Search

Abstract Aims Heart failure (HF) is a global health issue, with lipid metabolism and inflammation critically implicated in its progression. This study harnesses cutting‐edge, expanded genetic information for lipid and inflammatory protein profiles, employing Mendelian randomization (MR) to uncover genetic risk factors for HF. Methods We assessed genetic susceptibility to HF across 179 lipidomes and 91 inflammatory proteins using instrumental variables (IVs) from recent genome‐wide association studies (GWASs) and proteome‐wide quantitative trait loci (pQTL) studies. GWASs involving 47 309 HF cases and 930 014 controls were obtained from the Heart Failure Molecular Epidemiology for Therapeutic Targets (HERMES) Consortium. Data on 179 lipids from 7174 individuals in a Finnish cohort and 91 inflammatory proteins from a European pQTL study involving 14 824 individuals are available in the HGRI‐EBI catalogue. A two‐sample MR approach evaluated the associations, and a two‐step mediation analysis explored the mediation role of inflammatory proteins in the lipid–HF pathway. Sensitivity analyses, including MR‐RAPS (robust adjusted profile score) and MR‐Egger, ensured result robustness. Results Genetic IVs for 162 lipids and 74 inflammatory proteins were successfully identified. MR analysis revealed a genetic association between HF and 31 lipids. Among them, 18 lipids, including sterol ester (27:1/18:0), cholesterol, 9 phosphatidylcholines, phosphatidylinositol (16:0_20:4) and 6 triacylglycerols, were identified as HF risk factors [odds ratio (OR) = 1.037–1.368]. Cholesterol exhibited the most significant association with elevated HF risk [OR = 1.368, 95% confidence interval (CI) = 1.044–1.794, P = 0.023]. In the inflammatory proteome, leukaemia inhibitory factor receptor (OR = 0.841, 95% CI = 0.789–0.897, P = 1.08E‐07), fibroblast growth factor 19 (OR = 0.905, 95% CI = 0.830–0.988, P = 0.025) and urokinase‐type plasminogen activator (OR = 0.938, 95% CI = 0.886–0.994, P = 0.030) were causally negatively correlated with HF, whereas interleukin‐20 receptor subunit alpha (OR = 1.333, 95% CI = 1.094–1.625, P = 0.004) was causally positively correlated with HF. Mediation analysis revealed leukaemia inhibitory factor receptor (mediation proportion: 23.5%–25.2%) and urokinase‐type plasminogen activator (mediation proportion: 9.5%–10.7%) as intermediaries in the lipid–inflammation–HF pathway. No evidence of directional horizontal pleiotropy was observed (P > 0.05). Conclusions This study identifies a genetic connection between certain lipids, particularly cholesterol, and HF, highlighting inflammatory proteins that influence HF risk and mediate this relationship, suggesting new therapeutic targets and insights into genetic drivers in HF.

Abstract Background A previous study demonstrated that N-glycosylation profiles of IgG are associated with subclinical atherosclerosis in a British population. However, the generalisability of this finding to other ethnic groups remains to be investigated, and it has yet to account for additional traditional atherosclerotic risk factors. The present study, thus, aims to explore IgG N-glycosylation profiles in Han Chinese with atherosclerosis, and their potential role in atherosclerosis, while controlling for traditional atherosclerotic risk factors. Methods Data of this case-control study were obtained from an established umbrella Health Examination Cohort Study (registration number: ChiCTR2100048740). The investigation was conducted at the Health Care Centre of the First Affiliated Hospital of Shantou University Medical College in China, from August 1, 2021, to July 31, 2022. A sample of 69 carotid atherosclerosis (CAS) cases was recruited from the umbrella cohort, along with 69 controls without carotid atherosclerosis, matched by traditional atherosclerosis-related risk factors, including gender, age, smoking, alcohol consumption, hypertension, diabetes, dyslipidemia and obesity. Subsequently, serum IgG N-glycosylation was profiled using Ultra-Performance Liquid Chromatography. Results After propensity score matching, the relative abundance of IgG fucosylation in CAS cases was significantly lower than that in controls [95.32 (92.96, 95.99) vs. 95.96 (94.70, 96.58), P = 0.022]. The traditional atherosclerosis-related risk factors showed no statistically significant difference between CAS cases and controls (P > 0.05). Conclusions The reduced fucosylation of IgG in CAS cases underscores the pivotal role of afucosylation in CAS. Enhancing the inflammatory capability of IgG via initiating antibody-dependent cell-mediated cytotoxicity could be the potential mechanism behind this, which should be further verified by functional studies.

