The role of body composition in left ventricular remodeling, reverse remodeling, and clinical outcomes for heart failure with mildly reduced ejection fraction: more knowledge to the "obesity paradox".

BACKGROUND: Although the "obesity paradox" is comprehensively elucidated in heart failure (HF) with reduced ejection fraction (HFrEF) and HF with preserved ejection fraction (HFpEF), the role of body composition in left ventricular (LV) remodeling, LV reverse remodeling (LVRR), and clinical outcomes is still unclear for HF with mildly reduced ejection fraction (HFmrEF). METHODS: Our study is a single-centre, prospective, and echocardiography-based study. Consecutive HFmrEF patients, defined as HF patients with a left ventricular ejection fraction (LVEF) between 40 and 49%, between January 2016 to December 2021 were included. Echocardiography was re-examined at 3-, 6-, and 12-month follow-up to assess the LVRR dynamically. Body mass index (BMI), fat mass, fat-free mass, percent body fat (PBF), CUN-BAE index, and lean mass index (LMI) were adopted as anthropometric parameters in our study to assess body composition. The primary outcome was LVRR, defined as: (1) a reduction higher than 10% in LV end-diastolic diameter index (LVEDDI), or a LVEDDI < 33 mm/m2, (2) an absolute increase of LVEF higher than 10 points compared with baseline echocardiogram, or a follow-up LVEF ≥50%. The secondary outcome was a composite of re-hospitalization for HF or cardiovascular death. RESULTS: A total of 240 HFmrEF patients were enrolled in our formal analysis. After 1-year follow-up based on echocardiography, 113 (47.1%) patients developed LVRR. Patients with LVRR had higher fat mass (21.7 kg vs. 19.3 kg, P = 0.034) and PBF (28.7% vs. 26.6%, P = 0.047) compared with those without. The negative correlation between anthropometric parameters and baseline LVEDDI was significant (all P < 0.05). HFmrEF patients with higher BMI, fat mass, PBF, CUN-BAE index, and LMI had more pronounced and persistent increase of LVEF and decline in LV mass index (LVMI). Univariable Cox regression analysis revealed that higher BMI (HR 1.042, 95% CI 1.002-1.083, P = 0.037) and fat mass (HR 1.019, 95% CI 1.002-1.036, P = 0.026) were each significantly associated with higher cumulative incidence of LVRR for HFmrEF patients, while this relationship vanished in the adjusted model. Mediation analysis indicated that the association between BMI and fat mass with LVRR was fully mediated by baseline LV dilation. Furthermore, higher fat mass (aHR 0.957, 95% CI 0.917-0.999, P = 0.049) and PBF (aHR 0.963, 95% CI 0.924-0.976, P = 0.043) was independently associated with lower risk of adverse clinical events. CONCLUSIONS: Body composition played an important role in the LVRR and clinical outcomes for HFmrEF. For HFmrEF patients, BMI and fat mass was positively associated with the cumulative incidence of LVRR, while higher fat mass and PBF predicted lower risk of adverse clinical events but not LMI.

The Regulatory Role of Myomaker in the Muscle Growth of the Chinese Perch (Siniperca chuatsi).

The fusion of myoblasts is a crucial stage in the growth and development of skeletal muscle. Myomaker is an important myoblast fusion factor that plays a crucial role in regulating myoblast fusion. However, the function of Myomaker in economic fish during posthatching has been poorly studied. In this study, we found that the expression of Myomaker in the fast muscle of Chinese perch (Siniperca chuatsi) was higher than that in other tissues. To determine the function of Myomaker in fast muscle, Myomaker-siRNA was used to knockdown Myomaker in Chinese perch and the effect on muscle growth was determined. The results showed that the growth of Chinese perch was significantly decreased in the Myomaker-siRNA group. Furthermore, both the diameter of muscle fibers and the number of nuclei in single muscle fibers were significantly reduced in the Myomaker-siRNA group, whereas there was no significant difference in the number of BrdU-positive cells (proliferating cells) between the control and the Myomaker-siRNA groups. Together, these findings indicate that Myomaker may regulate growth of fast muscle in Chinese perch juveniles by promoting myoblast fusion rather than proliferation.

Gender differences in the relationship between serum uric acid and the long-term prognosis in heart failure: a nationwide study.

