Objective: To investigate the clinicopathological characteristics of lung transplantation and post-transplantation changes in patients with pneumoconiosis. Methods: A retrospective study was conducted to analyze the clinical and pathological data of 28 patients with pulmonary silicosis who underwent lung transplantation and were managed at the Department of Internal Medicine, Henan Provincial People's Hospital, Zhengzhou, China from January 2015 to December 2024. Among them, 8 patients underwent lung biopsy 6-20 months after transplantation to evaluate the histopathological changes of the recipient and the donor lungs post-transplantation. The expression of relevant indicators was examined using immunohistochemical EnVision staining, while presence of microorganisms was assessed using histochemical special staining. The patients were all followed up. Results: Among the 28 patients with pneumoconiosis who underwent lung transplantation, 26 were male and 2 were female, with a male-to-female ratio of 13∶1. Their ages ranged from 23 to 68 years, median 50.0 (46.0, 53.5) years. They were diagnosed with pneumoconiosis at local occupational disease prevention and control centers for 3 to 15 years (mean, 9.65 years), including 13 left single lung transplants and 15 right single lung transplants. Gross examination showed fleshy nodules with irregular cystic cavities at the periphery. The cut surfaces exhibited gray-brown color and firm texture. Microscopically, most alveolar structures of the lung were obliterated, with nodular or diffuse proliferation of collagen fibers accompanied by hyaline degeneration. Focal massive carbon dust deposition and massive silicotic fibrosis were observed, surrounded by lung parenchyma with emphysematous changes and localized bullae formation. Seven patients underwent re-biopsy after transplantation that showed extensive infiltration of inflammatory cells. In 4 cases, microscopy revealed complete coagulative necrosis, with negative acid-fast staining and TB-DNA results. Of the 4 cases, 3 cases exhibited Aspergillus infection confirmed by Grocott's methenamine silver and PAS stains, while 2 cases showed chronic bronchitis with squamous metaplasia. Follow-up revealed that 8 patients died of acute respiratory failure due to severe infection, while the remaining 20 demonstrated significant postoperative improvement in lung function. Conclusions: For patients with advanced pulmonary dust deposition disease who undergo lung transplantation, it is necessary to conduct standardized sampling and pathological assessment of the recipient lungs. In the early post-transplant period, the complications of re-biopsy tissues are mainly fungal infections. The combination of morphological manifestations and immunohistochemical detection is helpful to distinguish infection from rejection reactions. At the same time, it is essential to integrate clinical information and laboratory results to provide post-transplantation pathological assessment for individualized treatment.

This prospective study assessed the prevalence, type, and consequences of persistent symptoms following a nonhospitalized SARS-CoV-2 infection by comparing infected and noninfected children and adults of Dutch households. Two comparable prospective household studies were conducted during two pandemic phases. At baseline, all household members were tested for SARS-CoV-2 with 10 consecutive saliva samples during a 6-week period using RT-PCR. Questionnaires assessing persistent symptoms, health-related quality of life (HRQoL), anxiety, and depressive symptoms were collected at 6 and 12 months. Of the 297 included participants (median age 34 years, IQR 12-48), 201 (67.7%) tested positive for SARS-CoV-2. At 6 months, only one child reported persistent symptoms. SARS-CoV-2-infected adults (> 18 years) reported more pulmonary symptoms (15.2% vs. 3.4%, p = 0.023), and tended to report more fatigue (12.8% vs. 3.4%, p = 0.061) and exertion-related symptoms (8.8% vs. 1.7%, p = 0.107) compared to the negative adults. Adult participants with persistent symptoms reported decreased HRQoL and increased anxiety and depressive symptoms. This study found that SARS-CoV-2-positive adults tended to have higher prevalence of respiratory symptoms, fatigue, and exertion-related symptoms 6 months after SARS-CoV-2 infection, whereas children rarely reported persistent symptoms. Persistent symptoms were associated with a reduced HRQoL and increased anxiety and depression.