Abstract Aims Depressive symptoms are comorbid with coronary heart disease (CHD). There is a controversial debate about whether screening and intervention for depressive symptoms could improve cardiovascular prognosis. This study characterizes the prevalence, characteristics, cardiovascular prognosis and management need of depressive symptoms among CHD patients. Methods CHD patients were recruited between November 18, 2020 and November 26, 2021. Depressive symptoms were evaluated with the Patient Health Questionnaire (PHQ-9). During the 12-month follow-up, cardiovascular disease (CVD) was the endpoint. Time-to-event data were estimated by Kaplan-Meier curves and Cox models. Results Of 582 patients (25% women), 21.0% had mild depressive symptoms, and 7.5% had moderate-to-severe depressive symptoms during hospitalization. Mild and moderate-to-severe depressive symptoms were risk factor-adjusted predictors of the primary composite endpoints (adjusted HR = 2.20; 95%CI 1.19–4.03, and adjusted HR = 2.70; 95%CI 1.23–5.59, respectively). Platelet count and low-density lipoprotein were higher in mild depressive symptoms compared to no depressive symptoms. Conclusion Depressive symptoms are prevalent in CHD patients. Mild and moderate-to-severe depressive symptoms are associated with higher risk of further CVD in CHD patients. Platelet function and behavioral mechanisms may contribute to this association. Trial registration This research was registered at https://www.chictr.org.cn . Full data of first registration is 11/09/2020. The registration number is ChiCTR2000038139.

Abstract Background Triglyceride-glucose (TyG) index is an emerging surrogate indicator of insulin resistance, which has been demonstrated as a risk factor for various cardiovascular diseases including coronary syndrome, in-stent restenosis, and heart failure. However, association of TyG index with incident aortic dissection (AD) and aortic aneurysm (AA) remains to be investigated. Methods This study included 420,292 participants without baseline AD/AA from the large-scale prospective UK Biobank cohort. The primary outcome was incident AD/AA, comprising AD and AA. Multivariable-adjusted Cox proportional hazards regression models and restricted cubic spline (RCS) analyses were applied to assess the relationship between TyG index and the onset of AD/AA. In addition, the association between TyG index and incident AD/AA was examined within subgroups defined by age, gender, smoking status, drinking status, diabetes, hypertension, and BMI. Results Over a median follow-up period of 14.8 (14.1, 15.5) years, 3,481 AD/AA cases occurred. The incidence of AD/AA rose along with elevated TyG index. RCS curves showed a linear trend of TyG index with risk of incident AD/AA. TyG index was positively associated with risk of incident AD/AA after adjusting for age, gender, smoking status, drinking status, BMI, hypertension, LDL-c, and HbA1c, with adjusted HRs of 1.0 (reference), 1.20 (95% CI 1.08–1.35), 1.21 (95% CI 1.08–1.35), and 1.30 (95% CI 1.16–1.45) for TyG index quartiles 2, 3, and 4, respectively. Especially, participants in the highest TyG index quartile had highest risk of developing AA, with an adjusted HR of 1.35 (95% CI 1.20–1.52). Conclusions TyG index is independently associated with a higher risk of incident AD/AA, indicating the importance of using TyG index for risk assessment of AD/AA, especially for AA.

Abstract Background Aortic dissection (AD) is a lethal cardiovascular emergency involving high mortality and disability. However, its specific pathogenesis remains to be elucidated. Methods A bibliometric analysis based on the Web of Science database, VOSviewer software and Citex platforms was conducted to have a knowledge of the development trends, frontiers and hot spots of AD. Subsequently, the top five AD‐related genes from the titles and abstracts of published literature were searched. Lastly, the roles of the top five genes and their encoded proteins in the onset of AD were reviewed. Results The bibliometrics showed that most studies are exploring the molecular drivers related to AD, especially gene mutations. The top five AD‐related genes were transforming growth factor‐β (TGFB)‐related genes, elastin (ELN), fibrillin‐1 (FBN1), angiotensinogen (AGT) and matrix metalloproteinase 9 (MMP9). In particular, regulation of the structure of elastic fiber by TGFB‐related genes, ELN and FBN1, appears to be the principal mechanism contributing to AD onset. Activation of the renin‐angiotensin system is the principal mechanism by which AGT triggers AD. MMP9 promotes the formation and development of AD by degrading extracellular matrix components. Conclusion TGFB, ELN, FBN1, AGT and MMP9 are the five top molecular drivers of AD, providing a comprehensive mechanistic insight into AD.

