Different physical exercise modalities have been widely studied in patients having heart failure with preserved ejection fraction (HFpEF) but with variably reported findings. We, therefore, conducted a systematic review and meta-analysis to evaluate whether the efficacy of physical activity in the management of HFpEF is related to exercise modalities. PubMed and Embase were searched up to July 2021. The eligible studies included randomized controlled trials that identified effects of physical exercise on patients with HFpEF. Sixteen studies were included to evaluate the efficiency of physical exercise in HFpEF. A pooled analysis showed that exercise training significantly improved peak oxygen uptake (VO 2 ), ventilatory anaerobic threshold, distance covered in the 6-minute walking test, the ratio of early diastolic mitral inflow to annular velocities, the Short Form 36 physical component score, and the Minnesota Living with Heart Failure Questionnaire total score. However, the changes in other echocardiographic parameters including the ratio of peak early to late diastolic mitral inflow velocities, early diastolic mitral annular velocity, and left atrial volume index were not significant. Both high-intensity and moderate-intensity training significantly improved exercise capacity (as defined by peak VO 2 ), with moderate-intensity exercise having a superior effect. Furthermore, exercise-induced improvement in peak VO 2 was partially correlated with exercise duration. Physical exercise could substantially improve exercise capacity, quality of life, and some indicators of cardiac diastolic function in patients with HFpEF. A protocol of moderate-intensity exercise training lasting a longer duration might be more beneficial compared with high-intensity training for patients with HFpEF.

Myocardial ischemia is the major cause of death worldwide, and reperfusion is the standard intervention for myocardial ischemia. However, reperfusion may cause additional damage, known as myocardial reperfusion injury, for which there is still no effective therapy. This study aims to analyze the landscape of researches concerning myocardial reperfusion injury over the past three decades by machine learning. PubMed was searched for publications from 1990 to 2020 indexed under the Medical Subject Headings (MeSH) term “myocardial reperfusion injury” on 13 April 2021. MeSH analysis and Latent Dirichlet allocation (LDA) analyses were applied to reveal research hotspots. In total, 14,822 publications were collected and analyzed in this study. MeSH analyses revealed that time factors and apoptosis were the leading terms of the pathogenesis and treatment of myocardial reperfusion injury, respectively. In LDA analyses, research topics were classified into three clusters. Complex correlations were observed between topics of different clusters, and the prognosis is the most concerned field of the researchers. In conclusion, the number of publications on myocardial reperfusion injury increases during the past three decades, which mainly focused on prognosis, mechanism, and treatment. Prognosis is the most concerned field, whereas studies on mechanism and treatment are relatively lacking.

Background & Objective Selenium was one of the essential trace elements that played a pivotal role in human health. Although previous studies have investigated the relationship between selenium and non-alcoholic fatty liver disease (NAFLD) and fibrosis, these findings were still inconclusive. Our study was aimed to explore the association between blood selenium level and NAFLD and advanced liver fibrosis diagnosed by vibration controlled transient elastography (VCTE) in US adults. Methods All data were extracted from National Health and Nutrition Examination Survey database (2017–2018). Participants were divided into four groups according to quartile of blood selenium level. Liver stiffness and controlled attenuation parameter (CAP) were measured by VCTE. Multiple logistic regression models and subgroup analyses were conducted to determine the association between blood selenium level and NAFLD and advanced liver fibrosis diagnosed by a variety of methods. Results A total of 3336 participants were enrolled in main analysis. In multiple logistic regression models, the higher blood selenium level (>205.32, ≤453.62 μg/L) had a significant positive association with NAFLD (β = 1.31). Moreover, high blood selenium level had significantly inversely association to advanced liver fibrosis (β = 0.61). In subgroup analysis, the main inversely correlation between blood selenium and advanced liver fibrosis was found in males with high blood selenium level. Despite dietary selenium intake being adjusted or in different subgroups, the associations between blood selenium level and NAFLD/advanced liver fibrosis remained significant. Conclusions This study showed that blood selenium level were positively association with NAFLD among US population. Participants with lower blood selenium level showed a higher percentage of advanced liver fibrosis. Blood selenium is more likely to cause NAFLD and liver fibrosis due to imbalances in selenium homeostasis rather than dietary selenium intake. Key messages High blood selenium level was association with NAFLD diagnosed by vibration controlled transient elastography. Participants with lower blood selenium level had high percentage of advanced liver fibrosis. NAFLD and liver fibrosis are caused by an imbalance of selenium homeostasis, not by dietary selenium intake.

The senescence of vascular endothelial cells (ECs) is characterized as a hallmark of vascular aging, which leads to the initiation, progress, and advancement of cardiovascular diseases. However, the mechanism of the ECs senescence remains elusive. In this study, thoracic aortas were separated from young (8-week-old) and aged (18-month-old) mice. Decreased Ctsl expression and increased vascular remodeling were observed in senescent aorta. H2O2 was used to induce human umbilical vein endothelial cells (HUVECs) senescence, as shown by increased SA-β-gal positive cells and upregulated p21 level. CTSV significantly decreased after H2O2 treatment, while over-expression of CTSV by adenovirus reduced cellular senescence. RNA sequencing analysis was conducted subsequently, and ALDH1A2 was observed to significantly increased in H2O2 group and decreased after over-expression of CTSV. This result was further confirmed by RT-PCR and WB. Moreover, over-expression of CTSV reduced the increase of ERK1/2 and AKT phosphorylation induced by H2O2. Additionally, retinoic acid (RA), the major production of ALDH1A2, was added to CTSV over-expressed senescent HUVECs. Administration of RA activated AKT and ERK1/2, induced the expression of p21, and enhanced SA-β-gal positive cells, while not affecting the expression of CTSV and ALDH1A2. These results were further confirmed in doxorubicin (DOX)-induced senescent ECs. In conclude, we have identified that Ctsl/CTSV plays a key role in ECs senescence by regulating ALDH1A2 to activate AKT/ ERK1/2-P21 pathway. Therefore, targeting Ctsl/CTSV may be a potential therapeutic strategy in EC senescence.

BackgroundAs a cellular process, senescence functions to prevent the proliferation of damaged, old and tumor-like cells, as well as participate in embryonic development, tissue repair, etc. This study aimed to analyze the themes and topics of the scientific publications related to cellular senescence in the past three decades by machine learning.MethodsThe MeSH term “cellular senescence” was used for searching publications from 1990 to 2021 on the PubMed database, while the R platform was adopted to obtain associated data. A topic network was constructed by latent Dirichlet allocation (LDA) and the Louvain algorithm.ResultsA total of 21,910 publications were finally recruited in this article. Basic studies (15,382, 70.21%) accounted for the most proportion of publications over the past three decades. Physiology, drug effects, and genetics were the most concerned MeSH terms, while cell proliferation was the leading term since 2010. Three senolytics were indexed by MeSH terms, including quercetin, curcumin, and dasatinib, with the accumulated occurrence of 35, 26, and 22, separately. Three clusters were recognized by LDA and network analyses. Telomere length was the top studied topic in the cluster of physiological function, while cancer cell had been a hot topic in the cluster of pathological function, and protein kinase pathway was the most popular topic in the cluster of molecular mechanism. Notably, the cluster of physiological function showed a poor connection with other clusters.ConclusionCellular senescence has obtained increasing attention over the past three decades. While most of the studies focus on the pathological function and molecular mechanism, more researches should be conducted on the physiological function and the clinical translation of cellular senescence, especially the development and application of senotherapeutics.