Acute myocarditis is a non-ischemic cardiomyopathy with rapid onset and high mortality. Immunometabolic reprogramming of macrophages is a key pathological feature. However the understanding of its mechanisms remains to be clarified. In this study, we found that acute myocarditis induced an increase in glycolysis and lactate accumulation. Inhibition of lactate production ameliorated myocardial injury. Further, we demonstrated that lactate promoted a pro-inflammatory transition of macrophages, thereby amplifying the inflammatory response. Inhibition of lactate in macrophage shifted its phenotype from a pro-inflammatory to an anti-inflammatory subtype. We also observed a significant increase in H4K5 lactylation in macrophages. Next, we identified that H4K5la drove the transcriptional expression of the Rap1, which in turn upregulated the TNF/NF-κB signaling. This lactate-dependent H4K5la was enriched in inflammatory pathways, forming a positive feedback loop that amplified inflammation. Inhibition of Rap1 reduced cardiac inflammation and broke this loop. These consequently lowered H4K5la levels and delayed ventricular remodeling. Collectively, this study reveals the role of H4K5la in promoting inflammatory cascades in myocarditis, and provides a potential therapeutic target for inflammatory cardiomyopathy.

BACKGROUND:Chronic kidney disease (CKD) represents one of the most significant risk factors for adverse cardiovascular events and mortality. Data on real-world clinical practice of Chinese patients with CKD in the cardiology department is limited. OBJECTIVES:This study aims to investigate the proportion of underdiagnosis, guideline-directed therapy and awareness of CKD among Chinese patients. METHODS:It was a multicentre observational study conducted in 25 tertiary hospitals across China. Patients with two consecutive measurements (separated by 90-730 days) of either: (1) estimated glomerular filtration rate 20-60 mL/min/1.73 m², or (2) urinary albumin-to-creatinine ratio (UACR) ≥30 mg/g, with documented cardiology hospitalisation from 2022 to 2024 were eligible. Participants completed a lifestyle and awareness questionnaire after inclusion. The proportion of underdiagnosis, guideline-directed therapy and awareness of CKD was calculated. RESULTS:Among 2099 participants (median age 74.0 years; 64.6% male), 76.7% were underdiagnosed with CKD (lacked a CKD diagnostic code at discharge). Only 16.7% of participants underwent UACR testing and all individuals with isolated albuminuria (UACR >30 mg/g) remained underdiagnosed. Underdiagnosis was more common in patients aged 60-75, those with early-stage CKD, hospital stays <6 days or without comorbidities. The proportion of guideline-directed treatment was suboptimal: sodium-glucose cotransporter-2 inhibitors (36.5%), renin-angiotensin system inhibitors (56.5%) and only 32.2% of patients received guideline-directed treatment. CKD awareness lagged behind hypertension and diabetes, with <25% achieving guideline-recommended blood pressure and glycaemic targets. CONCLUSIONS:Alarmingly high proportion of underdiagnosed CKD, suboptimal guideline-directed treatment, and poor disease awareness of CKD in cardiology practice require urgent action. Closing these gaps is needed to reduce preventable cardiovascular morbidity and mortality.

Microvascular obstruction (MVO) is recognized as an independent risk factor for adverse prognosis in patients with myocardial infarction (MI), and its development is mechanistically linked to inflammation and micro-thrombus. Maresin 1 (MaR1), a specialized pro-resolving mediator, has demonstrated therapeutic potential in counteracting these processes, but its translation has been hindered by poor stability and rapid degradation. To overcome these limitations, we report the development of a cardiac-targeted liposomal nanotherapeutic (nano-MaR1) designed to stabilize and selectively deliver MaR1 to the injured myocardium. Nano-MaR1 was generated through a scalable nanoprecipitation method in a herringbone microfluidic mixer, with MaR1 encapsulated by a freeze-thaw approach to minimize degradation, and further modified with a cardiac-homing peptide for organ-specific targeting. In a murine MI model, intravenous administration of nano-MaR1 led to rapid myocardial enrichment within 12 h, with 20 mu M identified as the optimal therapeutic dose. Treatment markedly reduced infarct size, cardiomyocyte apoptosis, inflammatory infiltration, and MVO formation, while promoting reparative macrophage polarization toward the M2 phenotype. Mechanistic studies revealed that these effects were mediated by downregulation of Itgam (CD11b) within the coagulation cascade and inhibition of monocyte-platelet aggregate formation, which were abolished upon CD11b blockade. Collectively, this work establishes cardiac-targeted liposomal encapsulation as a powerful strategy to enhance the stability and bioactivity of MaR1, and highlights nano-MaR1 as a promising therapeutic candidate for mitigating MVO and improving post-MI repair.