Abstract Background The gut microbiota is involved in the pathogenesis of diabetic cardiomyopathy (DCM). Myricetin protects cardiac function in DCM. However, the low bioavailability of myricetin fails to explain its pharmacological mechanisms thoroughly. Research has shown that myricetin has a positive effect on the gut microbiota. We hypothesize that myricetin improves the development of DCM via regulating gut microbiota. Methods DCM mice were induced with streptozotocin and fed a high-fat diet, and then treated with myricetin by gavage and high-fat diet for 16 weeks. Indexes related to gut microbiota composition, cardiac structure, cardiac function, intestinal barrier function, and inflammation were detected. Moreover, the gut contents were transplanted to DCM mice, and the effect of fecal microbiota transplantation (FMT) on DCM mice was assessed. Results Myricetin could improve cardiac function in DCM mice by decreasing cardiomyocyte hypertrophy and interstitial fibrosis. The composition of gut microbiota, especially for short-chain fatty acid-producing bacteria involving Roseburia, Faecalibaculum, and Bifidobacterium, was more abundant by myricetin treatment in DCM mice. Myricetin increased occludin expression and the number of goblet cells in DCM mice. Compared with DCM mice unfed with gut content, the cardiac function, number of goblet cells, and expression of occludin in DCM mice fed by gut contents were elevated, while cardiomyocyte hypertrophy and TLR4/MyD88 pathway-related proteins were decreased. Conclusions Myricetin can prevent DCM development by increasing the abundance of beneficial gut microbiota and restoring the gut barrier function.

Objectives: Brain-derived neurotrophic factor (BDNF) as a biomarker of depressive symptoms manifests a novel role in the cardiovascular system. This study aims to indicate the association of BDNF levels between depressive symptoms and the cardiovascular prognosis in coronary heart disease (CHD) patients. Methods: Participants were recruited from hospitalized CHD patients between November 18, 2020 and November 26, 2021, in the First Affiliated Hospital of Shantou University Medical College. Serum BDNF levels were measured by the enzyme-linked immunosorbent assays. Depressive symptom was evaluated using Patient Health Questionnaire (PHQ-9). The cardiovascular events were the endpoint outcomes across the 12-month follow-up. Kaplan–Meier curves and Cox proportional hazards regression models were used to investigate the relationship of serum BDNF levels between depressive symptom and prognosis. Results: A total of 102 CHD patients (60.6 ± 10.4 year, 76% male) were enrolled. Based on the median serum BDNF levels, the participants were grouped into those “low BDNF (≤0.65 ng/mL)” versus “high BDNF (≥0.65 ng/mL).” CHD patients with low BDNF levels had a higher prevalence of depressive symptoms (PHQ–9 ≥10) compared with high BDNF levels. Within a median 540 days of follow-up, low serum BDNF increased the risk of cardiovascular events (adjusted hazard ratio = 3.26; 95% confidence interval = 1.18–9.02, P = 0.02) after adjustment for confounding factors. Conclusions: CHD patients with low serum BDNF levels were significantly associated with an increased risk of cardiovascular events, independently of depressive symptoms.

