Aims: The secreted glycoprotein leucine-rich α-2 glycoprotein 1 (LRG1) is implicated in atherosclerotic cardiovascular pathogenesis. Herein, we examined the relationship between LRG1 and cardiovascular events in patients with acute coronary syndrome (ACS). Methods and Results: Proteomics technology was used to identify the plasma LRG1 in ACS and chronic coronary syndrome (CCS) patients and control patients prospectively recruited in a multi-center investigative study. Plasma LRG1 was accessed in the 3 groups with sex- and age-matched healthy subjects serving as additional controls (n = 1820). Compared with both CCS and controls, ACS patients showed markedly elevated LRG1 levels (p<0.001) which were consistent in the Chui Yang Liu hospital (CYL) cohort (n=409) from another research center. Furthermore, among ACS patients, we evaluated the association of LRG1 with major adverse cardiovascular events (MACE), a composite of cardiac death, myocardial infarction, ischemic stroke, non-cardiovascular death, hospitalization for heart failure, recurrent angina pectoris and target vessel revascularization. After a median follow up of 1.23 (1.19-1.29) years, LRG1 was independently associated with increased MACE risk over 1 year (LRG1 tertile3 vs tertile1: HR: 4.35, 95% CI: 2.01-9.4, p=0.029) and 4-year (LRG1 tertile3 vs tertile1: HR:3.19, 95% CI 1.81-5.63, p< 0.001) after adjust for clinical variables, biomarkers and Grace 2.0 score. The results were similar in the UK cohort. Mediation analyses indicated that CRP partially mediated the association of LRG1 with MACE, with the mediation proportion being 13.4% (95% CI: 4.2-28.1%) in the derivation cohort and 43.3% (95%CI:13.4-123.2%) in the UK validation cohort, respectively. Besides, LRG1 was correlated with thin-cap fibroatheroma (p=0.007) and plaque rupture (p=0.02) in the culprit lesion detected by optical coherence tomography. Conclusion: LRG1 might be a novel and independent biomarker for cardiovascular events in patients presenting with ACS. LRG1 may provide prognostic information on the risk of recurrent cardiovascular events in the secondary prevention management of ACS and hold promise as a therapeutic target.

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.

We aimed to compare the prognostic value of Machine learning (ML) and traditional Cox regression method for predicting adverse clinical events in patients with acute coronary syndrome (ACS). In a prospective observational cohort of 2730 patients with ACS, we analyzed several candidate variables for median follow-up of 8.1 years from the Observation of Cardiovascular Events of ACS patients (OCEA) study. External validation was performed in 542 patients with ACS for median follow-up of 2.8 years from the management of cardiovascular risk and health (MCRH). The random survival forests (RSF)-based ML model including clinical traditional risk factors and plasma biomarkers were evaluated. A multivariable Cox regression model was subsequently used to develop a nomogram. Adverse clinical events refer to cardiovascular events and non-cardiovascular death. Cardiovascular events were defined as a combined endpoint of MI, ischemic stroke, cardiovascular death and heart failure for hospital. RSF based model exhibited the highest prognostic ability, achieving a C-index of 0.960 with 95

Total cholesterol to high-density lipoprotein (TC/HDL) ratio has not been fully established following acute myocardial infarction (AMI) undergoing percutaneous coronary intervention (PCI) in clinical practice. Therefore, we sought to evaluate the relationship between TC/HDL ratio and major adverse cardiovascular events (MACEs) in AMI undergoing PCI patients. 398 patients who subjected to AMI undergoing PCI were included in this study. Blood samples were obtained and analyzed before patients underwent PCI. Patients were followed up until 6 months after discharge, and MACEs were recorded. The incidence of MACEs was 25.4

