Cancers doi: 10.20517/2574-1209.2025.170

Authors: Sikai Xu,Yi Li,Fan Lin,Ping Zuo,Jingjing Fan,Xiaoyun Yang

Aim: Atrial fibrillation and atrial flutter (AF/AFL) represent a growing public health challenge in China amid rapid population aging. This study aimed to comprehensively assess long-term trends, sex- and age-specific patterns, driving factors, and future projections of AF/AFL burden in China from 1990 to 2023.

Methods: Data were obtained from Global Burden of Disease 2023. Temporal trends, driving factors, and future projections were evaluated using joinpoint regression, age-period-cohort models, decomposition analysis, frontier analysis, and autoregressive integrated moving average (ARIMA) models.

Results: From 1990 to 2023, the absolute numbers of AF/AFL cases, deaths, and disability-adjusted life years (DALYs) increased substantially in China, whereas age-standardized mortality and DALY rates declined overall, with a recent upturn after 2020. Incidence and prevalence were generally higher in males, whereas females had higher mortality and DALYs at older ages. Population aging was the dominant contributor to increases in incidence, prevalence, mortality, and DALYs. Age-period-cohort models analyses showed that among individuals born after 1944, the burden of AF/AFL was higher in males than in females. Frontier analysis indicated that China still lags behind several high Socio-demographic Index regions in AF/AFL burden control. ARIMA projections suggested declining mortality and DALYs but heterogeneous future trends in incidence and prevalence by sex.

Conclusions: Despite improvements in age-standardized mortality and DALYs, the overall burden of AF/AFL in China continues to increase, primarily driven by population aging. Targeted prevention, early detection, and optimized management strategies - particularly among older adults and high-risk males - are urgently needed.

Cancers doi: 10.20517/2574-1209.2025.134

Authors: Zifeng Yang,Zhi-Gang She

Atherosclerosis research has been significantly advanced by mouse models, particularly genetically engineered strains such as apolipoprotein E-deficient mice and low-density lipoprotein receptor-deficient mice (Ldlr^-/-). These mouse models replicate the hyperlipidemia-driven plaque pathogenesis, providing critical insights into lipid metabolism, inflammation, and therapeutic responses. Classic models play an important role in validating the effects of lipid-lowering therapies such as statins and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors. There are also some limitations, including species-specific lipoprotein profiles and incomplete replication of advanced human plaque complexity. Novel models have emerged to address these gaps, incorporating features such as hemodynamic stress, humanized lipid metabolism, and inducible gene regulation to complement the inadequacies of classic models, thereby better simulating the multifactorial complexity of atherosclerosis. For example, adeno-associated virus serotype 8 carrying the Pcsk9[D377Y] mutant gene and Ldlr-antisense oligonucleotide mice integrate hemodynamic stress, humanized lipid metabolism, and multifactorial comorbidities. However, there are still some shortcomings, including metabolic disparities, inadequate modeling of plaque rupture/thrombosis, and oversimplification of systemic disease interactions. Future directions prioritize next-generation models featuring humanized lipoprotein profiles, dynamic gene regulation, and combined with metabolic syndrome features. These approaches can be synergized with advanced phenotyping tools—including single-cell omics and intravital imaging—alongside artificial intelligence-driven multi-omics integration. By bridging translational gaps between murine pathophysiology and human disease complexity, these mouse models promise to accelerate the development of atherosclerosis therapies.

Cancers doi: 10.20517/2574-1209.2025.111

Authors: Wendi Yan,Huayang Zhang,Pingjing Zheng,Yuxiang Dai

Pan-vascular diseases comprise a spectrum of atherosclerosis-driven vascular disorders that involve multiple vital organs, including the heart, brain, kidneys, and peripheral circulation. Despite being distributed across different clinical specialties due to increasing medical subspecialization, conditions such as coronary artery disease, ischemic stroke, and peripheral artery disease are interconnected manifestations of a unified, systemic vascular pathology. This conceptual shift highlights the need to consider these disorders within an integrated pan-vascular framework rather than as isolated clinical entities. Inflammation is a central driver in pan-vascular pathogenesis, accelerating atherosclerosis and increasing cardiovascular event risk. In the inflammatory cascade of pan-vascular diseases, chemokines play a pivotal role as regulators, facilitating the recruitment and activation of immune cells. C-C motif chemokine ligand 17 (CCL17) is essential for T cell development in the thymus. It binds to the C-C chemokine receptor 4 (CCR4) and exhibits chemotactic activity towards T lymphocytes, mainly T helper 2 (Th2) cells and regulatory T cells. This review summarizes the biological properties of CCL17, its mechanistic roles in pan-vascular pathologies, and its clinical translational potential as a biomarker and therapeutic target.

Cancers doi: 10.20517/2574-1209.2025.115

Authors: Shao-Fei Liu,Si-Chang Fan,Rui-Qi Wang,Xiang-Jin Wang,Tian-Yang Lu,Jing-Wen Song,Yong-Jian Zhu,Zhifu Guo,Ni Zhu,Ping Yuan

Chronic lung diseases (CLDs) include a variety of disorders of the pulmonary vasculature and alveolar compartments, and they have become a considerable global health challenge due to their high morbidity and limited therapeutic options. Increasing evidence shows that cellular senescence, an irreversible cell-cycle arrest accompanied by altered secretory activity and resistance to apoptosis, plays a crucial role in the onset and progression of CLDs. One of the major consequences of senescence-associated secretory phenotype activity in senescent cells is the further exacerbation of CLD pathogenesis through the maintenance of chronic inflammation, tissue remodeling, and structural vascular changes. Although individual CLDs exhibit distinct pathological features, they share common mechanisms, including persistent inflammation and dysregulated tissue repair. Experimental models and new methods have advanced, demonstrating the promise of targeted approaches, such as senolytics and regulators of senescence-associated traits, for treating these diseases. This review evaluates how cell senescence is involved with pulmonary arterial hypertension, pulmonary fibrosis and chronic obstructive pulmonary disease, highlights both shared and different pathologic routes, and discusses using seno-therapeutic methods within precision medicine plans.

