Patients with pulmonary embolism (PE) at high altitude face an increased risk of developing chronic thromboembolic pulmonary hypertension (CTEPH). This study aims to establish a diagnosis model of CTEPH patients at high altitude to optimize early screening.

A retrospective cohort of CTEPH and PE patients was rigorously selected through inclusion/exclusion criteria. Clinical data encompassing biochemical profiles, echocardiography, and CT angiography (CTA) were collected, yielding 103 candidate variables. Feature parameters were screened using the Boruta algorithm, followed by predictive model development with seven machine learning architectures. The optimal model was identified based on area under the curve (AUC). The optimal Random Forest model was subsequently interpreted through Shapley Additive Explanations (SHAP) to quantify feature contributions.

Among 57 PE patients, 44% met echocardiographic criteria for pulmonary hypertension following PE. Diameter of right atrium, diameter of right ventricle, Vessel-Grade (of embolization) and Sup-inferior (superior or inferior of embolization) were key identified predictors. Random Forests model had the highest AUC of 0.842. Enlarged right heart, embolization of small vessels and superior pulmonary artery embolism increased the risk of CTEPH, while normal right heart structure and isolated inferior pulmonary embolism reduced it.

The Random Forests model demonstrated potential for detecting CTEPH in PE patients, enabling early and rapid pulmonary hypertension assessment.

Hypertrophic cardiomyopathy (HCM) is a common inherited disease with substantial residual morbidity despite established pharmacological and surgical therapies. We conducted a narrative review of the current evidence on cardiac myosin inhibitors, drawing on published studies up to July 2025, including pivotal clinical trials, real-world cohorts, and pharmacokinetic analyses. Mavacamten and Aficamten consistently reduced left ventricular outflow tract (LVOT) gradients, improved New York Heart Association class, and were generally well tolerated under echocardiography-guided titration. Long-term extensions and real-world registries confirmed sustained efficacy, while pharmacogenetic factors and monitoring strategies continue to shape individualized use. Comparative analyses suggest Aficamten offers more rapid pharmacokinetics and simplified dosing, though both require careful safety surveillance. Remaining challenges include limited data in non-obstructive HCM, uncertain antifibrotic and rhythm outcomes, high cost, and the burden of frequent imaging and genetic testing. Beyond HCM, early studies are exploring broader indications and next-generation modulators. Cardiac myosin inhibition is reshaping the therapeutic landscape of HCM, but cost-effective, precision-based implementation and long-term outcome studies remain critical priorities.

Mesenchymal stem cells (MSCs) hold immense promise in regenerative medicine due to their unique capabilities, including differentiation into various cell types and paracrine signaling. Among their secretions, extracellular vesicles (EVs) play a pivotal role in mediating therapeutic effects through their bioactive cargo, including microRNAs (miRNAs). These miRNAs are key regulators of gene expression, modulating critical biological processes such as inflammation, immune response, and tissue repair. MSC-derived EVs have demonstrated significant therapeutic potential across diverse diseases, including cardiovascular, neurological, autoimmune, and oncological conditions. This review explores the biogenesis, isolation, and characterization of MSC-EVs, with a focus on the functional roles of miRNAs in disease modulation. The therapeutic prospects of MSC-EV miRNAs as potential biomarkers, drug delivery agents, and modulators of pathophysiological pathways are discussed, providing insights into future translational research and clinical applications.

Chanarin-Dorfman syndrome (CDS) is an ultra-rare autosomal recessive subtype of neutral lipid storage disorder (NLSD); it is characterised by ichthyosis and intracytoplasmic accumulation of lipid droplets containing triglycerides, most commonly in granulocytes, muscle fibres, skin and liver. Several pathogenic variants in the ABHD5/CGI-58 gene have been described. Clinical manifestations include steatohepatitis, myopathy, ophthalmic disease, developmental delay. Liver involvement is an important cause of morbidity and mortality. We present a case of a 26-year-old male diagnosed with ichthyotic NLSD in childhood, who developed progressive myopathy and cardiac fibrosis in adulthood. He was treated with a combination of low-fat diet, MCT oil and co-enzyme Q10 which resulted in an initial improvement in muscle strength and stabilisation of muscle symptoms and well-being. Synopsis: Medical and dietetic management of liver and muscle complications in Chanarin-Dorfman syndrome.