CT-derived fractional flow reserve (CT-FFR) enables noninvasive physiological assessment from coronary CT angiography. This study aimed to evaluate its diagnostic performance across six prespecified anatomical and calcification-related factors to clarify lesion-specific clinical applications. In this prospective multicenter trial, 317 patients with 366 target vessels underwent coronary CT angiography and invasive fractional flow reserve (FFR) within 7 days. CT-FFR performance was evaluated according to target vessel, lesion location, lesion length, bifurcation involvement, target-lesion calcification, and per-patient coronary calcium burden. These factors were selected a priori to address distinct anatomical or pathophysiological hypotheses. Subgroup analyses were exploratory, and nominal P values are reported. Overall vessel-level accuracy, sensitivity, specificity, positive predictive value, negative predictive value (NPV), and area under the receiver operating characteristic curve were 87.2

BackgroundNew-onset atrial fibrillation (NOAF) is the most commonly encountered arrhythmia during the course of acute myocardial infarction (AMI) and is independently associated with a worse prognosis.AimsWe aimed to validate the discriminatory performance of cancer antigen-125 (CA-125) in predicting post-AMI NOAF in the Chinese population.MethodsA total of 488 consecutive patients with AMI from 1 January 2020 to 1 January 2022 without a previous history of AF were enrolled in this study. Risk factors for post-AMI NOAF were determined using univariable and multivariable logistic regression analyses. Receiver operating characteristic (ROC) curve analyses were used to evaluate the discrimination performance of different parameters and score models. Area under the curve (AUCs) were compared using Z tests.ResultsIn total, 48 (9.84%) patients developed post-AMI NOAF during hospitalization. The NOAF group was older and had a higher Killip class, B-type natriuretic peptide level, CA-125 level, left atrial diameter, left ventricular end-systolic diameter, CHA2DS2-VASc (Congestive heart failure, Hypertension, Age ≥75 years [2 points], Diabetes mellitus, Stroke/transient ischemic attack/thromboembolism history [2 points], Vascular disease, Age 65–74 years, Sex category [female]) score, Global Registry of Acute Coronary Events (GRACE) risk score (RS), and in-hospital mortality, and a lower low-density lipoprotein level, left ventricular ejection fraction, and initial β-receptor blocker and angiotensin-converting enzyme inhibitor/angiotensin receptor blocker use (P < 0.05 vs. the no-NOAF group for all measures). In the multivariate regression analyses, CA-125 remained an independent risk factor for post-AMI NOAF in different models. In the ROC curve analyses, CA-125 (AUC = 0.753, 95% CI: 0.665–0.84, P < 0.001), GRACE RS (AUC = 0.701, 95% CI: 0.593–0.809, P = 0.001), and CHA2DS2-VASc score (AUC = 0.644, 95% CI: 0.532–0.757, P = 0.014) were valid tools to predict post-AMI NOAF. After Z tests, the discriminatory performance of CA-125 was significantly higher than that of the CHA2DS2-VASc score (P = 0.038), but not statistically significantly higher than that of the GRACE RS (P = 0.353).ConclusionAn elevated plasma CA-125 level was independently associated with NOAF after AMI, with high discriminatory performance.

Background Data regarding the safety and efficacy of balloon expandable valves (BEVs) for transcatheter aortic valve replacement (TAVR) in patients with Sievers type 0 bicuspid aortic valve (BAV) stenosis remain limited. Aims This study aims to evaluate the clinical outcomes of BEVs implantation in patients with Sievers type 0 BAV. Methods We conducted a multicenter, retrospective study across 28 centers in China between October 2020 and March 2023. Consecutive patients with Sievers type 0 BAV anatomy undergoing TAVR with the Edwards Sapien 3 BEV were enrolled. Results The study included 131 patients with Sievers type 0 BAV (mean age 69.8 ± 7.5 years; 52.7 % male). The lateral-lateral type predominated (86.3 %). Calcification distribution analysis identified the superior leaflet margin as the most primary site (62.6 %). All procedures utilized femoral artery access. High implantation depth (The ratio of the aortic side of the prosthetic valve to the outflow tract side is > 8:2) was achieved in 80.2 % of cases. Prosthetic valves smaller than 26 mm were implanted in nearly half of the patients (49.6 %). The 30-day all-cause mortality rate was 0.8 %, with no incidence of disabling stroke. The overall technical success rate was 98.5 %. Conclusion The findings of this study demonstrate that BEVs implantation in patients with Sievers type 0 BAV is associated with favorable safety and efficacy outcomes. These results provide valuable insights for current TAVR practice in this specific patient population.

