Archives of Medical Science最新文献

Cardiovascular disease (CVD), particularly atherosclerotic cardiovascular disease (ASCVD), is the most common cause of death worldwide. Despite decades of research into lifestyle factors and medications, we still cannot effectively prevent the occurrence of ASCVD or the many incident CVD events and their complications. Yet, in most countries, only a small percentage of the healthcare budget is allocated to (primary) prevention, and only a few nations have introduced effective integrated (coordinated) programmes in primary prevention to promote health education, invest in health as early as possible, and prevent adverse CVD events. The International Lipid Expert Panel SiMple tIps for the heaLthy hEart (ILEP-SMILE) responds to this significant ineffectiveness by offering the most comprehensive population approach, including early, effective education, improvement of all recognised risk factors, alongside those that remain frequently unmeasured, such as lipoprotein(a), factors which are often overlooked such as sleep disturbances and alcohol consumption, and the challenging aspect of stress, and its effect on cardiovascular health. Finally, ILEP-SMILE places considerable emphasis on adherence as a result of education; without it, even efficient lifestyle changes and the most innovative drugs may not yield the expected outcomes. This is also a loud call to action and international collaboration to jointly address the lifetime burden of cardiovascular disease.

Introduction: Inflammatory bowel disease (IBD) includes Crohn's disease (CD) and ulcerative colitis (UC). Epidemiological studies have found that patients with IBD are more likely to suffer from cardiovascular diseases (CVDs) than the general population. However, so far, no exact causal association has been demonstrated between IBD and CVDs, and more research is needed to clarify this relationship.

Material and methods: The two-sample Mendelian randomization (MR) method was used to explore the causal effect of IBD on CVDs. The exposure factor was IBD, including CD and UC. The outcome was CVDs, including chronic heart failure, atrial fibrillation, coronary heart disease, myocardial infarction and hypertension. The single nucleotide polymorphisms (SNPs) are all from the FinnGen genome-wide association study sample database. The CD samples included 210,300 controls and 807 cases, and the UC samples included 215,806 controls and 2701 cases. The samples included are all European samples. SNPs associated with Crohn's disease and ulcerative colitis were extracted from the IEUGWAS database and quality control and screening were carried out. Inverse variance weighted (IVW), MR-Egger, weighted median and other methods were used to study the causal relationship between them and CVDs. Finally, Cochrane's Q test, MR-Egger and the leave-one method were used for sensitivity analysis.

Results: In this study, 4 SNPs strongly associated with Crohn's disease and 12 SNPs strongly associated with ulcerative colitis were screened. The IVW method of genetic prediction revealed a positive correlation between Crohn's disease and the risk of chronic heart failure (OR =1.02; 95% CI: 1.00-1.04), and there was a positive correlation between ulcerative colitis and the risk of chronic heart failure (OR = 1.03; 95% CI: 1.00-1.06). IVW, MR-Egger and weighted median showed that Crohn's disease and ulcerative colitis were not associated with the risk of atrial fibrillation, coronary heart disease, myocardial infarction or hypertension. Sensitivity analysis showed that the results are robust.

Conclusions: Crohn's disease and ulcerative colitis are associated with an increased risk of chronic heart failure, but they are not associated with the risk of other CVDs.

Introduction: Metabolic dysfunction related steatotic liver disease (MASLD) is a long-term liver disease. Oxidative stress plays a key role in MASLD. The oxidative balance score (OBS) measures oxidative and reactive stress, but its relationship with MASLD and fibrosis remains unclear.

Material and methods: The National Health and Nutrition Examination Survey records from 1999 to 2018 were used in this study. We used weighted multivariate logistic regression, subgroup studies, and restricted cubic spline regression to examine the associations between OBS and MASLD and fibrosis. Sensitivity studies were conducted to evaluate the robustness of the results.

Results: A total of 12,272 people enrolled in the study. There was a strong negative relationship between OBS and MASLD, and all p-values for interactions were less than 0.05. After adjusting for potential confounders, people with higher OBS had a lower risk of MASLD (OR = 0.37, 95% CI (0.27-0.51), p for trend < 0.001). Then, the stratified studies showed that lifestyle OBS was significantly associated with MASLD in both men and women, but dietary OBS was only significantly associated with MASLD in men (OR = 0.95, 95% CI (0.93, 0.98), p < 0.001). Finally, lifestyle OBS showed a strong association with MASLD-related fibrosis (OR = 0.37, 95% CI (0.24, 0.56), p for trend < 0.0001). In the subgroup studies, the findings remained consistent.

Conclusions: OBS was associated with a lower risk of MASLD, and lifestyle OBS showed strong protective effects against MASLD and fibrosis. Because of this, people who have MASLD and fibrosis should focus on researching and looking into antioxidant treatment that is based on dietary and lifestyle, with particular emphasis on lifestyle factors.

Introduction: Previous studies have indicated a potential association between the gut microbiota (GM) and dementia; however, the exact cause-and-effect relationships between GM, various types of dementia, and the potential influence of the plasma lipidome as intermediaries are still unclear.

Material and methods: We used genome-wide association study (GWAS) data to identify GM taxa, plasma lipid species (lipidome), and five types of dementia: Alzheimer's disease (AD), dementia with Lewy bodies (DLB), Parkinson's disease dementia (PDD), frontotemporal dementia (FTD) and vascular dementia (VD). We used Mendelian randomization (MR) to investigate the possible causal connections among the GM, plasma lipidome, and dementias. The inverse variance weighting (IVW) method served as the primary statistical approach. We investigated the role of plasma lipidome as a potential mediating factor in this relationship.

