BACKGROUND:Endothelial-to-mesenchymal transition (EndMTE) is implicated in atherosclerosis by contributing to endothelial dysfunction (ED). SMS2 (sphingomyelin synthase 2), a key enzyme in sphingomyelin synthesis, plays a significant role in both ED and atherosclerosis. Nonetheless, the precise mechanisms of SMS2-associated ED, and its potential modulation via EndMT remain unexplored in the context of ED and atherosclerosis progression. METHODS:To investigate this, we inhibited SMS2 activity using the inhibitor Ly93 and performed RNA sequencing on human umbilical vein endothelial cells. Furthermore, we validated the potential mechanisms of EndMT in human umbilical vein endothelial cells, Apo E-/- mice, and human atherosclerotic plaques. RESULTS:SMS2 inhibition suppressed EndMT by blocking the Wnt/β-catenin pathway. This blockade attenuated PPARγ (peroxisome proliferator-activated receptor gamma) ubiquitination-mediated degradation via PPARγ-β-catenin interaction, ultimately reducing CPT1A expression and fatty acid oxidation. In vivo, endothelial cell-specific overexpression of SMS2 in ApoE-/- mice enhances atherosclerosis, and SMS2 positively correlates with Wnt/β-catenin, EndMT, and ED, but inversely correlates with PPARγ activity and fatty acid oxidation. Furthermore, in the unstable atherosclerosis plaques of humans, the expression of SMS2 in endothelial cells is significantly higher compared with that in stable plaques. The relationship between SMS2 and Wnt/β-catenin, EndMT, ED, PPARγ, and fatty acid oxidation aligns with the aforementioned findings. CONCLUSIONS:SMS2 can activate the Wnt/β-catenin pathway, which is inversely correlated with the activity of PPARγ and fatty acid oxidation. This process facilitates EndMT and ED, ultimately contributing to the initiation and development of atherosclerosis. These findings suggest that inhibition of endothelial SMS2 activity with Ly93 could be beneficial for the treatment of atherosclerosis.

BACKGROUND:Whether fractional flow reserve (FFR)-guided revascularization improves outcomes in atherosclerotic renal artery stenosis (ARAS) remains uncertain. OBJECTIVES:This study will evaluate whether the benefit of FFR-guided stenting sustained at 1 year including renal outcomes. METHODS:FAIR pilot is an investigator-initiated, multicentre, open-label trial with blinded endpoint adjudication. Adults with ARAS were randomized 1:1 to FFR-guided vs angiography-guided groups. Stenting was performed in the FFR-guided group when FFR <0.80, and it was performed for all in the angiography-guided group regardless of FFR. The percentage changes in ambulatory daytime mean systolic blood pressure (DMSBP), composite index of antihypertensive medicines (CIAHM), and renal outcomes were analyzed for 1 year. RESULTS:Among all 107 randomized patients, 1-year follow-up was achieved in 50 (93%) in the FFR-guided group and 51 (96%) in the angiography-guided group. At 1 year, DMSBP, CIAHM, and renal outcomes were similar between the groups, while stenting rate was lower with FFR guidance (46% vs 100%, P < 0.01). Patients with FFR <0.80 who underwent stenting experienced the greatest blood pressure reductions (median [IQR] ΔDMSBP: 13 [4, 21] mm Hg at 3 months; 8 [3, 16] mm Hg at 6 months, 7 [0, 16] mm Hg at 12 months; all paired P < 0.05) and sustained declines in CIAHM (2 [0, 5] at 3, 6, and 12 months; all paired P < 0.05). Significant 12-month estimated glomerular filtration rate improvement after stenting was only observed when FFR <0.80, with greater percentage eGFR improvement under quantile regression analysis. CONCLUSIONS:At the 1-year follow-up, FFR-guided renal artery stenting reduced stent use without loss of blood pressure control or renal safety compared with angiography guidance.

