Cardiovascular diseases (CVDs) remain a leading global health burden, necessitating novel insights into their pathogenesis and therapeutic strategies. Ferroptosis, an iron-dependent form of regulated cell death driven by lipid peroxidation, has emerged as a pivotal mechanism in CVD progression. This review comprehensively synthesizes current knowledge on the molecular drivers of ferroptosis, including dysregulated iron metabolism, glutathione peroxidase 4 (GPX4) inactivation, and redox imbalance orchestrated by Nrf2, AMPK, and p53. Subcellular organelles such as mitochondria, lysosomes, and the endoplasmic reticulum are highlighted as critical hubs for initiating or amplifying ferroptotic signals through oxidative stress, metabolic dysfunction, and organelle-specific interactions. The role of ferroptosis in major cardiovascular pathologies-atherosclerosis, vascular calcification, heart failure, ischemia-reperfusion injury, and arrhythmias-is systematically explored, emphasizing its contribution to cellular damage, inflammation, and tissue remodeling. Notably, this review incorporates discussions on spatial metabolomics as a powerful analytical tool, highlighting its unique capacity to decipher region-specific metabolic alterations and spatial distribution patterns of key molecules involved in ferroptosis, thereby providing deeper insights into the spatiotemporal dynamics of ferroptotic mechanisms in CVDs. Furthermore, emerging therapeutic strategies targeting ferroptosis, including iron chelators, lipid peroxidation inhibitors, and metabolic modulators (e.g., metformin, trimetazidine), are discussed for their potential to mitigate cardiovascular damage. By bridging molecular mechanisms (enhanced by spatial metabolomics insights) to clinical applications, this review underscores ferroptosis as a promising therapeutic target, advocating for further research to translate these insights into precision interventions for CVD management.

Chronic obstructive pulmonary disease is one of the leading causes of morbidity and mortality worldwide, and its frequent coexistence with cardiovascular diseases significantly increases the risk of exacerbations, hospital readmissions, and mortality. However, current care approaches are often fragmented, hindering comprehensive management for these complex patients. A group of experts from the Spanish Society of Pulmonology and Thoracic Surgery and the Spanish Society of Cardiology have collaboratively developed a document outlining a theoretical framework for the implementation of cardiopulmonary units as an innovative model to provide more coordinated care for these patients. This framework establishes a structured care model with 2 levels, adaptable to the resources available at each centre, detailing key aspects such as organization, diagnostic and therapeutic functions, and quality parameters necessary for proper operation. Additionally, it emphasizes the importance of early diagnosis, individualized treatment plans, and the application of evidence-based interventions. The definition of this theoretical basis aims to establish a coordinated framework for managing patients with chronic obstructive pulmonary disease and cardiovascular diseases, optimizing available healthcare resources, and improving health outcomes.

The revised definition of pulmonary hypertension (PH) reclassifies patients previously diagnosed with chronic thromboembolic pulmonary disease (CTEPD) without pre-capillary PH as having chronic thromboembolic pulmonary hypertension (CTEPH). Reclassified CTEPH patients demonstrated oxygen desaturation during exercise and reduced ventilatory efficiency, as patients with more severe CTEPH, indicating impaired exercise physiology. These findings support the data of prior studies and the clinical relevance of the newly defined hemodynamic thresholds in patients with CTEPH.

Varicocele is a common cause of male infertility, but the mechanisms by which it disrupts testicular homeostasis and impairs spermatogenesis remain incompletely elucidated. This article reviews current evidence on the multifactorial disturbances in the testicular microenvironment induced by varicocele, with a focus on hemodynamic, biochemical, and structural abnormalities. Anatomical predisposition, venous valve incompetence, and impaired venous return collectively lead to chronic venous hypertension, causing progressive dilation of the pampiniform plexus and severe hemodynamic dysregulation. These primary vascular abnormalities subsequently establish a foundation for downstream cellular damage, including testicular hyperthermia, hypoxia, and metabolic stress. Among these pathological processes, oxidative stress is widely recognized as a central mediator of testicular injury. Excessive reactive oxygen species overwhelm intrinsic antioxidant defenses, disrupt mitochondrial function, damage germ cell DNA, and impair epididymal sperm maturation, ultimately leading to reduced sperm concentration, motility, and viability. Simultaneously, elevated inflammatory cytokines and immune dysregulation further compromise Sertoli and Leydig cell function, activate inflammasome signaling and amplify inflammatory injury. These inflammatory signals also synergize with oxidative damage to disrupt the blood-testis barrier, resulting in increased permeability, autoimmune activation, and accelerated loss of germ cells. Structural impairment of the seminiferous epithelium, mitochondrial dysfunction, and the activation of intrinsic and extrinsic apoptotic pathways further exacerbate spermatogenic failure. Ultimately, varicocele induces a multifaceted and sustained cycle of testicular microenvironment disruption, impairing spermatogenesis at multiple levels-from Sertoli cell function and blood-testis barrier integrity to germ cell survival and sperm DNA stability.