Results: A total of 41 positive and 39 negative causal relationships between genetic susceptibility in the GM taxa or bacterial pathways and dementia, as well as 14 negative causal relationships between the plasma lipidome and dementias, were identified. Additionally, only 1 potential mediation pathway was identified as having a significant mediating effect.

Conclusions: Our results suggest a link between the GM and the plasma lipidome with five distinct types of dementia, indicating that the phosphatidylcholine (O-16:1_18:2) level could play a role in the pathway from the species Bacteroides coprocola to vascular dementia.

Introduction: Lipid metabolism is pivotal in diabetic retinopathy (DR) development. Nevertheless, the relationship between lipid-lowering drugs and the risk of DR remains a topic of debate. This study employed Mendelian randomization (MR) to investigate the potential effects of pharmacological lipid-lowering targets on DR and to clarify the causal association between blood lipid characteristics and DR.

Material and methods: The data comprised genetic variations related to lipid traits and genetic variations associated with lipid-lowering drug targets obtained from the Global Lipid Consortium. Total DR, non-proliferative DR (NPDR), and proliferative DR (PDR) were sourced from the Finnish R9 database. Lipid-lowering drug targets were tested using inverse variance-weighted MR (IVW-MR) and statistics-based MR (SMR). Colocalization and mediation analysis were conducted to validate the results and explore potential mediating factors.

Results: A reduced risk of total DR and NPDR was associated with genetically improved 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) (OR = 0.62; 95% CI: 0.46-0.83; p = 1.30 × 10^-2; OR = 0.49; 95% CI: 0.34-0.70; p = 9.70 × 10^-4). Strong colocalization (PP.H4 = 0.85) was observed between whole blood tissue HMGCR expression and a significant MR relationship with total DR (OR = 0.66; ‌95% CI: 0.52-0.85; p = 7.31 × 10^-4). Furthermore, body mass index (BMI) and glycated hemoglobin (HbA_1c) are critical factors that mediate the impact of HMGCR and apolipoprotein B (APOB) on DR risk.

Conclusions: This Mendelian randomization study suggests that abnormalities in triglyceride (TG) levels serve as a pathogenic element in DR. Of the nine lipid-lowering drug targets assessed, HMGCR and APOB have emerged as potential promising targets for managing NPDR. These findings underscore the importance of controlling both BMI and HbA_1c levels to optimize outcomes in diabetic patients at risk for DR. The therapeutic mechanisms of HMGCR and APOB in DR go beyond lipid lowering alone, and a multimodal lipid-lowering strategy should be selected early and comprehensively to address the patient's medical conditions.

Introduction: This study aimed to investigate the relationship between serum cytokine levels, particularly interleukin 6 (IL-6), and diabetic nephropathy (DN) in patients with type 1 (T1D) and type 2 diabetes (T2D).

Material and methods: A cross-sectional study was conducted among 200 patients diagnosed with either T1D or T2D from January 2022 to December 2023 at the Endocrinology and Diabetes Department of Madinah Hospital, Saudi Arabia.

Results: A total of 200 individuals with T1D (n = 100) or T2D (n = 100) were enrolled in this research. Male patients (54%) and those aged 30-50 (67.5%) dominated the cohort. About 50% had diabetes for less than 10 years, and 49.5% were overweight. 63.5% (n = 117) had a reduced glomerular filtration rate (GFR), whereas 46% (n = 92) had albuminuria. T1D patients were mostly normal weight, while T2D patients were overweight or obese. Both diabetes types had identical kidney damage stages. T1D patients were more likely to have moderately elevated albuminuria (53% vs. 37%, p < 0.05) than T2D individuals. T1D patients had considerably lower serum cytokine levels than T2D patients. IL-6 levels were moderately correlated with fasting blood glucose (FBG) (r = -0.318, p < 0.01) and HbA_1c (r = -0.319, p < 0.01) in T1D patients. IL-6 had a modest correlation with renal dysfunction markers including GFR and urine albumin-creatinine ratio (UACR) (r = -0.250, p < 0.05 and r = 0.338, p < 0.001, respectively). In T1D patients there was a weak but significant correlation between GFR and IL6.

Conclusions: Lower serum IL-6 levels in T1D patients are linked to delayed onset of kidney damage. The pro-inflammatory role of IL-6 may contribute to the development of DN in T1D patients, as indicated by its association with albuminuria and renal function markers. Further research is warranted to explore IL-6 as a potential therapeutic target in diabetic nephropathy.

Introduction: Withaferin-A (WA) derived from natural products can inhibit the growth and metastasis of colorectal cancer (CRC) in vitro and in vivo.

Material and methods: WA effects on colorectal cancer cells were studied using HCT116 and SW480 lines. In vitro we used shRNA knockdown, plasmid overexpression, viability, proliferation, colony, migration, and invasion assays. And Xenograft and metastasis mouse models evaluated tumor growth and toxicity. Molecular analysis used qRT-PCR, Western blot, IHC, immunoprecipitation, and RNA sequencing.

Results: Transcriptome analysis showed WA suppressed EMT, HSP90, and HIF-1α in CRC. WA inhibited HSP90, HIF-1α, E-cadherin, and their interaction. HIF-1α knockdown reduced CRC migration, invasion, and lung metastasis. 17-AAG similarly inhibited HSP90/HIF-1α and metastasis. HSP90 overexpression rescued HIF-1α expression, binding, and migratory ability in HIF-1α knockdown cells.

Conclusions: These findings indicate that WA inhibits CRC's growth, migration, and invasion by inhibiting the HSP90/HIF-1α/EMT axis. And showed that WA could be a potential therapeutic agent for CRC.