The chronic digestive condition gallstones is quite common around the world, the development of which is closely related to oxidative stress, inflammatory response and abnormalities of lipid metabolism. In the last few years, as a novel biomarker of lipid metabolism, the non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio (NHHR) has garnered significant interest. However, its relationship with gallstones has not been studied yet. 3,772 people, all under 50, were included in this study, and their full data came from the National Health and Nutrition Examination Survey (NHANES) database for the years 2017–2020. Information on gallstones was obtained through self-reported questionnaires. Smoothed curve fitting multifactorial logistic regression was utilized to evaluate the connection of NHHR with gallstone formation incidence. Subsequently, subgroup analysis and interaction tests were applied. Finally, to create a prediction model, logistic regression and feature screening by last absolute shrinkage and selection operator (LASSO) were used. The resulting model was displayed using a nomogram. In multivariate logistic regression that accounted for all factors, there was a 77% increase in the likelihood of gallstones for every unit rise in lnNHHR (OR 1.77 [CI 1.11–2.83]). Following NHHR stratification, the Q4 NHHR level was substantially more linked to the risk of gallstones than the Q1 level (OR 1.86 [CI 1.04–3.32]). This correlation was stronger in women, people under 35, smokers, abstainers from alcohol, non-Hispanic White people, those with excessively high cholesterol, people with COPD, and people without diabetes. After feature screening, a predictive model and visualized nomogram for gallstones were constructed with an AUC of 0.785 (CI 0.745–0.819), which was assessed by DCA to be clinically important. In the group of people ≤ 50 years of age, elevated NHHR levels were substantially linked to a higher incidence of gallstones. This correlation was stronger in several specific groups such as females, under 35 years of age, smokers, and so on. Predictive models constructed using the NHHR have potential clinical value in assessing gallstone formation.

Background: With a rapidly growing and aging world population, ischemic heart disease (IHD) remains a major burden. This study aimed to reassess the prevalence trend of IHD from 1990 to 2021 from multiple dimensions to improve the shortcomings of the existing studies and provide a solid scientific basis for policymakers.Methods: This study extracted data on the prevalence, incidence, mortality, disability-adjusted life years (DALYs), and associated risk factors of IHD from the global burden of disease (GBD) 2021 study. Descriptive, decomposition, and risk factor analyses were used to provide insights into the epidemiologic patterns of IHD from 1990 to 2021 and project the burden of IHD from 2022 to 2045. Potential differences in burden and risk factors based on age, sex, 21 GBD geographic regions, five social development index (SDI) regions, and 204 countries are highlighted.Results: Globally, the age-standardized prevalence rate (ASPR) of IHD is increasing, while the age-standardized incidence rate (ASIR), age-standardized mortality rate (ASMR), and age-standardized disability-adjusted life years (ASDR) are decreasing. ASPR, ASIR, ASMR, and ASDR were highest in the low-middle SDI regions and lowest in the high SDI regions. ASMR and ASDR were highest in Nauru and lowest in Portugal. Men had an overall heavier burden of IHD than women; the 65–69 age group had the largest burden, and those aged >95 years had the highest crude incidence rate. In addition, the burden of IHD was negatively correlated with SDI across regions and countries, while decomposition analyses suggest that the main reasons for the current increase in the burden of IHD are aging and population growth. Risk factors have changed relatively little over the 32 years, with metabolic risk still ranking first. We forecast that the absolute burden of IHD will continue to increase till 2045; however, ASIR, ASMR, and ASDR will gradually decline.Conclusion: From 1990 to 2021, the global burden of IHD generally increased and varied across regions, sex, and age groups. Due to increasing population growth and aging, there is an urgent need for strategically directed measures to reduce the burden of IHD.

Oxidized low‑density lipoprotein (ox‑LDL) induces endothelial cell apoptosis and dysfunction. Statins are drugs that are clinically used to lower serum cholesterol levels, and they have been shown to exert vascular protective effects. In the present study, human umbilical vein endothelial cells were transfected with scramble control siRNA or siRNA specific for glutathione peroxidase (GPx)4 or cystine‑glutamate antiporter (xCT). MTT, Matrigel and Transwell assays were used to evaluate cell proliferation, tube formation and migration, respectively. The levels of TNF‑α, IL‑α, 4‑hydroxynonenal, GPx4 and xCT expression were detected by western blot analysis. It was demonstrated that ox‑LDL promoted cytokine production and reduced the proliferation, migration and angiogenesis of endothelial cells. It was also observed that ox‑LDL decreased GPx4 and xCT expression and induced ferroptosis. Furthermore, the inhibition of ferroptosis by deferoxamine mesylate attenuated ox‑LDL‑induced endothelial cell dysfunction and restored ox‑LDL‑decreased GPx4 and xCT expression. Consistent with these results, GPx4 and xCT knockdown by siRNA transfection aggravated ox‑LDL‑induced endothelial cell dysfunction and inhibition of proliferation. To the best of our knowledge, the present study was the first to discover that fluvastatin may protect endothelial cells from ox‑LDL‑induced ferroptosis and dysfunction. Furthermore, knockdown of GPx4 and xCT expression blunted the protective effects of fluvastatin on ox‑LDL‑treated endothelial cells. These data indicated a novel function of fluvastatin in the protection of endothelial cells from ox‑LDL‑induced ferroptosis, the mechanism of which involves the regulation of GPx4 and xCT.

