Heart failure with Sarcopenia: A Bibliometric review from 1995 to 2022.

This study aimed to dynamically track the priorities and potential research hotspots in the field of heart failure with sarcopenia. Using CiteSpace, we analyzed the literature on heart failure with sarcopenia from the Web of Science database from 1995 to 2022. The analysis encompassed 507 records, revealing an overall upward trend in annual publication volume. Europe and the United States emerged as the primary regions for publishing, particularly driven by contributions from developed countries such as the United States, Germany, and Italy. Productive institutions included the Charite Universitatsmedizin Berlin, University Medical Center Gottingen, the German Center for Cardiovascular Research (DZHK), Universita Cattolica del Sacro Cuore, and the National Institute on Aging (NIA). Noteworthy academic groups have formed around these institutions; von Haehling S, Anker Stefan D, Springer J, and Doehner W frequently collaborated. The core journals that frequently published articles in this area included Circulation, European Heart Journal, and The Journals of Gerontology Series A-Biological Sciences and Medical Sciences. Based on the keyword analysis, we identified three key research areas. First, the diagnosis and definition of sarcopenia emerged as significant themes. Second, researchers have focused on exploring the mechanisms underlying heart failure with sarcopenia, including inflammation, insulin resistance, and oxidative stress. Finally, treatment strategies, such as physical activity and nutritional support, constitute another critical research theme. Furthermore, potential research hotspots within this field include clinical randomized controlled trials, investigations into inflammatory mechanisms, cardiac rehabilitation, studies on physical activity, androgen receptor modulators, and investigations into clinical outcomes such as cognitive impairment.

Qi-Po-Sheng-Mai granule ameliorates Ach-CaCl2 -induced atrial fibrillation by regulating calcium homeostasis in cardiomyocytes.

BACKGROUND: Atrial fibrillation (AF) is one of the most common arrhythmias encountered in clinical settings. Currently, the pathophysiology of AF remains unclear, which severely limits the effectiveness and safety of medical therapies. The Chinese herbal formula Qi-Po-Sheng-Mai Granule (QPSM) has been widely used in China to treat AF. However, its pharmacological and molecular mechanisms remain unknown. PURPOSE: The purpose of this study was to investigate the molecular mechanisms and potential targets of QPSM for AF. STUDY DESIGN AND METHODS: The AF model was induced by Ach (66 µg/ml) and CaCl2 (10 mg/kg), and the dose of 0.1 ml/100 g was injected into the tail vein for 5 weeks. QPSM was administered daily at doses of 4.42 and 8.84 g/kg, and amiodarone (0.18 g/kg) was used as the positive control. The effect of QPSM on AF was assessed by electrocardiogram, echocardiography, and histopathological analysis. Then, we employed network pharmacology with single nucleus RNA sequencing (snRNA-Seq) to investigate the molecular mechanisms and potential targets of QPSM for AF. Furthermore, high performance liquid chromatography (HPLC) method was used for component analysis of QPSM, and molecular docking was used to verify the potential targets. Using the IonOptix single cell contraction and ion synchronization test equipment, single myocyte length and calcium ion variations were observed in real time. The expression levels of calcium Transporter-related proteins were detected by western blot and immunohistochemistry. RESULTS: Based on an Ach-CaCl2-induced AF model, we found that QPSM treatment significantly reduced atrial electrical remodeling-related markers, such as AF inducibility and duration, and attenuated atrial dilation and fibrosis. Network pharmacology identified 52 active ingredients and 119 potential targets for QPSM in the treatment of AF, and 45 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were enriched, among which calcium pathway had the greatest impact. Using single nucleus sequencing (snRNA-seq), we identified cardiomyocytes as the most differentially expressed in response to drug treatment, with nine differentially expressed genes enriched in calcium signaling pathways. High performance liquid chromatography and molecular docking confirmed that the core components of QPSM strongly bind to the key factors in the calcium signaling pathway. Additional experiments have shown that QPSM increases calcium transients (CaT) and contractility in the individual cardiomyocyte. This was accomplished by increasing the expression of CACNA1C and SERCA2a and decreasing the expression of CAMK2B and NCX1. CONCLUSION: The present study has systematically elucidated the role of QPSM in maintaining calcium homeostasis in cardiomyocytes through the regulation of calcium transporters, which could lead to new drug development ideas for AF.

