M2 macrophage­derived exosomes alleviate KCa3.1 channel expression in rapidly paced HL­1 myocytes via the NF­κB (p65)/STAT3 signaling pathway.

The present study was designed to explore the role of M2 macrophage­derived exosomes (M2­exos) on the KCa3.1 channel in a cellular atrial fibrillation (AF) model using rapidly paced HL­1 myocytes. M2 macrophages and M2­exos were isolated and identified. MicroRNA (miR)­146a­5p levels in M2 macrophages and M2­exos were quantified using reverse transcription­quantitative PCR (RT­qPCR). HL­1 myocytes were randomly divided into six groups: Control group, pacing group, pacing + coculture group (pacing HL­1 cells cocultured with M2­exos), pacing + mimic­miR­146a­5p group, pacing + NC­miR­146a­5p group and pacing + pyrrolidine dithiocarbamate (PDTC; a special blocker of the NF­κB signaling pathway) group. Transmission electron microscopy, nanoparticle tracking analysis, western blotting, RT­qPCR and immunohistochemistry were performed in the present study. A whole­cell clamp was also applied to record the current density of KCa3.1 and action potential duration (APD) in each group. The results revealed that miR­146a­5p was highly expressed in both M2 macrophages and M2­exos. Pacing HL­1 cells led to a shorter APD, an increased KCa3.1 current density and higher protein levels of KCa3.1, phosphorylated (p­)NF­κB p65, p­STAT3 and IL­1ß compared with the control group. M2­exos, miR­146a­5p­mimic and PDTC both reduced the protein expression of KCa3.1, p­NF­κB p65, p­STAT3 and IL­1ß and the current density of KCa3.1, resulting in a longer APD in the pacing HL­1 cells. In conclusion, M2­exos and their cargo, which comprised miR­146a­5p, decreased KCa3.1 expression and IL­1ß secretion in pacing HL­1 cells via the NF­κB/STAT3 signaling pathway, limiting the shorter APD caused by rapid pacing.

Integrative proteomics and metabolomics study reveal enhanced immune responses by COVID-19 vaccine booster shot against Omicron SARS-CoV-2 infection.

Since its outbreak in late 2021, the Omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been widely reported to be able to evade neutralizing antibodies, becoming more transmissible while causing milder symptoms than previous SARS-CoV-2 strains. Understanding the underlying molecular changes of Omicron SARS-CoV-2 infection and corresponding host responses are important to the control of Omicron COVID-19 pandemic. In this study, we report an integrative proteomics and metabolomics investigation of serum samples from 80 COVID-19 patients infected with Omicron SARS-CoV-2, as well as 160 control serum samples from 80 healthy individuals and 80 patients who had flu-like symptoms but were negative for SARS-CoV-2 infection. The multiomics results indicated that Omicron SARS-CoV-2 infection caused significant changes to host serum proteome and metabolome comparing to the healthy controls and patients who had flu-like symptoms without COVID-19. Protein and metabolite changes also pointed to liver dysfunctions and potential damage to other host organs by Omicron SARS-CoV-2 infection. The Omicron COVID-19 patients could be roughly divided into two subgroups based on their proteome differences. Interestingly, the subgroup who mostly had received full vaccination with booster shot had fewer coughing symptom, changed sphingomyelin lipid metabolism, and stronger immune responses including higher numbers of lymphocytes, monocytes, neutrophils, and upregulated proteins related to CD4+ T cells, CD8+ effector memory T cells (Tem), and conventional dendritic cells, revealing beneficial effects of full COVID-19 vaccination against Omicron SARS-CoV-2 infection through molecular changes.

"We are in the forgotten corner!" a qualitative study of experiences and challenges among Chinese older women at the onset of acute myocardial infarction.