Background and objectivesAcute aortic syndrome (AAS) is a life-threatening condition in which there is a fracture in the integrity of the aortic wall. gamma-glutamyl transferase to lymphocyte ratio (GLR) is recognized as a risk factor for liver cirrhosis, fibrosis, and hepatocellular carcinoma. However, there are no clinical reports of GLR and AAS. We attempted to determine whether GLR level is associated with AAS in patients from the Chaoshan region of southern China.MethodsA total of 2,384 patients were recruited in this study and were divided into AAS and no-AAS groups according to the results of CT angiography of the thoracoabdominal aorta. Univariate and multivariate logistic regression was performed to identify risk factors for the occurrence of AAS. ROC was applied to assess the value of D-Dimer, GLR alone, or in combination for the diagnosis of AAS. And a 1:1 propensity score-matched analysis was performed.ResultsMultivariate logistics regression analysis indicated that male, age, hypertension, diabetes, creatinine, D-dimer, and GLR were independent risk factors of AAS patients in the before propensity score-matching cohort. After propensity score-matching, it showed that D-dimer, GLR [OR 3.558(1.891, 6.697); p

Background: Aortic dissection (AD) is a lethal aortic disease with limited effective therapeutic strategies. Aging increases the risk of AD, yet the underlying mechanisms remain unclear. This study aims to analyze the association of aging-related genes (Args) and AD using bioinformatic analysis. This helps provide novel insights into AD pathogenesis and contributes to developing novel therapeutic strategies. Methods: mRNA (GSE52093, GSE153434), miRNA (GSE98770) and single-cell RNA-sequencing (scRNA-seq, GSE213740) datasets of AD were downloaded from GEO database. Args were downloaded from Aging Atlas database. Differentially-expressed Args were determined by intersecting Args and differentially-expressed mRNAs of two mRNA datasets. Cytoscape was used to identify hub genes and construct hub gene regulatory networks related to miRNAs. Seurat and clusterProfiler R package were used for investigating expression patterns of hub genes at single-cell level, and functional analysis, respectively. To validate the cellular expression pattern of hub genes, the same analysis was applied to our own scRNA-seq data. Drugs targeting hub Args were determined using the DGIdb database. Results: HGF, CXCL8, SERPINE1, HIF1A, TIMP1, ESR1 and PLAUR were identified as aging-related hub genes in AD. miR-221-3p was predicted to interact with ESR1. A decreased ESR1 expression in smooth muscle cell subpopulation 4 (SMC4) was observed in AD versus normal aortic tissues, which was validated by sequencing 197,605 aortic cells from 13 AD patients. Additionally, upregulated genes of SMC4 in AD tissues were enriched in the “cellular senescence” pathway. These data indicated that decreased ESR1 might promote SMC4 aging during AD formation. Eleven existing drugs targeting hub genes were identified, including ruxolitinib and filgrastim, which are associated with AD. Conclusions: By sequencing transcriptomic data, this study revealed aging-related hub genes and regulatory network involved in AD formation. Additionally, this study proposed a noteworthy hypothesis that downregulated ESR1 may exacerbate AD by promoting SMC aging, which requires further investigation.

Abstract Background Recent studies have demonstrated a correlation between intestinal flora and the severity of myocardial infarction as well as post-myocardial infarction repair. However, few studies have investigated whether probiotics reduce mortality and improve cardiovascular outcomes in patients with acute myocardial infarction. In this study, we will conduct a randomized controlled trial (RCT) to evaluate the effect of probiotics on in-hospital mortality and the incidence of major adverse cardiovascular events (MACE) in patients with acute myocardial infarction (AMI). Methods This is an open-label, randomized, controlled, superiority clinical trial involving 2594 adult patients who were diagnosed with acute myocardial infarction. Patients will be randomized to (1) receive bifidobacteria triple viable capsule (Bifidobacterium longum, Lactobacillus acidophilus, and Enterococcus faecalis) 840 mg, twice a day, plus standard treatment strategy during the hospital stay, for a maximum of 30 days, or (2) receive the standard treatment strategy and will not take the bifidobacterium triple live capsule. The primary outcome was in-hospital all-cause mortality. Discussion The purpose of this clinical trial is to determine whether probiotics can reduce in-hospital mortality and improve prognosis in patients with AMI, and the results will provide evidence for probiotics as a complementary treatment for AMI. Trial registration Chinese Clinical Trials Registry ChiCTR2000038797. Registered on 2 October 2020.