BACKGROUND AND AIMS:The optimal therapy for patients with atherosclerotic renal artery stenosis (ARAS) remains unresolved. This study compared the efficacy of renal fractional flow reserve (FFR)-guided revascularization and traditional angiography-guided revascularization. METHODS:In total, 101 patients with ARAS and hypertension were randomly assigned to either the FFR-guided or angiography-guided group (ClinicalTrials.gov identifier: NCT05732077). Stenting was performed in the angiography-guided group regardless of FFR, whereas stenting was only performed in the FFR-guided group for patients with FFR < 0.80. The primary endpoints were the percentage changes in ambulatory daytime mean systolic blood pressure (DMSBP) and composite index of antihypertensive medicines (CIAHM) after 3 months. RESULTS:The percentage changes in DMSBP (4% [-2%, 11%] vs 4% [-3%, 10%]; P = .97) and CIAHM (0% [0%, 3%] vs 1% [0%, 4%]; P = .33) did not differ between groups. However, the rate of stenting was significantly lower in the FFR-guided group (46.0% vs 100.0%, P < .01). Moreover, compared with the findings in patients with FFR ≥ 0.80 who did not receive stenting, stenting was beneficial in patients with FFR < 0.80 (adjusted mean DMSBP reduction, 6.2 [95% confidence interval {CI}, 0.6-11.9] mmHg; mean CIAHM reduction, 3.1 [95% CI, 1.5-4.7]), but not in those with FFR ≥ 0.80 (1.4 [95% CI, -4.5-7.2] mmHg, and 0.7 [95% CI, -1.1-2.5], respectively). CONCLUSIONS:FFR-guided revascularization significantly reduced unnecessary stenting compared with angiography-guided revascularization. Both blood pressure and antihypertensive medication usage decreased significantly after stenting in patients with FFR < 0.80.

BACKGROUND:Microvascular occlusion (MVO) determined by cardiac magnetic resonance (CMR) exists both in acute phase and recovery period after myocardial infarction. This study aimed to examine the long-term prognosis predictive value of persistent MVO for ST-segment elevation myocardial infarction (STEMI). METHODS:A prospective cohort enrolled 344 patients with STEMI who received primary percutaneous coronary intervention and underwent CMR both in 5 to 7 days and 6 months after STEMI to determine if MVO had occurred. All patients were followed up for 5 years, and major adverse cardiovascular events (MACE) were recorded. RESULTS:This study included 344 STEMI patients with an average age of 57 years at 6 centers in China. A total of 192 (55.81%) patients with STEMI did not have MVO by CMR, and 105 (30.52%) patients showed transient MVO in acute phase of myocardial infarction and 47 (13.66%) patients showed persistent MVO at 6 months after infarction. The patients with persistent MVO had the largest infarct size and the lowest left ventricular ejection fraction both in 5 to 7 days and 6 months after infarction (all P < .001). Patients with persistent MVO showed a significantly higher incidence of 5-years MACE than those without MVO or with MVO in only 1 week (66.0% vs 18.8% and 27.6%, respectively; P < .001). Persistent MVO was an independent strong predictor of MACE after adjustment for other CMR variables (OR: 3.912, 95% CI: 1.904-8.037; P < .001). A propensity score-matched population comprised 43 patients with persistent MVO and 43 patients with transient MVO in only 1 week. The patients with persistent MVO had a higher incidence of MACE than those with transient MVO (65.1% [28/43] vs 37.2% [16/43]; P = .010). CONCLUSION:Persistent MVO by CMR at the chronic phase of STEMI provides useful prognostic information regarding long-term outcomes after primary percutaneous coronary intervention.

Population aging has increased the demand for intensive care, with critically ill patients facing high mortality and prolonged hospital stays. New biomarkers are needed to predict outcomes early. The C-reactive protein-triglyceride-glucose index (CTI) integrates insulin resistance and inflammation, but its Link to outcomes in critically ill patients is unknown. This study aims to investigate the association between CTI and 30-day and 365-day all-cause mortality and length of hospital stay in critically ill patients. This retrospective study utilized data from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database, including 2,428 ICU patients admitted from 2008 to 2022. The primary outcomes were 30-day and 365-day all-cause mortality, while secondary outcomes included length of hospital stay and ICU stay. CTI was calculated based on biochemical data (CRP, triglycerides, and glucose). Kaplan-Meier survival analysis, Cox regression models, and mediation analysis were employed to assess the relationship between CTI and clinical outcomes. Higher CTI levels were associated with increased all-cause mortality at both 30 days (HR: 1.81, 95

