Pulmonary hypertension (PH) is a multifactorial, progressive disease characterized by pulmonary vascular remodeling and right heart failure, representing a substantial global health burden. Dysregulated interactions among multiple cell types within the pulmonary vascular microenvironment, particularly macrophage polarization imbalance with a predominant transition toward the M2 phenotype, play a critical role in driving pro-fibrotic and pro-remodeling processes in PH. Lactylation, a novel post-translational modification that covalently links lactate to lysine residues, translates glycolytic metabolic signals into persistent epigenetic changes. Recent advances have identified lactylation on histones (e.g., H3K18la), non-histone proteins, and mitochondrial proteins, revealing new layers of regulatory complexity. Elucidating the role of lactylation, particularly its impact on macrophage polarization and vascular cell function, may offer novel insights into the pathogenesis of PH and identify potential therapeutic targets. • Macrophage polarization imbalance (predominant M2 phenotype) is a critical driver of pulmonary vascular remodeling in pulmonary hypertension (PH), and lactylation serves as a novel metabolic–epigenetic bridge linking macrophage metabolic reprogramming and phenotypic switching. • Lactylation modifications occur extensively on histones, non-histone proteins, and mitochondrial proteins in PH, regulating fibrosis-related pathways, arginine metabolism signaling, and the dysfunction of pulmonary vascular cells. • Targeting lactylation and lactate metabolism represents a promising therapeutic strategy for PH, supported by our previous studies on M2 macrophage polarization and ongoing lactylomic research.

Chest pain evaluation has become increasingly imaging-led with widespread use of coronary CT angiography (CTCA) and stress imaging (e.g., CMR, stress echocardiography). In this context, the clinical role of exercise treadmill testing (ETT) is debated because its accuracy for obstructive coronary artery disease (CAD) is generally lower than that of contemporary imaging. This narrative review reassesses the value of ETT in current chest pain care by summarizing diagnostic performance, exercise-derived prognostic/functional information, cost and resource implications, and its positioning in major society guidelines, to clarify where ETT remains clinically useful. PubMed, Embase, and the Cochrane Library were searched for English-language studies published from 2010 onward. Priority was given to major clinical guidelines, diagnostic meta-analyses, prognostic cohort studies, and cost-effectiveness evaluations relevant to stable or low-to-intermediate risk chest pain assessment. Contemporary evidence shows that ETT has modest sensitivity for obstructive CAD but retains reasonable specificity when used in appropriately selected patients with an interpretable baseline ECG and adequate exercise capacity. Beyond diagnostic classification, ETT yields physiologic and functional markers—exercise capacity, chronotropic response, heart rate recovery, blood pressure response, symptom reproduction, and arrhythmia provocation—that are strongly associated with future cardiovascular outcomes and are not fully captured by anatomic testing alone. As an inexpensive, widely available test that avoids radiation and iodinated contrast, ETT remains a pragmatic option for low-risk patients and for systems with limited access to advanced imaging. Current ESC and AHA/ACC guidance continues to reserve a role for exercise ECG within risk-adapted pathways, particularly for functional assessment and selected diagnostic scenarios. ETT should be viewed as complementary to advanced imaging rather than competitive. When embedded in risk-stratified pathways and applied to the right population, it provides clinically meaningful functional and prognostic information at low cost. Its utility is greatest in low-risk stable chest pain, for exercise physiology assessment, and in resource-constrained settings.

High-altitude pulmonary hypertension (HAPH) is a condition characterized by elevated pulmonary arterial pressure exceeding normal physiological values, resulting from a combination of high-altitude low-pressure, hypoxic environments, genetic susceptibility, immune dysfunction, and neurogenic disturbances. This condition predominantly manifests as right heart failure, severely impacting quality of life and life expectancy. Macrophages, as one of the most prevalent innate immune cells, have been increasingly recognized for their crucial role in the pathogenesis of HAPH. The low-pressure and hypoxic environment, along with other etiological factors, lead to metabolic abnormalities in tissue cells and the microenvironment. This results in increased secretion of chemokines, cytokines, and growth factors in the microenvironment, which promote the proliferation of tissue-resident macrophages and the differentiation of monocytes recruited from the blood into macrophages. This exacerbates the inflammatory cascade, further promoting cell proliferation, tissue repair, and inhibition of apoptosis. These processes contribute to the migration and proliferation of pulmonary arterial smooth muscle cells, endothelial cells, and fibroblasts, leading to vascular remodeling and ultimately the development of pulmonary arterial hypertension. This review examines the role of macrophage-mediated immune responses in high-altitude pulmonary arterial hypertension, with a focus on hypoxia as a key feature.