Heart failure (HF) represents a critical stage of cardiac disease, associated with high morbidity and mortality. Cardiac resynchronization therapy (CRT) has become a pivotal treatment for HF patients with prolonged QRS duration. This therapy employs a biventricular pacing system to correct cardiac electromechanical dyssynchrony, thereby improving cardiac function, symptoms, and prognosis. Numerous clinical trials have consistently highlighted the benefits of CRT in this subgroup, leading to its unanimous recommendation in clinical practice guidelines. However, a significant proportion of patients do not achieve an adequate therapeutic response, despite adherence to these guidelines. As CRT treats patients by correcting cardiac electromechanical dyssynchrony, assessing electrical and mechanical dyssynchrony is crucial in candidate selection. This review explores the evidence, recent clinical practice guidelines, and insight into electrical and mechanical dyssynchrony to optimize CRT candidate selection in HF patients with prolonged QRS duration.

Background and Aims To evaluate the association of Chinese visceral adiposity index (CVAI) and its dynamic trends with risk of renal damage, and to compare its prediction performance with that of other obesity indices. Methods and Results A community-based population with 23 905 participants from Shantou city was included in the cross-sectional analysis. A total of 9,778 individuals from two separated cohort were included in the longitudinal portion. Five patterns of CVAI change were predefined (low-stable, decreasing, moderate, increasing, and persistent-high). Logistic and Cox regressions were used to evaluate the association between CVAI and renal damage. We explored potential mechanisms using the mediating effect method, and the prediction performance was determined by receiver operating characteristic curve analysis. Results from both cross-sectional and longitudinal data revealed a positive and linear association between CVAI and risk of renal damage. Pooled analysis of the two cohorts showed that per unit increase in Z score of CVAI induced 18% increased risk of renal damage (P = .008). Longitudinal trends of CVAI were also associated with renal damage, and the moderate, increasing, and persistent-high patterns showing a higher risk. Blood pressure and glucose had a mediating effect on renal damage induced by CVAI. Among several obesity indices, CVAI was the optimal for predicting renal damage. Conclusion A higher level of immediate CVAI and longitudinal increasing and persistent-high patterns of CVAI were independently associated with increased risk of renal damage. Monitoring immediate level and long-term trend of CVAI may contribute to the prevention of renal damage.

BackgroundGlobally, most deaths result from cardiovascular diseases, particularly ischemic heart disease. COVID-19 affects the heart, worsening existing heart conditions and causing myocardial injury. The mechanistic link between COVID-19 and acute myocardial infarction (AMI) is still being investigated to elucidate the underlying molecular perspectives.MethodsGenetic risk assessment was conducted using two-sample Mendelian randomization (TSMR) to determine the causality between COVID-19 and AMI. Weighted gene co-expression network analysis (WGCNA) and machine learning were used to discover and validate shared hub genes for the two diseases using bulk RNA sequencing (RNA-seq) datasets. Additionally, gene set enrichment analysis (GSEA) and single-cell RNA-seq (scRNA-seq) analyses were performed to characterize immune cell infiltration, communication, and immune correlation of the hub genes. To validate the findings, the expression patterns of hub genes were confirmed in clinical blood samples collected from COVID-19 patients with AMI.ResultsTSMR did not find evidence supporting a causal association between COVID-19 or severe COVID-19 and AMI. In the bulk RNA-seq discovery cohorts for both COVID-19 and AMI, WGCNA’s intersection analysis and machine learning identified TLR4 and ABCA1 as significant hub genes, demonstrating high diagnostic and predictive value in the RNA-seq validation cohort. Single-gene GSEA and single-sample GSEA (ssGSEA) revealed immune and inflammatory roles for TLR4 and ABCA1, linked to various immune cell infiltrations. Furthermore, scRNA-seq analysis unveiled significant immune dysregulation in COVID-19 patients, characterized by altered immune cell proportions, phenotypic shifts, enhanced cell-cell communication, and elevated TLR4 and ABCA1 in CD16 monocytes. Lastly, the increased expression of TLR4, but not ABCA1, was validated in clinical blood samples from COVID-19 patients with AMI.ConclusionNo genetic causal link between COVID-19 and AMI and dysregulated TLR4 and ABCA1 may be responsible for the development of immune and inflammatory responses in COVID-19 patients with AMI.