This study examines how corporate participation in green technology standard-setting affects two dimensions of green innovation-substantive and symbolic green innovation-through the mediating role of knowledge integration and across different stages of the firm life cycle. Analyzing panel data from Chinese A-share listed firms (2010-2023), we find that standard-setting participation significantly enhances both types of innovation, with a stronger and more enduring effect on substantive innovation. The effects exhibit clear life cycle heterogeneity: substantive green innovation is consistently enhanced across all stages of the firm life cycle, whereas symbolic green innovation is predominantly reinforced during the maturity stage. Grounded in the knowledge-based view and institutional theory, our findings highlight how institutional engagement fosters sustainable innovation by strengthening firms' capacity for knowledge acquisition and integration. This research advances understanding of the strategic value of standard-setting in sustainability efforts and provides actionable insights for aligning standardization practices with long-term innovation goals.

With the rapid acceleration of technological revolutions and industrial upgrading, firms are increasingly exposed to environmental uncertainty, intensified competition, and continuous technological disruption. Under such conditions, sustainable corporate development depends not only on innovation performance, but on the ability to sustain innovation activities over time. Innovation resilience, defined as the capacity to withstand shocks, reconfigure resources, and maintain innovation momentum, therefore represents a critical foundation of corporate sustainability. Using panel data from Chinese A-share listed firms from 2009 to 2024, this study examines how CEO power shapes sustainable innovation resilience. Drawing on upper echelons theory and signaling theory, we investigate the direct effect of CEO power, the mediating role of corporate reputation, and the moderating role of artificial intelligence adoption. Fixed-effects regression results indicate that CEO power is positively associated with sustainable innovation resilience, and this relationship is partially mediated by corporate reputation. Furthermore, artificial intelligence adoption strengthens the positive association between CEO power and innovation resilience. By linking executive governance, reputational mechanisms, and digital transformation to sustained innovation capacity, this study advances understanding of the organizational foundations of corporate sustainability under uncertainty. The findings provide theoretical insights and managerial implications for designing governance structures that support long-term sustainable development.

Mitochondrial dysfunction and cardiomyocyte death drive pressure overload-induced heart failure (HF). N-lactylphenylalanine (N-Lac-Phe) plays an important role in the myocardial metabolic network after infarction. However, its role in chronic pressure overload heart failure remains unclear. This study examines N-Lac-Phe’s effects on cardiac function in transverse aortic constriction (TAC)-induced heart failure and mitochondrial function in Angiotensin II (Ang II)-injured H9c2 cardiomyoblasts. Human plasma Lac‑Phe levels were measured by liquid chromatography-mass spectrometry (LC-MS) and correlated with heart failure. In mice, echocardiography and other methods assessed the impact of Lac‑Phe on cardiac function, H9c2 cardiomyoblasts, and mitochondria. In vitro, H9c2 cells were treated with Ang II and Lac‑Phe, followed by analysis of apoptosis and mitochondrial dysfunction using immunoblotting and fluorescent staining. Plasma Lac‑Phe levels were negatively correlated with cardiac function. In TAC‑induced heart failure mice, Lac‑Phe administration improved cardiac function, attenuated myocardial injury including fibrosis, hypertrophy, apoptosis and ferroptosis, and alleviated the downregulation of MFN2. In Ang II‑injured H9c2 cardiomyoblasts, Lac‑Phe reduced apoptosis, restored mitochondrial function, and upregulated p‑AMPK, PGC‑1α and MFN2 expression. N-Lac-Phe correlates with cardiac function and improves TAC-induced heart failure by reducing apoptosis, ferroptosis, and mitochondrial damage. It may attenuate Ang II-induced apoptosis and mitochondrial dysfunction via the AMPK/PGC-1α/MFN2 axis.