Knowledge Domain and Emerging Trends of Glucagon-Like Peptide 1 Receptor Agonists in Cardiovascular Research: A Bibliometric Analysis.

Patients with type 2 diabetes (T2DM) are more likely to have cardiovascular disease (CVD). Glucose-lowering drugs with cardiovascular benefits represented by Glucagon-like peptide 1 receptor agonists (GLP1RAs) were discovered and gained more and more attention. Data from 1985 to the 2021 were downloaded in the Web of Science Core Collection (WoSCC) database. CiteSpaceV was used for bibliometric analysis to find research hotspots and frontiers. The 2088 papers were published by 74 countries (regions), 876 institutions, and 2203 authors. The annual publications increased over time from 2005 to 2020. DIABETES OBESITY METABOLISM published the most papers. The USA and China were the top 2 productive nations. The leading institution was the University of Copenhagen, and the most productive researcher was John B Buse. The most cited paper is "Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes" (by Marso SP, 2016). The research hotspots include the effects of GLP1RA on cardiovascular outcomes, efficacy, complicated metabolic abnormalities, protective mechanisms, and other novel anti-diabetic drugs for cardiovascular protection. Research frontiers include cardiovascular studies on semaglutide, as well as the most prominent research approach in the field-placebo-controlled trial. Numerous countries, institutions, and authors have focused on GLP1RA in cardiovascular research and a great deal of literature has been published. Five research hotspots and two frontiers illustrate the current status and emerging trends of GLP1RA in cardiovascular research. The cardiovascular effects and clinical efficacy of GLP1RA are a current hot topic that is rapidly evolving and of high research value.

A Bibliometric Analysis of Familial Hypercholesterolemia From 2011 to 2021.

Familial Hypercholesterolemia (FH), an autosomal dominant genetic disease, is increasingly emerging as a global threat. To learn more about the development of FH, 1 617 papers about FH and related research were retrieved in the Web of Science Core Collection from 2011 to 2021. Then, these publications were scientometrically analyzed based on CiteSpace and VOSviewer in terms of spatiotemporal distribution, author distribution, subject categories, topic distribution, and references. The results showed that research on FH is at a stable stage. More FH research has been conducted in developed countries, implying the necessity for strengthening international cooperation and exchanges. We have obtained scholars, institutions, relevant journals, and representative literatures that play an important role in FH. The research direction of FH is on the mechanisms of FH and its complications, diagnosis, statin therapy, and new lipid-lowering drug therapy. Care is the research frontier in FH, and it is in an explosive period.

Bibliometric and visual analysis of cardiovascular diseases and COVID-19 research.

Background: The global community has been affected by the coronavirus disease 2019 (COVID-19), which emerged in December 2019. Since then, many studies have been conducted on cardiovascular diseases (CVDs) and COVID-19. The aim of this study was to perform a bibliometric and visual analysis of the published relationship between CVDs and COVID-19. Methods: 1,890 publications were retrieved from the Web of Science Core Collection database on January 5, 2022. Microsoft Office Excel and CiteSpace were then used to carry out scientometric analysis on the relevant literature according to seven aspects: document type, countries/regions, institutions, authors, journals, references, and keywords. Results: The research on CVDs and COVID-19 is currently in a period of rapid development, with China, USA, England, and Italy leading the field. There is active cooperation between most countries and institutions. Harvard Medical School stands out among the many institutions not only for the largest number of publications, but also for their high quality. Banerjee A, Solomon SD and Narula J are three representative authors in this field. Frontiers in Cardiovascular Medicine was the journal with the highest number of published studies, and The Lancet was the most cited journal. Two documents with a high degree of significance in this field were identified. Popular research topics in this field are specific diseases, such as acute coronary syndrome and heart failure; pathogenesis related to ACE2, insulin resistance and pericyte; the specific therapeutic drug chloroquine; and clinical characteristics, physical activity, and mental health. ACE2 and NF-κB will be the focus of future research. Conclusions: This study provides useful information for the research of CVDs and COVID-19, including potential collaborators, popular research topics, and a reference for more extensive and in-depth research in the future.