Objectives. Abdominal aortic aneurysm (AAA), a disease with high mortality, is limited by the current diagnostic methods in the early screening. This study aimed to screen novel and significant biomarkers and construct a diagnostic model for AAA by using a novel machine learning method, i.e., an ensemble of the random forest (RF) algorithm and artificial neural network (ANN). Methods and Results. Through a search of the Gene Expression Omnibus (GEO) database, two large‐sample gene expression datasets (GSE57691 and GSE47472) were downloaded and preprocessed. Differentially expressed genes (DEGs) in GSE57691 were identified by R software, followed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment using the Database for Annotation, Visualization, and Integrated Discovery (DAVID). Essential metabolic pathways related to positive regulation of cell death and NAD binding were found. Then, RF was used to identify key genes from the DEGs, and an AAA diagnostic model was established by ANN. A transcription factor (TF) regulatory network of key genes related to angiogenesis and endothelial migration was constructed. Finally, a validation dataset was used to validate the model and the area under the receiver operating characteristic curve (AUC) value was high. Conclusion. Potential AAA‐associated gene biomarkers were identified by RF, and a novel early diagnostic model of AAA was established by ANN. The AUC indicated that the diagnostic model had a highly satisfactory diagnostic performance. In conclusion, this study will provide a promising theoretical basis for further clinical and experimental studies.

Background: Cardiovascular disease (CVD) poses a significant global health and economic challenge, with atherosclerosis being a primary cause. Over the past 40 years, substantial research has been conducted into the prevention and reversal of atherosclerosis, resulting in the development of lipid-lowering agents such as statins and fibrates. Despite the extensive literature and formulation of numerous therapeutic guidelines in this domain, a comprehensive bibliometric analysis of the current research landscape and trends has not been performed. This study aimed to elucidate the evolution and milestones of research into lipid-lowering treatments for coronary heart disease (CHD) in conjunction with hyperlipidemia through bibliometric analysis, offering insights into future directions for treatment strategies.Methods: This study examined publications from 1986 to 2023 retrieved from the Web of Science database (Core Collection). Utilizing tools such as VOSviewer, Pajek, and CiteSpace, we analyzed publication and citation numbers, H-indexes, contributions by countries and institutions, authorship, journal sources, and keyword usage to uncover research trajectories and areas of focus.Results: Our analysis of 587 publications revealed a recent surge in research output, particularly post-2003. The American Journal of Cardiology published the highest number of studies, with 40 articles, whereas Circulation received the highest number of citations (6,266). Key contributors included the United States, Japan, and China, with the United States leading in citation numbers and the H-index. Harvard University and Leiden University emerged as pivotal institutions, and Professors J. Wouter Jukema and Robert P. Giugliano were identified as leading experts. Keyword analysis disclosed five thematic clusters, indicating a shift in research towards new drug combinations and strategies, signaling future research directions.Conclusion: The last 4 decades have seen a notable rise in publications on lipid-lowering therapies for CHD and hyperlipidemia, with the United States retaining world-leading status. The increase in international collaboration aids the shift towards research into innovative lipid-lowering agents and therapeutic approaches. PCSK9 inhibitors and innovative combination therapies, including antisense oligonucleotides and angiopoietin-like protein 3 inhibitors, provide avenues for future research, intending to maximize the safety and efficacy of treatment approaches.

Background: The non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio (NHHR) has emerged as a promising biomarker for lipid metabolism, with established links to mortality in various chronic diseases. However, its prognostic value in individuals with non-hyperhomocysteinemia (NHHcy), a population often overlooked in cardiovascular risk assessment, remains unexplored. This study aimed to determine the association between NHHR and all-cause and cardiovascular disease (CVD) mortality and its predictive value among adults with NHHcy.Methods: This study used the National Health and Nutrition Examination Survey database (1999–2006) and employed the National Death Index to determine mortality outcomes. The relationship between NHHR and mortality was evaluated using restricted cubic splines (RCS) and a multivariable Cox proportional hazards model. The threshold effects were assessed using a piecewise Cox proportional hazards model. Analysis of subgroups, interactions, and survival was done. Lastly, the NHHR's predictive value for mortality as well as its potential mediating effects were evaluated.Results: A total of 13,847 participants were included in our study. Over the course of the follow-up, there were a total of 2,886 mortality, of which 739 were due to CVD. A “U-shaped” correlation between NHHR and mortality was shown by the RCS. A one-unit rise in NHHR was linked to a 19 and 17.4% decrease in the odds of all-cause and CVD mortality, respectively, when NHHR was below the inflection point; the hazards rose by 6.4 and 11.9%, respectively, when NHHR was over the inflection point. There were interaction effects between several subgroups in the relationship between NHHR and mortality from all-cause and CVD. Additionally, NHHR's area under the curve for predicting death from all-cause and CVD was 0.897 (0.890–0.904) and 0.921 (0.910–0.932), respectively. According to mediation analysis, the association between NHHR and all-cause mortality was mediated by aspartate aminotransferase.Conclusion: NHHR was shown to have a “U-shaped” relationship with both all-cause and CVD mortality in the NHHcy population, as well as an excellent mortality predictive value. In the future, NHHR could be used for predicting mortality risk and prognosis in the NHHcy population.