BACKGROUND:In 2012, the randomised trial IABP SHOCK II demonstrated that IABP did not reduce 30-day mortality in patients with acute myocardial infarction complicating cardiogenic shock (CS). However, SCAI proposed a new standardised classification of cardiogenic shock in 2019. It is reasonably hypothesised that the use of IABP may have different benefits for patients in different stages of CS. METHODS:AMI patients ≥18 years who had received treatment of implantation of IABP during emergency setting in Beijing Chaoyang Hospital between December 2010 and July 2021 were enrolled in this study. CS stages were classified at admission for all eligible cases. During the same period, AMI patients without implantation of IABP were matched with each stage of CS above using propensity score matching (PSM). Data were as follows: Stage B (n = 302), Stage C (n = 290), Stage D (n = 68), and Stage E (n = 32). In-hospital mortality was compared between using and without using IABP at each stage. RESULTS:In stage C, the in-hospital mortality was significantly lower in the IABP group (31/145, 21.4%) than in the group without IABP (47/145, 32.4%) (OR 0.567, 95% CI, p = .034). In-hospital mortality had no significant difference between use and no-use of IABP in stage B (16.6% vs 14.6%, p = .634), stage D (47.1% vs 38.2%, p = .462), and in stage E (81.3%vs 68.8%, p = .414). CONCLUSIONS:For patients with acute myocardial infarction complicating cardiogenic shock, IABP has no effect on in-hospital mortality in SCAI stages B, D, and E. However, in SCAI stage C, IABP can reduce in-hospital mortality.

IntroductionThe gut microbiota metabolite, short-chain fatty acids (SCFAs), can protect against multiple cardiovascular diseases, while the molecular targets and underlying mechanisms need to be elucidated. One of the primary mechanisms of SCFA benefits was the direct activation of a group of G-protein-coupled receptors (GPCRs), termed free fatty acid receptors (FFARs), the FFAR2 (GPR43), and FFAR3 (GPR41). At present, the distribution of FFAR2/3 in cardiac cells has not been entirely clarified.MethodsUsing 18 public single-cell RNA-seq and single-nuclear RNA-seq data of human and mouse hearts, we illustrate the entire atlas of FFAR2/3 distribution in different regions and cell types in normal and infarcted hearts.Results and discussionWe present the atlas of FFAR2/3 in the whole human body, normal and infarcted hearts at single-cell resolution. We also illustrated the entire atlas of FFAR2/3 in normal/ischemic hearts of newborn and adult mice by combining public and newly built sc/snRNA-seq datasets. These findings provide valuable information on the possible effect of SCFAs via FFAR2/3 in the heart and valuable references for future studies.

Enhanced recovery after surgery (ERAS) protocols have been widely adopted to improve surgical outcomes. In this study, we aimed to assess the current state of awareness and specific knowledge of ERAS among Chinese anesthesiologists, examine difficulties in implementation, and identify future priorities for ERAS education and training. A self-designed, repeated national survey regarding awareness and practice of the ERAS concept, specific knowledge, learning modalities, and difficulties in ERAS implementation was conducted in 2019, 2021, and 2023. Factors related to mastery of knowledge were analyzed via subgroup analysis and multivariable linear regression. A total of 6385 participants were included; 96.2