Background The relationship between the serum creatinine to cystatin C ratio (sarcopenia index [SI]) and the risk of incident cardiovascular disease (CVD) remains unclear. Therefore, this study aims to explore the association between SI and the risk of incident CVD in middle‐aged and older Chinese adults using nationally representative data. Methods and Results We analyzed data from participants in CHARLS (China Health and Retirement Longitudinal Study) conducted in 2015 and 2018. The exposure variable was SI, calculated as the ratio of serum creatinine to cystatin C, multiplied by 100. The outcome variable was self‐reported CVD (heart disease or stroke). A cross‐sectional analysis was first performed using 2015 CHARLS data, which included 11 115 eligible participants (46.1% men; mean±SD age, 60.28±9.60 years). Logistic regression was used to estimate the association between SI and CVD. Longitudinal analysis was then conducted using the 2018 follow‐up data, which included 8589 participants (46.4% men; mean±SD age, 59.57±9.42 years), with a median follow‐up period of 3.0 years. Cox proportional hazard models were used to assess the relationship between SI and the risk of incident CVD, and a multivariate‐adjusted restricted cubic spline model was used to explore the dose–response relationship. In the cross‐sectional analysis, multivariate logistic regression revealed a significant negative association between SI and CVD. The longitudinal analysis identified 854 (9.94%) new CVD cases. Cox models showed that lower SI was significantly associated with an increased risk of incipient CVD. The multivariable adjusted hazard ratios for participants in the quartile 2 to quartile4 groups compared with those in the quartile 1 group were 0.94 (95% CI, 0.79–1.12), 0.63 (95% CI, 0.51–0.78), and 0.60 (95% CI, 0.47–0.75), respectively. Restricted cubic spline curves demonstrated a significant linear relationship between SI and CVD incidence (all P‐nonlinear>0.05). Conclusions A lower SI was significantly associated with an increased risk of new‐onset CVD in middle‐aged and older Chinese adults. This suggests that SI has an important potential application as a serum marker of sarcopenia in predicting CVD.

Triglyceride-glucose (TyG) index is linked to a poor prognosis for cardiovascular condition and is a valid indicator of insulin resistance. This study evaluated the potential predicting usefulness of the TyG index for all-cause mortality, both short- and long-term, for those concerning critical coronary artery disease (CAD). In this study, information from 5452 critically-ill individuals with CAD in intensive care units were gathered from the Medical Information Marketplace in Intensive Care (MIMIC-IV) database. Depending on the TyG index degree, the patients were categorized into three categories. Clinical outcomes included short-term (30-day) and long-term (365-day) all-cause mortality. The corresponding relationships involving the TyG index and clinical outcomes were examined by deploying restricted cubic spline (RCS) regression analysis and Cox proportional risk regression. An increased TyG index was associated with increased 30-day (Tertile 1: 6.1

Triglyceride glucose index (TyG) and waist circumstance have been well documented to be highly correlated with hypertension. However, the joint effect of waist circumstance and TyG on the risk of hypertension is unknown in middle-aged and elderly Chinese adults. The purpose of this study was to investigate the association between TyG and the risk of new-onset hypertension in middle-aged and elderly Chinese individuals with different waist circumstances. The multicentred prospective cohort study was conducted in 28 provinces of China including a total of 5865 eligible participants aged ≥ 45 years old. Cox regression was performed to examine the relationship of TyG index and hypertension with adjustments for the pertinent variables. Besides, the relationship was explored in different groups on the basis of waist circumstance. There was no significant correlation between TyG index and new-onset hypertension after adjustment for pertinent variables (hazards ratio [HR]: 0.99; 95% confidence interval [CI]: 0.80–1.24). When the association was explored in different waist circumstance groups, multivariate cox regression analyses revealed that TyG was an independent factor positively associated with the risk of hypertension in central obesity prophase group (HR: 1.57; 95% CI 1.13–2.16). Among individuals with central obesity, relative to population with lower TyG (Q1: 4.96–8.18), people who had higher TyG (Q3: 8.52–8.95; Q4: 8.95–12.14) were associated with significantly lower HR for hypertension. There was no conspicuous correlation between TyG index with new-onset hypertension in normal waist circumstance (HR: 1.05; 95% CI 0.84–1.30). The research demonstrated the positive relationship of TyG with risk of hypertension among individuals with central obesity prophase, negative relationship of TyG with hypertension among population with central obesity and inconspicuous correlation of TyG with hypertension among individuals with normal waist. In conclusion, the study findings supported the combined effects of TyG index and waist circumference in predicting hypertension in middle-aged and elderly Chinese individuals.

