Exploring the role of iNOS in HFpEF-Related myocardial fibrosis: Involvement of PTEN-PI3K/AKT signaling pathway.

BACKGROUND: Heart failure with preserved ejection fraction (HFpEF) is a challenging condition to treat with myocardial fibrosis being a pivotal pathological component. Previous studies have suggested a role for inducible nitric oxide synthase (iNOS) in the progression of this condition, but the precise mechanisms remain unclear. This study aimed to investigate the role of iNOS in HFpEF-related myocardial fibrosis and identify potential therapeutic targets. METHODS: A 'two-hit' mouse model of HFpEF was established, and echocardiography, histopathology and biochemical analyses were performed. In vitro experiments were conducted in mouse cardiac fibroblasts, with iNOS overexpression and application of iNOS or phosphatidylinositol 3 kinase (PI3K) inhibitors. The iNOS-S-nitrosylated phosphatase and TENsin homolog (SNO-PTEN)-phosphorylated-protein kinase B (p-AKT) pathway was investigated, along with the effects on fibrotic markers and cell proliferation and migration. RESULTS: HFpEF mice exhibited significant cardiac dysfunction and fibrosis, with increased expression of iNOS, SNO-PTEN, and p-AKT, indicative of the activation of the iNOS-SNO-PTEN-p-AKT pathway. iNOS overexpression in mouse cardiac fibroblasts led to increased SNO-PTEN, decreased PTEN, activated phosphorylated PI3K (p-PI3K) and p-AKT, and enhanced cell proliferation and migration, as well as increased collagen I and III expression. The use of an iNOS inhibitor (L-NIL) or a PI3K inhibitor (LY294002) partially reversed these changes. CONCLUSION: Our findings suggest that the iNOS-SNO-PTEN-p-AKT pathway may play a crucial role in HFpEF-related myocardial fibrosis, with iNOS and PI3K inhibitors offering potential therapeutic benefits. These insights may pave the way for the development of effective drug therapies for HFpEF.

Life Prediction of Rolling Bearing Based on Optimal Time-Frequency Spectrum and DenseNet-ALSTM.

To address the challenges faced in the prediction of rolling bearing life, where temporal signals are affected by noise, making fault feature extraction difficult and resulting in low prediction accuracy, a method based on optimal time-frequency spectra and the DenseNet-ALSTM network is proposed. Firstly, a signal reconstruction method is introduced to enhance vibration signals. This involves using the CEEMDAN deconvolution method combined with the Teager energy operator for signal reconstruction, aiming to denoise the signals and highlight fault impacts. Subsequently, a method based on the snake optimizer (SO) is proposed to optimize the generalized S-transform (GST) time-frequency spectra of the enhanced signals, obtaining the optimal time-frequency spectra. Finally, all sample data are transformed into the optimal time-frequency spectrum set and input into the DenseNet-ALSTM network for life prediction. The comparison experiment and ablation experiment show that the proposed method has high prediction accuracy and ideal prediction performance. The optimization terms used in different contexts in this paper are due to different optimization methods, specifically the CEEMDAN method.

Clinical performance of 0/1 h cardiac troponin algorithm for diagnosing non-STEMI in an emergency setting.

BACKGROUND: Non-ST-segment elevation myocardial infarction (NSTEMI) is a common form of acute myocardial infarction and rapid and accurate diagnosis is crucial for timely treatment. Current guidelines recommend using high-sensitivity cardiac troponin (hs-cTn) assays to determine circulating cTnI or cTnT levels. While the accuracy of the 0 h/1 h algorithm for diagnosing NSTEMI in different regions and patient populations remains controversial. Additionally, point-of-care testing (POCT) cTn assays have the potential to provide troponin readings to physicians within 15 min, but their accuracy in diagnosing NSTEMI in the emergency department (ED) requires further investigation. METHODS: A single-center prospective observational cohort study was conducted at Shaanxi Provincial People's Hospital to assess the analytical and diagnostic performance of the laboratory-based Roche Modular E170 hs-cTnT using the 0 h/1 h algorithm with Radiometer AQT90-flex POCT cTnT assay in undifferentiated chest pain patients presenting to the ED. Whole-blood samples were collected and hs-cTnT and POCT cTnI were measured simultaneously at baseline and after 1 h. RESULTS: The study results showed that the POCT cTnT assay using the 0 h/1 h algorithm had comparable diagnostic accuracy to the laboratory-based Roche Modular E170 hs-cTnT assay in diagnosing NSTEMI in patients with chest pain. CONCLUSION: The laboratory-based Roche Modular E170 hs-cTnT using the 0 h/1 h algorithm is reliable and accurate method for diagnosing NSTEMI in undifferentiated chest pain patients presenting to the ED. POCT cTnT assay has comparable diagnostic accuracy to the hs-cTnT assay and its rapid turnaround time makes it a valuable tool in expediting the diagnostic workup of chest pain patients.