Cancers doi: 10.20517/2574-1209.2025.47

Authors: Adine Rosalie de Keijzer,Reda Rhellab,Francesco Zito,Jolanda Kluin,Giovanni Melina,Johanna J.M. Takkenberg,Kevin M. Veen

Clinical decision-making for individuals undergoing valvular and aortic surgery remains challenging, particularly in young patients facing lifelong risk and repeated interventions. As predictive technologies such as artificial intelligence and advanced statistical modelling evolve, the surgical community must ensure that key foundational elements, namely data governance, including data standardization, and regulation, are firmly in place. Without high-quality, standardized, and ethically governed data, predictive models risk offering misleading guidance rather than meaningful personalization. While data governance ensures the scientific robustness of predictive technologies, shared decision-making (SDM) ensures these innovations remain closely aligned with the lived experiences, values, and preferences of individual patients. This perspective emphasizes that advancing decision-making in aortic surgery requires deliberate investment in building data ecosystems and fostering SDM communication practices, ensuring that innovation is both scientifically sound and truly responsive to patient needs.

Cancers doi: 10.20517/2574-1209.2025.85

Authors: Luca Galassi,Matteo Giulio Verri,Henri Bartolozzi,Apollonia Verrengia,Federica Facchinetti,Matteo Lino Ravini

Endovascular recanalization has revolutionized the treatment of peripheral artery disease (PAD), offering minimally invasive alternatives to open surgery. However, permanent metallic stents, while effective in restoring blood flow, are associated with long-term complications such as chronic inflammation, restenosis, and stent thrombosis. Bioresorbable scaffolds (BRS) have emerged as an innovative solution, providing temporary mechanical support while delivering antiproliferative drugs before fully degrading, thus eliminating the risks associated with permanent implants. Significant advancements in bioresorbable materials have led to the development of new-generation scaffolds with improved radial strength, controlled degradation rates, and enhanced drug-eluting properties. Several BRS platforms, including polymer- and magnesium-based designs, are undergoing clinical and preclinical evaluation for peripheral applications. Early trials suggest that BRS may offer comparable short-term patency rates to conventional stents while potentially reducing late adverse events. However, challenges such as scaffold thrombosis, mechanical integrity in large and calcified vessels, and long-term efficacy remain under investigation. This narrative review explores the evolution of BRS technology, the mechanisms of scaffold resorption, current clinical evidence, and future prospects for their use in peripheral endovascular interventions. As research progresses, BRS may represent a paradigm shift in the treatment of PAD, offering a balance between structural support and vascular restoration.

Cancers doi: 10.20517/2574-1209.2026.03

Authors: Barry A. Franklin,Haoshuo Li,Yang Zhang

In this special interview, Professor Barry A. Franklin shared key experiential and research-based insights on professional success, exercise-based cardiovascular therapy, and the impactful role of cardiorespiratory fitness in promoting long-term health outcomes. (a) Professional success is built on clearly defined written goals, consistent daily action, personal responsibility, a mindset of happiness, optimism, and gratitude, and exemplary service to others; (b) Outstanding academic and clinical careers require effective mentorship, strong communication skills, advanced training and continuing education, disciplined work habits, and proactive management of stress and health; (c) Aerobic and resistance training provide complementary benefits in combating cardiovascular disease, with aerobic exercise contributing most strongly to long-term survival; (d) Cardiorespiratory fitness or VO₂max (maximum volume of oxygen uptake), expressed as metabolic equivalents (METs), is a powerful, independent, and additive predictor of survival, with each 1-MET (one metabolic equivalent) increase associated with a mortality reduction of ~ 15%-17%; (e) Higher fitness levels significantly reduce the risk and improve the prognosis of heart failure with preserved ejection fraction and heart failure with reduced ejection fraction, independent of body mass index and traditional risk factors; (f) Although aerobic fitness declines rapidly with detraining, it is reversible, while muscle strength can be largely maintained with one resistance training session per week; (g) To date, no pharmacologic therapy can elicit the increases in metabolism needed to improve fitness, as well as the associated favorable adaptations, and safe, accessible activities such as stair climbing and daily walking provide substantial cardiovascular risk reduction.

Cancers doi: 10.20517/2574-1209.2025.84

Authors: Yuan Li,Shao-Fei Liu,Lin Deng

We read with great interest a recent study investigating the role of nuclear receptor coactivator 7 (NCOA7) as a critical regulator of lysosomal function, oxysterol, and bile acid metabolism, and its link to endothelial cells (ECs) inflammation and immune activation in pulmonary artery hypertension (PAH). The study demonstrated that NCOA7 deficiency exacerbated lysosomal dysfunction, leading to inflammatory sterol accumulation and immune activation, which subsequently triggers endothelial immune responses. Translationally, NCOA7 activation emerges as a promising therapeutic strategy, while plasma oxysterol and bile acid levels offer potential prognostic biomarkers for PAH severity and mortality.

Cancers doi: 10.20517/2574-1209.2025.143

Authors: Weibin Zhou,Lei Zeng,Yangxin Chen,Feng Zhang

Aim: Pulmonary vascular endothelial cells (ECs) comprise functionally distinct subpopulations, including arterial, venous, general capillary (gCap), and aerocyte capillary (aCap) ECs, that are essential for the maintenance of lung function. SMAD family member 4 (SMAD4) signaling is a critical contributor to vascular homeostasis. This study aims to elucidate how SMAD4 affects individual endothelial subpopulations in the lung.

Methods: We curated a previously published single-cell RNA sequencing (scRNA-seq) dataset from Smad4-deficient (Smad4^fl/fl; Rosa26CreER^T2) and control (Smad4^fl/fl) mouse lungs, using a unified bioinformatic pipeline. Integrated analyses of cell clustering, differential gene expression, high-dimensional weighted gene co-expression network analysis (hdWGCNA), and chromatin immunoprecipitation sequencing were applied to resolve subpopulation-specific transcriptomic shifts and regulatory modules in the pulmonary endothelial compartment.