Role of resveratrol in inhibiting pathological cardiac remodeling.

Cardiovascular disease is a group of diseases with high mortality in clinic, including hypertension, coronary heart disease, cardiomyopathy, heart valve disease, heart failure, to name a few. In the development of cardiovascular diseases, pathological cardiac remodeling is the most common cardiac pathological change, which often becomes a domino to accelerate the deterioration of the disease. Therefore, inhibiting pathological cardiac remodeling may delay the occurrence and development of cardiovascular diseases and provide patients with greater long-term benefits. Resveratrol is a non-flavonoid polyphenol compound. It mainly exists in grapes, berries, peanuts and red wine, and has cardiovascular protective effects, such as anti-oxidation, inhibiting inflammatory reaction, antithrombotic, dilating blood vessels, inhibiting apoptosis and delaying atherosclerosis. At present, the research of resveratrol has made rich progress. This review aims to summarize the possible mechanism of resveratrol against pathological cardiac remodeling, in order to provide some help for the in-depth exploration of the mechanism of inhibiting pathological cardiac remodeling and the development and research of drug targets.

A Systematic Review and Meta-Analysis of Phytoestrogen Protects Against Myocardial Ischemia/Reperfusion Injury: Pre-Clinical Evidence From Small Animal Studies.

Background: Phytoestrogens are a class of natural compounds that have structural similarities to estrogens. They have been identified to confer potent cardioprotective effects in experimental myocardial ischemia-reperfusion injury (MIRI) animal models. We aimed to investigate the effect of PE on MIRI and its intrinsic mechanisms. Methods: A systematic search was conducted to identify PEs that have been validated in animal studies or clinical studies as effective against MIRI. Then, we collected studies that met inclusion and exclusion criteria from January 2016 to September 2021. The SYRCLE's RoB tool was used to evaluate the quality. Data were analyzed by STATA 16.0 software. Results: The search yielded 18 phytoestrogens effective against heart disease. They are genistein, quercetin, biochanin A, formononetin, daidzein, kaempferol, icariin, puerarin, rutin, notoginsenoside R1, tanshinone IIA, ginsenoside Rb1, ginsenoside Rb3, ginsenoside Rg1, ginsenoside Re, resveratrol, polydatin, and bakuchiol. Then, a total of 20 studies from 17 articles with a total of 355 animals were included in this meta-analysis. The results show that PE significantly reduced the myocardial infarct size in MIRI animals compared with the control group (p < 0.001). PE treatment significantly reduced the creatine kinase level (p < 0.001) and cTnI level (p < 0.001), increased left ventricular ejection fraction (p < 0.001) and left ventricular fractional shortening (p < 0.001) in MIRI animals. In addition, PE also exerts a significant heart rate lowering effect (p < 0.001). Conclusion: Preclinical evidence suggests that PE can be multi-targeted for cardioprotective effects in MIRI. More large animal studies and clinical research are still needed in the future to further confirm its role in MIRI.

Psycho-Cardiological Disease: A Bibliometric Review From 2001 to 2021.