Interferon-γ decreases ATP-binding cassette subfamily G member 1-mediated cholesterol efflux through small ubiquitin-like modifier/ubiquitin-dependent liver X receptor-α degradation in macrophages.

The effects of interferon-γ (IFN-γ) on cholesterol accumulation and the development of foam cells are still unclear. In the present study, we found that IFN-γ promoted liver X receptor (LXR)-α degradation through the ubiquitin-proteasome system in macrophages. The process was dependent on its interactions with phosphorylated signal transducer and activator of transcription 1 (p-STAT1) and protein inhibitor of activated STAT 1 (PIAS1) because both fludarabine and PIAS1 shRNA reversed the decrease in LXR-α protein expression induced by IFN-γ. Additionally, IFN-γ enhanced the interactions of ubiquitin-conjugating enzyme 9 (UBC9), small ubiquitin-like modifier (SUMO)-1 and SUMO-2/3 with LXR-α. Moreover, treatment with shRNA specific for them not only reduced LXR-α polyubiquitination but also reversed the IFN-γ-induced decrease in its expression. Two specific sumoylation sites in LXR-α, K22 and K326, were indispensable for its IFN-γ-induced polyubiquitination because the K22R and K326R mutations inhibited the polyubiquitination and degradation of LXR-α in IFN-γ-treated macrophages. In addition, K22R or K326R mutation almost completely restored ATP-binding cassette subfamily G member 1 (ABCG1)-mediated cholesterol efflux in IFN-γ-treated macrophages. Taken together, these findings indicate that IFN-γ promotes LXR-α degradation through a SUMO-ubiquitin-dependent pathway, which may inhibit cholesterol efflux mediated by ABCG1 from macrophages and promote the development of atherosclerosis.

BMI differences among in-hospital management and outcomes in patients with atrial fibrillation: findings from the Care for Cardiovascular Disease project in China.

BACKGROUND: Underweight or obese status influences the prognosis of atrial fibrillation (AF). However, the association between stratification of body mass index (BMI) and in-hospital outcomes in patients with AF, remains lacking in China. METHODS: Using data from the Improving Care for Cardiovascular Disease in China-AF project, which was launched in February 2015 and recruited 150 hospitals in China, we compared characteristics, in-hospital treatments and clinical outcomes among the stratifications of BMI for Asians. RESULTS: A total of 15,867 AF patients with AF were enrolled, including 830 (5.23%) underweight, 4965 (31.29%) with normal weight, 3716 (23.42%) overweight, 5263 (33.17%) obese class I and 1093 (6.89%) obese class II participants. Compared with normal weight patients, underweight, overweight, and obese patients showed increased percentages of CHADS2 scores (3-6) and CHA2DS2-VASc scores (5-9). During hospitalization, overweight or obese patients showed greater use of rhythm control medications, anticoagulant drugs, and intervention therapies than underweight-normal weight patients. In adjusted logistic models, BMI was a strong predictor of in-hospital mortality. Especially, underweight BMI was associated with higher incidence of in-hospital mortality, with an adjusted odds ratio of 2.08 (95% confidence interval, 1.56-4.46; p = 0.04) than overweight and obese BMI. CONCLUSIONS: Asian patients with AF and high BMI received more medical treatments and presented less adverse in-hospital outcomes compared with those with underweight-normal weight. Although low BMI may be associated with other comorbidities and advanced age, underweight BMI retained a negative correlation with all-cause mortality in the patients with AF during hospitalization.

Design, synthesis and bioactivity of novel phthalimide derivatives as acetylcholinesterase inhibitors.