Results: SMAD4 deficiency induced markedly asymmetric transcriptomic changes across pulmonary vascular endothelial subpopulations. Upon Smad4 loss, arterial ECs largely preserved their core transcriptomic identity, whereas venous and gCap ECs transitioned into a vulnerable state characterized by aberrant proteostasis and reduced survival. Smad4-null gCap ECs also exhibited disrupted vascular homeostatic and morphogenic processes. Smad4-null aCap ECs displayed a distinct transcriptomic shift, manifested as gas-exchange dysregulation and immune activation, alongside shared defects in translation/protein folding and vascular morphogenic capacity. Regulatory modules and putative hub genes associated with venous/gCap EC vulnerability and aCap-specific transcriptomic shift upon SMAD4 deficiency were further identified.

Conclusion: These findings define a lineage-resolved framework for SMAD4 signaling in the pulmonary endothelium and uncover molecular vulnerabilities that may inform EC subpopulation-targeted vascular interventions.

Cancers doi: 10.20517/2574-1209.2025.122

Authors: Xingyu Li,Hongqiang Zhang,Junhao Zhang,Minghui Chen,Jie Shi,Lijie Sun,Haifeng Yao,Chenghua Li,Xueying Zheng,Sihua Liu,Hao Hu

Aim: Cardiovascular-kidney-metabolic (CKM) syndrome accelerates aging and increases mortality. We evaluated whether Triglyceride-Glucose-Waist-to-Height Ratio (TyG-WHtR), a marker of insulin resistance, predicts mortality in CKM and whether age acceleration mediates this association.

Methods: This investigation enrolled 16,145 individuals diagnosed with CKM syndrome. The relationships between TyG-WHtR and mortality were examined using multivariable Cox proportional hazards models, threshold effect analysis, and restricted cubic splines. Besides, the mediating role of age acceleration was investigated through mediation analysis. Risk within different populations was assessed using interaction tests and subgroup analysis.

Results: In multivariate Cox proportional hazards analyses, TyG-WHtR showed a positive association with mortality outcomes. Per one standard deviation (1-SD) increase, the hazard of cardiovascular death was 18% higher (hazard ratio (HR): 1.180; 95% confidence interval (CI): 1.08-1.29), while all-cause mortality risk rose by 8.6% (HR: 1.086, 95%CI: 1.01-1.17). Both cardiovascular and all-cause mortality showed a strong U-shaped association with TyG-WHtR. Mediation analysis revealed that PhenoAge acceleration and Klemera-Doubal Method age acceleration mediated 19.7% and 15.8% of the association between TyG-WHtR and all-cause mortality, respectively, and 20.7% and 16.8% of the association between TyG-WHtR and cardiovascular mortality, respectively.

Conclusion: TyG-WHtR is associated with mortality in patients with CKM syndrome, partly through accelerated aging. It is positively associated with age acceleration and exhibits a U-shaped relationship with mortality. Targeting the metabolic-aging crosstalk may help reduce mortality in CKM patients.

Cancers doi: 10.20517/2574-1209.2025.123

Authors: Chaofan Geng,Yi Tang

Panvascular aging-related diseases, including coronary artery disease, ischemic stroke, and peripheral artery disease, are leading global causes of death and disability, yet their management remains fragmented. Emerging technologies offer solutions to this challenge. Big data integration across imaging, multi-omics, wearables, and environmental exposures provides opportunities for cross-organ insights but faces issues of heterogeneity and privacy. Artificial intelligence enables early detection and refined risk prediction by recognizing subtle vascular changes and integrating biomarkers, though adoption is limited by interpretability and bias. Foundation models, through cross-modal learning, offer a unifying framework for mechanism discovery, personalized management, and digital twin applications. By linking technological innovation with clinical practice, these approaches can transform panvascular aging management and promote healthy longevity. Importantly, translating these innovations into policy and practice will be essential for advancing equitable vascular health and achieving population-level impact.

Cancers doi: 10.20517/2574-1209.2025.124

Authors: Yiwen Dai,Tonglin Fan,Ning Huangfu,Qingbo Xu,Ting Chen

The integrity of the vascular endothelium is fundamental to its barrier function, maintaining vascular homeostasis and microenvironmental stability, and serves as a prerequisite for preventing certain vascular diseases. After vascular integrity is compromised, endothelial progenitor cells (EPCs), a diverse population of progenitor cells with the capacity to develop into endothelial cells, can reconstruct blood vessels. This occurs primarily through two mechanisms: (1) direct integration into existing vessels for repair; and (2) paracrine secretion of proangiogenic factors to promote EPC mobilization and migration, regulate immune functions, and inhibit endothelial hyperplasia. This review aims to elucidate the mechanisms by which EPCs participate in vascular remodeling, and to discuss the latest advances in clinical translation strategies such as cell therapy, EPC-derived exosome therapy, and EPC functional modulation, as well as the current challenges in standardization and clinical application.

Cancers doi: 10.20517/2574-1209.2025.103

Authors: Jiaji Liu,Jiahao Cui,Liqun Chi,Jinglun Shen,Shuai Li,Lin Liang

Aim: This study examines the learning curve for vein-to-aorta anastomosis in minimally invasive coronary artery bypass grafting (MICS CABG) and develops a virtual reality (VR) simulation model for this procedure, with validation to confirm its clinical relevance.

Methods: We analyzed 132 consecutive off-pump MICS CABG procedures with multi-vessel grafting performed by a single surgeon (January 2017-January 2020). Proximal anastomosis time was plotted against case sequence, and the learning curve was quantified using cumulative summation analysis. A VR simulation platform was developed to reproduce key clinical challenges, using hierarchical geometric modeling and real-time physics simulation of tissue-instrument interactions with haptic feedback. Cardiac surgery experts evaluated the VR simulator via a structured questionnaire.