Hypertension represents a crucial risk factor in the development of cardiovascular diseases, including heart failure, stroke, coronary heart disease and myocardial infarction. Currently, synthetic angiotensin-converting enzyme (ACE) inhibitors are an important first-line treatment for hypertension. However, these synthetic ACE inhibitors often produce side effects in clinical application, such as cough, gustatory disturbance and skin rash. Thus, it is urgent to find safe and effective ACE inhibitors for the treatment of hypertension. Therefore, a series of ACE inhibitory peptides were studied using computational approaches. Initially, a reliable 3D-QSAR model was derived based on CoMFA (R _cv ² = 0.660, R _pred ² = 0.6674) and CoMSIA (R _cv ² = 0.646, R _pred ² = 0.6451) methods. Furthermore, molecular docking was also employed to explore the binding mode of the inhibitory peptides at the active site of ACE. At the same time, the ligand-receptor binding characteristics are consistent with the contour map information. Taken together, the derived 3D-QSAR and molecular docking results would offer trustworthy clues for further optimization of this series of ACE inhibitory peptides. Finally, three novel tri-peptides are designed as prospective ACE inhibitors, and the predicted activities by developed 3D-QSAR models, binding affinity by molecular docking, the experimental activity by DOJINDO ACE Kit-WST reagent box all show effective inhibition on ACE.

Vascular calcification, the deposition of calcium-phosphate crystals in the vasculature, occurs through a complex interplay between cellular processes and biochemical factors that are yet to be entirely defined. Vascular calcification results in stiffening of the arteries and ultimately cardiovascular complications. Deposition can occur either in the intima or media layers of a vasculature through discrete mechanisms and underlying pathologies. Medial calcification, the subject of this review, occurs in a specific set of pathologies including genetic disorders, diabetes, and chronic kidney disease. There are currently no approved therapies for prevention of medial vascular calcification leaving this an active area of unmet therapeutic need. One of the key molecule involved in preventing vascular calcification is pyrophosphate (PPi), long known as a potent inhibitor of mineralization. Many therapeutic avenues, both historical and current, have focused on increasing the plasma concentration of PPi. This can be accomplished by direct PPi supplementation or by use of bisphosphonates, acting as non-hydrolysable PPi analogs, though both approaches have limitations. Newer therapies utilize recombinant ENPP1, which generates PPi by hydrolysis of endogenous ATP, an approach which is currently being evaluated in clinical trials. Another approach to elevate plasma PPi concentration is by preventing enzymatic degradation of PPi through inhibition of alkaline phosphatase. Alternatively, chelation of either phosphate or calcium, the key constituent minerals of calcification, using phosphate binders represent other approaches as well as the use of magnesium and vitamin K supplementation. This review will first briefly discuss the pathophysiology of medial vascular calcification and describe the disease conditions involved before surveying the different therapeutic interventions evaluated to address the medial vascular calcification in the setting of genetic diseases as well as chronic diseases. We will present a bench to bedside view of development discussing therapeutic evidence in animal models, clinical trials and their relevance and applicability to clinical development.

The TTN gene (MIM:188840) encodes titin, the largest human protein with exclusive expression in the cardiac and skeletal muscles. Rare variants disrupting the TTN gene are frequent causes of dilated cardiomyopathy and several forms of skeletal myopathy. We report a unique occurrence of two novel, distinct but overlapping intragenic TTN deletions in multiple relatives from a single Czech family with the clinical manifestation of dilated cardiomyopathy (DCM). After clinical exome sequencing using the custom virtual gene panel, two distinct deletions affecting the TTN gene (NM_001267550.2) were detected. The first deletion (3.599 kb in length) encompasses five exons with the breakpoints in exons 326 and 330. The longer one (4.859 kb in length) disrupts exon 326 only. Both deletions segregate with the cardiomyopathy phenotype, and none of the tested individuals carry both. The familial segregation of two distinct intragenic TTN deletions extends the broad spectrum of rare variants in the pathogenesis of DCM. The presence of severely affected carriers of the reported DNA variants and obligatory healthy non-carriers raises the debate on their ancestral origin. Our data demonstrate the clinical benefits of the family cascade screening and molecular genetic analysis in familial DCM, enabling early and effective multidisciplinary medical care.

Vascular cognitive impairment (VCI) exhibits particularly high prevalence in East Asian populations. However, its pathogenesis remains elusive due to its multifactorial and complex nature. Emerging evidence highlights the microbiota-gut-brain axis as a novel and promising paradigm for elucidating VCI mechanisms and developing therapeutic interventions. This systematic review aims to synthesize recent advances in this field, offering critical perspectives to guide future research on VCI through the lens of gut-brain interactions. Notably, given Traditional Chinese Medicine's (TCM) holistic and multi-target therapeutic advantages, we incorporate TCM studies to complement conventional approaches.

We systematically searched PubMed, EMBASE, Web of Science, Cochrane Library, China National Knowledge Infrastructure (CNKI), Chinese Science and Technology Periodical Database (VIP), and Wanfang database for relevant studies from their inception to March 31, 2025, and conducted a comprehensive review.