A series of novel phthalimide derivatives related to benzylpiperazine were synthesized and evaluated as cholinesterase inhibitors. The results showed that all compounds were able to inhibit acetylcholinesterase (AChE), with two of them dramatically inhibiting butyrylcholinesterase (BuChE). Most compounds exhibited potent anti-AChE activity in the range of nM concentrations. In particular, compounds 7aIII and 10a showed the most potent activity with the IC50 values of 18.44 nM and 13.58 nM, respectively. To understand the excellent activity of these compounds, the structure-activity relationship was further examined. The protein-ligand docking study demonstrated that the target compounds have special binding modes and these results are in agreement with the kinetic study.

The Loop Technique in Cardiac Resynchronization Therapy: A Prospective Cohort Study.

Objective: A new approach called the loop technique has been proven safe and effective for repeated intraoperative transvenous left ventricular (LV) lead dislocations during cardiac resynchronization therapy (CRT) in a 3-year follow-up. This study aimed to report on the 5-year safety and effectiveness of the loop technique. Methods: This study was a prospective cohort study. Forty-four patients who underwent CRT device implantation at the Cardiology Department of Shaanxi Provincial People's Hospital between January 2013 and June 2019 were included. Data on patient demographics, medical history, laboratory test results, and echocardiography images at admission were collected. The loop technique was performed with repeated intraoperative dislocations of the LV lead. The intraoperative CRT parameters were also recorded. All patients were followed for 5 years. Several auxiliary examinations were performed during follow-up. Results: The 44 patients were divided into the traditional operation group (n=36, 81.8%) and loop technique group (n=8, 18.2%). The baseline patient characteristics were almost balanced. During the 5-year follow-up, 8 (22.2%) patients in the traditional operation group and 2 (25.0%) patients in the loop technique group died. No lead dislocation or other complications related to CRT were observed. There were no significant differences in mortality rate (P=0.87), cardiac function (P=0.56), echocardiographic indices, threshold (P=0.58), or impedance (P=0.22) of the LV lead. There were no significant differences in the threshold and impedance between postoperative, 3-year, and 5-year follow-ups in the loop technique group (P=0.53). Conclusion: The loop technique is an ideal solution for repeated intraoperative LV lead dislocation during CRT implantation.

Multi-omics analysis of the lipid-regulating effects of metformin in a glucose concentration-dependent manner in macrophage-derived foam cells.

Metformin has a long history of clinical application and has been shown to have outstanding ability in lowering glucose. Recent advances have further revealed its broad modulatory ability beyond glucose-lowering, expanding the scope of metformin applications. Metformin has now been applied as a viable lipid-lowering strategy in non-hyperglycemic obese patients. However, the benefits and underlying pharmacological mechanisms of metformin administration in non-hyperglycemic populations remain to be explained. Our study aimed to systematically investigate the differences in the lipid-lowering function and pharmacological mechanisms of metformin in high- and low-sugar conditions to facilitate the development of individualized metformin use regimens for different clinical patients. We constructed macrophage-derived foam cell models in vitro for subsequent analysis. ORO results showed that metformin significantly reduced lipid accumulation in macrophages in both high and low glucose environments, but the lipid decline was higher in the high glucose environment. By mutual validation and joint analysis of transcriptomics and metabolomics, significant differences in metformin transcriptional and metabolic patterns existed among high and normal glucose environments. The significant alterations of genes such as DGKA, LPL, DGAT2 and lipid metabolites such as LysPA and LysPC partially explained the glucose-dependent pharmacological function of metformin. In conclusion, our study confirmed that the lipid-lowering effect of metformin depends on the extracellular glucose concentration, and systematically studied the molecular mechanism of metformin in different glycemic environments, which provides a certain reference value for the subsequent in-depth study and clinical application.

Identification of Immuno-Inflammation-Related Biomarkers for Acute Myocardial Infarction Based on Bioinformatics.