Results: The learning curve for proximal anastomosis followed a three-phase progression, with proficiency achieved after 52 cases (model fit R² (the coefficient of determination) = 0.994). The VR simulation accurately replicated key surgical scenarios, focusing on bimanual suturing mechanics and needle-vessel interactions. Expert validation yielded an overall validity index of 0.78 (exceeding the 0.7 threshold), confirming good construct validity and clinical relevance of the simulator.

Conclusion: Proficiency in MICS CABG proximal anastomosis is achieved after 52 cases, marking the inflection point of the learning curve. Our physics-validated VR simulator, supported by expert evaluation, has potential to accelerate surgical skill acquisition and shorten the learning curve.

Cancers doi: 10.20517/2574-1209.2025.131

Authors: Yahui Li,Xuhui Liu,Xindi Yue,Ru Sun,Haojiang Li,Qingqing Li,Ling Zhou,Chunxia Zhao,Feng Wang

Aim: Reliable prognostic tools remain limited for patients with ST-segment elevation myocardial infarction (STEMI) undergoing percutaneous coronary intervention (PCI) more than 48 h after symptom onset. This study aimed to develop and externally validate a nomogram based on routinely available in-hospital clinical variables to predict post-discharge adverse outcomes in this population.

Methods: We retrospectively analyzed data from Tongji Hospital between June 2019 and August 2022 and identified 198 STEMI patients who underwent delayed PCI as the training cohort. Independent predictors of composite adverse events, defined as all-cause mortality, nonfatal myocardial infarction, and New York Heart Association class IV heart failure, were identified using multivariate Cox proportional hazards regression. A nomogram was subsequently constructed and internally validated using bootstrap resampling. External validation was performed in an independent cohort of 599 patients treated at the Second Hospital of Lanzhou University, with a median follow-up duration of 20 months.

Results: Four variables were identified as independent predictors of adverse outcomes and incorporated into the nomogram: (1) heart rate > 83 beats per minute (hazard ratio [HR] 2.786, 95% confidence interval [CI]: 1.226-6.32, P = 0.014); (2) absence of statin therapy (HR 0.213, 95%CI: 0.064-0.71, P = 0.012); (3) intraoperative slow-flow/no-reflow phenomenon (HR 2.889, 95%CI: 1.247-6.69, P = 0.013); and (4) requirement for mechanical ventilation (HR 7.469, 95%CI: 2.57-21.70, P < 0.001). The nomogram demonstrated good discrimination and calibration in the training cohort, with a concordance index of 0.782. External validation confirmed its robust predictive performance. Patients classified as high risk exhibited significantly lower event-free survival compared with those at low risk (P < 0.0001).

Conclusion: This validated nomogram, derived from routinely collected clinical variables, provides reliable prediction of adverse outcomes in STEMI patients undergoing delayed PCI and may facilitate individualized risk stratification and optimized post-discharge management.

Cancers doi: 10.20517/2574-1209.2025.128

Authors: Ze-Yang Wu,De-Yong Long,Rong-Hui Yu,Cai-Hua Sang,Chen-Xi Jiang,Wei Wang,Xin Zhao,Chang-Yi Li,Chang-Qi Jia,Xue-Yuan Guo,Man Ning,Li Feng,Wen-He Lv,Yu-Kun Li,Xue-Si Wang,Xiao-Ying Liu,Zhuo-Hang Du,Jian-Zeng Dong,Ri-Bo Tang,Chang-Sheng Ma

Aim: To evaluate the long-term impact of obstructive sleep apnea (OSA) risk profile on atrial fibrillation (AF) recurrence after catheter ablation in patients with paroxysmal AF.

Methods: This prospective study enrolled 161 patients with paroxysmal AF undergoing initial ablation. Patients were stratified by the Berlin Questionnaire (BQ) into high-risk (n = 94) and low-risk (n = 67) OSA groups. Atrial tachyarrhythmias occurring within the initial three months were defined as early recurrence, whereas recurrence beyond three months was defined as late recurrence. A subgroup of 71 patients with recurrence underwent a redo ablation.

Results: After 16.1 ± 0.4 years, multivariable models revealed that a BQ-defined high OSA risk was independently associated with early recurrence (odds ratio [OR] 1.99, 95% confidence interval [CI] 1.02-3.86, P = 0.043), whereas it was not independently associated with late recurrence after the initial procedure (hazard ratio [HR] 1.05, 95%CI: 0.70-1.57, P = 0.810). Cox regression identified early recurrence (HR 2.95, 95%CI: 1.99-4.39, P < 0.001) and baseline high-sensitivity C-reactive protein (hs-CRP; HR 1.02, 95%CI: 1.00-1.03, P = 0.022) as independent predictors of late recurrence after the initial procedure. Following redo ablation, early recurrence remained a strong independent predictor (HR 5.93, 95%CI: 2.13-16.50, P < 0.001).

Conclusions: The BQ-defined high OSA risk was an independent predictor of early recurrence; however, it was not significantly associated with late recurrence after AF ablation. Early recurrence was the strongest predictor of long-term outcome, highlighting the importance of management during the post-procedural blanking period.

Cancers doi: 10.20517/2574-1209.2025.156

Authors: XueJian Wang,Bo Li,JingYa Gao,ZhengYao Ma,SuMin Yang,MeiHua Zhang,Kun Wang

Heart failure (HF) is a syndrome of global concern with high morbidity and mortality, whose complex molecular regulatory mechanisms are not yet fully understood. Moving beyond the traditional research framework focused on microRNAs, long non-coding RNAs (ncRNAs), and circular RNAs, this review concentrates on the pivotal roles of emerging ncRNAs - specifically Piwi-interacting RNAs (piRNAs), transfer RNA-derived small RNAs (tsRNAs), and small nucleolar RNAs (snoRNAs) - in the pathological progression of HF. In the acute phase of HF, these molecules rapidly respond to stressors such as ischemia and hypoxia. They directly influence cardiomyocyte fate and acute injury outcomes by regulating processes including apoptosis, necroptosis, autophagy, and inflammatory responses. During the chronic phase, they are deeply involved in pathological myocardial remodeling. They precisely regulate cardiomyocyte hypertrophy, cardiac fibroblast activation, and interstitial fibrosis in a cell-specific manner, maintaining a fine-tuned balance between pro-pathological and protective functions. These discoveries significantly enrich the molecular regulatory map of HF and reveal the considerable potential of these ncRNAs as novel non-invasive biomarkers and promising therapeutic targets. Of particular note, strategies employing engineered exosomes to deliver specific snoRNAs have demonstrated therapeutic effects in preclinical models, such as reversing fibrosis and improving cardiac function. This marks a shift in the treatment paradigm for HF toward precise RNA-level regulation.