Pulmonary hypertension is a major cardiovascular disease characterized by the persistent elevation of pulmonary artery pressure, leading to vascular remodeling, fibrosis, and endothelial dysfunction. In recent years, the TGF-β signaling pathway and miRNAs have played important roles in the pathogenesis of PH. TGF-β regulates the proliferation, migration and fibrosis of vascular smooth muscle cells through the classical Smad pathway and non-classical pathways such as PI3K/Akt and MAPK. miRNAs such as miR-21, miR-145, and miR-204 play key roles. Among them, miR-21 promotes the proliferation and migration of vascular smooth muscle cells, miR-145 inhibits the overproliferation and fibrosis of vascular smooth muscle cells, and miR-204 alleviates vascular remodeling by inhibiting TGF-β signaling. The combination of CRISPR gene editing and an exosome delivery system can precisely regulate miRNA expression, thus providing new therapeutic targets for pulmonary hypertension.

BACKGROUND:Heart failure (HF) guidelines recommend routine testing for iron deficiency (ID) and, for those with ID, intravenous iron if the left ventricular ejection fraction is <50%. Guideline adherence to these recommendations by cardiologists in China is unknown. METHODS AND RESULTS:An independent academic web-based survey was designed and distributed via social networks to cardiologists across China. Overall, 1342 cardiologists (median age 34 years, IQR 30-39, 51% women) from all provinces of China completed this survey. More than half were unaware of the need to screen for ID in HF and did not do so routinely in their clinical practice. Approximately 80% were not familiar with the diagnostic criteria for ID in HF guidelines, and only 0.8% recognised transferrin saturation <20% as an independent marker of ID. Regarding iron repletion, only 14% preferred intravenous to oral iron for correcting ID compared with 68% favouring oral iron. Three-quarters were unfamiliar with methods for calculating intravenous iron dose. Furthermore, over 80% were unaware that current guidelines only recommend ferric carboxymaltose or ferric derisomaltose for correcting ID. The main barriers to using intravenous iron were lack of knowledge and experience. Despite such poor awareness and practice, most cardiologists were interested in learning more about managing ID in HF. CONCLUSIONS:In this nationwide survey of cardiologists in China, we identified large gaps in both knowledge and management of ID. This survey will help guide the development of educational programmes to improve care for patients with HF and ID in China.

Heart failure (HF) is a complex clinical syndrome influenced by diverse mechanisms of cellular demise. Recent findings indicate that ferroptosis also plays a role in the pathogenesis of HF. The present investigation utilized network pharmacology to investigate the suppressive impact of atorvastatin calcium (AC) on ferroptosis in a rat model of HF. The rats were categorized into three groups: the control group, the doxorubicin-induced group, and the doxorubicin (DOX)-induced group + AC-treated group. Echocardiography, enzyme-linked immunosorbent assay, and Western blotting were employed to evaluate cardiac structural and functional changes. Additionally, network pharmacology methods were utilized to ascertain the potential targets of AC and their interactions with regulatory genes associated with ferroptosis and HF. We identified four HF-related ferroptosis regulatory targets of AC: nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 1 (NOX1), tumor protein 53 (TP53), dipeptidyl peptidase 4 (DPP4), and glutathione peroxidase 4 (GPX4). Enrichment analysis revealed three signaling pathways influenced by AC in HF: ferroptosis, fluid shear stress and atherosclerosis, and lipid and atherosclerosis. This study indicated that AC can improve cardiac systolic dysfunction, reduce ventricular volume, and reverse myocardial remodeling in a doxorubicin-induced HF rat model. We highlight the role of ferroptosis in mediating this therapeutic effect through solute carrier family 7 member 11 (SLC7A11)/TP53 signaling pathway regulation and shed light on new directions for clinical treatment.

Objective:Transforming growth factor beta (TGF-β) is a key regulator of macrophage polarization, yet its role in high-altitude pulmonary hypertension (HAPH) remains poorly understood. This study aimed to explore the effects of TGF-β on macrophage polarization under high-altitude conditions and elucidate the molecular mechanisms driving macrophage phenotypic changes in HAPH, with potential therapeutic implications. Methods:A HAPH rat model was established by exposing rats to a hypoxic environment simulating 5,000 m altitude for 4 weeks. Rats were prophylactically treated weekly with the TGF-β inhibitor SB-431542. Pulmonary artery pressure and right ventricular hypertrophy index were measured to confirm model establishment. Hematoxylin and eosin staining, immunohistochemistry, and western blotting were used to assess TGF-β-Smad2/Smad3 signaling and macrophage polarization. Results:The HAPH group showed significantly increased pulmonary artery pressure and right ventricular hypertrophy index compared to controls. These changes were associated with elevated M2 macrophage levels, increased anti-inflammatory cytokines (IL-4 and IL-10), and enhanced TGF-β and Smad2/Smad3 signaling. TGF-β inhibition reversed these effects. Conclusion:The TGF-β-Smad2/Smad3 pathway promotes macrophage M2 polarization, driving HAPH progression through anti-inflammatory cytokine release. Inhibiting this pathway reduces M2 polarization and alleviates HAPH in rats, highlighting its therapeutic potential.