The aim of this study was to gain insight into the progress and dynamics of psycho-cardiological disease research and track its hot spots. We have analyzed psycho-cardiological disease-related literature extracted from the Web of Science (WOS) Core Collection from 2001 to 2021 with the help of Cite Space. As a result, we have included 5,032 records. Then, we have analyzed connected networks for the country, author, subject category, keywords, and cited reference. We have summarized the findings in four aspects. First, the annual quantitative distribution of publications is on the rise, although there is a slight drop. Second, in terms of country analysis, the United States, England, Australia, Germany, and Italy are the main research forces in psycho-cardiological diseases. At the same time, several academic entities represented by Andrew Steptoe and Roland von Känel, MD, have been formed based on the early consciousness of physical and mental health in these countries. Besides, China is also more concerned about it due to the rapid population aging process and the largest population. Third, the psycho-cardiological disease is multidisciplinary, including psychology, psychiatry, clinical medicine, such as cardiovascular system and neurology, public environmental and occupational health, and pharmacology. Finally, the results of keyword analysis and co-cited references indicate the hot spots and frontiers in psycho-cardiological disease. The hot spots in psycho-cardiological disease include three aspects. The first aspect includes psychosocial factors, such as depression, lack of social support, and low economic and social status; the second aspect includes priority populations, such as Alzheimer's disease dementia caregivers, elderly, and patients with cancer, and the third aspect includes interventions, such as exercise therapy and diet. In addition, there are three future research frontiers. The first is a psycho-cardiological disease in patients with COVID-19; the second is cardiac rehabilitation, especially exercise therapy and health behavior evaluation; and the final is evidence-based medical evaluation, such as systematic reviews and meta-analyses.

A Bibliometric Analysis of Heart Failure with Preserved Ejection Fraction From 2000 to 2021.

Heart Failure with preserved Ejection Fraction (HFpEF) is a heterogeneous disease, which is becoming a worldwide menace. By retrieving the relevant literature of HFpEF from 2000 to 2021, qualitative and quantitative evaluations are carried out to visualize the scientific achievements in this field. The data were from the Web of Science Core Collection database. The bibliometric tool-CiteSpace is used for scientific econometric analysis to understand the development of disciplines and research hotspots in this field. A total of 6318 HFpEF-related research papers were collected by Web of Science Core Collection database from 2000 to 2021, and the number of published papers and citations were in the rising stage. Fund-funded publications accounted for 80.4 percent of total publications, mainly at the national level, with the largest number being funded by the United States Department of Health and Public Services. The number of publications and centrality of the USA ranked first, indicating that the USA is mature in this research field and is in a leading position in the industry, which may benefit from the contributions of scientific research institutions such as Mayo Medical Center, Brigham Women's Hospital, Northwest University and Duke University. Low-income and middle-income countries lag far behind developed countries in terms of health care and scientific research and need to strengthen international cooperation. Bibliometric analysis shows that the main research directions of HFpEF are epidemiology, treatment, and comorbidity research of HFpEF and atrial fibrillation. Chronic microvascular inflammation is the latest research paradigm of HFpEF, especially phosphodiesterase 5 inhibitors.

Knowledge domain and emerging trends in Takotsubo cardiomyopathy: a scientometric review based on CiteSpace analysis.

Takotsubo cardiomyopathy (TTC) is often acute with a high mortality rate and is subject to relapse. Meanwhile, its complex pathogenesis has attracted increasing attention. To learn more about TTC, CiteSpace V.5.7 R5W was used in this study to analyze the research status, hot spots, and trends in TTC before 2020. The keywords, co-citation references, as well as country and institution distribution were explored. A total of 2,349 papers were reviewed. The United States, Italy, and Germany were the main countries studying TTC and had good cooperation relationships. The Mayo Clinic topped the institution list, but the rate of inter-institutional cooperation was not high. Research hotspots include disease features, auxiliary diagnostic methods, epidemiology, and pathophysiological mechanisms, and the latest ones are complications related to prognosis, such as cardiovascular abnormalities caused by myocardial infarction and normal or non-obstructive coronary arteries (MINOCA), atrial fibrillation, stroke, cancer, and COVID-19. In conclusion, the research of TTC is in a hot development period. Our research will help clinicians and researchers to better understand TTC and its research status by providing a foundation for research objectives. In doing this, our research will help to provide better scientific management, diagnosis, and treatment for patients with TTC, which will in turn improve the prognosis of this condition.