Cancers doi: 10.20517/2574-1209.2025.112

Authors: Jiarui Zhang,Sen Wang,Yue Zeng,Hualin Lan,Guangchao Zang

Cardiovascular diseases (CVDs) are among the leading causes of global morbidity and mortality, placing a substantial burden on public health and socioeconomic development. Early and accurate diagnosis is essential for reducing CVDs mortality and optimizing individualized treatment strategies. Although conventional detection methods, such as enzymatic analysis and immunoassays, have reached a relative level of maturity in clinical applications, they are still constrained by high costs, complex procedures, and limited real-time capabilities. In recent years, electrochemical immunosensors have shown significant potential for detecting CVD-related biomarkers, owing to their advantages of high sensitivity, excellent selectivity, rapid response, and portability. In this review, we explore the latest advancements in electrochemical immunosensors for CVDs research, analyze innovative designs and fabrication techniques for various sensor types, and summarize their applications in detecting CVD-related biomarkers.

Cancers doi: 10.20517/2574-1209.2025.167

Authors: Zhongyu Ren,Wenya Ma,Xiuxiu Wang,Yining Liu,Xinlu Gao,Benzhi Cai

Heart Failure (HF) represents the terminal stage of various cardiac diseases and is classified into Acute Heart Failure (AHF) and Chronic Heart Failure (CHF) based on the onset speed. Both are characterized by impaired myocardial function, neurohumoral disturbance, and ventricular remodeling, yet exhibit significant differences in pathophysiological mechanisms and clinical phenotypes. MicroRNAs (miRNAs), a class of non-coding RNAs approximately 18-25 nucleotides in length, regulate gene expression at the post-transcriptional level by targeting the 3' untranslated region (3'UTR) of target gene messenger RNAs. They are extensively involved in physiological and pathological processes such as cell proliferation, apoptosis, and fibrosis. A growing body of evidence has confirmed that abnormal miRNA expression profiles are closely associated with the occurrence and progression of HF, playing a crucial regulatory role in the pathological processes of both AHF and CHF. This review systematically examines the biological characteristics of miRNAs and elaborates on their core regulatory roles in the pathophysiological mechanisms of AHF and CHF. It analyzes differences and commonalities in miRNA expression and function between the two conditions, and explores the clinical application prospects of miRNAs as diagnostic markers, prognostic indicators, and therapeutic targets for HF. Finally, it summarizes current research challenges and future directions, aiming to provide a theoretical basis for the precise diagnosis and treatment of HF.

Cancers doi: 10.20517/2574-1209.2025.147

Authors: Shenghao Zuo,Tongshuai Guo,Hui Ren,Hang Cao,Yanjie Yang,Ruiyu Wang,Chenyang Liu,Yan Zhuo,Tian Xia,Xiao Yuan,Mingke Chang,Guilin Hu,Yue Sun,Xi Zhang,Mingfei Du,Hao Jia,Ziyue Man,Teng Zhang,Jianjun Mu,Mei Zuo

Aim: We aimed to resolve the paradoxical associations of limb circumference—inverse with mortality but positive with cardiovascular risk factors (CVRFs)—by systematically comparing the predictive value of the ratio of combined arm and thigh circumference (ATC) to waist circumference (WC) against that of the sum of ATC for mortality and key CVRFs.

Methods: Our analysis utilized data from 17,276 U.S. participants in the 1999-2006 NHANES (National Health and Nutrition Examination Survey). We utilized Cox proportional hazards, generalized linear, and restricted cubic spline models, with comprehensive adjustment for confounders including adiposity. The outcomes assessed were all-cause and cardiovascular mortality, hypertension, diabetes, and resting tachycardia.

Results: During median 18.04-year follow-up (3,927 deaths, 1,047 cardiovascular deaths), the highest versus lowest ATC/WC quartile showed consistently protective associations: all-cause mortality (hazard ratio (HR) = 0.47, 95% confidence interval (95%CI): 0.38-0.57), cardiovascular mortality (HR = 0.32, 0.21-0.49), hypertension (OR = 0.49, 0.41-0.59), diabetes (odds ratio (OR) = 0.26, 0.18-0.37), and resting tachycardia (OR = 0.28, 0.19-0.39; all P < 0.001). Conversely, ATC exhibited adiposity-dependent paradoxical associations: protective for mortality but harmful for CVRFs when unadjusted for adiposity. After adiposity adjustment, ATC's harmful CVRFs associations were attenuated or reversed, while mortality benefits persisted. ATC/WC demonstrated superior linearity in dose-response relationships compared to ATC.

Conclusion: The ATC/WC ratio consistently demonstrates protective associations with both mortality and CVRFs. The waist standardization approach clarifies the relationship between limb measurements, cardiovascular health, and mortality by adjusting for central adiposity-related confounding that limits the utility of absolute rather than relative peripheral limb measurements.