Resveratrol (RES) has been shown to be a promising protective agent against asthma. However, its role in the steroid-resistant asthma is unknown. Studies showed RES displayed hormetic action, protecting the cells at a lower dose while inducing cytotoxicity at higher doses, which limits its clinical application. In this study, we determined the efficacy of different doses of RES in a steroid-resistant asthma model. A toluene diisocyanate (TDI)-induced steroid-resistant murine asthma model was established. The effects of different doses of RES were tested both in vitro and in vivo. We observed low-doses RES (1, 10 mg kg^-1) ameliorated TDI-induced airway hyperresponsiveness, airway neutrophil accumulation, mucus production and collogen deposition as well as the release of Th2 and Th17-related cytokines. Yet, the high-dose RES (100 mg kg^-1) had no protective effects. As a SIRT1 activator, RES expectedly increased pulmonary SIRT1 expression at doses of 1,10 and 100 mg kg^-1, but only low-dose RES (1, 10 mg kg^-1 in mice and 10 μM in vitro) decreased TDI-induced bronchial epithelial HMGB1 acetylation, nucleocytoplasmic translocation and release. Further, we found pulmonary p300, a nuclear histone deacetyltransferase, significantly upregulated by TDI was suppressed by only low-doses RES (1, 10 mg·kg^-1). In addition, low-dose rather than high-dose RES attenuated TDI-induced bronchial epithelial DNA damage and mitochondrial oxidative stress. Our data suggested that low-dose RES inhibits HMGB1 acetylation and release and maintains SIRT1-p300 balance, which ameliorates airway inflammation in TDI-induced steroid-resistant asthma.

Chronic obstructive pulmonary disease (COPD) is a complex respiratory disorder with heterogeneous pathological manifestations. Emerging evidence highlights that autonomic nervous system (ANS) dysregulation may play an promising role in COPD progression. This narrative review aims to summarize a current mechanistic insights into ANS-mediated pathophysiology and explore novel therapeutic strategies targeting autonomic dysfunction.

We conducted a narrative analysis of preclinical and clinical studies from PubMed and Web of Science, focusing on ANS-related pathways in COPD. Key mechanisms and therapeutic interventions were evaluated through integrative interpretation of published evidence.

ANS imbalance, marked by diminished sympathetic tone and excessive parasympathetic activity, exacerbates core COPD pathologies. Mechanistically, cholinergic hyperactivity drives airway constriction and mucus hypersecretion, while sympathetic suppression impairs bronchodilation and immune responses. Neuroimmune crosstalk and systemic autonomic remodeling further link COPD to extrapulmonary comorbidities, including cardiovascular disorders and lung cancer. Emerging therapies, such as bioelectronic neuromodulation and phenotype-specific interventions, demonstrate potential in restoring autonomic equilibrium. For instance, vagus nerve stimulation attenuates inflammation, and targeted lung denervation reduces exacerbation risks in specific patient subgroups. Traditional approaches, including acupuncture, also show efficacy in improving functional outcomes.

Precision modulation of ANS plasticity represents a transformative approach to COPD management, bridging molecular mechanisms with clinical applications. Future research should prioritize combinatorial therapies and biomarker-driven stratification to address the multifaceted nature of ANS dysfunction. This paradigm shift holds promise for personalized interventions that mitigate disease progression and systemic complications.

The growing population of adults with congenital heart disease (ACHD) faces lifelong morbidities despite advancements in medical and surgical care. Sarcopenia, characterized by loss of muscle mass and strength, is linked to increased disability, poor quality of life and mortality. This study examines sex-specific thoracic skeletal muscle characteristics in ACHD patients using advanced imaging techniques, comparing them with healthy reference values and investigating their association with exercise capacity.

In this single-centre retrospective study, ACHD patients (age 18-50 years) who underwent both cardiopulmonary exercise tests and thoracic CT/MRI within a year were included. Skeletal muscle area (SMA) was manually measured and compared with healthy reference data.

Among 60 ACHD patients (mean age 28.3 ± 8.3 years; 48% females), males exhibited significantly lower SMA (T10: 116.8 ± 24.6 cm², p < 0.0001; T11: 114.4 ± 24.7 cm², p = 0.0002) and skeletal muscle index (SMI) (T10: 37.2 ± 8 cm²/m², p = 0.005; T11: 36.4 ± 8.1 cm²/m², p = 0.0014) at T10 and T11 vertebral level, whereas females showed a reduction in SMA at T10 (79.7 ± 14.9 cm², p = 0.0242) and T12 (74.2 ± 10.7 cm², p = 0.0015) compared with healthy individuals. Females had significantly lower skeletal muscle radiation attenuation (SMRA) at T10 (16.3 ± 14.6 HU, p < 0.001), T11 (17.1 ± 10.3 HU, p < 0.001) and T12 (25 ± 10.7 HU, p < 0.001) levels, suggesting increased muscle fat content. Peak O₂ pulse correlated with SMA at T10 (r = 0.57, R² = 0.32, p ≤ 0.0001), T11 (r = 0.61, R² = 0.38, p < 0.0001) and T12 (r = 0.73, R² = 0.53, p = 0.001) levels. Similar correlations were observed between peak O₂ pulse and SMI, whereas peak VO₂ correlated with SMA at T10 (r = 0.27, R² = 0.07, p = 0.0394) and T11 (r = 0.34, R² = 0.11, p = 0.02) and SMRA across all levels (T10: r = 0.64, R² = 0.41, p = 0.0076; T11: r = 0.85, R² = 0.72, p = 0.0003; T12: r = 0.62, R² = 0.38, p = 0.0327). SMA at T11 had a negative correlation with VE/VCO₂ (r = -0.36, R² = 0.13, p = 0.01). There was no correlation between the number of sternotomies and exercise parameters. Subjects with a pacemaker demonstrated significantly lower peak VO₂ (p = 0.04) and VO₂ at the anabolic threshold (p = 0.03) compared with ACHD patients without a pacemaker.

