Early detection of renal involvement in ANCA-associated vasculitis (AAV) is crucial, as functional changes often precede anatomical damage. Current diagnostic standards, such as the measurement of serum creatinine, renal biopsy and urinary analyses have limitations due to delayed detection and lack of specifity. Functional renal MRI (fMRI) techniques, including diffusion-weighted imaging (DWI), diffusion tensor imaging (DTI), arterial spin labeling (ASL) and blood oxygenation level dependent (BOLD) offer promising non-invasive alternatives for assessing renal function in AAV. The aim of this study was to evaluate the feasibility of non-invasive assessment of renal changes associated with AAV using mpMRI (multiparametric MRI).

This study evaluated 7 patients and 10 healthy controls: patients with rapidly progressive glomerulonephritis (RPGN) due to AAV (n = 3), AAV patients without clinical signs of renal involvement (n = 4), and healthy controls (n = 10). All participants underwent functional renal MRI. Key parameters, including the apparent diffusion coefficient (ADC), fractional anisotropy (FA), and ASL-based renal perfusion and T2* parameter maps, were acquired and analyzed.

The following differences in renal imaging parameters were observed between RPGN patients and healthy controls: RPGN patients showed reduced ADC values in the renal medulla and increased FA values compared to controls. Additionally, ASL values in the renal cortex were lower in RPGN patients. T2* values were lower in RPGN patients compared to the healthy control group in the cortex, and higher in the medulla. Patients with AAV without confirmed renal involvement also showed alterations in ADC, T2* and FA values compared to healthy controls.

Our findings indicate that mpMRI parameter might detect renal changes in AAV. Therefore, mpMRI might offer novel opportunities for non-invasive detection of disease-associated changes.

Inflammaging refers to the chronic, low-grade, sterile inflammatory state that emerges as a hallmark of biological aging and is increasingly recognized as a contributor to functional decline, frailty, and the progression of multiple age-associated diseases. While acute inflammation supports host defense and tissue repair, persistent and unresolved inflammatory signaling promotes tissue damage, metabolic dysregulation, and impaired immune homeostasis. Inflammaging reflects a dysregulated physiological state associated with elevated damage-associated molecular patterns (DAMPs), pro-inflammatory cytokines, altered immune cell composition, metabolic imbalance, and the accumulation of senescent cells exhibiting a senescence-associated secretory phenotype (SASP). Together, these processes impair immune surveillance, increase oxidative stress, and tissue vulnerability, potentially accelerating functional decline and amplifying disease trajectories that may originate earlier in life. Despite ongoing challenges in precisely defining and measuring inflammaging, evidence suggests that its development is shaped not only by chronological aging but also by behavioral, environmental, psychosocial, and genetic factors, highlighting its dynamic and potentially modifiable nature. In this review, we distinguish inflammaging from general chronic inflammation, synthesize current understanding of its biological origins and mechanistic drivers, and examine its role in clinical outcomes including sarcopenia, neurodegeneration, and cardiovascular disease. We propose a conceptual translational framework linking biological mechanisms of inflammaging to multilayer biomarker signatures, AI-based risk stratification, and precision interventions. Additionally, we discuss the opportunities and limitations of these approaches for identifying individuals at risk for chronic disease and informing multi-dimensional strategies to promote resilience and extend health-span.

Aging is the predominant risk factor for several chronic disorders; therefore, elucidating the molecular and cellular mechanisms underlying age-related pathologies is essential for therapeutic advancement. Micheliolide (MCL), a naturally occurring guaianolide sesquiterpene lactone derived from Michelia champaca and Michelia compressa, has attracted increasing attention for its pharmacological potential. Its derivative, ACT001, enables the sustained release of MCL into the plasma in vivo, thereby enhancing oral bioavailability and improving therapeutic efficacy. ACT001 has recently received orphan drug designation for glioblastoma treatment, highlighting its clinical feasibility and safety profile. Increasing evidence indicates that MCL regulates age-related diseases by modulating inflammation, cell cycle, mitochondrial dysfunction, oxidative stress, and autophagy. By targeting key signaling pathways, including NF-κB, STAT3, NRF2, AMPK, and NLRP3, MCL/ACT001 demonstrated its protective effect against age-related diseases. This paper summarizes the current mechanistic insight and disease-specific evidence regarding MCL/ACT001 and further evaluates their therapeutic repositioning potential for age-related diseases, including cardiovascular and cerebrovascular diseases, fibrotic conditions, immune disorders, metabolic diseases, and tumors. Additionally, we discussed key translational challenges.