AimThe aim of this study is to evaluate the association between serum sodium concentrations at hospital admission and all-cause mortality within 365 days post-discharge in patients with atrial fibrillation (AF) without heart failure (HF).MethodsThe prospective cohort study enrolled 1,446 patients with AF without HF between November 2018 and October 2020. A follow-up was performed 30, 90, 180, and 365 days after enrollment through outpatient visits or telephone interviews. All-cause mortality was estimated in three groups according to serum sodium concentrations: hyponatremia (< 135 mmol/L), normonatremia (135–145 mmol/L), and hypernatremia (> 145 mmol/L). We estimated the risk of all-cause mortalities using univariable and multivariable Cox proportional hazards models with normonatremia as the reference.ResultsThe all-cause mortalities of hyponatremia, normonatremia, and hypernatremia were 20.6, 9.4, and 33.3% within 365 days post-discharge, respectively. In the univariable analysis, hyponatremia (HR: 2.19, CI 1.5–3.2) and hypernatremia (HR: 4.03, CI 2.32–7.02) increased the risk of all-cause mortality. The HRs for hyponatremia and hypernatremia were 1.55 (CI 1.05–2.28) and 2.55 (CI 1.45–4.46) after adjustment for age, diabetes mellitus, loop diuretics, antisterone, antiplatelet drugs, and anticoagulants in the patients with AF without HF. The association between serum sodium concentrations and the HRs of all-cause mortality was U-shaped.ConclusionDysnatremia at hospital admission was an independent factor for all-cause mortality in patients with AF without HF within 365 days post-discharge.

Introduction Immune-inflammatory response plays a key role in the pathogenesis of atherosclerosis. IgG N-glycosylation is reported to be associated with the 10-year atherosclerotic cardiovascular disease risk score and subclinical atherosclerosis. However, the relationship of IgG glycosylation with actual clinical cardiovascular disease (CVD) events and plaque phenotypes has rarely been investigated. Therefore, this study aims to understand whether IgG glycosylation traits are correlated with actual clinical CVD events and plaque phenotypes.Methods and analysis Designed to verify the efficacy of IgG glycosylation as a risk for CVD events and screen potential biomarkers of CVD to prevent atherosclerosis occurrence, this longitudinal prospective cohort study will be conducted at the First Affiliated Hospital of Shantou University Medical College, China. In total, 2720 participants routinely examined by carotid ultrasound will be divided into different groups according to plaque phenotype characteristics. Ultra-performance liquid chromatography will be performed to separate and detect IgG N-glycans in serum collected at baseline and at the end of the first, second and third years. The primary outcome is the actual clinical CVD composite events, including non-fatal myocardial infarction, death due to coronary heart disease, and fatal or non-fatal stroke.Ethics and dissemination The Clinical Ethics Committee of the First Affiliated Hospital of Shantou University Medical College approved this study (number: B-2021-127). Findings of this study will be submitted for publication in peer-reviewed journals.Trial registration number ChiCTR2100048740.

Background: The association between impaired fasting glucose level (IFG) and coronary heart disease (CAD) remain controversial. In the present study, we sought to ascertain a relationship of IFG with the number of diseased coronary artery and occurrence of myocardial infarction, among CAD cases.Methods: We studied 1,451 consecutive no-diabetic patients who underwent coronary angiography at the First Affiliated Hospital of Shantou University Medical College in Southern China. Demographic, biochemical, clinical and angiographic data were collected.Results: The prevalence of IFG was higher in patients with angiographically confirmed CAD than in subjects without angiographic evidence of CAD (33.4 versus 28.2%, p = 0.034). Compared with CAD cases without IFG, CAD cases with IFG had a higher odds ratio (OR) of having triple-vessel disease as opposed to having single- or double-vessel disease [OR = 1.53, 95% confidence interval (CI) = 1.13–2.07]. Furthermore, the occurrence of MI was higher in CAD cases with IFG than in CAD cases without IFG (OR = 1.73, 95% CI = 1.27–2.36).Conclusions: There is an association between IFG and a predisposition to severe CAD indicated by triple vessel disease or myocardial infarction.