Background:Systemic inflammation plays a critical role in the prognosis of coronary heart disease, and the Systemic Immune-Inflammation Index (SII) reflects both inflammatory status and immune balance. While elevated SII has been associated with adverse outcomes, its prognostic value in chronic coronary syndrome (CCS), particularly among diabetic patients, remains unclear. Hyperglycemia-induced inflammation, which enhances neutrophil activation and platelet reactivity, contributes to a more severe atherosclerosis burden in diabetes. This study investigated the predictive value of SII in CCS patients and examined whether diabetes modifies this relationship. Methods:From January to December 2022, a cohort of 853 individuals with CCS who underwent coronary angiography was retrospectively analyzed and stratified by SII and glycometabolic status. This retrospective cohort study utilized fully anonymized data from the Coronary Heart Disease Database of Nanjing Drum Tower Hospital. Major adverse cardiovascular and cerebrovascular events (MACCEs), comprising cardiovascular death, nonfatal myocardial infarction, heart failure, ischemia-driven revascularization, and stroke, served as the primary endpoints. Kaplan-Meier analysis, Cox proportional hazard models, and restricted cubic spline (RCS) models were performed to evaluate the independent and combined effects of SII and glycometabolic status on clinical outcomes. Results:Over a median follow-up period of 36 months, 85 patients (9.96%) experienced MACCEs. Higher log-transformed SII remained an independent predictor of MACCEs in the whole cohort (hazard ratio (HR) 1.63, 95% confidence interval (CI) 1.05-2.55, P = 0.031) and particularly among patients with diabetes (HR 2.24, 95% CI 1.31-3.82, P = 0.003) after full adjustment. However, there was no statistical significance among non-diabetic individuals (P = 0.772). Comparable findings were observed when SII was analyzed using the optimal cutoff value or quartiles. RCS analysis showed that MACCEs risk appeared to increase linearly with rising SII levels among diabetic patients. Furthermore, the combination of elevated SII and diabetes identified the subgroup with the poorest prognosis (P< 0.01). Conclusion:Elevated SII levels independently predict adverse outcomes in patients with CCS, with a stronger prognostic effect among those with diabetes. These findings suggest that SII may serve as a simple and accessible marker for personalized risk stratification in CCS, especially in patients with diabetes.

BACKGROUND AND AIM:Serum uric acid (SUA) is associated with cardiovascular disease (CVD) prognosis, and statins may modulate SUA levels. The purpose of this study is to investigate the prognostic value of SUA in statin-treated CVD patients. METHODS AND RESULTS:This study included and evaluated a cohort of 2739 CVD participants taking statins in 10 NHANES cycles between 1999 and 2018. The primary endpoints were defined as all-cause mortality and cardiovascular mortality by linkage to national death records. Kaplan-Meier analysis compared survival across SUA levels, while restricted cubic splines (RCS) evaluated dose-response relationships. Evaluate the hazard ratio and 95% CI of all-cause and cardiovascular mortality in CVD patients and subgroups using a weighted Cox proportional hazards regression model. The median SUA of patients in the queue was 5.9 (4.9-7.1) mg/dl. During a median follow-up period of 74 months, 1167 all-cause death and 479 cardiovascular death were recorded. The highest SUA quartile had a significantly increased risk of developing the primary endpoint (P < 0.001), and the RCS showed a linear relationship between SUA levels and endpoint events (P < 0.001). In the LDL-C < 70 mg/dL subgroup, fully adjusted models showed SUA positively correlated with all-cause mortality (HR: 1.148, 95% CI: 1.021-1.291, P = 0.021) and cardiovascular mortality (HR: 1.229, 95% CI: 1.014-1.490, P = 0.036). CONCLUSIONS:High SUA levels are associated with poor prognosis in CVD patients who achieve LDL-C control targets by taking statins. SUA is a potential indicator reflecting residual risk in CVD patients.