Background: Acute myocardial infarction (AMI) is a common and serious cardiovascular disease (CVD) that is one of the leading causes of death among women globally and in China. However, there are sex-associated differences and inequalities in the detection and management of AMI, especially in older people. There is little research demonstrating how challenges and barriers affect older women's help-seeking behavior and health-related procedures in China. Purpose: The objective of this study was to explore the experiences of older women with AMI, focusing on their perception, challenges, and coping strategies at the onset of AMI in Wuhan, China. Methods: This study utilized a qualitative research design approach and conducted semi-structured, in-depth, and audio-recorded interviews with 18 women aged 65-84 years, purposively selected from two tertiary hospitals in Wuhan City from November 2021 to April 2022. Results: Interpretative Phenomenological Analysis (IPA) was used in this study to analyze the data on 18 participants and three major themes were generated: disease perception disorder, negative coping strategies, and barriers due to social-environmental contexts. Conclusion: To reduce older women's delay in seeking help, healthcare professionals should provide public health education that emphasizes sex-related disparities, and age-specific knowledge-attitude aspects to high-risk groups. Policy-based and health administration recommendations, including e-health information support, access to care, and social-environmental factors, should be highlighted to promote women's health behavior.

Multi-omics data integration using ratio-based quantitative profiling with Quartet reference materials.

Characterization and integration of the genome, epigenome, transcriptome, proteome and metabolome of different datasets is difficult owing to a lack of ground truth. Here we develop and characterize suites of publicly available multi-omics reference materials of matched DNA, RNA, protein and metabolites derived from immortalized cell lines from a family quartet of parents and monozygotic twin daughters. These references provide built-in truth defined by relationships among the family members and the information flow from DNA to RNA to protein. We demonstrate how using a ratio-based profiling approach that scales the absolute feature values of a study sample relative to those of a concurrently measured common reference sample produces reproducible and comparable data suitable for integration across batches, labs, platforms and omics types. Our study identifies reference-free 'absolute' feature quantification as the root cause of irreproducibility in multi-omics measurement and data integration and establishes the advantages of ratio-based multi-omics profiling with common reference materials.

MetaPro: a web-based metabolomics application for LC-MS data batch inspection and library curation.

INTRODUCTION: Metabolomics analysis based on liquid chromatography-mass spectrometry (LC-MS) has been a prevalent method in the metabolic field. However, accurately quantifying all the metabolites in large metabolomics sample cohorts is challenging. The analysis efficiency is restricted by the abilities of software in many labs, and the lack of spectra for some metabolites also hinders metabolite identification. OBJECTIVES: Develop software that performs semi-targeted metabolomics analysis with an optimized workflow to improve quantification accuracy. The software also supports web-based technologies and increases laboratory analysis efficiency. A spectral curation function is provided to promote the prosperity of homemade MS/MS spectral libraries in the metabolomics community. METHODS: MetaPro is developed based on an industrial-grade web framework and a computation-oriented MS data format to improve analysis efficiency. Algorithms from mainstream metabolomics software are integrated and optimized for more accurate quantification results. A semi-targeted analysis workflow is designed based on the concept of combining artificial judgment and algorithm inference. RESULTS: MetaPro supports semi-targeted analysis workflow and functions for fast QC inspection and self-made spectral library curation with easy-to-use interfaces. With curated authentic or high-quality spectra, it can improve identification accuracy using different peak identification strategies. It demonstrates practical value in analyzing large amounts of metabolomics samples. CONCLUSION: We offer MetaPro as a web-based application characterized by fast batch QC inspection and credible spectral curation towards high-throughput metabolomics data. It aims to resolve the analysis difficulty in semi-targeted metabolomics.

Stereotactic arrhythmia radioablation: A novel therapy for cardiac arrhythmia.

Cardiac arrhythmia is a global health problem, and catheter ablation has been one of its main treatments for decades. However, catheter ablation is an invasive method that cannot reach the deep myocardium, and it carries a considerable risk of side effects and recurrence. Therefore, it is necessary to explore a novel approach. Stereotactic body radiotherapy, which has been widely used in the field of radiation oncology, has recently expanded in the treatment of cardiac arrhythmia; when used in this context, it is known as stereotactic arrhythmia radioablation (STAR). As a noninvasive, effective, and well-tolerated treatment, STAR may be a suitable alternative method for patients with cardiac arrhythmia who are resistant or intolerant to catheter ablation. The main particles used to deliver energy in STAR are photons, protons, and carbon ions. Most studies have shown the short-term effectiveness of STAR, but problems such as a high long-term recurrence rate with a cumulative ventricular tachycardia-free survival rate from the published literature of 38.6% and related complications have also emerged. Therefore, in this article, we review the application of stereotactic body radiotherapy in cardiac arrhythmia, analyze its potential problems, and explore methods for improvement.

The Tp-e/QT ratio as a predictor of nocturnal premature ventricular contraction events in patients with obstructive sleep apnea.