A total of 22 relevant studies were included in the final review. Current research primarily focused on analyzing the altered gut microbiota in VCI patients, with findings indicating significant changes in both the structure and abundance of gut microbiota. Enterobacteriaceae exhibited potential as a diagnostic biomarker for post-stroke cognitive impairment (PSCI) (AUC=0.629), while distinct microbial signatures involving Bifidobacterium, Lactobacillus gasseri, and Anaerostipes hadrus may effectively differentiated PSCI patients from stroke survivors without cognitive deficits (AUC values of 0.785, 0.792, and 0.750, respectively). Furthermore, multiple interventional studies from both basic and clinical research systematically explored the microbiota-gut-brain axis as a promising therapeutic target for VCI. They evaluated the efficacy of diverse approaches-such as fecal microbiota transplantation, aerobic exercise, pharmacological interventions, and acupuncture-on key outcome including gut microbiota composition, cognitive function, hippocampal integrity, and inflammatory markers. Basic experimental studies revealed that Prevotella histicola, Clostridium butyricum, aerobic exercise, and TCM improved cognitive function, whereas trimethylamine N-oxide exacerbated cognitive impairment. The efficacy of TCM was further confirmed by clinical studies.

Research is in its early stages, but the microbiota-gut-brain axis already offers promising prospects for a deeper understanding and discovery of potential new therapeutic targets for VCI.

https://www.crd.york.ac.uk/prospero, identifier CRD42024560293.

We hypothesize that specific macrophage differentiation trajectories in heart failure (HF) are coupled with subtype-specific and context-dependent engagement of programmed cell death (PCD) pathways, particularly ferroptosis and anoikis, which in turn influence disease progression and remodeling. HF is a progressive and heterogeneous clinical syndrome characterized by adverse immune remodeling, yet the precise contributions of macrophage heterogeneity, lineage dynamics, and PCD programs to its pathogenesis remain unclear. This study aimed to delineate, at single-cell resolution, the cellular and molecular landscape of cardiac macrophage subpopulations and their engagement with immunogenic cell death programs.

We profiled human cardiac tissues from HF and non-failing donors using scRNA-seq from the SCP1303 dataset, initially comprising ~600,000 cells and reduced to ~120,000 high-quality cells from 18 samples after stringent quality control to retain biologically valid but metabolically distinct populations. Standardized cell-type annotation and pseudotime trajectory reconstruction were applied. Pathway activity was quantified using AUCell (primary) and GSVA (complementary) for cell death-related signatures. Integrated differential expression analysis, protein-protein interaction network mapping, and multi-algorithm feature selection (LASSO, SVM-RFE, Random Forest) were performed, and candidate biomarkers were validated using an independent bulk RNA-seq dataset (GSE57345).

Thirteen major cardiac cell types were identified, with macrophages showing the highest transcriptional heterogeneity. We resolved four macrophage subtypes and mapped bifurcating disease-associated differentiation trajectories, revealing distinct activation patterns of ferroptosis- and anoikis-related pathways. Ferroptosis-associated genes and anoikis-associated genes displayed subtype-specific enrichment and significant differential activation in HF. Pseudotime analysis demonstrated that suppression of ferroptosis and anoikis was linked to late-stage, HF-enriched macrophage states. Key biomarkers-including CD163, FPR1, and VSIG4-achieved robust diagnostic performance (AUC > 0.80) in discriminating HF phenotypes.

This is the first study to integrate scRNA-seq, differentiation trajectory inference, and PCD pathway scoring to define the context-dependent engagement of ferroptosis and anoikis in macrophage subtypes in HF. The identification of subtype-specific biomarkers and functional states provides novel mechanistic insight and potential diagnostic and therapeutic targets, underscoring the value of high-resolution immune profiling for precision immunology in cardiovascular disease.

Renal ischemia-reperfusion injury (IRI) is a key driver of the progression from acute kidney injury (AKI) to chronic kidney disease (CKD), primarily through mechanisms involving oxidative stress, ferroptosis, and inflammation that promote fibrotic remodelling. This study investigates the therapeutic potential of MIT-001, a mitochondria-targeted reactive oxygen species (ROS) scavenger, in mitigating renal IRI. In vitro, MIT-001 attenuated ferroptotic cell death and fibrotic responses in HK-2 cells challenged with TGF-β or RSL3. MIT-001 restored GPX4 expression and activity, activated Nrf2 signalling, reduced lipid ROS and suppressed fibrogenic markers (α-SMA, Snail, collagen IV), while preserving E-cadherin levels. In a bilateral renal IRI mouse model, administration of MIT-001 significantly improved renal function and histology. Oxidative stress (DHE staining), apoptosis (TUNEL) and ferroptosis (4-HNE, xCT, GPX4) were markedly reduced. Additionally, MIT-001 inhibited the NF-κB/HMGB1 inflammatory axis and enhanced antioxidant defence via the Nrf2/HO-1 pathway, resulting in decreased immune infiltration and fibrosis. These findings demonstrate that MIT-001 confers renal protection by concurrently targeting oxidative stress, ferroptosis and inflammation, underscoring its promise as a therapeutic strategy to prevent AKI-to-CKD progression.