BACKGROUND: Serum uric acid (SUA) is an important pathogenetic and prognostic factor for heart failure (HF). Gender differences are apparent in HF. Furthermore, gender differences also exist in the association between SUA and prognosis in various cardiovascular diseases. However, the gender difference for SUA in the prediction of long-term prognosis in HF is still ambiguous. METHODS: A total of 1593 HF patients (897 men, 696 women) from the National Health and Nutrition Examination Survey (NHANES) 1999-2018 cycle were enrolled in our final analysis. Participants were categorized according to gender-specific SUA tertile. We assessed the association between SUA and long-term prognosis of HF patients, defined as all-cause mortality and cardiovascular mortality, in different genders via Kaplan-Meier curve analysis, Cox proportional hazard model, and Fine-Gray competing risk model. The restricted cubic spline (RCS) was performed to investigate the dose-response relationship between SUA and outcomes. RESULTS: Gender differences exist in demographic characteristics, clinical parameters, laboratory tests, and medication of HF patients. After a median follow-up of 127 months (95% CI 120-134 months), there were 853 all-cause deaths (493 events in men, 360 events in women) and 361 cardiovascular deaths (206 events in men, 155 events in women). Kaplan-Meier analysis showed that SUA had gender difference in the prediction of cardiovascular mortality (Log-rank p < 0.001, for male, Log-rank p = 0.150, for female), but not in all-cause mortality. Multivariate Cox regression analysis revealed that elevated SUA levels were associated with higher all-cause mortality and cardiovascular mortality in men (HR 1.11, 95% CI 1.05-1.18, p < 0.001, for all-cause death; HR 1.18, 95% CI 1.09-1.28, p < 0.001, for cardiovascular death), but not in women (HR 1.05, 95% CI 0.98-1.12, p = 0.186, for all-cause death; HR 1.01, 95% CI 0.91-1.12, p = 0.902, for cardiovascular death). Even using non-cardiovascular death as a competitive risk, adjusted Fine-Gray model also illustrated that SUA was an independent predictor of cardiovascular death in men (SHR 1.17, 95% CI 1.08-1.27, p < 0.001), but not in women (SHR 0.98, 95% CI 0.87 - 1.10, p = 0.690). CONCLUSIONS: Gender differences in the association between SUA and long-term prognosis of HF existed. SUA was an independent prognostic predictor for long-term outcomes of HF in men, but not in women.

Transcriptomic analysis reveals the potential crosstalk genes and immune relationship between Crohn's disease and atrial fibrillation.

Background: At present, there is a paucity of research on the link between Crohn's disease (CD) and atrial fibrillation (AF). Nevertheless, both ailments are thought to entail inflammatory and autoimmune processes, and emerging evidence indicates that individuals with CD may face an elevated risk of AF. To shed light on this issue, our study seeks to explore the possibility of shared genes, pathways, and immune cells between these two conditions. Methods: We retrieved the gene expression profiles of both CD and AF from the Gene Expression Omnibus (GEO) database and subjected them to analysis. Afterward, we utilized the weighted gene co-expression network analysis (WGCNA) to identify shared genes, which were then subjected to further Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. Furthermore, we employed a rigorous analytical approach by screening hub genes through both least absolute shrinkage and selection operator (LASSO) regression and support vector machine (SVM), and subsequently constructing a receiver operating characteristic (ROC) curve based on the screening outcomes. Finally, we utilized single-sample gene set enrichment analysis (ssGSEA) to comprehensively evaluate the levels of infiltration of 28 immune cells within the expression profile and their potential association with the shared hub genes. Results: Using the WGCNA method, we identified 30 genes that appear to be involved in the pathological progression of both AF and CD. Through GO enrichment analysis on the key gene modules derived from WGCNA, we observed a significant enrichment of pathways related to major histocompatibility complex (MHC) and antigen processing. By leveraging the intersection of LASSO and SVM algorithms, we were able to pinpoint two overlapping genes, namely CXCL16 and HLA-DPB1. Additionally, we evaluated the infiltration of immune cells and observed the upregulation of CD4+ and CD8+ T cells, as well as dendritic cells in patients with AF and CD. Conclusions: By employing bioinformatics tools, we conducted an investigation with the objective of elucidating the genetic foundations that connect AF and CD. This study culminated in the identification of CXCL16 and HLA-DPB1 as the most substantial genes implicated in the development of both disorders. Our findings suggest that the immune responses mediated by CD4+ and CD8+ T cells, along with dendritic cells, may hold a crucial role in the intricate interplay between AF and CD.

Impact of short-term starvation and refeeding on the expression of KLF15 and regulatory mechanism of branched-chain amino acids metabolism in muscle of Chinese soft-shelled turtle (Pelodiscus sinensis).

The branched-chain amino acids (BCAA) play an important role in muscle energy metabolism, and Krüppel-like factor 15 (KLF15) is an essential regulator of BCAA metabolism in muscle under nutritional deficiency. In this study, we analyzed the effect of normal feeding (starvation for 0 day), starvation for 3, 7, 10, 15 days, and refeeding for 7 days after 15 days of starvation on the expression of KLF15 and BCAA metabolism in muscle of Chinese soft-shelled turtles by a fasting-refeeding trial. The results showed that the level of KLF15 transcription was increased first and then decreased in muscle during short-term starvation, and the protein level was gradually increased. Both the mRNA and protein level of the KLF15 returned to normal feeding level after refeeding for 7 days. The changing trend of the activities of branched-chain aminotransferase (BCAT) and alanine aminotransferase (ALT) was consistent to that of KLF15 mRNA, but at the transcription level, the expression of BCAT mRNA was consistent with the change of enzyme activity as well as ALT continued to increase in muscle under starvation. In addition, BCAA content showed a trend that decreased first and then increased under starvation, while the alanine (Ala) was the contrary. The above results indicated that the regulatory role of KLF15 in BCAA catabolism of muscle in Chinese soft-shelled turtles under nutritional deficiency, which might be activated the catabolism of BCAA in muscle to provide energy and maintain the homeostasis by KLF15-BACC signaling axis.