AIMS:Myocardial ischaemia‒reperfusion (I/R) injury triggers a robust inflammatory storm cascade that critically compromises reperfusion efficacy following acute myocardial infarction. Enhanced efferocytosis by cardiac resident macrophages (RMs) has therapeutic potential for inflammation resolution. The unsaturated long-chain fatty acid Maresin1 (MaR1) exhibits potent anti-inflammatory properties that is devoid of immunosuppressive effects. However, its therapeutic potential in myocardial I/R injury and regulatory mechanisms in cardiac RMs remains unexplored. METHODS AND RESULTS:A clinical case‒control study was conducted and revealed a negative association between circulating MaR1 levels and inflammatory markers and the severity of I/R injury in patients with ST-elevation myocardial infarction. Mice treated with MaR1 after myocardial I/R injury showed improvements in cardiac function and efferocytosis by cardiac RMs. Genetic ablation of cardiac RMs abolished MaR1-mediated cardioprotection. To explore the mechanism underlying this protection, we performed transcriptomic, metabolomics, and lipidomic analyses and identified fatty acid β-oxidation potentiation as a key metabolic signature in MaR1-treated RMs. Moreover, MaR1 directly bound peroxisome proliferator-activated receptor γ (PPARγ), inducing the transcriptional activation of its downstream efferocytosis-related target CD204. Specific knockout of PPARγ in RMs significantly attenuated MaR1-enhanced efferocytosis. Notably, oral supplementation with the MaR1 precursor docosahexaenoic acid (DHA) recapitulated these cardioprotective effects. CONCLUSION:Our findings prove that MaR1 plays a protective role in myocardial I/R injury by facilitating efferocytosis by RMs and the resolution of inflammation. These results offer novel therapeutic perspectives for the management of myocardial I/R injury.

Recent studies have highlighted the close relationship between gut microbiota and the cardiovascular system; however, the precise mechanisms and modes of their interaction remain incompletely understood. Among the various factors involved, bacterial extracellular vesicles (EVs) are often overlooked, despite their potential roles in multiple pathological processes. To investigate the role of bacterial EVs in shaping the inflammatory microenvironment following myocardial ischemia-reperfusion injury, we colonized the intestines of Rosa26.tdTomato reporter mice with Escherichia coli (E. coli) expressing Cre recombinase. Using FACS-beads and immunofluorescence techniques, we found that myocardial ischemia-reperfusion injury in mice significantly enhanced the invasion of gut-derived bacterial EVs. Meanwhile, in patients with ST-segment elevation myocardial infarction, we also confirmed the invasion of bacterial EVs via the FACS-bead method, and there was a significant correlation between extracellular vesicles in peripheral blood and LPS, suggesting that these EVs can be key carriers for LPS translocation. In this pathological process, invading E. coli EVs exacerbate the mobilization and infiltration of systemic and local inflammatory cells, thereby aggravating myocardial damage and impairing cardiac function. Notably, glucagon-like peptide-2 can effectively alleviate inflammatory responses and myocardial injury by inhibiting the translocation of E. coli-derived EVs. In conclusion, our study is the first to confirm the impact of gut-derived EVs on myocardial ischemia-reperfusion injury, revealing that E. coli EVs can amplify inflammatory responses. These findings provide new insights into the gut-heart axis and offer a theoretical basis for the therapeutic potential of glucagon-like peptide-2 in cardiovascular diseases.