Abnormal skeletal muscle parameters observed on thoracic cross-sectional imaging are associated with diminished exercise capacity in ACHD patients. Assessment of thoracic skeletal muscle characteristics may enable early detection of muscle loss, providing valuable insights into the complex factors contributing to exercise limitations in this population.

Pediatric hypertension presents unique challenges in its management and treatment. A previous study demonstrated the safety and efficacy of azilsartan in children 6-15 years old, but evaluation in children under 6 years old has not been conducted.

This phase 3, open-label study assessed the safety and efficacy of azilsartan in Japanese pediatric patients (2 to <6 years old) with hypertension. Patients received azilsartan once daily for 52 weeks, starting with 0.1 mg/kg and titrating up to a maximum of 0.8 mg/kg if target blood pressure (BP) had not been achieved. The primary objective was the incidence of treatment-emergent adverse events (TEAEs) and other safety parameters.

All nine patients who received azilsartan experienced TEAEs; most (88.9%) were mild-to-moderate in severity. Three patients (33.3%) experienced drug-related TEAEs (acute kidney injury, anemia, and renal impairment). Acute kidney injury was the only serious drug-related TEAE, which resolved following treatment interruption. There were no deaths or study discontinuations due to TEAEs. At weeks 12 and 52, mean (SD) changes in systolic BP from baseline (last observation carried forward) were -8.0 (6.7) and -10.9 (8.3) mmHg, respectively. The mean changes in diastolic BP from baseline were -10.9 (11.0) and -14.8 (8.4) mmHg, respectively.

Azilsartan was generally well tolerated and associated with sustained BP reductions over 52 weeks in nine Japanese pediatric patients with hypertension. No new safety signals were identified. Our results indicate that azilsartan can be a therapeutic option for managing pediatric hypertension, potentially improving long-term cardiovascular outcomes.

Frontal base mixed pial-dural arteriovenous malformations (MPD-AVMs) are rare intracranial vascular malformations with both pial and dural components. Although they share some angioarchitectural similarities with anterior cranial fossa dural arteriovenous fistulas (ACF-DAVFs), the two represent different pathological processes, as ACF-DAVFs are supplied exclusively by dural arteries. This study provides an overview of frontal base MPD-AVMs, highlighting their differences from ACF-DAVFs, and discusses the therapeutic implications of their distinct angioarchitectural features.

This is a single-center case series study conducted between January 2018 and December 2024. The data of 11 patients who underwent endovascular treatment for frontal base MPD-AVMs and 29 patients diagnosed with ACF-DAVFs were retrospectively reviewed.

In patients diagnosed with MPD-AVMs, all lesions were supplied by the anterior ethmoidal artery (AEA) and orbitofrontal artery (OFA). Flow-related aneurysms in the OFA were identified in seven patients (7/11, 63.6%), with three presenting with hemorrhagic events. Treatment approaches included transarterial embolization (TAE) in eight patients, with one requiring additional transvenous embolization (TVE). Primary TVE was employed in three patients, including two hemorrhagic patients who underwent staged treatment with initial aneurysm embolization. Complete obliteration was achieved in 72.7% of cases (8/11), although one patient experienced postoperative hemorrhage. In patients presenting with ACF-DAVFs, venous aneurysm (18/29, 62.1%) might represent a risk factor for bleeding (13/29, 44.8%) (p = 0.003). In the MPD-AVM group, venous aneurysms were detected in five patients (5/11, 45.5%), but none of whom experienced hemorrhage.

Frontal base MPD-AVMs represent distinct vascular anomalies from ACF-DAVFs, often featuring anterior cerebral artery branch involvement. Tailored multi-arterial endovascular strategies are crucial for optimizing outcomes and minimizing complications. Further studies with larger cohorts are essential to validate these observations and refine treatment guidelines.

This study aimed to investigate the prevalence of hypertension among young adults with MAFLD, assess the association between the presence and severity of MAFLD and hypertension, and explore potential mediating mechanisms linking MAFLD and hypertension in this population.