BACKGROUND: Obstructive sleep apnea (OSA) is significantly associated with a higher risk of ventricular arrhythmia (VA). QT, the Tp-e/QT ratio, and QT dispersion (QTd) are used to evaluate myocardial repolarization and are highly correlated with VA. The aim was to evaluate the predictive value of the Tp-e/QT ratio and other electrocardiogram (ECG) parameters for nocturnal premature ventricular contractions (PVCs) in patients with OSA. METHODS: We retrospectively analyzed data from patients with OSA and conducted a 1:1 matched cohort study. Patients diagnosed with OSA who met our criteria for the PVC group, and sex- and age-matched patients with OSA who met our criteria for the control group were enrolled in the study. The Tp-e, Tp-e/QT ratio, corrected QT interval (QTc), corrected Tp-e interval (Tp-ec), and QTd were measured, calculated and analyzed. RESULTS: Patients in the PVC group (n = 31) showed a greater Tp-e, Tp-ec, QTc, Tp-e/QT ratio, and QTd than patients in the control group (n = 31). In the univariate binary logistic regression analysis, higher Tp-ec (OR: 1.025; P = 0.042), QTc (OR: 1.014; P = 0.036), Tp-e/QT ratio (OR: 1.675; P < 0.001), and QTd (OR: 1.052; P = 0.012) values were all significantly associated with nocturnal PVCs. In multivariate analysis and receiver operating characteristic analysis, a higher Tp-e/QT ratio (OR: 2.168; 95% CI: 0.762-0.952; P < 0.001) was an independent predictor of nocturnal PVCs. CONCLUSIONS: The QTc, Tp-e/QT ratio, and QTd in patients with OSA with nocturnal PVCs were significantly increased compared with those in patients without nocturnal PVCs. A prolonged Tp-e/QT ratio was an independent predictor of nocturnal PVCs in patients with OSA.

A comparison between children and adolescents with autism spectrum disorders and healthy controls in biomedical factors, trace elements, and microbiota biomarkers: a meta-analysis.

Introduction: Autism spectrum disorder (ASD) is a multifaceted developmental condition that commonly appears during early childhood. The etiology of ASD remains multifactorial and not yet fully understood. The identification of biomarkers may provide insights into the underlying mechanisms and pathophysiology of the disorder. The present study aimed to explore the causes of ASD by investigating the key biomedical markers, trace elements, and microbiota factors between children with autism spectrum disorder (ASD) and control subjects. Methods: Medline, PubMed, ProQuest, EMBASE, Cochrane Library, PsycINFO, Web of Science, and EMBSCO databases have been searched for publications from 2012 to 2023 with no language restrictions using the population, intervention, control, and outcome (PICO) approach. Keywords including "autism spectrum disorder," "oxytocin," "GABA," "Serotonin," "CRP," "IL-6," "Fe," "Zn," "Cu," and "gut microbiota" were used for the search. The Joanna Briggs Institute (JBI) critical appraisal checklist was used to assess the article quality, and a random model was used to assess the mean difference and standardized difference between ASD and the control group in all biomedical markers, trace elements, and microbiota factors. Results: From 76,217 records, 43 studies met the inclusion and exclusion criteria and were included in this meta-analysis. The pooled analyses showed that children with ASD had significantly lower levels of oxytocin (mean differences, MD = -45.691, 95% confidence interval, CI: -61.667, -29.717), iron (MD = -3.203, 95% CI: -4.891, -1.514), and zinc (MD = -6.707, 95% CI: -12.691, -0.722), lower relative abundance of Bifidobacterium (MD = -1.321, 95% CI: -2.403, -0.238) and Parabacteroides (MD = -0.081, 95% CI: -0.148, -0.013), higher levels of c-reactive protein, CRP (MD = 0.401, 95% CI: 0.036, 0.772), and GABA (MD = 0.115, 95% CI: 0.045, 0.186), and higher relative abundance of Bacteroides (MD = 1.386, 95% CI: 0.717, 2.055) and Clostridium (MD = 0.281, 95% CI: 0.035, 0.526) when compared with controls. The results of the overall analyses were stable after performing the sensitivity analyses. Additionally, no substantial publication bias was observed among the studies. Interpretation: Children with ASD have significantly higher levels of CRP and GABA, lower levels of oxytocin, iron, and zinc, lower relative abundance of Bifidobacterium and Parabacteroides, and higher relative abundance of Faecalibacterium, Bacteroides, and Clostridium when compared with controls. These results suggest that these indicators may be a potential biomarker panel for the diagnosis or determining therapeutic targets of ASD. Furthermore, large, sample-based, and randomized controlled trials are needed to confirm these results.