Background:ST-elevation myocardial infarction (STEMI) poses a significant threat to global mortality and disability. Advances in percutaneous coronary intervention (PCI) have reduced in-hospital mortality, highlighting the importance of post-discharge management. Machine learning (ML) models have shown promise in predicting adverse clinical outcomes. However, a systematic approach that combines high predictive accuracy with model simplicity is still lacking. Methods:This retrospective study applied three data processing and ML algorithms to address class imbalance and support model development. ML models were trained to predict one-year mortality in STEMI patients post-PCI, with performance evaluated using accuracy, sensitivity, precision, F1-score, area under the receiver operating characteristic curve (AUROC), and the area under the precision-recall curve (AUPRC). Results:We analyzed data from 1,274 patients, incorporating 46 clinical and laboratory features. Using the Random Forest (RF) algorithm, we achieved an AUROC of 0.94 (95% confidence interval (CI): 0.90-0.98), an AUPRC of 0.44 (95% CI:0.15-0.76) in the internal validation set, identifying five key predictors: cardiogenic shock, creatinine, NT-proBNP, diastolic blood pressure, and left ventricular ejection fraction. By integrating risk stratification, the model's performance improved, achieving an AUROC of 0.97 (95% CI: 0.96-0.99) and an AUPRC of 0.74 (95% CI: 0.60-0.84). Conclusion:This study highlights the feasibility of constructing accurate and interpretable ML models using a minimal set of predictors, supplemented by risk stratification, to improve long-term outcome prediction in STEMI patients.

BackgroundThe acute myocardial infarction (AMI) is a prevalent and severe cardiovascular disease, characterized by its sudden onset, high mortality rate, and unfavorable prognosis. The presence of type 2 diabetes not only signifies a chronic metabolic disorder, but also serves as a catalyst for various cardiovascular and cerebrovascular ailments such as coronary heart disease and stroke. Xining is situated in a region of middle to high altitude and due to its unique geographical environment, coupled with the population's limited health awareness, unequal medical standards and other factors, there remain some AMI patients who are difficult to diagnose early on. The objective of this study is to investigate the efficacy and prognosis of dapagliflozin in patients with acute myocardial infarction complicated by type 2 diabetes in the Xining region.Methodanalysis on January 1, 2018 to January 1, 2020, in Qinghai province people's hospital of cardiovascular internal medicine hospital treatment of 245 cases of acute myocardial infarction combined the clinical data of patients with type 2 diabetes. The patients were divided into dapagliflozin group and control group according to whether they took dapagliflozin during hospitalization. The basic data, laboratory examination indicators and long-term prognosis of the two groups were observed. Follow-up deadline is December 31, 2023, at the end of follow-up, including the primary endpoint and the secondary endpoint.Results245 patients were included in this study, age 34–94, the average age (61–11), 200 cases (81.63%) of men, women, 45 cases (18.37%), dapagliflozin group of men 92 cases (77.97%) and control group, 108 cases (85.04%). Two groups of patients' age, gender, diabetes duration, merge disease, echocardiogram and blood biochemical indexes, had no statistical difference (P > 0.05). There were no significant differences in the number of coronary artery lesions, treatment regimens, cardiovascular and hypoglycemic drugs between the two groups (P > 0.05). However, up to dapagliflozin group of patients after discharge significantly lower than the control group, the incidence of cardiovascular adverse events at dapagliflozin group of 4 cases of heart failure and cardiovascular death in 1 case and control group in heart failure 13 cases, 10 cases of cardiovascular death, cerebral hemorrhage 2 cases died. KaplanMeier survival analysis showed that the primary endpoint of survival was significantly higher in the dapagliflozin group than in the control group (P < 0.05). In addition, the overall survival rate of the dapagliflozin group was significantly higher than that of the control group, and the difference was statistically significant (P < 0.05).ConclusionsDapagliflozin is safe and reliable in the treatment of patients with acute myocardial infarction and type 2 diabetes, and can effectively reduce the incidence of cardiovascular events and improve the overall survival rate of patients.