Network Pharmacology and Molecular Docking Analysis on Molecular Mechanism of Qingzi Zhitong Decoction in the Treatment of Ulcerative Colitis.

Ulcerative colitis (UC) is a disease with complex pathological mechanisms. We explored the potential molecular mechanisms behind the therapeutic functions of Qingzi Zhitong decoction (QZZTD) in the treatment of UC by network pharmacology and molecular docking. QZZTD is a formula of Chinese traditional medicine consisting of 10 herbs. The potential active ingredients of QZZTD and their target genes were obtained from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform database, and UC-related target genes were obtained from GeneCards and OMIM databases. A total of 138 co-identified target genes were obtained by plotting the intersection target Venn diagram, and then the STRING database and Cytoscape software were used to establish protein-protein interaction networks and herb-ingredient-target networks. Four key active compounds and nine key proteins were identified. Then, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses showed that the biological functions of potential target genes were associated with DNA transcription, signaling receptor and ligand activity, cytokine activity, cellular autophagy, and antioxidant pathways, with related pathways involving the phosphatidylinositol 3-kinase (PI3K)-Akt signaling pathway, advanced glycosylation end product (AGE)-RAGE signaling pathway, tumor necrosis factor (TNF) signaling pathway, and IL-17 signaling pathway. Moreover, the binding activities of key target genes and essential active compounds of Chinese herbal medicines in QZZTD were further validated by molecular docking. This demonstrated that quercetin, luteolin, hyndarin, and beta-sitosterol had good binding to eight key proteins, and Akt1 was the target protein with the best binding activity, suggesting that Akt1 could be the essential mediator responsible for signaling transduction after QZZTD administration. The rat experiment verified that QZZTD inhibited PI3K-Akt pathway activation and reduced inflammation in UC. In conclusion, our study suggested four potential key active components, including quercetin, were identified in QZZTD, which could interact with Akt1 and modulate the activation of the PI3K-Akt pathway. The other three pathways may also be involved in the signaling transduction induced by QZZTD in the treatment of UC.

Relationships Between Obstructive Sleep Apnea and Cardiovascular Disease: A Bibliometric Analysis (2010-2021).

BACKGROUND Obstructive sleep apnea (OSA) is a common disease that can lead to intermittent hypoxia, increased sympathetic overdrive, and excessive oxidative stress, and eventually lead to cardiovascular/cerebrovascular diseases and metabolic disorders. The prevalence of OSA is reported to be higher in people with certain cardiovascular diseases (CVD). Therefore, the relationship between OSA and CVD has been gradually favored by researchers. MATERIAL AND METHODS Data were downloaded from the Web of Science Core Collection database. Citespace was used to remove duplicated data and construct knowledge visual maps. RESULTS A total of 7047 publications were obtained. The USA was the largest contributor as well as an important player in the cooperation network between nations. The leading institution was the Mayo Clinic. Our study ultimately identified the top 5 hotspots and 4 research frontiers in this field. Top 5 hotspots were: the specific types of obstructive sleep apnea-related cardiovascular and metabolic co-morbidities, the curative effects of CPAP on these co-morbidities, the specific mechanisms of co-morbidities, the importance of polysomnography on OSA and its co-morbidities with CVD, and the prevalence of OSA and its co-morbidities with CVD in particular populations. The top 4 frontiers were: the relationship between OSA and resistant hypertension, the molecular mechanisms of OSA and its co-morbidities with CVD, specific medications and treatment guidelines for the co-morbidities, and the mainstream research methods in this field. CONCLUSIONS This study provides insight and valuable information for researchers and helps to identify new perspectives concerning potential collaborators and cooperative institutions, hot topics, and research frontiers in this field.

Use of Network Pharmacology to Explore the Mechanism of Gegen (Puerariae lobatae Radix) in the Treatment of Type 2 Diabetes Mellitus Associated with Hyperlipidemia.