Acquired hypothalamic obesity (aHO) is a disease characterized by rapid, clinically significant, and persistent weight gain resulting from damage to hypothalamic structures. aHO is associated with substantial morbidity, increased mortality, and marked impairment in quality of life. Etiologies include craniopharyngioma and other space-occupying lesions of the sellar/parasellar region, neurosurgical procedures, cranial irradiation, and traumatic brain injury. A multidisciplinary panel comprising ten specialists in neuroendocrinology, neurooncology, and neurosurgery from Germany, Austria, and Switzerland convened in Frankfurt am Main, Germany, on November 10, 2025, to discuss contemporary challenges and advances in this field. aHO should be conceptualized and treated within the broader clinical entity of hypothalamic syndrome, a complex disorder involving multiple neuroendocrine deficiencies, disturbances of circadian regulation, impaired control of hunger, satiety, and thirst, altered thermoregulation, and a range of cognitive, sleep-related, and psychosocial dysfunctions. Long-term outcomes for affected individuals are frequently unfavorable, largely due to increased risks of metabolic syndrome, cardiovascular disease, profound reductions in health-related quality of life, and elevated rates of premature mortality. The management of hypothalamic syndrome remains particularly challenging. Pharmacological strategies, including dextroamphetamine and glucagon-like peptide-1 receptor agonists, have demonstrated potential benefits for weight and hyperphagia-related outcomes. Recently, preliminary findings from a prospective, randomized, placebo-controlled clinical trial (TRANSCEND) provided encouraging evidence for the efficacy of setmelanotide, a melanocortin-4 receptor agonist. This perspectives report reviews clinical advances in epidemiology, diagnostics, treatment, and follow-up of patients with aHO and outlines key directions for future research aimed at improving outcomes in this vulnerable population.

Cardiovascular disease (CVD) remains the leading cause of mortality and disability worldwide, imposing a substantial burden on individuals, families, and healthcare systems. Despite major advances in controlling conventional risk factors (e.g., blood pressure, glycaemia, and lipids), a considerable residual risk persists, highlighting the need to elucidate additional pathogenic mechanisms and to develop more effective preventive and therapeutic strategies. Accumulating experimental and clinical evidence indicates that immune dysregulation and chronic low-grade inflammation are not merely associated with CVD but actively drive disease progression-from lesion initiation to acute thrombotic events. These processes are further shaped by metabolic status, lifestyle factors, psychosocial stress, and environmental exposures, and age-related genetic immune changes such as clonal hematopoiesis of indeterminate potential (CHIP). Atherosclerosis, the predominant pathological substrate of most CVDs, is now widely recognized as a chronic immune-inflammatory disease. Emerging concepts including immunometabolic reprogramming, trained immunity(distinguished by central and peripheral subtypes), the thrombo-inflammatory axis, and allostatic load provide an integrative framework for understanding CVD as a systemic disorder. Here, we synthesize recent advances in innate and adaptive immune mechanisms, immunometabolic dysregulation, and inflammation-thrombosis crosstalk that collectively govern plaque formation, destabilization, and clinical events. We also discuss how lifestyle-related factors (e.g., diet, fasting, physical activity, and stress) may modulate long-term cardiovascular risk through trained immunity and inflammatory pathways, and we highlight progress in immune biomarkers and anti-inflammatory interventions, and the immunometabolic effects of modern cardiometabolic drugs (GLP-1 receptor agonists, SGLT2 inhibitors). Additionally, we elaborate on the translational potential of short chain fatty acid derivatives in reversing innate immune inflammatory memory, and clarify the distinct cardiovascular toxic mechanisms of immune checkpoint inhibitors (ICIs) and chimeric antigen receptor T-cell (CAR-T) therapy in cardio-oncology. Conceptualizing CVD as a systemic immune-metabolic-inflammatory disease may facilitate improved risk stratification and inform precision prevention and treatment strategies.

One-lung ventilation (OLV) is used to isolate one lung during thoracic surgery, but manipulation and positioning can affect heart-lung interaction. Cardiomegaly may exacerbate these changes, especially in the left lateral decubitus (LLD) position.

To investigate the effect of cardiomegaly on heart-lung interaction during OLV, particularly in the LLD position.

A 20-year-old male with recurrent spontaneous pneumothorax was scheduled for right-sided bronchopleural fistula repair via thoracotomy. The patient presented with cardiomegaly (cardiothoracic ratio 75%) and echocardiographic evidence of right ventricular and atrial dilation. In the LLD position, OLV led to desaturation when both lungs were ventilated, but oxygenation improved when only the left lung was ventilated.

Cardiomegaly alters heart-lung interaction during OLV, particularly in the LLD position. The enlarged heart exerts pressure on the left lung, impairing ventilation. When both lungs are ventilated in this position, ventilation is directed toward the right lung, reducing oxygenation and causing desaturation. However, restricting ventilation to the left lung improved oxygenation due to better lung compliance and less interference from the enlarged heart.

Cardiomegaly affects heart-lung interaction during OLV in the LLD position. Oxygenation improves when only the left lung is ventilated, likely due to less compression of the left lung. The supine position may further enhance oxygenation even with bilateral ventilation. This case highlights the importance of considering cardiomegaly in OLV management. This section should be written as per the CARE checklist item 3.