Purpose: Previous studies have confirmed that inflammation and immunity are involved in the pathogenesis of acute myocardial infarction (AMI). However, only few related genes are identified as biomarkers for the diagnosis and treatment of AMI. Patients and Methods: GSE48060 and GSE60993 datasets were retrieved from Gene Expression Omnibus. The differentially expressed immuno-inflammation-related genes (DEIIRGs) were obtained from GSE48060, and the biomarkers for AMI were screened and validated using the "Neuralnet" package and GSE60993 dataset. Further, the biomarker-based nomogram was constructed, and miRNAs, transcription factors (TFs), and potential drugs targeting the biomarkers were explored. Furthermore, immune infiltration analysis was analyzed in AMI. Finally, the biomarkers were verified by assessing their mRNA levels using real-time quantitative PCR (RT-qPCR). Results: First, eight biomarkers were screened via bioinformatics, and the artificial neural network model indicated a higher prediction accuracy for AMI even in the validation dataset. Nomogram had accurate forecasting ability for AMI as well. The TFs GTF2I, PHOX2B, RUNX1, and FOS targeting hsa-miR-1297 could regulate the expressions of ADM and CBLB, and RORA could effectively interact with melatonin and citalopram. RT-qPCR results for ADM, PI3, MMP9, NRG1 and CBLB were consistent with those of bioinformatic analysis. Conclusion: In conclusion, eight key immuno-inflammation-related genes, namely, SH2D1B, ADM, PI3, MMP9, NRG1, CBLB, RORA, and FASLG, may serve as the potential biomarkers for AMI, in which the downregulation of CBLB and upregulation of ADM, PI3, and NRG1 in AMI was detected for the first time, providing a new strategy for the diagnosis and treatment of AMI.

Prediction of diagnostic gene biomarkers for hypertrophic cardiomyopathy by integrated machine learning.

OBJECTIVES: Hypertrophic cardiomyopathy (HCM), a leading cause of heart failure and sudden death, requires early diagnosis and treatment. This study investigated the underlying pathogenesis and explored potential diagnostic gene biomarkers for HCM. METHODS: Transcriptional profiles of myocardial tissues from patients with HCM (dataset GSE36961) were downloaded from the Gene Expression Omnibus database and subjected to bioinformatics analyses, including differentially expressed gene (DEG) identification, enrichment analyses, and protein-protein interaction (PPI) network analysis. Least absolute shrinkage and selection operator (LASSO) regression and support vector machine recursive feature elimination were performed to identify candidate diagnostic gene biomarkers. mRNA expression levels of candidate biomarkers were tested in an external dataset (GSE141910); area under the receiver operating characteristic curve (AUC) values were obtained to validate diagnostic efficacy. RESULTS: Overall, 156 DEGs (109 downregulated, 47 upregulated) were identified. Enrichment and PPI network analyses indicated that the DEGs were involved in biological functions and molecular pathways including inflammatory response, platelet activity, complement and coagulation cascades, extracellular matrix organization, phagosome, apoptosis, and VEGFA-VEGFR2 signaling. RASD1, CDC42EP4, MYH6, and FCN3 were identified as diagnostic biomarkers for HCM. CONCLUSIONS: RASD1, CDC42EP4, MYH6, and FCN3 might be diagnostic gene biomarkers for HCM and can provide insights concerning HCM pathogenesis.

The long-term safety and effectiveness of the loop technique in left ventricular lead dislocation.

Objectives: Cardiac resynchronization therapy (CRT) is a well-established method that improves the clinical symptoms and long-term prognosis of specific heart failure (HF) patients by restoring systolic synchronicity and enhancing myocardial function. However, the high rate of intraoperative and postoperative left ventricular (LV) lead dislocation limits its application to a great extent. The aim of this study was to demonstrate the long-term safety and effectiveness of a new approach named the loop technique for patients who experience repeated intraoperative transvenous LV lead dislocations during CRT. Methods: The current study was a single-centre, prospective, nonrandomized controlled trial. Forty-four HF patients who underwent CRT were included. All patients were followed to death or 3 years. Results: Among 44 HF patients, 36 underwent the traditional operation, and 8 underwent the loop technique due to repeated intraoperative LV lead dislocations. Intergroup comparison revealed no significant differences between the two groups with respect to most preoperative indices, intraoperative pacing and sensing parameters. At the end of the 3-year follow-up, 4 (11.1%) patients in the traditional operation group and 2 (25.0%) patients in the loop technique group had died. There was no significant difference in the mortality rate (P = 0.30). No complications related to this new technique were observed, such as intracoronary thrombosis, infection or dislocation. Intergroup comparison showed no significant difference in the New York Heart Association (NYHA) class, echocardiography indices, N-terminal pro brain natriuretic peptide (NT-proBNP) level or pacemaker programming parameters. Conclusions: The loop technique is a safe and effective alternative method for patients who experience repeated intraoperative transvenous LV lead dislocations during CRT.