Aging is a major risk factor for chronic diseases. Unlike the general population, members of long-lived families maintain exceptional health as they age, with over 10 years delayed onset of their first chronic disease. We therefore hypothesize that one of the key features explaining healthy survival up to high ages (longevity) is the absence of chronic disease risk alleles. We investigated this hypothesis in the Leiden Longevity Study, a cohort with data from more than 420 long-lived families in three generations and the Leiden 85-plus study. To analyze our data, we constructed a set of polygenic scores (PGS) covering the top diseases causing most deaths in the Netherlands. We showed that having an increasing number of long-lived ancestors is additively associated with lower genetic risk for coronary artery disease (CAD). Using accelerated failure time modelling, we further showed that a lower PGS for CAD explains up to 20% of the delay in cardiovascular disease incidence in descendants of long-lived families. Finally, we constructed a novel cholesterol-metabolism-PGS, based on gene-annotation enrichment analysis, that predicted time to all-cause mortality in two independent 90 + study populations. Our findings demonstrate that the absence of chronic disease risk alleles is one key feature linked to longevity and that alleles linked to cholesterol metabolism are a key component in healthy aging trajectories.

Kawasaki disease (KD) is an acute, immune-mediated medium-vessel vasculitis and the leading cause of acquired heart disease in children, yet its underlying etiology remains only partially defined. Emerging evidence implicates the gut microbiota as a key modulator of KD susceptibility, immune dysregulation, and therapeutic response. This narrative review aims to synthesise current insights linking gut microbial dysbiosis and microbial metabolites to the pathogenesis, clinical expression, and treatment of KD, and to explore microbiome-informed strategies with diagnostic and therapeutic potential. We conducted a comprehensive search of PubMed, Embase, Web of Science, and Google Scholar from database inception to April 2025 for English-language studies on Kawasaki disease and the gut microbiota, including terms related to microbiome, microbial dysbiosis, metabolites, pathogenesis, immunity, inflammation, and therapy. Reference lists of relevant articles and key reviews were also screened. Children with acute KD exhibit characteristic alterations in gut microbial composition, including an overrepresentation of Streptococcus species, depletion of short-chain fatty acid (SCFA)-producing taxa such as Faecalibacterium, Ruminococcus, and Roseburia, and a significant reduction in fecal butyrate. These changes have been associated with impaired intestinal barrier integrity, heightened NLRP3 inflammasome activation, and dysregulated cytokine signalling, contributing to systemic inflammation and vascular injury. Additional factors, such as antibiotic exposure and concurrent respiratory or oropharyngeal infections, can intensify dysbiosis and have been linked to resistance to intravenous immunoglobulin (IVIG) and an increased risk of coronary artery aneurysms. Conclusions: Gut microbial imbalance and metabolite disruption are likely associated with KD, potentially through interaction with host genetics and immune pathways. Microbiome-targeted approaches, including probiotics, dietary modulation, and metabolite-based therapies, hold promise for improving diagnostic precision, predicting treatment response, and guiding the development of targeted interventions in KD.

Quantitative assessment of myocardial perfusion using ¹³N-ammonia PET with compartmental modeling enables evaluation of myocardial flow reserve (MFR) and prediction of patient prognosis. However, the reliability of these assessments can depend on the analytical methods used for quantitation.

The present study aimed to evaluate the variability and agreement of values obtained using three quantitative software tools and to assess the impact of kinetic model selection on myocardial blood flow (MBF) and MFR estimates in a clinical setting.

We analyzed 100 patients who underwent ¹³N-ammonia PET/CT, including 60 with normal perfusion and 20, 10, and 10 with single-, two-, and three-vessel disease, respectively. We derived MBF and MFR at global (entire left ventricle) and regional (coronary territories) levels and evaluated five analytical pipelines: SyngoMBF, QPET, and three implementations of PMOD tools (1-tissue compartment, Hutchins, and UCLA models).