Ferroptosis is a novel, iron-dependent cell death characterized by the excessive accumulation of ferroptosis lipid peroxides ultimately leading to oxidative damage to the cell membrane. Iron, lipid, amino acid metabolism, and other signaling pathways all control ferroptosis. Numerous bodily tissues experience hypoxia under normal and pathological circumstances. Tissue cells can adjust to these changes by activating the hypoxia-inducible factor (HIF) signaling pathway and other mechanisms in response to the hypoxic environment. In recent years, there has been increasing evidence that hypoxia and ferroptosis are closely linked, and that hypoxia can regulate ferroptosis in specific cells and conditions through different pathways. In this paper, we review the possible positive and negative regulatory mechanisms of ferroptosis by hypoxia-inducible factors, as well as ferroptosis-associated ischemic diseases, with the intention of delivering novel therapeutic avenues for the defense and management of hypoxic illnesses linked to ferroptosis.

To explore the research hotspots and frontier trends of ferroptosis and its association with clinical diseases both in China and internationally over the past decade. Utilizing the CNKI, PubMed, and Web of Science literature databases as data sources, we employed CiteSpace 6.2.R4 and VOSviewer software to visualize and analyze the authors, institutions, countries, and keywords related to ferroptosis and clinical diseases from 2013 to 2023. China Medical University has published the highest number of studies in the field of ferroptosis and clinical diseases in China. Furthermore, China leads globally in attention to this research area. In 2022, domestic and international scholars exhibited the closest collaboration in this field. The year 2020 saw the most extensive range of sub-studies on ferroptosis and clinical diseases both at home and abroad. The keywords "cancer" and "long non-coding RNAs (LncRNAs)" emerged as the most prominent research topics in recent years. Future research on ferroptosis-related diseases, including cancer, heart failure, type 2 diabetes, and Alzheimer's disease, should further investigate the regulatory mechanisms linking ferroptosis with mitochondria, the Golgi apparatus, and multi-site LncRNA interactions. This could provide valuable insights for subsequent studies on cancer and other diseases in the context of ferroptosis.

Background and Objective: Right heart failure (RHF) represents a complex clinical challenge, often resulting from pulmonary hypertension, left heart dysfunction or congenital heart diseases. Unlike left heart failure, treatments and interventions specifically targeting RHF are less defined, contributing to poorer patient outcomes and quality of life. SacubitrilNalsartan, a novel therapy originally approved for treating left heart failure, has shown potential due to its dual action of inhibiting neprilysin and blocking angiotensin receptors. Given its success in improving left ventricular function, there is increasing interest in exploring its efficacy and mechanisms in managing right heart failure. This study aims to fill the gap in current knowledge by systematically assessing the impact of SacubitrilNalsartan on right heartfunction, utilizing comprehensive diagnostic tools and functional assessments to delineate its potential benefits and implications for therapy in right heart failure. Materials and Methods: A randomized, controlled trial was conducted involving patients diagnosed with right heart failure. Participants were divided into two groups: The treatment group received SacubitrilNalsartan,while the control group received standard care. Baseline and post-treatment assessments included echocardiographic evaluation of rightventricular function, electrocardiographic analysis and the 6-Minute WalkTest (6MWT) to measure functional capacity. Statistical analysis was performed to compare the changes within and between groups. Results:The treatment group showed significant improvements post-treatment in echocardiographic parameters (RV ejection fraction (%), TAPSE, RA size), electrocardiographic findings (narrowing of QRS duration, shortening of QT interval and reduced heart rate) and functional capacity as measured by the 6MWT. These changes were statistically significant compared to the control group, indicating enhanced right ventricular function, improved cardiac electrical stability and increased exercise capacity. SacubitrilNalsartan demonstrated significant benefits in patients with right heart failure, improving right ventricular function, cardiac electrical activity and functional capacity. Conclusion:These findings suggest SacubitrilNalsartan as a viable therapeutic option for enhancing the clinical outcomes of patients with right heart failure. Further research is encouraged to explore the long-term benefits and potential integration into standard care protocols.

肠道菌群(GM)/肠道微生态(IM)在维持人体内环境稳态及维护健康方面具有重要意义.心血管疾病(CVD)是当前全球发病率及致死率均较高的一类疾病.已有研究证实,GM/IM失衡与CVD的发生及发展密切相关.GM/IM部分代谢产物也可作为CVD的生物标志物,对其进行检测或干预可能成为CVD诊断、预防或治疗的一种手段;从GM/IM层面进行临床药物代谢评价、药效评估、优效筛选也是临床药理学的一个研究方向.随着精准医学及大健康理念的推广实施,GM/IM全基因组测序及代谢组学等研究的深入,GM/IM与CVD关系的基础研究及临床应用转化也将成为今后的研究热点.本文就GM/IM与CVD的关系研究现状进行综述,旨在为CVD的防治提供诊疗思路及相关参考.