Relation of Red Cell Distribution Width to Glucose Metabolism and Adverse Long-Term Prognosis in Patients with Acute Coronary Syndrome.

Introduction: Red cell distribution width (RDW) reflects the heterogeneity of red blood cell size. However, few studies examined whether RDW is related to glucose metabolism indices, such as fasting blood glucose (FBG) and hemoglobin A1c (HbA1c), diabetic mellitus (DM) state or long-term outcomes of acute coronary syndrome (ACS) patients. Methods and Results: A total of 448 consecutive patients with ACS were enrolled in this study. All patients were followed up for major cardiovascular adverse events (MACEs), and the mean follow-up was 952 days. Linear regression analysis showed that RDW inversely correlated with FBG but not HbA1c or DM. Kaplan-Meier survival curve analysis demonstrated that higher RDW levels were significantly positively associated with MACEs in the whole study population and the ACS patients with high FBG but not the low FBG group. Cox multivariate regression analysis revealed the independent function of RDW on MACEs in all ACS patients and ACS patients with high FBG. The receiver operating characteristic (ROC) curve demonstrated the optimal cutoff value of RDW for MACEs. Conclusion: We first reported that higher RDW was associated with decreased FBG but not HbA1c or DM and an increased risk of MACEs in patients with ACS. This relationship was also found in ACS patients with higher FBG levels but not in ACS patients with lower FBG.

Diagnostic potential of energy metabolism-related genes in heart failure with preserved ejection fraction.

Background: Heart failure with preserved ejection fraction (HFpEF) is associated with changes in cardiac metabolism that affect energy supply in the heart. However, there is limited research on energy metabolism-related genes (EMRGs) in HFpEF. Methods: The HFpEF mouse dataset (GSE180065, containing heart tissues from 10 HFpEF and five control samples) was sourced from the Gene Expression Omnibus database. Gene expression profiles in HFpEF and control groups were compared to identify differentially expressed EMRGs (DE-EMRGs), and the diagnostic biomarkers with diagnostic value were screened using machine learning algorithms. Meanwhile, we constructed a biomarker-based nomogram model for its predictive power, and functionality of diagnostic biomarkers were conducted using single-gene gene set enrichment analysis, drug prediction, and regulatory network analysis. Additionally, consensus clustering analysis based on the expression of diagnostic biomarkers was utilized to identify differential HFpEF-related genes (HFpEF-RGs). Immune microenvironment analysis in HFpEF and subtypes were performed for analyzing correlations between immune cells and diagnostic biomarkers as well as HFpEF-RGs. Finally, qRT-PCR analysis on the HFpEF mouse model was used to validate the expression levels of diagnostic biomarkers. Results: We selected 5 biomarkers (Chrna2, Gnb3, Gng7, Ddit4l, and Prss55) that showed excellent diagnostic performance. The nomogram model we constructed demonstrated high predictive power. Single-gene gene set enrichment analysis revealed enrichment in aerobic respiration and energy derivation. Further, various miRNAs and TFs were predicted by Gng7, such as Gng7-mmu-miR-6921-5p, ETS1-Gng7. A lot of potential therapeutic targets were predicted as well. Consensus clustering identified two distinct subtypes of HFpEF. Functional enrichment analysis highlighted the involvement of DEGs-cluster in protein amino acid modification and so on. Additionally, we identified five HFpEF-RGs (Kcnt1, Acot1, Kcnc4, Scn3a, and Gpam). Immune analysis revealed correlations between Macrophage M2, T cell CD4+ Th1 and diagnostic biomarkers, as well as an association between Macrophage and HFpEF-RGs. We further validated the expression trends of the selected biomarkers through experimental validation. Conclusion: Our study identified 5 diagnostic biomarkers and provided insights into the prediction and treatment of HFpEF through drug predictions and network analysis. These findings contribute to a better understanding of HFpEF and may guide future research and therapy development.

Efficacy and safety of three species of Rhodiola L. in patients with chronic obstructive pulmonary disease: A systematic review and meta-analysis.

