Heart rate variability (HRV) is a non-invasive marker of autonomic cardiovascular regulation that reflects beat-to-beat fluctuations in cardiac cycle length. Reduced HRV has been associated with adverse cardiovascular outcomes across multiple disease states, yet its clinical use remains limited by substantial interpretive complexity. Unlike static biomarkers, HRV is highly sensitive to measurement modality, recording duration, circadian timing, behavioral factors, environmental exposures, medications, and comorbidities. Therefore, isolated HRV values cannot be interpreted as direct indicators of autonomic health without careful consideration of context. This review summarizes the physiological basis of HRV, key time-domain, frequency-domain, and nonlinear/complexity metrics, and major acquisition methods, including 24 h electrocardiography (ECG), short-term ECG, chest strap monitors, and wrist-worn devices. It also examines how sleep, physical activity, diet, psychological stress, substance use, age and sex, medications, and cardiovascular or metabolic diseases influence HRV interpretation. We propose a context-aware framework for interpreting HRV as a dynamic physiological signal rather than a standalone diagnostic marker. When appropriately contextualized, HRV may serve as a complementary tool for cardiovascular risk assessment and provide insight into residual risk not fully captured by conventional clinical models.

The oral mucosa is a dynamic barrier. T‑cell dysregulation contributes to chronic oral mucosal inflammatory diseases, but the role of age‑related immune remodeling remains unclear..

We performed a narrative review of PubMed/Medline (1972-2026) on T‑cell subsets, immunosenescence, exhaustion, and inflammation in oral lichen planus (OLP), Behçet's disease (BD), and recurrent aphthous stomatitis (RAS). After screening, we synthesized 121 publications.

Disease‑specific patterns emerged. In OLP, activated CD8⁺ and tissue‑resident memory T cells associate with basal keratinocyte injury, while senescent mesenchymal cells may amplify inflammation via SASP. In BD, Th1/Th17 polarization, reduced regulatory control, and neutrophil activation drive systemic and mucosal inflammation. In RAS, Th1‑skewed and CD8⁺ responses correlate with epithelial damage. Direct causal evidence for senescent or exhausted T cells is limited, especially for BD and RAS.

T‑cell senescence may modulate disease course, but its effects are context‑dependent rather than universal drivers. The strongest support exists for senescence‑associated stromal signaling in OLP; evidence in BD and RAS is mainly associative. Therapeutic strategies targeting senescence remain hypothesis‑generating and largely preclinical.

Heart failure is the end-stage of various cardiovascular diseases. Although a variety of drugs have slowed down the progression of the disease, the prognosis of heart failure patients remains unsatisfactory. Vericiguat can improve left ventricular function, but there is relatively less research on its effect on right ventricular function. This study aimed to evaluate whether vericiguat can improve the right ventricular function of heart failure patients.

Patients with left ventricular ejection fraction < 45% who were hospitalized for the first time in the Department of Cardiology, The Second Affiliated Hospital of Soochow University from January 1, 2023, to December 31, 2024 were included and divided into two groups. The baseline and 3-month follow-up clinical characteristics, laboratory data, routine transthoracic echocardiogram parameters, and medication use of patients were collected.

A total of 90 eligible patients were finally included, with 60 cases in the vericiguat group and 30 cases in the control group. In the vericiguat group, right ventricular function improved significantly after treatment. The tricuspid annular plane systolic excursion to pulmonary artery systolic pressure (TAPSE/PASP) ratio increased significantly [0.51 ± 0.22 vs. 0.60 ± 0.22, p = 0.001]. Right atrial longitudinal dimension index significantly decreased [30.07 ± 5.80 mm/m² vs. 28.57 ± 5.43 mm/m², p = 0.001], as did the Right atrial transverse dimension index [23.21 ± 5.13 mm/m² vs. 21.86 ± 4.40 mm/m², p = 0.012] and right ventricular basal diameter index [22.48 ± 3.96 mm/m² vs. 21.07 ± 3.59 mm/m², p < 0.001]. Pulmonary arterial systolic pressure decreased significantly [41.47 ± 16.25 mmHg vs. 36.20 ± 14.32 mmHg, p = 0.006]. In the control group, no significant changes were observed in right heart function parameters. Multiple linear regression analysis showed that the increase in ΔTAPSE/PASP was not significantly associated with changes in left ventricular function.

Vericiguat treatment was associated with a reduction in pulmonary artery systolic pressure, improves right ventricle-pulmonary artery coupling, and promotes structural reverse remodeling of the right atrium and right ventricle in heart failure patients. These right heart benefits occur independently of changes in left ventricular structure and function. Vericiguat showed good short-term safety.

Ischemia-reperfusion injury remains a major challenge in liver transplantation and plays a major role in pathophysiology leading to graft failure. Machine perfusion (MP) is a promising approach to restitute marginal donor livers. However, the impact of MP on innate immunity remains insufficiently defined. We hypothesized that MP activates the innate inflammatory response. Thus, we investigated whether the ischemic injury and perfusate composition [plasma-rich perfusate (PRP) versus plasma-poor perfusate (PPP)] modulate the inflammatory response, identified by complement activation and cytokine release.