Background: Cardiovascular disease (CVD) remains a leading cause of mortality globally. Environmental pollutants, specifically volatile organic compounds (VOCs), have been identified as significant risk factors. This study aims to develop a machine learning (ML) model to predict CVD risk based on VOC exposure and demographic data using SHapley Additive exPlanations (SHAP) for interpretability. Methods: We utilized data from the National Health and Nutrition Examination Survey (NHANES) from 2011 to 2018, comprising 5098 participants. VOC exposure was assessed through 15 urinary metabolite metrics. The dataset was split into a training set (70 %) and a test set (30 %). Six ML models were developed, including Random Forest (RF), Light Gradient Boosting Machine (LightGBM), Decision Tree (DT), Extreme Gradient Boosting (XGBoost), Multi-Layer Perceptron (MLP), and Support Vector Machines (SVM). Model performance was evaluated using the Area Under the Receiver Operating Characteristic Curve (AUROC), accuracy, balanced accuracy, F1 score, J-index, kappa, Matthew's correlation coefficient (MCC), positive predictive value (PPV), negative predictive value (NPV), sensitivity (sens), specificity (spec) and SHAP was applied to interpret the bestperforming model. Results: The RF model exhibited the highest predictive performance with an ROC of 0.8143. SHAP analysis identified age and ATCA as the most significant predictors, with ATCA showing a protective effect against CVD, particularly in older adults and those with hypertension. The study found a significant interaction between ATCA levels and age, indicating that the protective effect of ATCA is more pronounced in older individuals due to increased oxidative stress and inflammatory responses associated with aging. E-values analysis suggested robustness to unmeasured confounders. Conclusions: This study is the first to utilize VOC exposure data to construct an ML model for predicting CVD risk. The findings highlight the potential of combining environmental exposure data with demographic information to enhance CVD risk prediction, supporting the development of personalized prevention and intervention strategies.

BackgroundWhile body mass index (BMI) defines obesity as a well-established risk factor for cardiovascular disease, the paradoxical theory of BMI suggests that obesity may indeed have a favorable impact on the prognosis of cardiovascular disease. Therefore, this study aims to assess the correlation between body shape index (ABSI), which is a novel measure of obesity, and coronary heart disease (CHD) among obese individuals in the United States.MethodsThe data from the National Health and Nutrition Examination Survey (NHANES) were evaluated by us for 5046 patients. We assessed the exposure variable ABSI, which includes waist circumference (WC), height, and BMI. The outcome variable was CHD.ResultsThe cross-sectional study included a total of 5046 obese adults aged over 20 years, with an average age (standard deviation: SD) of 49.86 (16.24) years and a male proportion of 44.57%.The odds ratio (OR) values for CHD in Model 1, Model 2, 3 were found to be 2.45 (95%CI: 2.12, 2.83), 1.53 (95%CI:1.30, 1.81) and 1.31 (95%CI:1.09, 1.56) per SD increase in ABSI, respectively. In the fully adjusted model, we designated participants in the T1 group as the reference group. Our findings indicate a significant increase in the prevalence of CHD (OR:1.82, 95%CI: 1.07-3.10) only within the T3 group. Although there is an increased prevalence of CHD (OR:1.32, 95%CI: 0.77-2.29) in the T2 group, no statistically significant difference was observed.ConclusionsThe increase in ABSI is strongly associated with the rise in CHD prevalence among obese individuals in the United States.