Background: Chronic obstructive pulmonary disease (COPD) is characterized by chronic hypoxia, inflammation, oxidative stress, and irreversible airflow limitations. Rhodiola L. is a genus of botanical drugs used in traditional medicine that may influence COPD. Objective: A systematic review of the safety and efficacy of Rhodiola L. in patients with COPD. Material and methods: We searched the PubMed, Embase, Cochrane Library, Web of Science, Scopus, China National Knowledge Infrastructure (CNKI), Chongqing VIP, Wanfang, and SinoMed databases. The search strategy used terms including "COPD" and "Rhodiola." Two independent reviewers conducted the literature screening, data extraction, and risk of bias assessment, with a third reviewer involved to resolve disagreements. Statistical analysis was conducted in Review Manager (version 5.4.1), following the Cochrane Handbook. Results: This review included nine studies, of which two focused on Rhodiola crenulata (Hook.f. and Thomson) H. Ohba (R. crenulata) and two on Rhodiola kirilowii (Regel) Maxim (R. kirilowii); the remaining five focused on Rhodiola wallichiana (Hook.) S.H.Fu (R. wallichiana). Compared with the placebo, patients who received Rhodiola L. presented no more adverse events (p = 0.65) but showed significant improvement in the percentage of forced expiratory volume in 1 s at prediction (FEV1%pred), forced expiratory volume in 1 s (FEV1), the ratio of forced expiratory volume in 1 s on forced vital capacity (FEV1/FVC), saturation of oxygen in arterial blood, partial pressure of oxygen in arterial blood (PaO2), partial pressure of carbon dioxide in arterial blood (PaCO2), systolic pulmonary arterial pressure, diastolic pulmonary arterial pressure, COPD assessment test, efficient rate, C-reactive protein, and N-terminal pro-B-type natriuretic peptide (all p < 0.01). Compared with ambroxol, R. kirilowii provided additional benefits to patients with COPD in FEV1%pred, FEV1, FEV1/FVC, PaO2, PaCO2, 8-iso-prostaglandin F2α, superoxide dismutase, glutathione, malondialdehyde, and total antioxidant capacity (all p < 0.01). Conclusion: Among the Rhodiola L. genus, this review included R. wallichiana, R. crenulata, and R. kirilowii, which might be safe and effective in COPD. Although this study has several limitations, further RCTs are needed. Systematic Review Registration: [https://www.crd.york.ac.uk/PROSPERO/ display_record.php?RecordID=302881], identifier [CRD42022361890].

The Key Genes Underlying Pathophysiology Correlation Between the Acute Myocardial Infarction and COVID-19.

Introduction: Accumulating evidences disclose that COVID-19, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has a marked effect on acute myocardial infarction (AMI). Nevertheless, the underlying pathophysiology correlation between the AMI and COVID-19 remains vague. Materials and Methods: Bioinformatics analyses of the altered transcriptional profiling of peripheral blood mononuclear cells (PBMCs) in patients with AMI and COVID-19 were implemented, including identification of differentially expressed genes and common genes between AMI and COVID-19, protein-protein interactions, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses, TF-genes and miRNA coregulatory networks, to explore their biological functions and potential roles in the pathogenesis of COVID-19-related AMI. Conclusion: Our bioinformatic analyses of gene expression profiling of PBMCs in patients with AMI and COVID-19 provide us with a unique view regarding underlying pathophysiology correlation between the two vital diseases.

Influence of hemoglobin concentration on the in-hospital outcomes in newly diagnosed heart failure patients with atrial fibrillation: Finding from CCC-AF (improving care for cardiovascular disease in China-atrial fibrillation) project.

ABSTRACT: Atrial fibrillation (AF) and heart failure (HF) coexistence is common of clinical significance. Although anemia is a well-recognized risk factor for adverse outcomes, the prognostic value of hemoglobin is controversial in AF and HF. We aimed to determine whether hemoglobin is associated with in-hospital outcomes in such patients.On the basis of the data from the CCC-AF (Improving Care for Cardiovascular Diseases in China-Atrial Fibrillation) project, 2367 inpatients with a definitive diagnosis of AF and HF and record of admission hemoglobin concentration were included. Logistic regression analysis was performed to investigate the relationship between hemoglobin and in-hospital outcomes.All patients were divided into 4 groups according to quartiles of hemoglobin values. Compared with patients with higher hemoglobin, patients with lower hemoglobin had higher proportion of males, heart rate (HR), and diastolic blood pressure (DBP). On the contrary, they had lower age, medical history, left ventricular ejection fraction (LVEF), and brain natriuretic peptide (P < .05). Spearman correlation showed that hemoglobin was negatively correlated with age, LVEF, international normalized ratio, and serum creatinine but positively correlated with HR, DBP, and blood urea nitrogen (P < .05). Multivariable logistic regression analysis revealed that increasing hemoglobin was an independent protective factor for in-hospital outcomes (odds ratio = 0.989; 95% confidence interval: 0.979-1.000; P = .046).Admission hemoglobin concentration was an independent protective factor for in-hospital outcomes in HF patients with AF. Our study indicated that increasing hemoglobin level and improving anemia degree might improve the prognosis of patients with AF and HF.