Hemophagocytic syndrome, also known as hemophagocytic lymphohistiocytosis (HLH), is a rare clinical disease that is highly challenging to diagnose, has a low long-term survival rate and a high mortality rate. Currently, due to the particularity of HLH and the lack of effective understanding of the severity and prognosis of the disease in clinical practice, HLH patients are often missed or misdiagnosed in clinical practice, causing them to miss the best opportunity for diagnosis and treatment. This study aimed to retrospectively summarize and analyze the clinical characteristics, diagnosis and treatment, and prognosis of HLH patients from four medical centers, aiming to explore the risk factors affecting the prognosis of HLH patients and further enhance the understanding of HLH.

The clinical data of 162 patients with HLH diagnosed in four medical centers from May 2017 to May 2025 were collected. The general conditions, laboratory results, diagnosis and treatment processes, and prognosis of these patients were analyzed, and univariate and multivariate analyses of prognostic factors were conducted.

A total of 162 HLH patients were included in this study, of whom 90 cases survived (55.56%), 72 cases died (44.44%), and there were 78 male patients (48.15%) and 84 female patients (51.85%), with a median age at onset of 52 years (range: 1-83 years). The most common etiological factor was Epstein-Barr virus (EBV) infection, and the primary presenting symptom was fever. First-line treatment primarily involved anti-infective therapy and symptomatic management, which was administered to 147 cases (90.74%). Prognostic analysis revealed that age, history of malignancy, infection history, presence of dermatological symptoms, APTT, INR, PCT, CRP, TG, TBIL, ferritin level, sCD25, lactate, SOFA score and time to treatment initiation, glucocorticoid monotherapy, gamma globulin treatment were significantly associated with patient outcomes in HLH. Tumor history, ferritin level, sCD25, lactate, SOFA score, time to treatment initiation, gamma globulin treatment were independent risk factors for mortality. Univariate Cox regression analysis identified that age, tumor history, history of rheumatic and autoimmune disorders, CRP, ferritin level, sCD25, lactate, SOFA score and time to treatment initiation, chemotherapy, glucocorticoid monotherapy, gamma globulin treatment were significant prognostic factors for OS in HLH patients. Multivariate analysis confirmed that tumor history, CRP, ferritin level, sCD25, lactate, SOFA score and time to treatment initiation, chemotherapy, glucocorticoid monotherapy, gamma globulin treatment were independent prognostic factors affecting OS in HLH patients. Age, APTT, INR, ferritin level, SOFA score, time to treatment initiation, glucocorticoid monotherapy, gamma globulin treatment were independent prognostic factors affecting OS in infection-triggered HLH patients. While age, INR, ferritin level, SOFA score, time to treatment initiation, chemotherapy were independent prognostic factors affecting OS in malignancy-associated HLH patients. Combined therapy regimens (especially chemotherapy combined with gamma globulin, glucocorticoid combined with gamma globulin) showed better clinical efficacy and survival benefits in the treatment of HLH.

HLH is a rare clinical disease, EBV was the predominant trigger for HLH. Prognostic factors differed between infection- and malignancy-associated subgroups. Combined regimens, particularly those including gamma globulin, offered superior survival benefits, underscoring the need for etiology-specific treatment strategies.

Histone deacetylase 6 (HDAC6) is a unique, predominantly cytoplasmic enzyme that regulates a broad spectrum of cellular and physiological processes, including cell proliferation, migration, intracellular transport, and differentiation. Its distinct structural configuration, comprising two catalytic deacetylase domains and a zinc finger ubiquitin-binding domain (ZnF-BUZ), enables HDAC6 to deacetylate a variety of non-histone substrates, such as α-tubulin, heat shock protein 90 (Hsp90), cortactin, and peroxiredoxin (Prdx). Furthermore, HDAC6 plays a key role in cellular stress responses and cell survival by facilitating the clearance of misfolded proteins, inducing autophagy, and modulating the unfolded protein response. Despite its cytoprotective roles, HDAC6 has emerged as a therapeutic target due to its involvement in multiple pathological pathways and age-related disorders. Tubastatin A (Tub A), a novel and highly selective HDAC6 inhibitor, demonstrates strong therapeutic potential against neurodegenerative, cardiovascular, autoimmune, metabolic, cancer, and other diseases. Tub A enhances the acetylation of both histone and non-histone proteins, thereby modulating gene expression and diverse cellular processes. It shows pharmacological effects, including anti-inflammatory, neuroprotective, anti-diabetic, anti-obesity, anti-oxidant, and other activities. Moreover, preclinical evidence suggests that Tub A effectively regulates multiple pathological pathways by inhibiting HDAC6, which contributes to ameliorating age-related disorders. Therefore, Tub A represents a promising epigenetic modulator with broad therapeutic relevance. Hence, further comprehensive and large-scale investigations are warranted to elucidate its clinical potential and its roles in disease management, as no clinical data related to Tub A activity are available. This review highlights the therapeutic potential of the selective HDAC6 inhibitor Tub A across various pathological conditions, discusses current preclinical findings, and outlines key challenges and future directions for clinical translation.