Cancers doi: 10.20517/2574-1209.2025.120

Authors: Yalan Wu,Xiao Yu Tian

Panvascular aging is characterized by a systemic decline in vascular integrity that underlies the pathogenesis of multiple age-related diseases. Rather than affecting isolated vascular beds, aging triggers widespread changes across the entire circulatory system, including both large vessels and microcirculation in multiple organs. Core mechanisms encompass endothelial dysfunction, glycocalyx degradation, oxidative stress, inflammaging, and disturbed mechanotransduction, which converge to impair vascular homeostasis. At the cellular level, telomere shortening, epigenetic remodeling, and vascular smooth muscle cell phenotypic switching accelerate senescence and extracellular matrix stiffening. Importantly, panvascular aging propagates through systemic inter-organ axes, such as the brain-vascular and heart-kidney networks, thereby amplifying shared pathogenic pathways and promoting organ dysfunction. Consequently, it constitutes an integrative framework linking cardiovascular disease, diabetes, chronic kidney disease, and neurodegeneration. Recognizing panvascular aging as a common pathophysiological axis underscores the importance of developing systemic strategies that enhance vascular resilience beyond singular disease-oriented approaches. Emerging therapeutic strategies - including senotherapeutics, epigenetic modulators, glycocalyx restoration, and metabolic restoration - are being explored as promising interventions to attenuate vascular aging and mitigate multimorbidity. This review synthesizes current insights into the molecular and mechanobiological mechanisms of panvascular aging and frames it as a conceptual keystone in aging biology, highlighting translational opportunities for the prevention and treatment of chronic age-related diseases.

Cancers doi: 10.20517/2574-1209.2026.01

Authors: Xin Wang,Wenrui Sun,Shaoping Nie,Wei Gong

Heart failure (HF) is a complex syndrome driven by structural remodeling, fibrosis, metabolic imbalance, and oxidative stress. Circular RNAs (circRNAs) have emerged as pivotal regulators in HF, distinguished by their covalently closed structure, stability, and tissue specificity. While they modulate myocardial hypertrophy, fibrosis, and metabolic pathways through mechanisms including microRNA (miRNA) sponging, protein interactions, and transcriptional regulation, emerging evidence highlights their critical role in regulating intracellular Ca²⁺ homeostasis and excitation-contraction (E-C) coupling. By modulating key calcium-handling proteins, circRNAs directly influence cardiomyocyte contractility and arrhythmia susceptibility, linking RNA networks to dynamic cardiac function beyond structural remodeling. Beyond their mechanistic roles, the inherent stability and tissue-specificity of circRNAs position them as highly promising biomarkers for early diagnosis, risk stratification, and therapeutic monitoring. Furthermore, their therapeutic potential is rapidly unfolding; strategies involving extracellular vesicle delivery or targeted silencing offer viable cell-free approaches to inhibit fibrosis and restore cardiac function. This review systematically dissects the multifaceted roles of circRNAs in HF, from their fundamental impact on pathophysiology to their translational journey as biomarkers and therapeutic targets. We also explore current challenges and future directions, providing a comprehensive theoretical framework for the development of circRNA-based precision interventions for heart failure.

Cancers doi: 10.20517/2574-1209.2025.142

Authors: Jinhong Fan,Ziqi Li,Lihua Lin,Jiaqi Hou,Qianqian Chai,Longjiang Wu,Jing Huang,Jianghua Du,Qian Liu

Heart failure (HF), a major cause of cardiovascular mortality worldwide, develops through a multifaceted process involving cardiomyocyte apoptosis and necrosis, metabolic dysregulation, fibrosis, and sustained inflammatory activation. Although B-type natriuretic peptide (BNP) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) are routinely used in clinical assessment, their susceptibility to external influences limits their capacity to fully capture the molecular progression of HF. Emerging evidence has identified long non-coding RNAs (lncRNAs) as important epigenetic regulators that contribute to reduced myocardial contractility and ventricular remodeling. Clinical studies further indicate that circulating lncRNAs - particularly those packaged within exosomes - possess notable stability and strong disease specificity, making them promising candidates for improving diagnostic and prognostic evaluation. With ongoing advances in transcriptomic profiling and exosome-based technologies, the potential use of lncRNAs is also extending into forensic identification. This review synthesizes current insights into lncRNA-mediated regulation in HF progression, evaluates recent developments in circulating lncRNA detection, and explores their emerging forensic applications. It also outlines key limitations in existing research and discusses future directions to support deeper investigation into the molecular mechanisms underlying cardiac death and their relevance to forensic practice.

Cancers doi: 10.20517/2574-1209.2025.172

Authors: Mengmeng Long,Xinya Han,Jingyi Sheng,Ning Gu

Ischemia-reperfusion injury (IRI) is a pathophysiological process occurring after blood supply restoration to tissues or organs, causing unexpected cellular damage. It involves multiple complex mechanisms, but inflammation and oxidative stress are the main causes. IRI can damage vital organs such as the heart, brain, liver, and kidneys, affecting patient prognosis and quality of life. Therefore, the prevention and treatment of IRI have become a key area in clinical and basic research. Prussian blue, a metal-organic framework material, is approved by the U.S. Food and Drug Administration for treating heavy metal poisoning. In 2016, research indicated that Prussian blue nanoparticles had multi-enzyme activities like catalase, peroxidase, and superoxide dismutase, enabling them to scavenge reactive oxygen species and combat inflammation, establishing them as a highly promising nanozyme. Leveraging their unique antioxidative and anti-inflammatory properties, Prussian blue nanozyme (PBNZ) can directly target key pathological pathways of IRI. Furthermore, PBNZ can serve as efficient drug delivery systems, and through functional modifications, they enable the targeted delivery of therapeutic agents, thereby synergistically enhancing treatment efficacy. Currently, PBNZ have demonstrated significant therapeutic potential in IRI models involving various organs and tissues such as the heart, brain, liver, kidneys, and skin flaps. This review aims to outline IRI's key pathological mechanisms, analyze how PBNZ combats oxidative stress and inflammation, and summarize its recent application advancements in treating IRI in different organs. The goal is to offer theoretical reference and research insights for the future development of novel nanozyme-based therapeutic strategies against IRI.