Aims The prediction of atrial fibrillation (AF) progression and post-ablation recurrence is currently based on empirical estimates, leading to suboptimal predictive accuracy. This study investigates whether atrial remodelling, a key factor in the severity of atrial cardiomyopathy, could serve as a shared substrate influencing both AF progression and recurrence. We aimed to identify circular RNAs (circRNAs) associated with atrial remodelling and to evaluate their ability to predict AF progression and recurrence. Methods and results We assessed the differential expression of plasma circRNAs between paroxysmal (PAF) and persistent AF (PsAF) patients using microarray analysis. Selected candidate circRNAs were validated through qPCR following rigorous statistical and bioinformatics analysis. circDGCR8 was consistently found to be up-regulated in PsAF compared with PAF patients. Additionally, circDGCR8 was significantly up-regulated in human atrial fibroblasts treated with angiotensin II (AngII). Gain- and loss-of-function studies suggested that circDGCR8 could promote atrial remodelling at cellular level by enhancing collagen production and fibroblast proliferation. Overexpression of circDGCR8 in human cardiac fibroblasts significantly altered the gene expression spectrum, impacting pathways including IL-17 signalling and TNF signalling. Moreover, circDGCR8 levels were positively correlated with atrial fibrosis, as indicated by increased percentages of low voltage zones. The predictive value of circDGCR8 was evaluated in two cohorts: (i) PAF patients monitored for 36 months with progression to PsAF as the endpoint, and (ii) AF patients who underwent radiofrequency ablation followed for 12 months to assess recurrence. In both cohorts, higher level of circDGCR8 was associated with increased risks of AF progression and post-ablation recurrence. Conclusion Our results suggest that circDGCR8, associated with atrial remodelling, holds potential as a predictive biomarker for both AF progression and post-ablation recurrence.

Background Atherosclerosis is a chronic inflammatory disease of the arterial wall characterized by the accumulation of cholesterol-rich lipoproteins in macrophages. Leucine-rich alpha-2 glycoprotein 1 (LRG1) is a circulating protein associated with inflammation, however, its role in atherosclerosis remains unclear. This study identified its role in macrophage pro-inflammatory differentiation and revealed the relationship between LRG1 and atherosclerosis. Method We evaluated the impact of LRG1 on atherosclerosis progression by analyzing atherosclerotic tissue and serum samples from patients with coronary artery disease (CAD) and healthy individuals and analyzed its role in such a process using two types of mice models: Apoe knock-out mice ( Apoe-/- ) and Apoe and Lrg1 double knock-out mice ( Apoe-/-/Lrg1-/- ). These mice were fed with a high-fat diet for 16 to 32 weeks to simulate conditions exacerbating atherosclerosis. To examine the effects of inhibiting LRG1 on atherogenesis, we administered intraperitoneal injections of LRG1 neutralizing antibody (50μg/kg) weekly to Apoe-/- mice for 8 weeks. We conducted in vitro assays using bone marrow-derived macrophages isolated from wild-type mice and analyzed transcriptional signatures using RNA sequencing. Additionally, we utilized small molecular inhibitors to validate the signaling pathway through which LRG1 promotes macrophage-driven inflammation. Results LRG1 levels were found to be elevated in patients with atherosclerosis and correlated with higher levels of a plasma pro-inflammatory biomarker high-sensitive C-reactive protein (hsCRP), and several macrophage-related pro-inflammatory markers including CD68, VE-Cadherin and VCAM-1. In a high fat diet induced Apoe-/- mouse atherosclerosis model, the deletion of LRG1 gene significantly delayed atherogenesis progression and reduced levels of macrophage-related pro-inflammatory cytokines. Addition of purified LRG1 to cultured macrophages stimulated those macrophages to pro-inflammatory M1-like polarization regulated by the activation of ERK and JNK pathways. An anti-LRG1 neutralizing antibody effectively blocked LRG1-induced macrophage M1-like polarization in vitro and conferred therapeutic benefits to animals with ApoE deficiency-induced atherosclerosis. Conclusion LRG1 plays an important pro-inflammatory role in atherosclerosis by influencing macrophage polarization towards a pro-inflammatory state. The inhibition of LRG1 with neutralizing antibodies may offer a potential therapeutic strategy for patients with atherosclerosis by mitigating the pro-inflammatory response and delaying disease progression, offering a novel therapy in atherosclerosis management. Translational Perspective Atherosclerosis, a persistent inflammatory condition affecting the arterial wall, serves as the underlying pathophysiological basis for acute ischemic cardiovascular events. The involvement of macrophages is crucial in the advancement of atherosclerosis. In this investigation, heightened levels of plasma LRG1 were observed in individuals with coronary artery disease. Moreover, this study presents initial evidence highlighting LRG1 as a pivotal activator of macrophages, instigating a pro-inflammatory M1 polarization during atherogenesis through the activation of ERK1/2 and JNK pathways. The use of an anti-LRG1 neutralizing antibody demonstrated a delay in atherosclerosis progression in an animal model, suggesting a potential therapeutic target for atherosclerosis treatment. Suppression of LRG1 production could impede atherosclerosis advancement and enhance plaque stability. Utilizing neutralizing antibodies against LRG1 emerges as a promising therapeutic approach for treating atherosclerosis. ### Competing Interest Statement The authors have declared no competing interest.