MBF and MFR showed high correlations among the software tools, although stress MBF statistically differed between PMOD and QPET. Correlation coefficients between software tools ranged from 0.81 to 0.91 at the global level, and Bland-Altman analysis demonstrated overall agreement with residual variability. In contrast, MBF and MFR values varied depending on the compartment model. The UCLA model yielded the highest stress MBF and MFR, and correlation coefficients between models ranged from 0.43 to 0.99 at the global level. Although Bland-Altman analysis showed overall agreement, noticeable scatter persisted and the UCLA model exhibited a positive bias.

Quantitative MBF and MFR estimates from ¹³N-ammonia PET show good overall agreement across commonly used software tools but remain strongly dependent on kinetic model selection. These findings indicate that quantitative results are not directly interchangeable across different software and modeling approaches, underscoring the importance of methodological consistency when interpreting myocardial perfusion PET in clinical practice.

Mitochondrial encephalomyopathy with lactic acidemia and stroke-like episodes (MELAS) syndrome is a maternally inherited mitochondrial disorder caused by mutations in mitochondrial DNA, most commonly the m.3243A>G variant. This mutation impairs oxidative phosphorylation, leading to inadequate cellular energy production, particularly in high-demand tissues such as the brain and muscles. The resultant energy deficit manifests as neurological and muscular dysfunction, including stroke-like episodes, seizures, and lactic acidosis.

Twin brothers presented with heterogeneous clinical characteristics. The elder twin experienced seizures, blurred vision, hypertrichosis, exercise intolerance, and had learning difficulties since age 10. The younger twin developed hearing loss at age 12, followed by persistent epileptic seizures 3 months later. Both had a history of progressive neurological and multisystemic symptoms suggestive of a metabolic disorder.

Diagnostic evaluations included electroencephalography (EEG), which showed widespread mixed high-amplitude slow waves, and cranial magnetic resonance imaging, which revealed migratory lesions that changed with recurrent episodes. Genetic testing confirmed the m.3243A>G mutation in both twins. Their mother was identified as an asymptomatic carrier with an estimated heteroplasmy level of 30.79%.

The elder twin was initially treated with acyclovir (antiviral) and methylprednisolone (anti-inflammatory) for suspected viral encephalitis, with symptomatic support. After genetic confirmation of MELAS, supportive therapies included coenzyme Q10, adenosine triphosphate disodium, levocarnitine, and arginine. During recurrent admissions for status epilepticus, antiepileptic regimens were maintained or adjusted, and imaging (magnetic resonance imaging/electroencephalogram) was repeatedly used for monitoring. His brother received similar interventions - levetiracetam, coenzyme Q10, and adenosine triphosphate disodium - upon diagnosis, with additional management for seizures, headaches, and gastrointestinal symptoms.

Both twins were definitively diagnosed with MELAS syndrome. The elder twin was diagnosed first based on clinical and genetic findings, while the younger twin was diagnosed after the emergence of hearing loss and seizures. The condition highlights the progressive and variable nature of MELAS.

The case underscores the significant phenotypic heterogeneity of MELAS, which often leads to misdiagnosis or delayed diagnosis. Early genetic testing is critical for accurate identification and prompt intervention. Family screening is recommended due to the maternal inheritance pattern, and tailored management should address the multifaceted clinical manifestations.