BackgroundHypertrophic cardiomyopathy (HCM) is a genetic disorder characterized by left ventricular hypertrophy that can lead to heart failure, arrhythmias, and sudden cardiac death. Despite extensive research, the molecular mechanisms underlying HCM are not fully understood, and effective treatments remain limited. By leveraging bioinformatics and experimental validation, this study aims to identify key genes and pathways involved in HCM, uncover novel drug candidates, and provide new insights into its pathogenesis and potential therapeutic strategies.MethodsCommonly upregulated and downregulated genes in hypertrophic cardiomyopathy (HCM) were identified using Gene Expression Omnibus (GEO) datasets, including three mRNA profiling datasets and one miRNA expression dataset. Enrichment analysis and hub-gene exploration were performed using interaction networks and consistent miRNA-mRNA matches. Potential drugs for HCM were screened. HCM cellular and animal models were established using isoproterenol. Key unstudied differentially expressed genes (DEGs) were validated. Animals were treated with novel potential drugs, and improvements in HCM were assessed via ultrasound metrics. Hematoxylin and eosin (H&E) staining was used to assess myocardial fibrosis. Immunohistochemistry was employed to detect DEGs in cellular experiments.ResultWe discovered 145 key upregulated and 149 downregulated DEGs associated with HCM development, among which there are eight core upregulated and seven core downregulated genes. There are 30 upregulated and six downregulated miRNAs. Between the six downregulated miRNAs and 1291 matched miRNAs (against eight core upregulated DEGs), there is one common miRNA, miR-1469. Using the CTD database, drugs that impact the expression/abundance/methylation/metabolic process of core DEGs (after the exclusion of toxic drugs) included acetaminophen, propylthiouracil, methapyrilene, triptolide, tretinoin, etc. In the HCM cell model, only ATRNL1 and WNT9A were significantly increased. In the HCM animal model, propylthiouracil, miR-1469, and triptolide demonstrated varying degrees of therapeutic effects on HCM. Propylthiouracil, but not miR-1469 or triptolide, significantly inhibited the expression of ATRNL1 in the HCM model, and all three drugs suppressed WNT9A expression.ConclusionWe identified several novel genes in HCM development, among which ATRNL1 and WNT9A were validated by cell and animal models. A deficiency of hsa-miR-1469 may be a mechanism behind HCM development. Novel medications for HCM treatment include propylthiouracil and triptolide.

BackgroundBlood counts and biochemical markers are among the most common tests performed in hospitals and most readily accepted by patients, and are widely regarded as reliable biomarkers in the literature. The aim of this study was to assess the causal relationship between blood counts, biochemical indicators and pulmonary arterial hypertension (PAH).MethodsA two-sample Mendelian randomization (MR) analysis was performed to assess the causal relationship between blood counts and biochemical indicators with PAH. The genome-wide association study (GWAS) for blood counts and biochemical indicators were obtained from the UK Biobank (UKBB), while the GWAS for PAH were sourced from the FinnGen Biobank. Inverse variance weighting (IVW) was used as the primary analysis method, supplemented by three sensitivity analyses to assess the robustness of the results. And we conducted an observational study using data from National Health and Nutrition Examination Survey (NHANES) 2003–2018 to verify the relationship.ResultsThe MR analysis primarily using the IVW method revealed genetic variants of platelet count (OR=2.51, 95% CI 1.56-4.22, P<0.001), platelet crit(OR=1.87, 95% CI1.17-7.65, P=0.022), direct bilirubin (DBIL)(OR=1.71, 95%CI 1.18-2.47,P=0.004), insulin-like growth factor (IGF-1)(OR=0.51, 95% CI 0.27-0.96, P=0.038), Lipoprotein A (Lp(a))(OR=0.66, 95% CI 0.45-0.98, P=0.037) and total bilirubin (TBIL)(OR=0.51, 95% CI 0.27-0.96, P=0.038) were significantly associated with PAH. In NHANES, multivariate logistic regression analyses revealed a significant positive correlation between platelet count and volume and the risk of PAH, and a significant negative correlation between total bilirubin and PAH.ConclusionOur study reveals a causal relationship between blood counts, biochemical indicators and pulmonary arterial hypertension. These findings offer novel insights into the etiology and pathological mechanisms of PAH, and emphasizes the important value of these markers as potential targets for the prevention and treatment of PAH.

