Xianqing Ren

Cough-variant asthma (CVA) is characterized by chronic dry cough as its predominant manifestation, lacking the wheezing typical of classic asthma. Violent paroxysmal coughing generates distinct mechanical loads across different airway segments: the larynx and glottis participate in airflow generation; the intrathoracic trachea and main bronchi undergo dynamic compression; bronchial bifurcations and narrowed segments experience elevated wall shear; and distal lung tissue is mainly subjected to volume change and tissue stretch. To address this gap, this review introduces “mechanoinflammation” as a concept—a pathogenic process in which physical forces directly gate mechanosensitive ion channels on immune and structural cells to initiate sterile innate immune cascades and establish self-amplifying inflammatory loops, distinct from the existing concept of “mechanotransduction,” which focuses on physiological force-to-signal conversion. Alveolar, interstitial, and inflammation-recruited macrophages occupying different niches may sense corresponding local mechanical changes and together constitute the candidate cellular basis of airway macrophage mechanotransduction. Cough-induced membrane tension may open Piezo1 and mediate calcium influx, which is amplified through the PI3K/AKT axis to license NLRP3 inflammasome assembly and mature IL-1β release. The latter may sensitize vagal C-fiber terminals and may close a physical–immune–neural feedback loop in which coughing initiates inflammation and inflammation reinforces coughing. This signaling axis provides a possible mechanistic explanation for corticosteroid resistance in refractory CVA and provides novel therapeutic directions targeting Piezo1 modulators, NLRP3 inhibitors, and IL-1 blockade to disrupt chronic cough.

Glomerular disease (GD) is a heterogeneous group of renal disorders involving the glomeruli, which may arise primarily from the kidney itself or secondarily from systemic diseases. Their pathologic...

Introduction: Endothelial activation is implicated in childhood IgA vasculitis, but candidate endothelial markers may reflect systemic inflammation rather than endothelial perturbation. Methods: In this single-centre cross-sectional pilot study, we enrolled 13 children with acute IgA vasculitis and 20 age- and sex-comparable healthy controls screened to exclude acute infection, allergic disease and other inflammatory conditions. Plasma soluble fms-like tyrosine kinase 1, soluble vascular endothelial cadherin, von Willebrand factor (vWF) and vascular endothelial growth factor were measured by enzyme-linked immunosorbent assay (ELISA); CD45-low CD31 ⁺ CD146 ⁺ endothelial-lineage events were quantified by three-colour flow cytometry in a subset. Results: Children with IgA vasculitis had higher C-reactive protein, neutrophil proportion and platelet count than controls. In the pooled analysis, vWF was higher in patients than controls (median 811.1 vs. 439.9 ng/mL; Hodges-Lehmann difference 335 ng/mL, 95% confidence interval 133-539; P = 0.008; Benjamini-Hochberg q = 0.03), but this contrast did not persist after ELISA plate stratification (van Elteren P = 0.38) and is therefore hypothesis-generating. Within patients, no clear monotonic associations were detected between vWF and C-reactive protein or neutrophil indices; these exploratory analyses were underpowered to establish independence from systemic inflammation. No clear group differences were detected in the other soluble analytes. Endothelial-lineage events were nominally higher in patients, but this readout was strongly affected by CD45-low gate size and acquisition-session variability. Discussion: These findings support batch-controlled validation of vWF and more rigorous endothelial-cell enumeration in future pediatric IgA vasculitis studies.

Objective: IgA vasculitis nephritis (IgAVN) is the principal cause of morbidity and mortality in children with IgA vasculitis (IgAV),the pathogenesis of the renal injury and predictive biomarkers are still unclear. In this study, we performed an integrated untargeted and targeted metabolomics to identify candidate biomarkers and explore oxidative stress-related alterations associated with IgAVN. Methods: Serum samples were collected from 115 IgAV and 111 IgAVN children. We conducted untargeted metabolomics for preliminary screening of potential biomarkers on 50 IgAV and 50 IgAVN children and then performed validation experiments based on targeted LC-MS/MS on 65 IgAV and 61 IgAVN children. In addition, an IgAVN animal model was established to preliminarily verify oxidative stress-related alterations associated with key metabolic abnormalities by assessing the levels of GSH, GSH/GSSG, MDA, 4-HNE, NRF2, HO-1, and GPX4. Results: A total of 45 differential metabolites were identified between the IgAV and IgAVN groups, including 23 upregulated and 22 downregulated metabolites, which were mainly enriched in glutathione metabolism, pyruvate metabolism, the citrate cycle, sphingolipid metabolism, and steroid hormone biosynthesis. Further targeted validation confirmed that six metabolites, including sphinganine, dehydroepiandrosterone, kynurenine, glutathione, nervonic acid, and creatine differed significantly between the two groups. The combined model based on these six metabolites showed good discriminatory performance, with an AUC of 0.903 and an area under the PRC curve of 0.909. In the animal experiments, the model group exhibited decreased GSH levels, a disrupted GSH/GSSG balance, increased MDA and 4-HNE levels, as well as abnormal expression of NRF2, HO-1, and GPX4. Conclusion: Children with IgAVN exhibit a distinct metabolic profile characterized by glutathione depletion, activation of inflammation-related tryptophan metabolism, lipid/membrane remodeling, and disordered energy metabolism. Sphinganine, dehydroepiandrosterone, kynurenine, glutathione, nervonic acid, and creatine may serve as potential biomarkers for IgAVN, and the combined model based on these metabolites showed good discriminatory ability and potential clinical utility. The consistency between the clinical metabolomics findings and the experimental evidence supports supports glutathione-related oxidative stress and the GSH-NRF2/HO-1/GPX4 axis as candidate pathways associated with IgAVN-related renal injury. These findings provide a basis for early risk identification and future mechanistic and pharmacological investigations in pediatric IgAVN.