Exploration of the shared gene signatures and molecular mechanisms between atherosclerosis and rheumatoid arthritis via multi-microarray data analyses.

Background: Accumulating evidence indicates the inflammatory state of rheumatoid arthritis (RA) predisposes to the acceleration of atherosclerosis (AS). Nevertheless, the potential mechanisms of accelerating AS in RA have not been fully elucidated. Our current study was to probe the problem via multi-microarray data analyses. Methods: The transcriptional profiling of synovial tissues from RA (GSE55235 and GSE55457) and that of atherosclerotic plaques from AS (GSE28829 and GSE41571) were downloaded from the Gene Expression Omnibus database. Bioinformatics analyses procedures included identifying common differentially expressed genes (DEGs), constructing protein-protein interaction network, key modules analysis and identifying hub genes, validating hub genes by using external datasets (GSE77298 and GSE163154), Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses, constructing transcription factor (TF)-miRNA coregulatory network and exploiting candidate drugs targeting hub genes. Results: A total of 67 common DEGs were identified for downstream analyses. GO and KEGG analyses of these genes expounded a critical role of inflammatory mediators and reactions in the comorbidities. Sixteen hub genes were identified, and their functional analyses further highlighted a complicated inflammatory micro-environment and signaling pathways involving RA and AS. Six TFs and four miRNAs interacted with hub genes, and the candidate drugs targeting them were simvastatin, 5-azacytidine, bisindolylmaleimide, retinoic acid, and verteporfin, etc. Conclusions: Our comprehensive bioinformatics analyses provided a novel view regarding the potential pathogenesis of AS in RA. Furthermore, exploitation of candidate drugs might hold great promise in the future fight against the comorbidities.

Diagnostic performance of coronary computed tomography angiography-derived fractional flow reverse in lesion-specific ischemia patients with different Gensini score levels.

Background: Coronary pressure-derived fractional flow reverse (FFR) is the standard of the functional assessment of lesion severity. In spite of its strengths in determining ischemia-related coronary stenosis, the invasive operation involved still limits its clinical application. Coronary computed tomography angiography-derived FFR (CCTA-FFR) or computed tomography-derived FFR (CT-FFR) has been indicated as an effective and non-invasive index to evaluate lesion-specific ischemia. However, its diagnostic performance, especially in patients with different severity of coronary stenosis, remains unknown. The current research attempted to demonstrate this problem and provided the foundation for extensive clinical application of CCTA-FFR. Methods: The design of this study was a diagnostic test. A total of 97 vessels from 91 patients who performed CCTA and coronary angiography (CAG) during a hospitalization collected from two research centers were included in this study. CCTA-FFR and FFR were obtained by CCTA and CAG separately. The Gensini score was calculated according to the CAG in each patient. FFR was indicated as the golden diagnosis of lesion-specific ischemia with a cut-off value of 0.80, which was consistent with most contemporary studies. A receiver-operating characteristic (ROC) curve, simple linear analysis, and Bland-Altman plot were performed to determine the diagnostic performance of CCTA-FFR. Results: CCTA-FFR was well correlated with invasive FFR (R2=0.745, P<0.001) and the area under the curve (AUC) was 0.976. The sensitivity was 94.6% and the specificity was 95.1%. The mean difference between FFR and CT-FFR was 0.011, and the 95% confidence interval was -0.173 to 0.196. The AUCs were 0.989 and 0.928 in the low and high Gensini groups, respectively, and there was no significant difference in the diagnostic accuracies between these two groups (Z=0.003, P>0.500). CT-FFR still exhibited a good correlation with FFR (R2=0.713, P<0.001 in the low Gensini group and R2=0.743, P<0.001 in the high Gensini group). The systematic differences were calculated, and the mean difference between FFR and CT-FFR was -0.005 and 0.025, respectively, in these two groups. Conclusions: CCTA-FFR exhibited good diagnostic performance in patients with different Gensini score levels. Our results indicate that CCTA-FFR could be an effective tool to screen lesion-specific ischemia in patients with coronary artery disease.