The triglyceride glucose body mass index (TyG-BMI) is a potential indicator for insulin resistance, but its association with mortality in diabetic patients is unclear. This study investigates the relationship between TyG-BMI and all-cause and cardiovascular mortality in diabetics. The study included 3109 diabetic patients from the National Health and Nutrition Examination Survey (2001-2018). Mortality data were obtained from National Death Index records until 31 December 2019. Multivariate Cox models analyzed the association between TyG-BMI and mortality. Non-linear correlations were assessed using restricted cubic splines, and a two-piecewise Cox model evaluated the relationship on both sides of the inflection point. Over a median 7.25-year follow-up, 795 total and 238 cardiovascular deaths occurred. A U-shaped link was found between initial TyG-BMI and mortality in diabetic patients. Low TyG-BMI (< 279.67 for all-cause, < 270.19 for CVD) reduced death risks (all-cause: HR 0.77, 95% CI 0.69-0.86; CVD: HR 0.64, 95% CI 0.48-0.86). High TyG-BMI (> 279.67 for all-cause, > 270.19 for CVD) increased these risks (all-cause: HR 1.26, 95% CI 1.10-1.44; CVD: HR 1.33, 95% CI 1.06-1.68). In the NHANES study population, a U-shaped association was observed between the baseline TyG-BMI index and all-cause mortality or CVD in diabetic patients.

Objective::Data comparing the outcomes of MiStent (Micell Technologies, Durham, North Carolina, USA) microcrystalline biodegradable polymer (BP) drug-eluting stent (DES) and those of another post-marketing BP-DES, TIVOLI (EssenTech, Beijing, China) are rare. This study sought to compare the angiographic efficacy and clinical outcomes of the microcrystalline BP sirolimus-eluting stent (SES) system MiStent and those of TIVOLI BP-SES.Methods::The DESSOLVE-C trial was a prospective, single-blinded, multicenter, randomized trial (NCT02448524), which randomly assigned patients with de novo coronary lesions to receive MiStent or TIVOLI BP-SES by a 1:1 ratio. The primary endpoint was a non-inferiority comparison of in-stent late lumen loss (LLL) by quantitative coronary angiography at 9 months. The secondary endpoint was device-related clinical cardiovascular composite events (target lesion failure (TLF), composite of cardiac death, target vessel myocardial infarction (MI), and clinically driven target lesion revascularization) and 1-year outcomes. Results::A total of 428 patients (216 patients in the MiStent group and 212 patients in the TIVOLI group) were enrolled and included in an intention-to-treat analysis. MiStent was not only non-inferior but superior to TIVOLI for in-stent LLL at 9 months ((0.23 ± 0.37) mm vs. (0.34 ± 0.48) mm, P for non-inferiority <0.001, P for superiority = 0.02). Although without significant difference, the rate of TLF in MiStent was quantitatively lower than that in TIVOLI (3.70% vs. 6.60%; P = 0.17). Conclusion::Compared with TIVOLI BP-SES, the MiStent system was superior in in-stent LLL at 9 months and had a comparable clinical benefit at 1 year in de novo coronary lesions.

复制心肌缺血再灌注损伤模型是进行心肌缺血再灌注损伤研究的基础,复制稳定且高效的动物和细胞模型尤为重要.目前,心肌缺血再灌注损伤模型分为结扎动物冠状动脉左前降支的在体模型、动物心脏灌流装置及细胞缺氧再灌注的离体模型,但在模型复制过程中仍存在成功率低、重复性差等问题.因此,该文结合近年研究对该模型的复制和改良方法进行归纳和综述,为复制更为稳定的模型提供新的思路和方向.