Complex regional pain syndrome (CRPS) is a disabling condition that usually affects the extremities after trauma or surgery. At present, there is no FDA-approved pharmacological treatment for patients with CRPS. We performed this systematic review and meta-analysis to evaluate the efficacy and safety of pharmacological therapies and determine the best strategy for CRPS. We searched the databases, including PubMed, Embase, Cochrane, Web of Science, Scopus, and ClinicalTrials.gov, for published eligible randomized controlled trials (RCTs) comparing pharmacological treatment with placebo in CRPS patients. Target patients were diagnosed with CRPS according to Budapest Criteria in 2012 or the 1994 consensus-based IASP CRPS criteria. Finally, 23 RCTs comprising 1029 patients were included. We used the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach to rate certainty (confidence in evidence and quality of evidence). Direct meta-analysis showed that using bisphosphonates (BPs) (mean difference [MD] −2.21, 95% CI −4.36–−0.06, p = 0.04, moderate certainty) or ketamine (mean difference [MD] −0.78, 95% CI −1.51–−0.05, p = 0.04, low certainty) could provide long-term (beyond one month) pain relief. However, there was no statistically significant difference in the efficacy of short-term pain relief. Ketamine (rank p = 0.55) and BPs (rank p = 0.61) appeared to be the best strategies for CRPS pain relief. Additionally, BPs (risk ratio [RR] = 1.86, 95% CI 1.34–2.57, p < 0.01, moderate certainty) and ketamine (risk ratio [RR] = 3.45, 95% CI 1.79–6.65, p < 0.01, moderate certainty) caused more adverse events, which were mild, and no special intervention was required. In summary, among pharmacological interventions, ketamine and bisphosphonate injection seemed to be the best treatment for CRPS without severe adverse events.

Background: Sirtuin 7 (SIRT7), as a nicotinamide adenine dinucleotide-dependent protein/histone deacetylase, has been implicated in the pathogenesis of cardiovascular diseases. However, whether SIRT7 is related to hypertension remains largely unclear. Thus, this study aims to explore the effects and correlation between SIRT7 and hypertension. Methods: A total of 72 patients with essential hypertension and 82 controls with non-hypertension were recruited at Beijing Tongren Hospital Affiliated with Capital Medical University from July 2022 to June 2023. Plasma SIRT7 expression was measured using enzyme-linked immunosorbent assay analysis. Clinical baseline characteristics, laboratory measurements, echocardiographic data, and medical therapy were collected. Results: Plasma levels of SIRT7 were lower in hypertensive patients compared with non-hypertensive patients [0.97 (0.58-1.30) vs. 1.24 (0.99-1.46) ng/mL, P < 0.001, respectively]. Furthermore, compared with the low SIRT7 group, there were lower levels of systolic blood pressure, hyperlipidemia, and the ultrasonic electrocardiogram parameters left ventricular end-diastolic diameter and left atrial in diastole in the high SIRT7 group (P < 0.05, respectively). More importantly, multivariate logistic regression analyses indicated that plasma SIRT7 was a predictor of hypertension [OR: 0.06, 95 % CI (0.02-0.19), P < 0.001]. Receiver operating characteristics curve analysis revealed that the optimal cutoff value for plasma SIRT7 levels in detecting hypertension was determined as 0.85 ng/mL with a sensitivity of 73.6 % and a specificity of 89.0 %. The area under the curve for SIRT7 was 0.821 (95 % CI, 0.751-0.878; P < 0.001). Conclusion: Plasma levels of SIRT7 are decreased in patients with essential hypertension, implying its potential as a biomarker for diagnosing essential hypertension..