Heart failure with preserved ejection fraction (HFpEF) constitutes a considerable global health burden and a major clinical challenge due to the absence of effective therapies, and the underlying pathophysiology remains elusive. Coronary microvascular dysfunction (CMD), which is highly prevalent in patients with HFpEF, triggers myocardial ischemia that impairs both left ventricular diastolic and systolic function. Given that microvascular dysfunction is a central feature of HFpEF, CMD is now considered an important factor in its pathogenesis. Coronary flow reserve (CFR), defined as the ratio of maximal hyperemic to resting blood flow velocity, is a highly valuable marker of myocardial ischemia. Furthermore, it serves as a comprehensive indicator of coronary vasomotor dysfunction, measuring the combined hemodynamic effects of both epicardial and microvascular coronary arteries on myocardial perfusion. This protocol focused on assessing the changes in CFR in a mouse model of HFpEF using Doppler echocardiography. In this study, control mice showed a greater than twofold increase in peak coronary blood flow velocity with isoflurane-induced vasodilation compared to resting values, whereas this response was significantly attenuated in HFpEF mice. In HFpEF, a reduced CFR predicts adverse outcomes and reflects underlying microvascular dysfunction, positioning it as a key tool for studying disease progression and guiding patient selection.

Abstract Urban green space (UGS) is a promising nature-based solution for cardiovascular health, yet its associative pathways in pollution-saturated, high-density environments remain contested. We applied a two-stage framework combining gradient boosting decision trees and structural equation modeling to a clinical cohort of 23,312 patients in Nanjing, China. Air-quality-related pathways accounted for more than 75% of the relative statistical contribution to model variance, exceeding psychological restoration proxies. At the macroscale, the aggregated air-quality pathway showed a marginal positive coefficient; although this may conceptually resemble aerodynamic interference, the interpretation remains speculative because no morphological or fluid-dynamics data were available. Stage 2 models identified distinct protective associative networks. For chronic ischemic heart disease, vegetation vitality was inversely associated with NO2 and SO2 and was linked to more favorable metabolic markers. For heart failure, the vegetation condition was associated with mixed pollutants and hemodynamic-metabolic indicators. Age-stratified analyses suggested heterogeneity in canopy density-PM2.5 associations, but subgroup slopes were nonsignificant, and effect sizes were extremely small, indicating fragile relative fluctuations rather than structural reversal. These findings characterize UGS primarily as a biophysical modulator and support targeted ecological strategies in traffic corridors and aging communities.

Background: Heart failure is a clinical syndrome caused by underlying cardiac structural functional impairment, leading to insufficient cardiac output and abnormally elevated intracardiac pressures in both resting and stress conditions. The stimulator of interferon genes (STING), a transmembrane protein in the endoplasmic reticulum, plays a pivotal role in initiating and sustaining chronic inflammatory responses. Aim: We investigated whether macrophage-derived STING contributes to the pathogenesis of heart failure with preserved ejection fraction (HFpEF). Methods and Results: Activated STING was detected in heart tissues of HFpEF mice. To study macrophage-cardiomyocyte interactions, we constructed a co-culture system bone marrow-derived macrophages (BMDMs) and HL-1 cardiomyocytes. STING activation in BMDMs, either via a gain-of-function mutation or an agonist, promoted hypertrophy co-cultured HL-1 cells. Mechanistically, macrophage STING activation increased Z-DNA binding protein 1 (ZBP1) expression in HL-1 cells and facilitated ZBP1-mediated inflammasome assembly. Conclusion: These findings provide novel insight into HFpEF pathogenesis and suggest that macrophage STING may serve as a potential therapeutic target.

In recent years, many countries and regions have witnessed a decline or lapse in voluntary blood donation, leading to blood shortages and instability in transfusion services. However, little is known about why previously active donors discontinue donating. Drawing on over 230 semi-structured interviews and 5,310 social media comments, this study employs grounded theory to construct an explanatory framework of donor lapse. The findings reveal five major drivers: institutional trust gap, cost-benefit imbalance, weakening of social norms, motivational instrumentalisation, and negative donation/use experiences. Based on these results, the study proposes a multidimensional “Push-Pull-Mooring-Trigger (P-P-M-T)” framework: institutional trust gap and weakening of social norms act as push forces driving donors away; perceived cost-benefit imbalance serves as a pull force toward discontinuation; motivational instrumentalisation operates as a key mediating mechanism; and negative donation/use experiences function as proximal triggers that catalyze final withdrawal decisions. This study advances understanding of the psychosocial and institutional mechanisms underlying donor lapse and provides actionable implications for sustaining voluntary blood donation systems.

