An insight into the causal relationship between sarcopenia-related traits and venous thromboembolism: A mendelian randomization study.

BACKGROUND: As a geriatric syndrome, sarcopenia has a high prevalence in the old population and represents an impaired state of health with adverse health outcomes. A strong clinical interest in its relationship with venous thromboembolism (VTE), which is a complex trait disease with a heterogeneous annual incidence rate in different countries, has emerged. The relationship between sarcopenia and venous thromboembolism has been reported in observational studies but the causality from sarcopenia to VTE remained unclarified. We aimed to assess the causal effect of sarcopenia on the risk of VTE with the two-sample Mendelian randomization (MR) method. METHODS: Two sets of single-nucleotide polymorphisms (SNPs), derived from two published genome-wide association study (GWAS) meta-analyses and genetically indexing muscle weakness and lean muscle mass separately, were pooled into inverse variance weighted (IVW), weighted median and MR-Egger analyses. RESULTS: No evidence was found for the causal effect of genetically predicted muscle weakness (IVW: OR = 0.90, 95% CI = 0.76-1.06, p = 0.217), whole body lean mass (IVW: OR = 1.01, 95% CI = 0.87-1.17, p = 0.881) and appendicular lean mass (IVW: OR = 1.13, 95% CI = 0.82-1.57, p = 0.445) on the risk of VTE. However, both genetically predicted whole-body lean mass and appendicular lean mass can causally influence diabetes mellitus (IVW of whole-body lean mass: OR = 0.87, 95% CI = 0.78-0.96, p = 0.008; IVW of appendicular lean mass: OR = 0.71, 95% CI = 0.54-0.94, p = 0.014) and hypertension (IVW of whole-body lean mass: OR = 0.92, 95% CI = 0.87-0.98, p = 0.007; IVW of appendicular lean mass: OR = 0.84, 95% CI = 0.73-0.96, p = 0.013). CONCLUSIONS: Genetically predicted sarcopenia does not causally influence VTE directly, but it might still have an indirect effect on VTE incidence via diabetes mellitus and hypertension.

Effects of high intensity interval training versus moderate intensity continuous training on exercise capacity and quality of life in patients with heart failure: A systematic review and meta-analysis.

INTRODUCTION AND AIMS: High intensity interval training (HIIT) is considered as an alternative exercise modality to moderate intensity continuous training (MICT) for heart failure (HF) patients. Yet a growing number of trials demonstrated inconsistent findings about the effectiveness of HIIT versus MICT until SMARTEX study and OptimEx-Clin study have made a consistent negative conclusion that HIIT was not superior to MICT. The aim of this study was to conduct a meta-analysis involving a subgroup analysis of total exercise time (TET) and disease categories of HF to investigate if TET could affect the superiority of HIIT when compared with MICT. METHODS AND RESULTS: An electronic literature search of Pubmed, Embase, Cochrane Central Register of Controlled Trials and ClinicalTrials.gov was performed for this review. 16 studies of 661 patients were finally pooled into quantitative synthesis. The weighted mean difference (WMD) and standard mean difference (SMD) with 95% confidence interval (CI) were calculated for quantitative synthesis of outcomes. HIIT was superior to MICT in improving peak oxygen consumption (Peak VO2) (WMD: 1.68 ml · kg-1 · min-1 95% CI: 0.81 to 2.55 n = 661). The subgroup analysis of TET showed that HIIT was superior to MICT in improving Peak VO2 in "short time" subgroup (WMD: 1.61 ml · kg-1 · min-1 95% CI: 0.45 to 2.77 n = 166) and in "medium time" subgroup (WMD: 1.74 ml · kg-1 · min-1 95% CI: 0.53 to 2.95 n = 420), and that there was no significant difference between HIIT and MICT in improving Peak VO2 in "long time" subgroup (WMD: 0.62 ml · kg-1 · min-1 95% CI: -1.34 to 2.58 n = 75). CONCLUSIONS: The superiority of HIIT to MICT in improving Peak VO2 arose in a short to medium length of TET whereas it was effaced by an increment of TET. This "paradox" of TET on HIIT versus MICT might be due to the increasing poor adherence to target exercise intensity over time. TRIAL REGISTRATION: PROSPERO registration number: CRD42022375076.

The inhibitory role of microRNA-141-3p in human cutaneous melanoma growth and metastasis through the fibroblast growth factor 13-mediated mitogen-activated protein kinase axis.

Human cutaneous melanoma (CM) is a highly invasive malignancy arising from melanocytes, and accompanied by ever-increasing incidence and mortality rates worldwide. Interestingly, microRNAs (miRNAs) possess the ability to regulate CM cell biological functions, resulting in the aggressive progression of CM. Nevertheless, a comprehensive understanding of the underlying mechanism remains elusive. Accordingly, the current study sought to elicit the functional role of miR-141-3p in human CM cells in association with fibroblast growth factor 13 (FGF13) and the MAPK pathway. First, miR-141-3p expression patterns were detected in human CM tissues and cell lines, in addition to the validation of the targeting relationship between miR-141-3p and FGF13. Subsequently, loss- and gain-of-function studies of miR-141-3p were performed to elucidate the functional role of miR-141-3p in the malignant features of CM cells. Intriguingly, our findings revealed that FGF13 was highly expressed, whereas miR-141-3p was poorly expressed in the CM tissues and cells. Further analysis highlighted FGF13 as a target gene of miR-141-3p. Meanwhile, overexpression of miR-141-3p inhibited the proliferative, invasive, and migratory abilities of CM cells, while enhancing their apoptosis accompanied by downregulation of FGF13 and the MAPK pathway-related genes. Collectively, our findings highlighted the inhibitory effects of miR-141-3p on CM cell malignant properties via disruption of the FGF13-dependent MAPK pathway, suggesting a potential target for treating human CM.