Background: Reperfusion injury often persists even with successful primary percutaneous catheterization intervention (PPCI) in patients with ST-segment elevation myocardial infarction (STEMI). Therefore, we developed volume-controlled reperfusion (VCR), a method combined with accurate gentle reperfusion for active protection against unstable plaque formation. This study aimed to investigate the feasibility, safety, and efficacy of VCR as an adjunct for PPCI in patients with STEMI.Methods: The STEMI VCR trial (http://www.chictr.org.cn; Unique identifier: ChiCTR2100052856) was a single-center prospective, interventional, randomized controlled trial. Sixty patients were randomized to the VCR (n = 30, VCR + routine PCI) or control (n = 30, routine PCI only) groups. In-hospital late gadolinium enhancement-cardiac magnetic resonance imaging (LGE-cMRI) was subsequently performed, with follow-up patient evaluation after 12 months.Results: No differences were observed in the occurrence of major adverse cardiac events (MACE) between the two groups. Similarly, there was no procedure failure in the VCR group. In-hospital echocardiographic left ventricular ejection fraction (LVEF) revealed significant differences between the VCR and control groups, with similar results observed in the anterior subgroups. However, LGE-cMRI and CMR-LVEF revealed no significant differences in infarct size, microvascular obstruction (MVO) mass, or MVO mass/infarct mass ratio in the anterior subgroup. Follow-up echocardiographic LVEF revealed significant differences between the two groups and the anterior subgroups.Conclusions: VCR was feasible and clinically safe in patients with STEMI undergoing PPCI, indicating that this adjunctive therapy might attenuate reperfusion injury.Trial Registration: ChiCTR2100052856.Funding: The trial was sponsored by the Clinical Research Incubation Fund (CYFH202204), Beijing Chao-Yang Hospital, Capital Medical University.Declaration of Interest: None.Ethical Approval: The study was conducted in accordance with the Declaration of Helsinki, and the protocol was approved by the Ethics Committee of Beijing Chao-Yang Hospital, Capital Medical University (CYFH202204).

Macrophage accumulation and activation function as hallmarks of atherosclerosis and have complex and intricate dynamics throughout all components and stages of atherosclerotic plaques. In this review, we focus on the regulatory roles and underlying mechanisms of macrophage phenotypes and metabolism in atherosclerosis. We highlight the diverse range of macrophage phenotypes present in atherosclerosis and their potential roles in progression and regression of atherosclerotic plaque. Furthermore, we discuss the challenges and opportunities in developing therapeutic strategies for preventing and treating atherosclerotic cardiovascular disease. Dysregulation of macrophage polarization between the proinflammatory M1 and anti-inflammatory M2 phenotypealters the immuno-inflammatory response during atherosclerosis progression, leading to plaque initiation, growth, and ultimately rupture. Altered metabolism of macrophage is a key feature for their function and the subsequent progression of atherosclerotic cardiovascular disease. The immunometabolism of macrophage has been implicated to macrophage activation and metabolic rewiring of macrophages within atherosclerotic lesions, thereby shifting altered macrophage immune-effector and tissue-reparative function. Targeting macrophage phenotypes and metabolism are potential therapeutic strategies in the prevention and treatment of atherosclerosis and atherosclerotic cardiovascular diseases. Understanding the precise function and metabolism of specific macrophage subsets and their contributions to the composition and growth of atherosclerotic plaques could reveal novel strategies to delay or halt development of atherosclerotic cardiovascular diseases and their associated pathophysiological consequences. Identifying biological stimuli capable of modulating macrophage phenotypes and metabolism may lead to the development of innovative therapeutic approaches for treating patients with atherosclerosis and coronary artery diseases.