KDM3A Attenuates Myocardial Ischemic and Reperfusion Injury by Ameliorating Cardiac Microvascular Endothelial Cell Pyroptosis.

Cardiac microvascular endothelial cell ischemia-reperfusion (CMEC I/R) injury occurs in approximately 50% of acute myocardial infarction patients subjected to successful revascularization therapy. This injury leads to cardiac microcirculatory system dysfunctions, which seriously affect cardiac functions and long-term prognostic outcomes. Previously, we elucidated the role of lysine-specific demethylase 3A (KDM3A) in protecting cardiomyocytes from I/R injury; however, its roles in CMEC I/R injuries have yet to be fully established. In this study, hypoxia/reoxygenation (H/R) treatment significantly impaired CMEC functions and induced their pyroptosis, accompanied by KDM3A downregulation. Then, gain- and loss-of-function assays were performed to investigate the roles of KDM3A in CMEC H/R injury in vitro. KDM3A knockout enhanced CMEC malfunctions and accelerated the expressions of pyroptosis-associated proteins, such as NLRP3, cleaved-caspase-1, ASC, IL-1ß, GSDMD-N, and IL-18. Conversely, KDM3A overexpression developed ameliorated alternations in CMEC H/R injury. In vivo, KDM3A knockout resulted in the deterioration of cardiac functions and decreased the no-reflow area as well as capillary density. Mechanistically, KDM3A activated the PI3K/Akt signaling pathway and ameliorated I/R-mediated CMEC pyroptosis. In conclusion, KDM3A is a promising treatment target for alleviating CMEC I/R injury.

Cardiac Fibroblasts Promote Ferroptosis in Atrial Fibrillation by Secreting Exo-miR-23a-3p Targeting SLC7A11.

The exact mechanism of atrial fibrillation (AF) has been not well elucidated. Ferroptosis is an iron-dependent cell death due to excessive accumulation of peroxidized polyunsaturated fatty acids. However, the molecular mechanism underlying AF and ferroptosis has never been reported. Here, we established the rapid pacing model in vivo and vitro to investigate the relationship between AF and ferroptosis. In canine model of rapid atrial pacing, the content of malondialdehyde and total ions in the atrial tissue of the Pacing group was significantly increased and the exosome inhibitor GW4869 reduced ferroptosis, fibrosis, and inflammation and improved histological and electrophysiological remodeling. In rapid pacing h9c2 cells, the expression of antioxidative stress genes associated with ferroptosis presented sequential changes and proteins involved in ferroptosis such as FTH1, SLC7A11, and GPX4 were gradually depleted. Furthermore, pacing cardiac fibroblast-derived exosomes (CF-exos) exacerbated ferroptosis in h9c2 cells and pretreated pacing-CF-exos with GW4869 alleviated injury to h9c2 cells. In mechanism, our results demonstrated that pacing-CF-exos highly expressed miR-23a-3p by informatics analysis and experimental verification. Inhibitor-miR-23a-3p protected h9c2 cells from ferroptosis accompanying with upregulation of SLC7A11. In addition, SLC7A11 was shown to be the target gene of miR-23a-3p. In conclusion, our results suggest that CF-exos-miR-23a-3p may promote ferroptosis. The development of AF in a persistent direction could be prevented by intervening with exosomal miRNAs to reduce oxidative stress injury and ferroptosis.

Proteomic and metabolomic profiling of urine uncovers immune responses in patients with COVID-19.

The utility of the urinary proteome in infectious diseases remains unclear. Here, we analyzed the proteome and metabolome of urine and serum samples from patients with COVID-19 and healthy controls. Our data show that urinary proteins effectively classify COVID-19 by severity. We detect 197 cytokines and their receptors in urine, but only 124 in serum using TMT-based proteomics. The decrease in urinary ESCRT complex proteins correlates with active SARS-CoV-2 replication. The downregulation of urinary CXCL14 in severe COVID-19 cases positively correlates with blood lymphocyte counts. Integrative multiomics analysis suggests that innate immune activation and inflammation triggered renal injuries in patients with COVID-19. COVID-19-associated modulation of the urinary proteome offers unique insights into the pathogenesis of this disease. This study demonstrates the added value of including the urinary proteome in a suite of multiomics analytes in evaluating the immune pathobiology and clinical course of COVID-19 and, potentially, other infectious diseases.