BackgroundRecent studies of fibroblast growth factor 21 (FGF21), first recognized as a regulator of glucose and lipid metabolism, have found that the level of in serum FGF21 is associated with the prognosis of many cardiovascular diseases, but its relationship to acute heart failure (AHF) patients remains unknown. Our study aimed to investigate whether circulating FGF21 could predict the short-term prognosis of AHF patients.MethodsFour hundred and two AHF patients and 19 healthy controls were recruited into the prospective cohort study, and blood samples of participants were collected, in tubes without anticoagulant, within the first 24 h after hospital admission. Serum FGF21 levels were detected by enzyme-linked immunosorbent assay (ELISA). All patients were followed-up at least 6 months after discharge. The primary endpoint was all-cause death, and secondary endpoint was a composite endpoint of death and heart failure readmission. Mortality and composite end point events were analyzed using Kaplan-Meier curves. ROC curves compared the difference between the FGF21 and NT-proBNP in predicting 3- and 6-months mortality. Time-to-event data were evaluated using Kaplan-Meier estimation and Cox proportional hazards models.ResultsIn the present study, the serum FGF21 concentrations were significantly higher in the 402 AHF patients enrolled, compared with the 19 healthy controls (p < 0.001). The average age was 70 (±12) years, and 58% were males. Participants were divided into two groups according to the median FGF21 level (262 pg/ml): a high FGF21 group (n = 201, FGF21 ≥ 262 pg/ml) and low FGF21 group (n = 201, FGF21

Abstract Gastric cancer (GC) is the 5th most prevalent cancer and the 4th primary cancer-associated mortality globally. As the first identified m6A demethylase for removing RNA methylation modification, fat mass and obesity-associated protein (FTO) plays instrumental roles in cancer development. Therefore, we study the biological functions and oncogenic mechanisms of FTO in GC tumorigenesis and progression. In our study, FTO expression is obviously upregulated in GC tissues and cells. The upregulation of FTO is associated with advanced nerve invasion, tumor size, and LNM, as well as the poor prognosis in GC patients, and promoted GC cell viability, colony formation, migration and invasion. Mechanistically, FTO targeted specificity protein 1 and Aurora Kinase B, resulting in the phosphorylation of ataxia telangiectasia mutated and P38 and dephosphorylation of P53. In conclusion, the m6A demethylase FTO promotes GC tumorigenesis and progression by regulating the SP1-AURKB-ATM pathway, which may highlight the potential of FTO as a diagnostic biomarker for GC patients’ therapy response and prognosis.

This paper aims to explore the optimum modelling data for predicting cerebrovascular disease mortality in China by using GM(1,1) model. Also, it will discuss the applicability of grey relational analysis to analyze the related factors of cerebrovascular disease mortality. The subsequence sets with different data lengths were used to establish rolling GM(1,1), and predictive efficiency was judged by prediction error. Grey relational analysis was used to analyze the interrelationships between population, health expenses, environmental pollution factors and mortality. Results show that GM (1,1) grey prediction model can well predict the mortality of cerebrovascular diseases in China, especially when the modelling data is 8, the overall prediction effect is the best. In recent years, the prediction effect of 4 or 5 data modelling is better than that of more data modelling. Grey relational analysis suggests that population aging has a greater impact on the mortality of cerebrovascular diseases than other risk factors. The grey system theory is suitable for the epidemiological study of cerebrovascular diseases. [ABSTRACT FROM AUTHOR]

Summary: Gastric cancer (GC) is a prevalent digestive tract malignant tumor characterized by an insidious onset, ease of metastasis, rapid growth, and poor prognosis. Here, we report that fibronectin type III domain containing 1 (FNDC1) has high expression in GC and indicates poor outcomes in patients with GC. FNDC1 over-expression or knockdown promotes or inhibits tumorigenesis and metastasis, respectively. The expression of FNDC1 is upregulated by TWIST1, strengthening its interaction with Gβγ and VEGFR2. The formation of the trimers, TWIST1 plus Gβγ and VEGFR2, increases VEGFR2 phosphorylation and Gβγ trafficking, which activates RAS-MAPK and PI3K-AKT signaling, benefiting GC progression. In this study, we demonstrated that arsenite can efficiently suppress FNDC1 expression, attenuating the formation of the trimers and downstream pathways. Altogether, our results indicate that FNDC1 might be a promising target for clinical treatment and prognostic judgment, while FNDC1 inhibition by arsenite provides a new opportunity for overcoming this fatal disease.