BACKGROUND:The prevalence of atrial fibrillation (AF) and coronary events (CEs) overlap, yet their differential associations with risk factors and reciprocal mediation remain poorly characterized. METHODS:In a large Swedish cohort study (baseline: 1991-1996), subjects without preexisting AF, CEs, stroke, or heart failure were analyzed. Associations between baseline risk factors (age, sex, body mass index or waist circumference, smoking, alcohol intake, systolic blood pressure, diabetes, apoA1 (apolipoprotein A1) and apoB (apolipoprotein B) levels, leukocyte counts, education, physical activity, and medications) and incident AF or CEs were assessed using multivariable-adjusted Cox models, with association strengths compared using competing risk analysis. For each risk factor, we performed multivariable-adjusted mediation models for survival data separately, first with AF as a time-varying mediator for CEs, then reciprocally with CEs for AF, to estimate bidirectional mediation pathways. RESULTS:Among 25 963 subjects (aged 58.0±7.60 years, 62.0% women), 5447 incident AF and 3462 incident CEs occurred (1125 overlapped cases) over a median follow-up of 24.6 and 24.9 years, respectively. Various traditional risk factors were predominantly associated with CEs, whereas certain ones, particularly adiposity indices, demonstrated stronger associations with AF. Notably, higher apoA1 levels were associated with higher AF risk but lower CEs risk, whereas higher apoB showed opposite associations (P for equal associations <0.0001). Significant bidirectional mediation effects were found between AF and CEs. Prior CEs mediated 41.5% (95% CI, 8.5%-84.4%; P=0.0031) of the diabetes-associated AF risk, representing the highest degree of mediation among all risk factors analyzed. Conversely, prior AF mediated 26.1% (11.8%-48.2%; P<0.0001) of the effects of adiposity indices on subsequent CEs development. CONCLUSIONS:AF and CEs demonstrated divergent risk profiles and bidirectional mediation effects. These findings inform risk stratification for AF, CEs, and their co-occurrence, and highlight the need for integrated prevention strategies for the comorbidity of AF and CEs.

BackgroundMesenchymal stem cell (MSC)-based therapy has emerged as a promising alternative treatment for Alzheimer's disease (AD) but is limited by low cell survival rates and complex handling.ObjectiveThe present study explored the therapeutic potential of subcutaneous transplantation of MSC spheroids in a mouse AD model.MethodsWe prepared uniform size MSC spheroids with good stemness properties, and performed three consecutive subcutaneous treatments with MSC spheroids on early-stage AD APP/PS1 mice (6 months old), with each injection administered one month apart. Following treatment, behavioral experiments were conducted to evaluate learning and cognitive functions. Additionally, positron emission tomography (PET) and functional magnetic resonance imaging (fMRI) were utilized to assess cerebral glucose metabolism and neuronal functional connectivity. Subsequently, brain tissue sections were prepared and stained to evaluate amyloid plaque deposition, levels of inflammation, and other pathological changes.ResultsAPP/PS1 mice treated with MSC spheroids demonstrated better performance in cognitive behavioral tests compared to the AD model group. Imaging studies showed that brain glucose metabolism was higher in the MSC spheroids-treated group than in the AD model group, with enhanced functional brain connectivity. Moreover, pathological analysis revealed that MSC spheroids treatment resulted in a reduced amyloid-β plaque burden and attenuated inflammatory phenotypes in AD mice. MSC spheroids also protected neurons from apoptosis and restored synaptic plasticity.ConclusionsOur study suggests that subcutaneous transplantation of MSC spheroids reduced key pathological changes in AD by improving brain glucose metabolism and alleviating inflammation.