BackgroundEpidemiological studies suggest a bidirectional association between atrial fibrillation and breast cancer. This study aimed to conduct a meta-analysis to elucidate the prevalence of atrial fibrillation among breast cancer patients, and the bidirectional association between atrial fibrillation and breast cancer.MethodsPubMed, the Cochrane Library, and Embase were searched to identify studies reporting the prevalence, incidence, and bidirectional association between atrial fibrillation and breast cancer. The study was registered with PROSPERO (CRD42022313251). Levels of evidence and recommendations were assessed by the Grading of Recommendations Assessment, Development and Evaluation (GRADE).ResultsTwenty-three studies (17 retrospective cohort studies, 5 case-control studies and 1 cross-sectional study) involving 8,537,551 participants were included. Among patients with breast cancer, the prevalence of atrial fibrillation was 3% (11 studies; 95% CI: 0.6 to 7.1%) and the incidence was 2.7% (6 studies; 95% CI: 1.1 to 4.9%). Breast cancer was associated with increased risk of atrial fibrillation (5 studies; hazard ratio [HR]: 1.43, 95% CI: 1.12 to 1.82, I2 = 98%). Atrial fibrillation was also significantly associated elevated risk of breast cancer (5 studies HR: 1.18, 95% CI: 1.14 to 1.22, I2 = 0%). Grade assessment shown low certainty of the evidence for the risk of atrial fibrillation and moderate certainty of the evidence for the risk of breast cancer.ConclusionAtrial fibrillation is not uncommon in patients with breast cancer and vice versa. There is a bidirectional association between atrial fibrillation (low certainty) and breast cancer (moderate certainty).

Gallstone disease (GSD) is thought to be associated with the risk of coronary heart disease (CHD) or acute myocardial infarction (AMI), which may be due to abnormal cholesterol metabolism. We used multiple Mendelian randomization (MR) methods based on publicly available genome-wide association study data to assess whether this association is genetically causal and to search for loci driving causality. Pooled data for GSD were obtained from FinnGen Biobank and Biobank Japan, while CHD and AMI were obtained as pooled data from the CARDIoGRAMplusC4D consortium. In this MR study, we found a significant negative causal effect of genetic susceptibility to GSD on AMI in the Finnish population, but no causal effect was found on CHD. This causal effect was not confounded by reverse causality and the same findings were obtained in the Japanese population. Furthermore, the negative causal effect of GSD on AMI risk may be driven by the rs4245791-regulated ABCG5/8 protein. In conclusion, the results of this MR study support a negative causal effect of GSD on AMI and suggest that rs4245791 is the causal driver locus of this effect, which provides new ideas and evidence for the prevention and etiologic study of AMI in patients with GSD.

Hyperhomocysteinemia (HHcy) is an independent risk factor of atherosclerosis (AS). Some reports have shown that homocysteine (Hcy) could accelerate the development of AS by promoting endothelial cell senescence. miRNAs were widely involved in the pathophysiology of HHcy. However, few studies have focused on the changes of miRNA-mRNA networks in the artery of HHcy patients. For this reason, RNA-sequencing was adopted to investigate the expression of miRNA and mRNA in HHcy model mouse arteries. We found that the expression of 216 mRNAs and 48 miRNAs were significantly changed. Using TargetScan and miRDB web tools, 29 miRNA-mRNA pairs were predicted. Notably, miR-20b-5p and FJX1 shared the highest predicted score in TargetScan, and further study indicated that the miR-20b-5p inhibitor significantly upregulated the FJX1 expression in HHcy human umbilical vein endothelial cells (HUVECs) model. PPI analysis revealed an important sub-network which was centered on CDK1. Gene ontology (GO) enrichment analysis showed that HHcy had a significant effect on cell cycle. Further experiments found that Hcy management increased reactive oxygen species (ROS) generation, the activity of senescence associated β-galactosidase (SA-β-gal) and the protein expression of p16 and p21 in HUVECs, which were rescued by miR-20b-5p inhibitor. In general, our research indicated the important role of miR-20b-5p in HHcy-related endothelial cell senescence.