Hypertensionis one of the leading causes of cardiovascular disease and premature death worldwide, affecting more than 1.2 billion adults, with a significant part living in low- and middle-income countries. Pediatric hypertension is also a growing concern, with an estimated 4.5% of children in the United States affected. The 2024 European Society of Cardiology guidelines provide updated protocols for diagnosing and treating hypertension in adults, while pediatrics diagnosis is based on age and weight-specific percentiles. The renin-angiotensin-aldosterone system plays a crucial role in blood pressure (BP) regulation, with 2 pathways: classical pathway and alternative pathway. classical pathway increases BP and fluid retention, while alternative pathway counteracts these effects. Neuropeptides such as Nesfatin-1 (Nes-1) and Galanin (Gal), along with the endocannabinoid system, also influence BP regulation. The study focused on adolescents with hypertension, obesity, or combination. From the hospital, 128 patients were recruited to the study. Plasma samples were analyzed for Nes-1, Gal, anandamide (AEA), and 2-arachidonoylglycerol levels. The results showed significantly lower levels of Nes-1 and Gal in the obese hypertensive patients (P = .005 and P = .022 respectively) and obesity groups (P = .022 and P = .035 respectively) compared to the controls. AEA levels did not show significant differences, while 2-arachidonoylglycerol levels were tendential to higher concentration in hypertensive patients. The lower concentration of Nes-1 and Gal can be considered as predictive factors of hypertension in obese patients, with Nes-1 negatively correlated with systolic pressure. Endocannabinoid system, through cannabinoid receptors 1, may also influence BP, though its role requires further research. Understanding these systems could improve the management of hypertension, particularly in pediatric populations.

The application of Xingnaojing injection is widespread; however, drug-induced fever associated with this medication is challenging to diagnose. Previous literature rarely reports cases of drug-induced fever resulting from the use of Xingnaojing injection.

A 46-year-old male patient, who underwent surgery for cerebral hemorrhage, presented with fever. The condition is considered to be drug fever induced by the administration of Xingnaojing.

Considering the potential for drug fever associated with the administration of Xingnaojing injection.

Discontinue the use of Xingnaojing injection.

The patient has shown improvement and is being discharged.

Clinical practitioners should enhance the prevention and management of adverse drug reactions to reduce both patient hospitalization duration and economic costs, thereby ensuring the safety of medication use for patients.

Anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV) is a group of small-vessel necrotizing vasculitides with minimal immune complex deposition. Hypertrophic cranial pachymeningitis, a rare complication of AAV, is characterized by focal/diffuse dural thickening and fibrosis, causing neurological dysfunction such as headache and optic nerve injury. While AAV-associated hypertrophic cranial pachymeningitis is well documented, reports of concurrent spinal dural involvement remain scarce. This case highlights the rare co-occurrence of cranial and spinal dural involvement in AAV, providing new clinical evidence to expand the understanding of AAV-related dural manifestations and improve diagnostic awareness among clinicians.

A 57-year-old male presented with fever, headache, otalgia, and hearing loss, and was diagnosed with granulomatosis with polyangiitis based on positive anti-proteinase 3 antibodies (664.3), cytoplasmic anti-neutrophil cytoplasmic antibody (1:10). Symptoms resolved with glucocorticoids, disease-modifying antirheumatic drugs, and anti-infective therapy. He later developed recurrent headache and lumbodorsal pain.

Thoracic magnetic resonance imaging (MRI) revealed a T10 to 12 epidural lesion, which was surgically resected. Pathology confirmed epidural vasculitis with necrotic/fibrous tissue, granulation, and inflammatory cell infiltration. Methylprednisolone and cyclophosphamide relieved back pain, but headaches persisted. Cranial MRI showed dural thickening in the cerebellar, posterior fossa, and foramen magnum regions, consistent with pachymeningitis. Cerebrospinal fluid analysis showed elevated mononuclear cells (35.00 × 106/L), nucleated cells (40.00 × 106/L), and protein (1.49 g/L), with negative cultures. The final diagnosis was granulomatosis with polyangiitis complicated by concurrent cranial and spinal dural involvement.

Initial management included glucocorticoids, disease-modifying antirheumatic drugs, and anti-infective therapy, which resolved the patient's fever, otalgia, and hearing loss. Surgical resection was performed for the T10 to 12 epidural lesion, followed by immunosuppressive therapy with methylprednisolone and cyclophosphamide. After adjustment of the treatment regimen, the patient's headache improved.

Initial therapy resolved the patient's fever, otalgia, and hearing loss. Surgical resection combined with immunosuppressive therapy relieved lumbodorsal pain but failed to resolve headaches initially; cranial MRI confirmed pachymeningitis, and cerebrospinal fluid analysis indicated inflammatory changes. After adjustment of the treatment regimen, the patient's headache improved, and he has remained clinically stable during follow-up.

This case demonstrates that AAV can involve both cranial and spinal dura mater. Clinicians should consider dural involvement in AAV patients presenting with lumbodorsal pain.