Cancers doi: 10.20517/2574-1209.2025.121

Authors: Siyu He,Junting Zhang,Yiying Li,Huiyu Liu,Xiaowei Nie,Jin-Song Bian

Pulmonary hypertension (PH) is a progressive and life-threatening disorder characterized by elevated pulmonary arterial pressure, vascular remodeling, and right ventricular failure. While the pathogenesis of PH involves endothelial dysfunction, inflammation, and excessive extracellular matrix (ECM) deposition, emerging evidence highlights the pivotal role of integrin-mediated signaling in driving vascular cell behavior and tissue stiffness. Integrins, a family of heterodimeric transmembrane receptors, serve as critical mechanosensors and signal transducers between cells and the ECM. The dysregulation of integrins has been confirmed to promote pathological vascular remodeling through the following mechanisms: (1) Activating focal adhesion kinase (FAK) and Src family kinases, driving excessive proliferation and resistance to apoptosis of pulmonary artery smooth muscle cells; (2) Enhanced transforming growth factor-beta (TGF-β) signaling leads to the transformation of fibroblasts into myofibroblasts and excessive collagen deposition; (3) Ras homolog gene family, member A/Rho-associated protein kinase-mediated cytoskeletal recombination disrupts the integrity of the endothelial barrier, exacerbating inflammation and thrombosis. These pathways collectively increase vascular hardness and maintain a pro-remodeling microenvironment of pulmonary vessels. This review summarizes the current understanding of integrin signaling pathways in PH, with a focus on αvβ3, α5β1, and β1-containing integrins, their downstream effectors (e.g., FAK, TGF-β), and their interplay with inflammatory and fibrotic processes. We also discuss preclinical and clinical evidence supporting integrin-targeted therapies, including Myocardin-related transcription factor 1 and Cilengitide, as potential strategies for modulating vascular remodeling in PH. However, their clinical transformation remains challenged by limited efficacy, context-dependent signaling, and safety concerns. A deeper understanding of integrin biology may facilitate the development of more precise and effective therapeutic strategies for PH.

Cancers doi: 10.20517/2574-1209.2025.136

Authors: Jie Min,Mengyu Zhang,Zeyu Xu,Qiurong Wang,Lin Yang,Subat Turdi,Mengyuan Wang,Wei Guo,Fangpeng Li,Russel J. Reiter,Jun Tao,Zhaohui Pei,Jun Ren

Aim: Maternal overnutrition predisposes offspring to an increased prevalence of cardiovascular disease, yet the specific underlying mechanisms remain elusive.

Methods: This study examined the roles of inflammation and ferroptosis in driving fetal cardiac structural and functional alterations following maternal overnutrition. Multiparous ewes were fed either a control diet [100% of National Research Council (NRC) recommended requirements] or an overnutrition diet (150% of NRC requirement) from 60 days preconception until gestational day 135. Cardiac geometry, histomorphology, immune cell infiltration, cardiomyocyte function, intracellular Ca²⁺ handling, and expression of inflammatory and ferroptotic markers were assessed in fetal hearts.

Results: Despite comparable fetal crown-rump lengths and organ weights (e.g., brain and liver), fetuses from overnourished ewes exhibited significantly lower body and heart weights. Maternal overnutrition induced marked cardiac atrophy, interstitial fibrosis, lipid deposition, and oxidative damage, coupled with increased neutrophil and monocyte infiltration. At the cellular level, cardiomyocytes from overnourished fetuses exhibited impaired contractile and intracellular Ca²⁺ properties. Molecular profiling revealed that maternal overnutrition significantly upregulated proinflammatory markers (CD14, CD68, IL1A, IL1B, IL6, TLR4, and iNOS), and increased IκB phosphorylation (indicating NFκB activation). Concurrently, overnutrition suppressed IL18 and M-CSF expression, alongside the ferroptosis-defense proteins GPX4 and SLC7A11.

Conclusion: These findings demonstrate that maternal overnutrition creates a proinflammatory and ferroptosis-prone myocardial environment, resulting in pathological structural remodeling and functional impairment of fetal hearts. Our data suggest that targeting the inflammation-ferroptosis signaling may help to mitigate the developmental programming of cardiovascular disease.

Cancers doi: 10.20517/2574-1209.2025.145

Authors: Yuzhe Han,Jiazhen Sui,Hongyu Cao,Xinru Jiang,Haifeng Zhang,Yu Wang,Jianxun Wang

Small nucleolar RNAs (snoRNAs) are increasingly recognized as key regulatory factors in cardiovascular disease (CVD), with functions that extend far beyond the traditional scope of ribosomal RNA modification. This review synthesizes current knowledge regarding the biology of snoRNAs and their emerging roles in CVD, aiming to provide a clear theoretical framework for their pathogenic mechanisms and clinical significance. We first discuss the biogenesis, classification, and functional diversity of snoRNAs, covering both classical modification roles and non-classical functions such as the regulation of messenger RNA splicing, participation in the DNA damage response, and the generation of snoRNA-derived small RNAs. In CVD, snoRNAs exhibit spatiotemporal dysregulation and are extensively involved in pathological processes ranging from congenital heart defects and cardiomyopathy to coronary artery disease, myocardial infarction, arrhythmias, and heart failure. Specific gene clusters, particularly 14q32 snoRNAs, repeatedly emerge as key regulatory nodes in processes such as vascular remodeling and platelet activation. However, the majority of dysregulated snoRNAs remain orphaned with unknown targets, limiting our understanding of their mechanisms and clinical translation. We emphasize that combining computational modeling with multi-omics approaches can accelerate target identification and functional elucidation. Finally, we systematically examine the opportunities and challenges facing the clinical translation of snoRNA research, including their potential as dynamic biomarkers, limitations of detection technologies, and barriers to therapeutic delivery. By comprehensively reviewing existing evidence and future directions, this review highlights the significant potential of snoRNAs as novel biomarkers and therapeutic targets for the precision diagnosis and treatment of cardiovascular diseases.

Cancers doi: 10.20517/2574-1209.2025.153

Authors: Xiangyi Wang,Xin Tu

Cardiovascular diseases (CVDs) involve structural and functional abnormalities of the heart and blood vessels, in which genetic factor plays a significant role. Non-coding RNAs (ncRNAs), as important products of genetic material, are important contributors to CVDs. They mainly regulate the expression of targets and participate in various biological processes such as cell proliferation, cell apoptosis, and signal transduction. Genetic variation in ncRNAs can affect the expression levels of ncRNAs themselves and their downstream targets, leading to the dysregulation of biological processes and contributing to the occurrence and development of CVDs. This review aims to summarize the current research status of ncRNA genetic variation in CVDs and clarify the functions and biological mechanisms of ncRNA genetic variation involved in CVDs.