Atrial fibrillation in obstructive sleep apnea: Neural mechanisms and emerging therapies.

Obstructive sleep apnea (OSA) has been reproducibly identified as a risk factor for initiation and progression of atrial fibrillation (AF) and reduces the efficacy of antiarrhythmic drugs, electrical cardioversion, and catheter ablation in AF. It is still controversial whether continuous positive airway pressure ventilation (CPAP) could improve the successful rate of AF treatment in OSA patients. Besides, CPAP has shown relative low compliance in patients with OSA. Therefore, novel optional therapies might be needed to improve the control of AF associated with OSA. A growing body of evidence suggests that autonomic activation contributes to the pathogenesis of AF in OSA. Acute apneic episodes result in sympathovagal co-activation, shortening atrial refractoriness and promoting the initiation of AF. Chronic OSA-induced sympathetic activation plays a crucial role in atrial autonomic, structural, and electrical remodeling, thus providing substrates for AF maintenance and recurrence. Therefore, the autonomic nervous system may be a promising therapeutic target for OSA and AF. Autonomic modulation as a treatment for OSA-associated AF has been well established in several preclinical studies. Further clinical studies are needed to provide a more precise definition of the role of autonomic modulation in the treatment of AF in OSA.

Profiles of liver function abnormalities in elderly patients with Coronavirus Disease 2019.

BACKGROUND: The profiles of liver function abnormalities in COVID-19 patients need to be clarified. METHODS: In this retrospective study, consecutive COVID-19 patients over 60 years old in Renmin Hospital of Wuhan University from January 1 to February 6 were included. Data of demographics, clinical characteristics, comorbidities, laboratory tests, medications and outcomes were collected and analysed. Sequential alterations of serum alanine aminotransferase (ALT) were monitored. RESULTS: A total of 330 patients were included and classified into two groups with normal (n = 234) or elevated ALT (n = 96). There were fewer females (40.6% vs 54.7%, P = .020) and more critical cases (30.2% vs 19.2%, P = .026) in patients with elevated ALT compared with the normal group. Higher levels of bacterial infection indices (eg, white blood cell count, neutrophil count, C-reactive protein and procalcitonin) were observed in the elevated group. Spearman correlation showed that both ALT and AST levels were positively correlated with those indices of bacterial infection. No obvious effects of medications on ALT abnormalities were found. In patients with elevated ALT, most ALT elevations were mild and transient. 59.4% of the patients had ALT concentrations of 41-100 U/L, while only a few patients (5.2%) had high serum ALT concentrations above 300 U/L. ALT elevations occurred at 13 (10-17) days and recovered at 28 (18-35) days from disease onset. For most patients, the elevation of serum ALT levels occurred at 6-20 days after disease onset and reached their peak values within a similar time frame. The recovery of serum ALT levels to normal frequently occurred at 16-20 days or 31-35 days after disease onset. CONCLUSIONS: Liver function abnormalities were observed in 29.1% of elderly people COVID-19 patients, which were slightly and transient in most cases. Liver function abnormalities in COVID-19 may be correlated with bacterial infection.

Association of Interleukin-6 Levels with Morbidity and Mortality in Patients with Coronavirus Disease 2019 (COVID-19).

The prognostic value of interleukin-6 (IL-6) in coronavirus disease 2019 (COVID-19) needs to be clarified. In this retrospective study, COVID-19 patients treated at Renmin Hospital of Wuhan University from January 7 to February 8, 2020 with measurements of serum IL-6 levels within 1 week after admission were included. Data regarding demographics, clinical characteristics, laboratory tests, complications, and outcomes were collected and analyzed. Sixty-six patients diagnosed with COVID-19 were included in this study (31 patients were females). They were divided into a normal group (serum IL-6 <10 pg/mL, n = 35) and an abnormal group (serum IL-6 <10 pg/mL, n = 31). Compared with the normal group, the incidence of critical cases (P <0.001), acute respiratory distress syndrome (ARDS) (P = 0.001), acute cardiac injury (P = 0.002), cardiac insufficiency (P = 0.039), mechanical ventilation rate (P = 0.002), and mortality (P = 0.021) was significantly increased in the abnormal group. Serum IL-6 concentration was an independent predictor of fatal outcome (P = 0.04). The optimal cutoff value of serum IL-6 concentration for predicting fatal outcomes was 26.09 pg/mL (P <0.001). In COVID-19, elevated serum IL-6 levels were associated with critical illness, use of mechanical ventilation, and complications, including heart injury and ARDS, and could predict a fatal outcome. Early detection of serum IL-6 levels after admission should be necessary in COVID-19 patients.