BackgroundCerebral infarction (ischemic stroke) is a highly time-sensitive acute cerebrovascular event, yet prehospital delays in patients’ accessing medical care remain prevalent across various countries and healthcare systems. Previous studies have primarily attributed delays to inadequate symptom recognition or barriers in healthcare accessibility, with limited systematic exploration of their formation mechanisms from a decision-making process perspective.MethodsThis study integrated the Self-Regulation Model and the three-stage delay model, employing an explanatory sequential mixed-methods approach to examine the cognitive and decision-making processes among cerebral infarction patients who delayed seeking care. A total of 68 patients completed the Brief Illness Perception Questionnaire, and semi-structured interviews were conducted with 16 of these patients.ResultsFindings indicate that delays in seeking medical care result from distinct mechanisms operating at different stages. During the appraisal delay stage, patients tended to normalize early or atypical symptoms. In the illness delay stage, optimism bias, self-regulatory overestimation, and doubts about medical efficacy reinforced a “wait-and-see” strategy. At the utilization delay stage, considerations of financial burden, family responsibilities, and societal role consequences significantly inhibited immediate healthcare-seeking behavior. Both quantitative and qualitative analyses revealed a cognitive-behavioral disconnect between illness perceptions and actual healthcare decisions.ConclusionThis study extends the explanatory power of Self-Regulation Model in healthcare decision-making contexts from a process-oriented perspective and offers a theoretical basis for designing staged, cognition-focused interventions aimed at reducing treatment delays.

Homozygous familial hypercholesterolemia (HoFH) is a rare inherited metabolic disorder. Meanwhile, HoFH is characterized by extremely high plasma levels of low-density lipoprotein cholesterol (LDL-C) from birth, alongside xanthomas and premature atherosclerotic cardiovascular diseases (ASCVDs). Traditional drugs such as statins have difficulty maintaining serum lipids at an ideal level. Here, we report the case of a 12-year-old child with HoFH who underwent liver transplantation. The goal of lipid reduction could not be achieved in this patient by any other means, and the patient had also experienced mild cardiovascular damage. During the 5-year post-transplant follow-up, the serum lipids were controlled in the patient, while the progression of atherosclerotic plaques was detected without the use of any lipid-lowering drugs. Additionally, we review the progress of current treatments for HoFH and discuss new lipid-lowering medications, as well as the challenges associated with liver transplantation.

Angio-based microvascular resistance (AMR) as a potential alternative to the index of microcirculatory resistance (IMR) and its relationship with microvascular obstruction (MVO) and other cardiac magnetic resonance (CMR) parameters still lacks comprehensive validation. This study aimed to validate the correlation between AMR and CMR-derived parameters and to construct an interpretable machine learning (ML) model, incorporating AMR and clinical data, to forecast MVO in ST-segment elevation myocardial infarction (STEMI) patients undergoing primary percutaneous coronary intervention (PPCI). We enrolled 452 STEMI patients from Nanjing Drum Tower Hospital between 2018 and 2022, who received both PPCI and CMR. After PPCI, AMR measurements and CMR-derived parameters were recorded, and clinical data were gathered. The ML workflow comprised feature selection using the Boruta algorithm, model construction with seven classifiers, hyperparameter optimization via ten-fold cross-validation, model comparison based on the area under the curve (AUC), and a Shapley additive explanations (SHAP) analysis to analyze the significance of different features. 32.29% of patients showed inconsistency between AMR and MVO, but we successfully constructed a predictive model for MVO. Among the classifiers, Extreme gradient boosting (XGBoost) post hyperparameter optimization displayed superior performance, achieving an AUC of 0.911 and 0.846 in the training and validation sets, respectively. SHAP analysis identified AMR as a pivotal predictor of MVO. Although we observed the inconsistency between AMR and MVO but the ML-based construction of MVO prediction model is feasible, which brings the possibility of timely prediction of patients with MVO and timely imposition of interventions during PPCI.