Cancers doi: 10.20517/2574-1209.2025.144

Authors: Jiazheng Yang,Wenzi Wu,Yijie Duan,Meichen Pan,Longjiang Wu,Shujuan Wang,Jing Huang,Jianghua Du,Qian Liu

Aortic dissection (AD) is a rapidly progressive cardiovascular disease associated with high mortality. The core pathogenic mechanisms of AD include apoptosis and phenotypic switching of vascular smooth muscle cells (VSMCs), remodeling and degradation of the extracellular matrix (ECM), and vascular inflammation. However, the detailed molecular mechanisms remain incompletely understood. Noncoding RNAs (ncRNAs) are RNA molecules that do not encode proteins. Recent studies have confirmed that ncRNAs with aberrant expression exert critical regulatory functions in the pathogenesis and progression of AD, and several ncRNAs have shown significant application potential in the early diagnosis, conservative treatment, and prognostic assessment of AD. This review summarizes the latest research progress on the regulatory mechanisms of various ncRNAs in AD, and critically evaluates their potential clinical utility as clinical biomarkers and therapeutic targets for AD.

Cancers doi: 10.20517/2574-1209.2025.175

Authors: Yiheng Wang,Fan Yang,Yutong Zuo,Yan Zheng,Quanchi Liu,Jianlong Cui,Zhaoyi Luo,Ruilin Chen,Xiaoming Xu,Yunlong Xia

Heart failure (HF) is characterized by profound mitochondrial dysfunction, a central pathogenic mechanism driven by interconnected defects in metabolic dysregulation, excessive oxidative stress, impaired biogenesis, imbalanced dynamics, and defective mitophagy. This compromised mitochondrial fitness leads to bioenergetic deficiency, cardiomyocyte death, and progressive cardiac remodeling. MicroRNAs (miRNAs) have emerged as critical post-transcriptional regulators of mitochondrial homeostasis, capable of simultaneously modulating multiple components within these pathways. By fine-tuning the expression of key genes involved in fission/fusion, mitophagy, and biogenesis, miRNAs can either exacerbate or ameliorate HF progression, forming a complex and context-dependent regulatory network, and highlighting the potential of targeting the miRNA-mitochondria axis. However, clinical translation faces significant hurdles including target specificity, tissue-selective delivery and patient heterogeneity. Future research should focus on deciphering the mechanistic interplay between miRNA regulation and mitochondrial function in diverse HF contexts. This review aims to elucidate the molecular mechanisms by which miRNAs regulate mitochondrial dysfunction in HF, revealing novel therapeutic targets. A deeper understanding of this regulatory network is crucial for advancing HF management from symptom palliation toward mechanism-based precision medicine.

Cancers doi: 10.20517/2574-1209.2025.135

Authors: Yahui Li,Xuhui Liu,Yidan Chen,Xujie Wang,Ru Sun,Haojiang Li,Qingqing Li,Ling Zhou,Chunxia Zhao,Feng Wang

Aim: To identify factors associated with late atrial fibrillation (AF) recurrence after radiofrequency catheter ablation and to develop a nomogram for individualized risk prediction, followed by external validation in an independent cohort.

Methods: We conducted a retrospective cohort study of patients with AF who underwent catheter ablation at Tongji Hospital (training cohort, January 2020-December 2022) and the Second Hospital of Lanzhou University (validation cohort, June 2020-June 2023). Follow-up visits were scheduled at 1, 3, 6, 12, and 18 months after the procedure. Candidate predictors were identified using the Boruta algorithm and the least absolute shrinkage and selection operator. Selected variables were then entered into multivariable Cox proportional hazards models. Model performance was evaluated using Harrell’s C-index, time-dependent area under the receiver operating characteristic curve, calibration plots, and decision curve analysis.

Results: A total of 256 patients in the training cohort and 203 in the validation cohort were included, with a median follow-up of 12 months. Late AF recurrence occurred in 21.9% and 21.2% of patients, respectively. Six variables were included in the final model: early recurrence (HR = 7.616), left atrial diameter (HR = 1.684), intraoperative electrical cardioversion (HR = 1.423), serum creatinine (HR = 1.018), use of angiotensin-converting enzyme inhibitor (ACEI)/angiotensin receptor blocker (ARB)/angiotensin receptor-neprilysin inhibitor (ARNI) (HR = 0.426), and AF duration (HR = 1.003). The nomogram showed good discrimination, calibration, and clinical usefulness in both cohorts.

Conclusion: We developed and externally validated a six-variable nomogram for predicting late AF recurrence after catheter ablation. This model may support individualized risk stratification and guide post-ablation management.

Cancers doi: 10.20517/2574-1209.2025.93

Authors: Giulia Ciccarelli,Luca Weltert,Hans-Joachim Schäfers,Ruggero De Paulis

Understanding the geometry and thus the possibility of repairing the aortic valve (AV) has evolved over time thanks to the integration of historical insights and technological advances. The aortic root geometry has proven to be central to understanding valve function. Today, with modern finite element models and flow studies supported by four-dimensional magnetic resonance imaging, we have provided a better understanding of the importance of the sinuses of Valsalva in blood flow dynamics. Their presence reduces cusp stress, improves repair durability, and promotes the adoption of valve prostheses with incorporated sinuses. Looking to the future, the scientific community must push towards a better fusion of currently available technologies to address AV repair, towards personalizing procedures to fit the unique anatomy of each patient. New technologies, including artificial intelligence, can provide personalized surgical simulations. The goal is to make techniques more standardized, reproducible and accessible, while maintaining flexibility to address anatomical variability. Additionally, new materials and tools are being explored to further improve outcomes.