In-Hospital Management and Outcomes of Acute Myocardial Infarction Before and During the Coronavirus Disease 2019 Pandemic.

The outbreak of coronavirus disease 2019 (COVID-19) has rapidly spread worldwide. This study sought to share our experiences with in-hospital management and outcomes of acute myocardial infarction (AMI) during the COVID-19 pandemic. We retrospectively analyzed consecutive AMI patients, including those with ST-elevation myocardial infarction (STEMI) and non-STEMI (NSTEMI), from February 1, 2020, to April 15, 2020 (during the COVID-19 pandemic), and from January 1, 2019, to December 31, 2019 (before the COVID-19 pandemic), respectively. Fifty-three AMI patients (31 STEMI, 22 NSTEMI) during the COVID-19 pandemic were matched to 53 AMI patients before the pandemic. Baseline characteristics were comparable between the matched patients. STEMI patients during the COVID-19 pandemic had a longer delay time, less primary or remedial PCI and more emergency thrombolysis than those before the pandemic. Less coronary angiography and stenting were performed in AMI patients during the COVID-19 pandemic than before the pandemic. There were no statistically significant differences in the clinical outcomes between the matched patients. However, STEMI patients during the COVID-19 pandemic had a 4-fold (12.9% vs. 3.2%) increase in all-cause mortality rate compared with those before the pandemic. AMI combined with COVID-19 infection was associated with higher rates of mortality than AMI alone. This study demonstrates that the COVID-19 pandemic results in significant reperfusion delays in STEMI patients and has a marked impact on the treatment options selection in AMI patients. The mortality rate of STEMI patients exhibits an increasing trend during the pandemic of COVID-19.

Downregulation of P300/CBP-Associated Factor Attenuates Myocardial Ischemia-Reperfusion Injury Via Inhibiting Autophagy.

Cardiomyocyte autophagy plays an important role in myocardial ischemia-reperfusion injury (MIRI). P300/CBP-associated factor (PCAF) was involved in the regulation of autophagy. However, the role of PCAF in MIRI is currently unknown. This study was to investigate whether downregulation of PCAF attenuate MIRI. The results showed that the expression of PCAF was significantly increased in MIRI in vivo and in vitro. Downregulation of PCAF not only inhibited autophagy and damage of H9c2 cells induced by hypoxia-reoxygenation, but also reduced autophagy and myocardial infarct size during myocardial ischemia-reperfusion in rats. In addition, downregulation of PCAF promoted activation of PI3K/Akt/mTOR signaling pathway in cardiomyocytes during hypoxia-reoxygenation. Wortmannin, a PI3K/Akt inhibitor, could abrogate the effects of downregulation of PCAF on cardiomyocytes autophagy. These results demonstrated that downregulation of PCAF alleviated MIRI by inhibiting cardiomyocyte autophagy through PI3K/Akt/mTOR signaling pathway. Thus, PCAF may be a potential target for prevention and treatment of MIRI.

Proteomic and Metabolomic Characterization of COVID-19 Patient Sera.

Early detection and effective treatment of severe COVID-19 patients remain major challenges. Here, we performed proteomic and metabolomic profiling of sera from 46 COVID-19 and 53 control individuals. We then trained a machine learning model using proteomic and metabolomic measurements from a training cohort of 18 non-severe and 13 severe patients. The model was validated using 10 independent patients, 7 of which were correctly classified. Targeted proteomics and metabolomics assays were employed to further validate this molecular classifier in a second test cohort of 19 COVID-19 patients, leading to 16 correct assignments. We identified molecular changes in the sera of COVID-19 patients compared to other groups implicating dysregulation of macrophage, platelet degranulation, complement system pathways, and massive metabolic suppression. This study revealed characteristic protein and metabolite changes in the sera of severe COVID-19 patients, which might be used in selection of potential blood biomarkers for severity evaluation.