Abstract Background Atrial fibrillation (AF) is associated with circulating inflammation. Short-chain fatty acids (SCFAs) derived from gut microbiota (GM) regulate leukocyte function and inhibit the release of inflammatory cytokines, which are partly mediated by the G-protein-coupled receptor 43 (GPR43) signaling. This study aimed to investigate the expression of GPR43/NOD-like receptors family pyrin domain containing 3 (NLRP3) in leukocytes and the interaction with intestinal SCFAs levels in AF patients. Methods Expressions of GPR43 and NLRP3 mRNA in peripheral blood leukocytes from 23 AF patients and 25 non-AF controls were detected by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Expressions of leukocyte GPR43 and NLRP3 protein were evaluated by western blot analysis. The levels of plasma IL-1β were measured by enzyme-linked immunosorbent assay (ELISA). The fecal SCFAs levels based on GC/MS metabolome of corresponding 21 controls and 14 AF patients were acquired from our published dataset. To evaluate the expression of NLRP3 and GPR43 and the release of IL-1β, human THP-1 cells were stimulated with or without SCFAs (acetate, propionate, and butyrate), lipopolysaccharide (LPS), and nigericin in vitro, respectively. Results Compared to the controls, the mRNA expression in peripheral leukocytes was significantly reduced in AF patients (P = 0.011) coupled with the increase in downstream leukocyte NLRP3 mRNA expression (P = 0.007) and plasma IL-1β levels (P < 0.001), consistent with changes in GPR43 and NLRP3 protein expression. Furthermore, leukocyte GPR43 mRNA levels were positively correlated with fecal GM-derived acetic acid (P = 0.046) and negatively correlated with NLRP3 mRNA expression (P = 0.024). In contrast to the negative correlation between left atrial diameter (LAD) and GPR43 (P = 0.008), LAD was positively correlated with the leukocyte NLRP3 mRNA levels (P = 0.024). Subsequent mediation analysis showed that 68.88% of the total effect of intestinal acetic acid on AF might be mediated by leukocyte GPR43/NLRP3. The constructed GPR43–NLRP3 score might have a predictive potential for AF detection (AUC = 0.81, P < 0.001). Moreover, SCFAs treatment increased GPR43 expression and remarkably reduced LPS/nigericin-induced NLRP3 expression and IL-1β release in human THP-1 cells in vitro. Conclusions Disrupted interactions between GPR43 and NLRP3 expression in peripheral blood leukocytes, associated with reduced intestinal GM-derived SCFAs, especially acetic acid, may be involved in AF development and left atrial enlargement by enhancing circulating inflammation.

BACKGROUND:Coronary computed tomography angiography provides valuable information for evaluating the difficulty of chronic total occlusion (CTO) percutaneous coronary intervention. This study aimed to investigate the value of CTO plaque characteristics derived from radiomics analysis for predicting the difficulty of percutaneous coronary intervention. METHODS:Patients with CTO were retrospectively enrolled from a hospital as training and internal test sets and from the other 2 territory hospitals as external test sets. Radiomics characteristics were extracted from the CTO segment on coronary computed tomography angiography. Radiomics and combined models were developed to predict successful guidewire crossing within 30 minutes (guidewire success) of CTO percutaneous coronary intervention. Subgroup analysis was conducted to investigate the influence of potential risk factors on the radiomics model performance. RESULTS:A total of 551 patients (median, 60; interquartile range, 52.00-66.00 years, 460 men) with 565 CTO lesions were finally enrolled. In the training, internal test, and external test sets, 203 of 357, 85 of 149, and 38 of 59 CTO lesions achieved guidewire success, respectively. Six radiomics features were selected for constructing the radiomics model. In the external test set, the area under the receiver operating characteristic curve of the radiomics model was significantly higher than prior prediction models (P<0.05 for all) with the area under the receiver operating characteristic curve, accuracy, sensitivity, and specificity of 0.86, 74.58%, 81.58%, and 61.90%, respectively. The performance of the radiomics model was dependent on calcification, CTO location, adjacent branch(es), and operator caseload. CONCLUSIONS:CTO characteristics revealed by radiomics analysis can be used as effective imaging biomarkers for predicting guidewire success. However, the performance of the radiomics model depends on anatomic and operator factors.