A total of 5,327 individuals aged 18-45 years from the National Health and Nutrition Examination Survey (2017-2023) were included. Multivariable logistic regression analysis was performed to evaluate the independent associations of MAFLD and its severity with hypertension and isolated diastolic hypertension. Mediation analysis assessed the mediating effects of inflammatory markers, including white blood cell (WBC) count, neutrophil count, and systemic immune-inflammation index (SII).

The prevalence of MAFLD in the study population was 44.05%. Hypertension prevalence in the MAFLD group was significantly higher than in the non-MAFLD group (37.68% vs. 15.19%, P < 0.001). After adjusting for sex, age, race, alcohol consumption, and comorbidities such as diabetes and renal insufficiency, individuals with MAFLD and moderate-to-severe fibrosis exhibited a significantly higher risk of hypertension compared to non-MAFLD individuals (OR = 3.414, 95% CI: 2.522-4.622), P < 0.001). Mediation analysis demonstrated that WBC, neutrophils, and SII mediated 7.62% (95% CI: 2.75-15.00), 6.71% (95% CI: 2.48-12.65), and 5.90% (95% CI: 2.40-10.88) of the association between MAFLD and hypertension, respectively.

MAFLD, particularly in the presence of advanced liver fibrosis, is strongly and independently associated with hypertension in young adults. Systemic inflammation acts as a key mediator in this relationship, highlighting its potential as a therapeutic target for precision antihypertensive strategies in this population.

BackgroundRepetitive transcranial magnetic stimulation (rTMS) is a noninvasive intervention aimed at enhancing neuroplasticity and supporting motor recovery in stroke survivors. This meta-analysis examines the efficacy of rTMS in enhancing upper limb motor function and independance in daily activities, utilizing key assessment tools such as the Fugl-Meyer Assessment for Upper Extremity (FMA-UE), Wolf Motor Function Test (WMFT), Modified Barthel Index (MBI), and Action Research Arm Test (ARAT).MethodsA systematic review of 10 studies involving 382 participants was conducted. Outcomes were analyzed for mean differences (MD) and 95% confidence intervals (CI) using forest plots. Subgroup analyses examined the influence of stroke stage and session length. Evidence quality was assessed using the GRADE framework.ResultsrTMS significantly improved motor performance, with the FMA-UE showing the most consistent and clinically meaningful gains, where the overall standardized mean difference (SMD) was 1.28 (95% CI: 1.82 to 0.74, p < 0.0001, I² = 0%), particularly during subacute and subacute-to-chronic stages. Furthermore, protocols with 15-20 sessions yielded significantly better outcomes (SMD = 1.50, 95% CI: 1.90 to 1.10, p < 0.001) than shorter protocols. ARAT results were less consistent, indicating challenges in fine motor recovery, particularly in chronic stroke populations.ConclusionThis meta-analysis confirms that rTMS effectively enhances upper limb motor function and independence in post-stroke patients. Tailored protocols during subacute stages optimize recovery, though further research is needed to refine protocols and explore long-term outcomes.

Mitochondrial dysfunction and impaired neurogenesis are central to mitochondrial DNA polymerase (POLG)-related disorders, yet therapeutic options remain limited. Here, patient-derived induced pluripotent stem cell (iPSC)-based cortical organoids are used to model POLG-associated neurodegeneration and assess the therapeutic potential of metformin. Single-cell RNA-seq reveals distinct vulnerabilities in dopaminergic, glutamatergic, and GABAergic neuronal subtypes, with dopaminergic neurons exhibiting the most severe loss and mitochondrial transcriptomic deficits. Metformin treatment (250 µm, 2 months) significantly restores neuronal identity, subtype-specific gene expression, and mitochondrial function. Functional assays demonstrate improved mitochondrial membrane potential (TMRE), increased mitochondrial mass (MTG, MTDR), and reduced oxidative stress (MitoSOX, BAX/cleaved caspase 3). Notably, mitochondrial DNA (mtDNA) copy number and the expression of mitochondrial replisome proteins (POLG, POLG2) are upregulated, indicating enhanced mitochondrial genome maintenance. Calcium measurement confirms improved neuronal excitability. Untargeted metabolomics further reveals metformin-induced metabolic reprogramming, including enrichment of the tricarboxylic acid (TCA) cycle, amino acid metabolism, and redox-related pathways. Together, these findings demonstrate that metformin enhances mitochondrial integrity and neural function across multiple neuronal subtypes and offer mechanistic insights into its potential as a treatment for POLG-related disorders.