Thirty porcine livers were subjected to ex situ MP. The first 24 porcine livers were subject to induced biliary ischemic injury (BileINJ, n = 8), global ischemic injury (GlobalINJ, n = 8), or no induced ischemic injury (CTRL, n = 8) using PRP during MP. The subsequent six porcine livers were subjected to the same ex situ MP protocol using PPP (n = 6) with no induced ischemic injury. MP was conducted in three phases: 1 h hypothermic, 1 h controlled rewarming, and 4 h normothermic perfusion.

Except for interleukin-1β (IL-1β) in bile tissue in the BileINJ group and tumor necrosis factor (TNF) in plasma in the GlobalINJ group, all mediators assessed whether in perfusate, liver, or bile tissue did not differ significantly between ischemic injury groups and CTRL. Data were therefore combined into a common PRP group for further comparisons. In PRP perfusate, MP induced robust complement activation (sC5b-9: median fold change (FC) 4 [2-6 interquartile range]) and cytokine release (IL-1β: FC 88 [51-165], IL-6: FC 1,549 [587-3,053], IL-8: FC 389 [120-1,259], IL-10: FC 404 [222-656], all p < 0.001). This pattern persisted in PPP group perfusate, liver, and bile tissue, though the concentrations were significantly lower compared to PRP (sC5b-9, IL-10, IL-6, IL-1β, and IL-8, all p < 0.05).

Liver MP reliably induced innate immune-driven inflammation regardless of prior ischemic injury. The magnitude of the inflammatory response was substantially lower in the PPP group compared to the PRP group. Future therapeutic trials targeting innate immunity during ex situ MP are warranted to improve the preservation of liver grafts.

Immune checkpoint inhibitors (ICIs) have revolutionized the therapeutic landscape for a broad spectrum of malignancies, substantially prolonging patient survival. However, the widespread clinical adoption of ICIs is challenged by a diverse array of cardiovascular immune-related adverse events (CV-irAEs). Among these, arrhythmias pose a considerable threat to patient safety and treatment continuity, given their insidious onset and potential lethality. Traditionally, these arrhythmias have been largely conceptualized as secondary complications of ICI-induced myocarditis, a perspective that has obscured their true clinical features. Emerging evidence indicates that ICI-associated arrhythmias exhibit distinct risk profiles and pathogenic mechanisms, suggesting that arrhythmias may be substantially more common than previously recognized and frequently manifest as standalone clinical entities rather than mere secondary complications. Accordingly, to mitigate cardiovascular risk and optimize long-term patient outcomes, this review synthesizes the epidemiology, risk factors, pathogenesis, and management strategies of ICI-associated arrhythmias, while highlighting the transformative potential of artificial intelligence-enhanced monitoring in advancing precision cardio-oncology.

Neonatal hypoxic-ischemic encephalopathy (HIE) causes severe neurodevelopmental impairment, but the upstream immune mechanisms that initiate this process remain unclear. We investigated whether mast cell (MC)-derived tryptase contributes to aberrant microglia-mediated synaptic pruning through PAR-2/MAPK/NF-κB signaling after neonatal hypoxic-ischemic (HI) injury.

A postnatal Day-7 rat HI model was established using the Rice-Vannucci method. MC abundance, c-Kit and tryptase expression, PAR-2/MAPK/NF-κB signaling, and synaptic integrity were assessed using histological, immunofluorescence, biochemical, ultrastructural, and three-dimensional (3D) reconstruction analyses. Microglia-targeted F2rl1 silencing and pharmacological inhibition with FSLLRY-NH2 or APC366 were used to examine PAR-2 and tryptase-related signaling. Complementary oxygen-glucose deprivation/reperfusion (OGD/R) experiments were performed in BV-2 microglia. Cognitive outcomes were assessed using the Morris water maze and Y maze.

HI increased hippocampal MC abundance and tryptase expression, and these changes were associated with acute neurological deficits. HI insult also increased complement associated synaptic labeling, PAR-2/MAPK/NF-κB signaling, CD68 expression, and engulfment of PSD95 positive synaptic material. Microglia-targeted F2rl1 silencing attenuated pathway activation and synaptic engulfment. FSLLRY-NH2 and APC366 similarly reduced HI associated signaling and microglial synaptic engulfment, while APC366 preserved dendritic spine density and synaptic ultrastructure and improved long-term spatial learning and memory. In BV-2 microglial cells, exogenous tryptase enhanced OGD/R associated CD68 expression and MAPK/NF-κB phosphorylation, which were attenuated by F-NH2.

MC-derived tryptase is an upstream contributor to pathological microglial synaptic pruning and cognitive impairment after neonatal HI, potentially involving the PAR-2/MAPK/NF-κB axis.