Benign upper gastrointestinal diseases (BUGDs) are chronic conditions characterized by inflammation, tissue damage, or functional impairment, primarily gastroesophageal reflux disease (GERD), gastr...

CD163 is a surface marker expressed by M2c macrophages. This study aims to evaluate the level of urinary soluble CD163 (u-sCD163) in children with IgA vasculitis with nephritis (IgAVN) and its potential diagnostic value. U-sCD163 was analyzed in 73 children with IgAVN who underwent a kidney biopsy, 37 children with IgA nephropathy and 50 normal controls. CD163 expression was analyzed by immunohistochemistry. Correlation analyses and inter-group comparison were performed to assess the association between u-sCD163 levels and clinicopathological features of IgAVN. The comparison of u-sCD163 levels before and after treatment was conducted. The level of u-sCD163 was significantly higher in children with IgAVN than healthy controls. Compared with grade II IgAVN subjects, u-sCD163 level was significantly elevated in grade III-IV subjects. There was no difference in u-sCD163 level between IgAVN and IgA nephropathy groups. There was no difference in serum CD163 level among different groups. In the IgAVN group, abundant CD163-positive cells were observed in glomeruli showing endocapillary proliferation, especially in areas of thrombosis and fibrinoid necrosis. In contrast, CD163-positive cells were scarce within cellular crescents, but increased in fibrocellular crescents. Levels of u-sCD163 showed a significant positive correlation with proportions of endocapillary proliferation, and moderately correlated with proteinuria, CD163 score of glomerular area, and weakly correlated with proportions of cellular crescents, D-dimer and fibrin degradation products (FDP). The level of u-sCD163 decreased significantly after treatment. U-sCD163 emerges as a promising marker associated with endocapillary proliferation and coagulation in pediatric patients with IgAVN.

Membranous Nephropathy (MN) is the leading cause of primary nephrotic syndrome in adults, characterized by significant clinical heterogeneity ranging from spontaneous remission to end-stage kidney disease. Current management of membranous nephropathy, which relies heavily on renal biopsy and static serological markers such as anti-PLA2R antibodies, often fails to predict individual disease trajectories. This limitation frequently leads to empirical immunosuppressive therapy with a trial-and-error approach. This review explores the transformative potential of Artificial Intelligence (AI) in reshaping MN management from evidence-based to data-driven and predictive medicine. We examine AI-driven innovations across the clinical spectrum: from computational pathology systems that automate glomerular morphometry with high objectivity and reproducibility, to non-invasive diagnostic models integrating radiomics and serology for non-invasive diagnosis. In therapeutics, we discuss machine learning algorithms that predict individual responses to Rituximab versus Cyclophosphamide, enabling personalized regimen selection. Furthermore, we highlight the role of AI in prognostic stratification, where dynamic in silico patient models and multi-omics integration unravel molecular subtypes and forecast renal survival with high granularity. While acknowledging critical challenges such as data silos, model interpretability gaps, and the need for global validation, we conclude that AI serves as a powerful augmentation tool. By synthesizing high-dimensional data into actionable insights, AI has the potential to facilitate increasingly predictive, preventative, and personalized care strategies in MN management.

Acute kidney injury (AKI) is a complex syndrome with multiple causes, associated with high morbidity and mortality rates. Despite advances in intensive care, effective therapeutic strategies for AKI remain limited. In this review, we examine the roles of oxidative stress and endoplasmic reticulum stress (ERS) in the pathogenesis of AKI. Oxidative stress, marked by the excessive production of reactive oxygen species (ROS), can trigger ERS, leading to misfolded protein accumulation and activation of the unfolded protein response (UPR) in an attempt to restore cellular homeostasis. When ERS becomes prolonged or excessive, persistent activation of UPR pathways such as IRE1, PERK and ATF6 induces apoptosis and further worsens kidney injury. In addition to apoptosis, oxidative stress and ERS also regulate autophagy, a cellular stress response. Together, these pathways promote cellular dysfunction and advance AKI progression. We also discuss potential therapies that target oxidative stress and ERS, such as antioxidants and pharmacological agents targeting UPR pathways, which may offer promising approaches to mitigate AKI. A deeper understanding of the interplay between oxidative stress and ERS in AKI is essential for developing effective therapeutic interventions to improve patient outcomes.