted indirect comparison will be used to compare the diagnostic value of different biomarkers. RESULTS: The results of this study will be submitted to a peer-reviewed journal for publication. CONCLUSION: This study will reanalyze the published data based on SRs to find a biomarker with the superior diagnostic performance for the diagnosis of MPM. ETHICS AND DISSEMINATION: Ethics approval and patient consent are not required as this study is an overview based on published systematic reviews. PROSPERO REGISTRATION NUMBER: CRD42019125880.

Downregulation of growth arrest­specific transcript 5 alleviates palmitic acid­induced myocardial inflammatory injury through the miR­26a/HMGB1/NF­κB axis.

Palmitic acid (PA) can induce lipotoxic damage to cardiomyocytes, although its precise mechanism of action has not been completely elucidated. Growth arrest­specific transcript 5 (GAS5) is a long noncoding RNA that serves a regulatory role in several pathological processes, including tumorigenesis, stroke, cardiac fibrosis and osteoarthritis; however, its role in PA­induced myocardial injury remains elusive. The present study aimed to explore the role and underlying mechanism of GAS5 on PA­induced myocardial injury. The expression of GAS5 in PA­treated cardiomyocytes (H9c2 cells) was detected by reverse transcription­quantitative polymerase chain reaction (RT­qPCR), and its effects on PA­induced myocardial injury were measured by Cell Counting Kit­8 and lactate dehydrogenase (LDH) assays. The activities of cytokines and nuclear factor (NF)­κB were also detected by enzyme­linked immunosorbent assay, while interactions between GAS5 and microRNA (miR)­26a were evaluated by luciferase reporter assay and RT­qPCR. The regulation of GAS5 on high mobility group box 1 (HMGB1) expression was detected by RT­qPCR and western blotting. The results demonstrated that GAS5 was significantly upregulated in cardiomyocytes following treatment with PA. GAS5­knockdown increased the viability of PA­treated cardiomyocytes and reduced the activity of LDH, tumor necrosis factor­α and interleukin­1ß. Furthermore, the present study identified that GAS5 specifically binds to miR­26a, and a reciprocal negative regulation exists between the two. The present study also demonstrated that GAS5 downregulation inhibited HMGB1 expression and NF­κB activation, while these suppressive effects were mediated by miR­26a. In conclusion, the present study demonstrated that PA can induce GAS5 expression and that the downregulation of GAS5 alleviated PA­induced myocardial inflammatory injury through the miR­26a/HMGB1/NF­κB axis. These data may provide a novel insight into the mechanism of myocardial lipotoxic injury.

Pharmacokinetics and tissue distribution study of clevidipine and its primary metabolite H152/81 in rats.

This present study was designed to investigate the pharmacokinetic profiles and tissue distribution characteristics of clevidipine and its primary metabolite H152/81 in rats following a single intravenous administration of clevidipine butyrate injectable emulsion. For this study, a sensitive and selective liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was established and validated for the simultaneous quantitation of clevidipine and H152/81 in rat whole blood and various tissues. A Hedera ODS-2 column with two gradient elution programs was employed for the troubleshooting of matrix effect on the detection of analytes among different biological samples. The experimental data showed that clevidipine represented quick elimination from blood with a half-life of about 4.3 min and rapid distribution in all of the investigated tissues after administration; the highest concentration of clevidipine was found in the heart whereas the lowest concentration was detected in the liver. In addition, clevidipine was almost undetectable in most tissues except for heart and brain at 90 min post-dosing, suggesting that there was no apparent long-term accumulation in rat tissues. For H152/81, the peak concentration of 3714 ± 319 ng/mL occurred at 0.129 ± 0.048 h, the half-life was 10.08 ± 1.45 h and area under the concentration-time curve was 42091 ± 3812 ng h/mL after drug administration. In addition, H152/81 was found at significant concentration levels in all tissues, in descending order of lung, kidney, heart, liver, spleen and brain at each time point. The results of current study offer useful clues for better understanding the distribution and metabolism of clevidipine butyrate injectable emulsion in vivo.

Libman-sacks endocarditis exclusively involving the tricuspid valve in a patient with systemic lupus erythematosus.

Libman-Sacks endocarditis, characterized by sterile verrucous vegetations, is a rare but typical cardiac manifestation of systemic lupus erythematosus. It primarily leads to lesions of the mitral and aortic valves, but isolated tricuspid valve involvement is exceptional. We report the case of a 40-year-old woman with large tricuspid valve vegetations, thickening, and regurgitation. Clinical findings and laboratory tests confirmed the diagnosis of systemic lupus erythematosus. The patient successfully recovered following tricuspid valve replacement. Echocardiography is the definitive imaging modality for assessing cardiac valvular involvement, choosing appropriate therapy, and evaluating the prognosis of Libman-Sacks endocarditis in systemic lupus erythematosus. © 2014 Wiley Periodicals, Inc. J Clin Ultrasound 43:265-267, 2015.

Simultaneous quantitation of folic acid and 5-methyltetrahydrofolic acid in human plasma by HPLC-MS/MS and its application to a pharmacokinetic study.

A sensitive method based on high-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) has been developed for the simultaneous determination of folic acid (FA) and its active metabolite, 5-methyltetrahydrofolic acid (5-M-THF), in human plasma. The analytes were extracted from plasma with methanol solution containing 10 mg/mL of 2-mercaptoethanol and 0.025% (v/v) ammonium hydroxide. FA and 5-M-THF were more stable after the addition of 2-mercaptoethanol and ammonium hydroxide in the sample preparation procedures of this study than they were in the previously published methods. Chromatographic separation was performed on a Hedera ODS-2 column using a gradient elution system of acetonitrile and 1 mM ammonium acetate buffer solution containing 0.6% formic acid as mobile phase. LC-MS/MS was carried out with an ESI ion-source and operated in the multiple reaction monitoring (MRM) mode. The assay was linear over the concentration ranges of 0.249-19.9 ng/mL for FA, and 5.05-50.5 ng/mL for 5-M-THF. The developed LC-MS/MS method offers increased sensitivity for quantification of FA and 5-M-THF in human plasma and was applicable to a pharmacokinetic study of FA and 5-M-THF.