Omecamtiv mecarbil is a cardiac-selective myosin activator and potential heart failure treatment, but its electrophysiological profile remains incompletely characterized. We investigated omecamtiv mecarbil in a Langendorff-perfused rabbit heart model. Forty-eight rabbit hearts were retrogradely perfused; twenty-four in a ventricular and twenty-four in an atrial setup. In the ventricular setup, action potential duration at 90% repolarization (APD₉₀), QT interval, and dispersion of repolarization were assessed during pacing at seven cycle lengths. After baseline recordings, Group 1 (n = 12) received 1, 5 and 10 µM omecamtiv mecarbil sequentially, while Group 2 (n = 12) received 100 µM sotalol followed by 5 µM omecamtiv mecarbil. In the atrial setup, Group 3 (n = 12) received 5 and 10 µM omecamtiv mecarbil, and Group 4 (n = 12) received isoproterenol/acetylcholine (IsoACh) to increase atrial fibrillation (AF) susceptibility, followed by 5 µM omecamtiv mecarbil. Omecamtiv mecarbil alone shortened ventricular APD₉₀ and QT interval, increased dispersion of repolarization, and raised ventricular arrhythmia incidence. Sotalol prolonged APD₉₀, QT interval, and dispersion, with a marked rise in VT episodes; additional omecamtiv mecarbil did not further prolong repolarization but increased arrhythmia susceptibility further. In the atrial setup, omecamtiv mecarbil alone prolonged conduction time and increased AF inducibility. Under IsoACh, which shortened atrial APD and refractoriness and increased AF episodes, additional omecamtiv mecarbil slowed atrial conduction and markedly suppressed AF. In summary, omecamtiv mecarbil was proarrhythmic at the ventricular level, particularly under reduced repolarization reserve, but showed antiarrhythmic effects in an IsoACh-induced AF model and proarrhythmic properties in the healthy atrium, indicating a substrate-dependent electrophysiological profile.

Atrial fibrillation (AF) is the most common sustained arrhythmia, conferring risks of stroke and heart failure. Monocyte activation-associated inflammation is implicated in AF, yet the recruitment of monocytes and their role in atrial remodeling remain unclear. Here we show that monocytes from AF patients upregulate phospholipase C gamma 2 (PLCG2). In a combined AF male mouse model, phospho-PLCγ2⁺ monocytes are recruited to the atria, where they trigger endothelial‑to‑mesenchymal transition (EndMT) through the secreted phosphoprotein 1 (SPP1)-integrin α9β1 signaling axis. Monocyte-specific deletion of PLCG2 blocks atrial recruitment of these monocytes and reduces AF. Depletion of the gut microbiota with antibiotics reduces the number of phospho-PLCγ2⁺ monocytes in the atria, suppresses EndMT, and attenuates AF inducibility, and these effects are reversed by fecal microbiota transplantation (FMT). Mechanistically, gut microbiota-derived bacterial membrane vesicles activate spleen tyrosine kinase (Syk)/PLCG2 signaling in monocytes. These findings establish a gut microbiota-monocyte-EndMT axis, wherein monocyte-endocardial crosstalk drives AF.

Nitric oxide's (NO) crucial role in various physiological processes, such as vascular regulation, inflammation, and wound healing, has led to the development of various NO delivery platforms. However, delivering NO in a controlled and sustained manner is challenging due to its short half-life of less than 5 s. To address this challenge, we synthesized polyacrylamide (PAAm) hydrogels loaded with selenium nanoparticles (SeNPs) or polydopamine-coated selenium nanoparticles (Se@PDA NPs), which can catalytically generate NO from both endogenous and exogenous NO donors. Structural characterization confirmed that nanoparticle loading did not alter the intrinsic properties of the PAAm-gel. By adjusting the concentration of NPs loaded within the hydrogels, tunable NO generation was achieved. Both Se-gel and Se@PDA-gel exhibited sustained NO generation, with Se@PDA-gel demonstrating superior recyclability and stability, even after long-term storage under various conditions. The hydrogels exhibited excellent biocompatibility, and their biological activity was validated by elevated interleukin-10 (IL-10) and α-smooth muscle actin (α-SMA) expression, indicating anti-inflammatory effects and potential for wound healing, respectively. These findings establish Se@PDA-gel as a promising platform for controlled and sustained NO delivery, offering therapeutic potential in wound healing and anti-inflammatory therapies, particularly for cardiovascular and infectious diseases.

Macrophages are important immune cells for cardiac development, homeostasis, and the response to pathological injury and inflammation. Single-cell sequencing and fate-mapping technologies have revealed the heterogeneity and development of cardiac macrophages. They are classed into two main groups: embryonic tissue-resident and bone marrow-derived macrophages. These different macrophage subsets show complex functions in cardiac diseases such as inflammation regulation, tissue repair, metabolic reprogramming and intercellular communication within the cardiac microenvironment. This review discusses the developmental sources, phenotypic diversity, metabolic features and mechanistic functions of cardiac macrophages in different cardiac disorders. We focus on macrophage polarization, metabolic regulation during disease progression and targeted strategies and future research directions.