The above article from Cell Biology International, published online on 5 December 2022, on Wiley Online Library (https://doi.org/10.1002/cbin.11920), has been withdrawn by agreement between the journal Editor in Chief, Sergio Schenkman, and John Wiley and Sons Ltd. The withdrawal has been agreed due to a technical error at the publisher that caused the article to be mistakenly published online.

Atrial fibrillation（AF） is one of the most common arrhythmias in clinical practice. Its incidence is increasing, and it is an important factor causing adverse cardiovascular and cerebrovascular events, which seriously endangeres human health. Type 2 diabetes mellitus（T 2 DM） is one of the common chronic diseases, which can increase the risk of AF. Sodium-glucose cotransporter-2 inhibitors（SGLT2i） have been used in clinical practice as new hypoglycemic drugs and new anti-heart failure drugs, but little is known about their anti-arrhythmic properties. A large number of clinical trial data have shown that SGLT2i reduce the incidence of AF in patients with T 2 DM. This review summarizes the mechanism of action of SGLT2i reducing the occurrence of AF in patients with T 2 DM, and discusses the latest data from clinical studies and Meta-analysis studies, so as to provide new ideas for the prevention and treatment of AF.

急性心肌梗死是临床较为常见的心血管疾病之一,是在冠状动脉粥样硬化发生发展基础上,因血栓形成、斑块破裂所致心肌持久性缺血缺氧,造成局部心肌坏死.炎症因子参与冠状动脉粥样硬化斑块的形成和进展,与急性心肌梗死的发生发展存在密切的关系.本文就相关炎症因子在急性心肌梗死中的研究进展进行综述.

铁死亡是一种铁离子依赖的、以脂质活性氧簇累积为主要标志的全新程序性细胞死亡方式.铁死亡参与许多病理过程,除与肿瘤、老年性疾病、神经退行性疾病、代谢性疾病等发生发展密切相关外,还参与了心力衰竭、心肌病、冠状动脉粥样硬化等多种疾病过程.该文对铁死亡在心血管疾病中各种病理机制进行了综述,并简要阐述各类药物对铁死亡的作用,以提高人们对铁死亡作为心血管疾病治疗新靶点的认识.

The above article from Cell Biology International, published online on 5 December 2022, on Wiley Online Library (), has been withdrawn by agreement between the journal Editor in Chief, Sergio Schenkman, and John Wiley and Sons Ltd. The withdrawal has been agreed due to a technical error at the publisher that caused the article to be mistakenly published online.

目的:探讨高海拔藏族人群心电图P波参数与老年阵发性心房颤动(房颤)术后复发的关系.方法:选取2018年4月至2020年4月首次接受导管消融术的老年阵发性房颤患者132例,在术前、术后24 h内进行心电图检查,测量各导联P波时限(PWD)、P波振幅(PWA)、P波离散度(P-d)及P波指数(P-index)等.根据术后1年内是否复发AF分为复发组与非复发组,比较2组心电图P波参数,采用非条件logistic回归分析法分析导管消融术后AF复发的风险因子.结果:在132例接受射频消融术的房颤患者中,复发40例.术前复发组PWD、Pd、P-index等均高于非复发组[(143.22±13.47)ms对(126.54±10.38)ms,(48.49±10.35)ms对(38.53±11.04)ms,(10.64±3.14)ms对(9.25±2.57)ms,P均<0.05];术后复发组PWD、Ptf绝对值高于非复发组([(137.43±15.61)ms对(120.15±11.31)ms,(31.90±10.36)ms对(26.28±9.84)ms,P均<0.05].采用非条件Logistic回归分析发现PWD、P-d和Ptf绝对值升高是房颤患者射频消融术后复发的独立风险因素(P均<0.05).结论:术前P波参数PWD、P-d、Ptf绝对值升高可能增加射频消融术后房颤复发的概率.

Hypoparathyroidism predisposes patients to hypocalcemia. Patients with hypoparathyroidism are thus at risk of electrocardiographic abnormalities, including T-wave alternans. T-wave alternans is poorly understood and lacks uniform diagnostic criteria. Its presence suggests myocardial electrical instability, and it has become an important sign for identifying patients at high risk of malignant arrhythmias and sudden cardiac death. We report a rare case of T-wave alternans with torsade de pointes due to hypocalcemia. The etiology of T-wave alternans may easily be overlooked. It should thus be thoroughly investigated to avoid misdiagnosis and poor outcomes.