Rapid increases in metabolic disorders, such as type 2 diabetes mellitus (T2DM) and hyperlipidemia, are becoming a substantial challenge to worldwide public health. Traditional Chinese medicine has a long history and abundant experience in the treatment of diabetes and hyperlipidemia, and Puerariae lobatae Radix (known as Gegen in Chinese) is one of the most prevalent Chinese herbs applied to treat these diseases. The underlying mechanism by which Gegen simultaneously treats diabetes and hyperlipidemia, however, has not been clearly elucidated to date. Therefore, we systematically explored the potential mechanism of Gegen in the treatment of T2DM complicated with hyperlipidemia based on network pharmacology. We screened the potential targets of Gegen, T2DM, and hyperlipidemia in several online databases. Then, the hub targets were analyzed by performing protein-protein interaction, Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment assays, and finally, the complicated connections among compounds, targets, and pathways were visualized in Cytoscape. We found that isoflavones, including daidzein, genistein, and puerarin, as well as ß-sitosterol, are the key active ingredients of Gegen responsible for its antidiabetic and antihyperlipidemia effects, which mainly target AKR1B1, EGFR, ESR, TNF, NOS3, MAPK3, PPAR, CYP19A1, INS, IL6, and SORD and multiple pathways, such as the PI3K-Akt signaling pathway; the AGE-RAGE signaling pathway in diabetic complications, fluid shear stress, and atherosclerosis; the PPAR signaling pathway; insulin resistance; the HIF-1 signaling pathway; the TNF signaling pathway; and others. These active ingredients also target multiple biological processes, including the regulation of glucose and lipid metabolism, the maintenance of metabolic homeostasis, and anti-inflammatory and antioxidant pathways. In conclusion, Gegen is a promising therapeutic phytomedicine for T2DM with hyperlipidemia that targets multiple proteins, biological processes, and pathways.

Causal Association Between Heart Failure and Alzheimer's Disease: A Two-Sample Bidirectional Mendelian Randomization Study.

Background: Traditional observational studies have demonstrated an association between heart failure and Alzheimer's disease. The strengths of observational studies lie in their speed of implementation, cost, and applicability to rare diseases. However, observational studies have several limitations, such as uncontrollable confounders. Therefore, we employed Mendelian randomization of genetic variants to evaluate the causal relationships existing between AD and HF, which can avoid these limitations. Materials and Methods: A two-sample bidirectional MR analysis was employed. All datasets were results from the UK's Medical Research Council Integrative Epidemiology Unit genome-wide association study database, and we conducted a series of control steps to select the most suitable single-nucleotide polymorphisms for MR analysis, for which five primary methods are offered. We reversed the functions of exposure and outcomes to explore the causal direction of HF and AD. Sensitivity analysis was used to conduct several tests to avoid heterogeneity and pleiotropic bias in the MR results. Results: Our MR studies did not support a meaningful causal relationship between AD on HF (MR-Egger, p = 0.634 > 0.05; weighted median (WM), p = 0.337 > 0.05; inverse variance weighted (IVW), p = 0.471 > 0.05; simple mode, p = 0.454 > 0.05; weighted mode, p = 0.401 > 0.05). At the same time, we did not find a significant causal relationship between HF and AD with four of the methods (MR-Egger, p = 0.195 > 0.05; IVW, p = 0.0879 > 0.05; simple mode, p = 0.170 > 0.05; weighted mode, p = 0.110 > 0.05), but the WM method indicated a significant effect of HF on AD (p = 0.025 < 0.05). Because the statistical powers of IVW and MR-Egger are more than that of WM, we think that there is no causal effect of HF on AD. Sensitivity analysis and horizontal pleiotropy were not detected in the MR analysis. Conclusion: Our results did not provide significant evidence indicating any causal relationships between HF and AD in the European population. Therefore, more large-scale datasets or datasets related to similar factors are expected for further MR analysis.