Sex differences in the impact of day/night distribution of ST-segment elevation myocardial infarction onset on in-hospital outcomes: findings from the Improving Care for Cardiovascular Disease in China-Acute Coronary Syndrome Project.

BACKGROUND: Circadian system plays an important role in cardiovascular health. Experimental studies have also identified sex differences in circadian system. We aim to explore the impact of sex on the association between symptom-onset pattern of STEMI and in-hospital adverse outcomes in Chinese population. METHODS: Data were used from the Improving Care for Cardiovascular Disease in China-Acute Coronary Syndrome Project. 18271 STEMI patients undergoing primary percutaneous coronary intervention entered the study, including 14785 (80.9%) men and 3486 (19.1%) women. The outcomes included all-cause mortality and a composite of major adverse cardiovascular and cerebrovascular events (MACCE) during hospitalization. RESULTS: Most participants experienced STEMI onset during 06:00 h to noon, and there was no difference in onset pattern between men and women (p = 0.582). Logistic regression showed that, after adjustment for cardiovascular risk factors, symptom onset time was significantly associated with in-hospital mortality in men, but not in women or the total population. The odds ratios (ORs) for male patients were 1.86 (95% CI 1.05 to 3.27) for midnight to 06:00 h, 1.58 (95% CI 0.95 to 2.64) for 06:00 h to noon, and 0.80 (95% CI 0.49 to 1.73) for 18:00 h to midnight as compared with STEMI presenting during noon to 18:00 h. But symptom onset time was not associated with MACCE in both sexes or the entire cohort. CONCLUSIONS: These findings show that STEMI onset time was independently associated with in-hospital mortality in male Chinese patients, indicating that sex should be taken into account in studying impact of circadian system on myocardial infarction.

Serum Anion Gap is Associated with Risk of All-Cause Mortality in Critically Ill Patients with Acute Myocardial Infarction.

PURPOSE: Anion gap (AG) is a valuable and easily obtained clinical tool for differentially diagnosis of acid-base disorders. Current understanding of the prognostic impact of AG on mortality after acute myocardial infarction (AMI) is limited. We aimed to investigate whether AG is a predictor of short-term and long-term all-cause mortality after AMI. PATIENTS AND METHODS: We examined 1806 patients diagnosed with AMI in intensive care unit from the Medical Information Mart for Intensive Care III (MIMIC-III) database. We analyzed the association of AG with 30-day, 180-day and 1-year all-cause mortality on a continuous scale and in categories, using multivariable Cox regression. We utilized restricted cubic splines to evaluate the linearity between hazard ratio (HR) and AG concentrations. RESULTS: AG was associated with a higher risk of 30-day, 180-day and 1-year all-cause mortality, with adjusted HRs of 1.083 (95% CI 1.051 to 1.117), 1.077 (95% CI 1.049 to 1.105), and 1.074 (95% CI 1.047 to 1.101), respectively. The results were consistent in subgroup analyses. The association between AG and all-cause mortality was linear for 180-day and 1-year mortality, and near linear for 30-day mortality, as higher concentrations were associated with high all-cause mortality. When stratified according to quartiles, AG was associated with 30-day mortality (HR[95% CI]: second quartile, 2.243[1.273, 3.955]; third quartile, 3.026[1.763, 5.194]; top quartile, 4.402[2.573, 7.531]), 180-day mortality (HR[95% CI]: second quartile, 1.719[1.118, 2.645]; third quartile, 2.362[1.575, 3.542]; top quartile, 3.116[2.077, 4.676]), and 1-year mortality (HR[95% CI]: second quartile, 1.700[1.143, 2.528]; third quartile, 2.239[1.536, 3.264]; top quartile, 2.876[1.969, 4.201]) using bottom quartile as reference. CONCLUSION: We firstly demonstrated that higher AG was significantly associated with increased 30-day, 180-day and 1-year all-cause mortality in AMI patients. AG as an easily obtained marker is of strong and reliable predictive value for AMI mortality during follow-up.