Serum N-Acetylneuraminic Acid Is Associated with Atrial Fibrillation and Left Atrial Enlargement.

PURPOSE: Recent studies have indicated that N-acetylneuraminic acid (Neu5Ac) plays a key role in severe coronary artery diseases, involving RhoA signaling pathway activation, which is critically involved in cardiac fibrosis. There is convincing evidence from many studies that left atrium fibrosis is involved in the pathophysiology of AF. Therefore, we speculated that Neu5Ac may be associated with atrial fibrillation (AF) and involved in the development of AF. This study aims to investigate the clinical relationship between Neu5Ac and AF and left atrial enlargement. METHODS: Forty-five patients with AF (AF group) and forty-five patients with non-AF (control group) matched for age, sex, and hospitalization date were recruited for our study. Plasma concentrations of Neu5Ac from peripheral venous blood were analyzed using enzyme-linked immunosorbent assay (ELISA). The baseline characteristics, plasma level of Neu5Ac, and echocardiographic characteristics were evaluated. RESULTS: The plasma level of Neu5Ac was significantly higher in the AF group than in the control group (107.66 ± 47.50 vs 77.87 ± 39.09 ng/ml; P < 0.05); the left atrial diameters were positively correlated with the plasma Neu5Ac level (R = 0.255; P < 0.05). The plasma Neu5Ac level (R = 0.368; P < 0.05) and the left atrial diameters (R = 0.402; P < 0.05) were positively correlated with AF history times. Neu5Ac (odds ratio 1.018, 95% CI 1.003-1.032; P < 0.05) and the left atrial diameter (odds ratio 1.142, 95% CI 1.020-1.280; P < 0.05) were independent risk factors for AF in multivariate regression analysis. CONCLUSIONS: Serum Neu5Ac is associated with atrial fibrillation, and the mechanism may involve left atrial enlargement.

Coronavirus disease 2019 in elderly patients: Characteristics and prognostic factors based on 4-week follow-up.

OBJECTIVE: To investigate the characteristics and prognostic factors in the elderly patients with COVID-19. METHODS: Consecutive cases over 60 years old with COVID-19 in Renmin Hospital of Wuhan University from Jan 1 to Feb 6, 2020 were included. The primary outcomes were death and survival till March 5. Data of demographics, clinical features, comorbidities, laboratory tests and complications were collected and compared for different outcomes. Cox regression was performed for prognostic factors. RESULTS: 339 patients with COVID-19 (aged 71±8 years,173 females (51%)) were enrolled, including 80 (23.6%) critical, 159 severe (46.9%) and 100 moderate (29.5%) cases. Common comorbidities were hypertension (40.8%), diabetes (16.0%) and cardiovascular disease (15.7%). Common symptoms included fever (92.0%), cough (53.0%), dyspnea (40.8%) and fatigue (39.9%). Lymphocytopenia was a common laboratory finding (63.2%). Common complications included bacterial infection (42.8%), liver enzyme abnormalities (28.7%) and acute respiratory distress syndrome (21.0%). Till Mar 5, 2020, 91 cases were discharged (26.8%), 183 cases stayed in hospital (54.0%) and 65 cases (19.2%) were dead. Shorter length of stay was found for the dead compared with the survivors (5 (3-8) vs. 28 (26-29), P < 0.001). Symptoms of dyspnea (HR 2.35, P = 0.001), comorbidities including cardiovascular disease (HR 1.86, P = 0.031) and chronic obstructive pulmonary disease (HR 2.24, P = 0.023), and acute respiratory distress syndrome (HR 29.33, P < 0.001) were strong predictors of death. And a high level of lymphocytes was predictive of better outcome (HR 0.10, P < 0.001). CONCLUSIONS: High proportion of severe to critical cases and high fatality rate were observed in the elderly COVID-19 patients. Rapid disease progress was noted in the dead with a median survival time of 5 days after admission. Dyspnea, lymphocytopenia, comorbidities including cardiovascular disease and chronic obstructive pulmonary disease, and acute respiratory distress syndrome were predictive of poor outcome. Close monitoring and timely treatment should be performed for the elderly patients at high risk.