Zhaofu Li

Background: Knee osteoarthritis (KOA) is a prevalent musculoskeletal disorder and a major cause of pain and disability. As short-video platforms increasingly shape how the public accesses health information, concerns have grown regarding the quality, reliability, and completeness of KOA-related content. This study evaluated KOA-related videos on three major Chinese short-video platforms, TikTok, Kwai, and Bilibili, to compare information quality, user engagement, and implications for digital public health communication. Methods: In this cross-sectional study, standardized Chinese keywords were used to retrieve KOA-related videos from TikTok, Kwai, and Bilibili on December 24, 2025. After deduplication and screening, 300 videos were included, 100 from each platform. Video characteristics and engagement indicators were recorded. Information quality was assessed using the DISCERN reliability section, Global Quality Score (GQS), content completeness score (CS, range 0–10), and engagement score (ES, range 0–4). Uploaders were categorized by source type. Statistical analyses included the Kruskal–Wallis H test, chi-square test, and Spearman correlation analysis. Results: Substantial cross-platform differences were identified. Bilibili videos had the longest duration (median 402 s) and the highest information quality, with superior DISCERN scores (median 32), GQS (mean 4.3), and CS (mean 7), and had the highest proportion of certified medical professionals among uploaders (38.0%). TikTok videos were the shortest (median 86 s) but showed the highest user engagement, including likes, comments, shares, and the highest ES (median 3.6). TikTok and Kwai videos were generally less complete, focusing mainly on symptoms and treatment while providing limited information on etiology and prognosis. Correlation analysis showed that higher information quality and completeness were negatively associated with user interaction metrics, whereas ES was positively associated with engagement. Conclusions: The three major short-video platforms in China represent distinct digital health information ecosystems for KOA, revealing a consistent trade-off between scientific rigor and audience engagement. Platform recommendation mechanisms may may preferentially surface content that is more attractive and interactive rather than more accurate and comprehensive. These findings highlight an important public health challenge in the governance of online health information and suggest that improving chronic disease communication on social media will require both stronger platform-level quality prioritization and more engaging evidence-based content produced by health professionals.

Gout is a prototypical sterile inflammatory disease caused by the deposition of monosodium urate (MSU) crystals in joints and periarticular tissues. Although acute gout flares are characterized by rapid and intense neutrophil-dominated inflammation, they often resolve spontaneously, suggesting that neutrophils may contribute not only to inflammatory amplification but also to endogenous resolution. In this review, we summarize current evidence on the multifaceted roles of neutrophils in gout across different stages of disease. We discuss how MSU crystals activate innate immune signaling and promote neutrophil recruitment, activation, and effector responses, thereby driving acute inflammation. We further examine the diverse neutrophil programs involved in gout, including apoptosis, necroptosis, pyroptosis, autophagy, efferocytosis, and NET release. Particular attention is given to the dual roles of NETs in gout, as they can both amplify inflammation and, in their aggregated form, facilitate cytokine degradation, crystal sequestration, and inflammation resolution. In addition, we address the potential contribution of neutrophil-derived extracellular vesicles and neutrophil-associated mechanisms to tophus formation and chronic disease progression. By integrating recent advances and ongoing controversies, this review highlights neutrophils as dynamic regulators of both inflammatory injury and resolution in gout, and underscores their potential as therapeutic targets in immune-mediated crystal inflammation.

Rheumatoid arthritis (RA) is a chronic autoimmune disorder characterized by persistent synovitis, immune dysregulation, and progressive joint destruction. Its pathogenesis is multifactorial and primarily involves disruption of immune homeostasis, accompanied by sustained activation of the local inflammatory microenvironment within the joints. Adverse effects, therapeutic resistance, and suboptimal efficacy limit the effectiveness of current clinical interventions. Extracellular vesicles (EVs), including exosomes, microvesicles, and apoptotic bodies, are natural vesicular carriers with intrinsic biocompatibility, low immunogenicity, and efficient intercellular communication capacity. By delivering diverse bioactive molecules, EVs modulate immune cell activation and functional equilibrium and enable targeted delivery of therapeutic agents to RA lesion sites via surface marker modification or functional molecule engineering. This strategy represents an emerging direction in rheumatology and immunology research. This review systematically summarizes recent progress in the immunoregulatory mechanisms and targeted delivery applications of EVs in RA, examines the technical limitations and major challenges associated with clinical translation, and outlines a theoretical foundation and research perspectives for advancing precision and personalized therapeutic strategies for RA.

Rheumatoid arthritis (RA) is an autoimmune disease primarily characterized by chronic, erosive polyarthritis. It is associated with a high rate of disability, and its pathogenesis remains incompletely understood. Uncontrolled chronic inflammation, synovial hyperplasia, Pannus formation, and bone destruction in RA patients remain the core challenges facing current clinical treatment, and the inflammatory response is generally considered the initiating factor for this series of pathological processes. In an inflammatory environment, the body’s metabolic rate accelerates, leading to increased local oxygen consumption and ultimately creating a hypoxic microenvironment. Research has shown that under hypoxic conditions, glycolysis serves as the body’s primary energy pathway and is essential for sustaining the inflammatory response. Furthermore, lactate, a byproduct of glycolysis, functions not only as a metabolic byproduct but also as a precursor molecule; through lactylation, it contributes to the progression of RA. Although this metabolic–epigenetic axis is a common feature of various chronic inflammatory diseases, its effects on joint pathology may contribute to RA progression. Therefore, this article focuses on the intrinsic connections among hypoxia, glycolysis, and lactylation, and systematically reviews the immunological and inflammatory mechanisms of glycolysis in RA, the relationship between glycolysis and synovial hyperplasia, Pannus formation, and bone destruction in RA, and the role of lactate modification in promoting the pathological progression of RA. It also summarizes the latest research advances in RA therapies targeting hypoxia, glycolysis, and lactate modification, aiming to provide a theoretical basis for a deeper understanding of the pathogenesis of RA and the development of targeted treatment strategies.

Tophus is a hallmark lesion of chronic gout, formed through the combined effects of monosodium urate (MSU) crystal deposition, persistent inflammation, and progressive tissue fibrosis. These lesions can cause joint deformities, functional impairment, and renal damage, resulting in a significant decline in patients’ quality of life. Although hyperuricemia has traditionally been regarded as the primary cause of tophus formation, this explanation does not fully account for the considerable clinical heterogeneity observed among patients. In this study, we describe the multistage and dynamic pathological process underlying tophus formation. Building upon the foundation of hyperuricemia, the study focuses on MSU crystal nucleation, growth, and aggregation; crystal-triggered innate immune activation and NLRP3 inflammasome-mediated inflammatory cascades; the dual roles of neutrophil infiltration and neutrophil extracellular traps; macrophage phenotypic conversion, fibroblast activation, and extracellular matrix remodeling; the formation of multinucleated giant cells, complex cellular infiltration, and pathological angiogenesis; and the final formation of a mature, dense fibrous capsule structure. The study identifies the core regulatory nodes at each stage. Additionally, it explores potential therapeutic strategies for tophi and outlines future research directions. Together, these insights provide new therapeutic targets and a more comprehensive conceptual framework for early intervention and drug development. This research carries significant clinical and scientific value, with strong potential to improve outcomes for patients with chronic gout and to reduce the associated healthcare burden.

Gouty nephropathy (GN) is a chronic kidney disorder driven by persistent hyperuricemia; however, its pathogenesis remains under-investigated. Emerging evidence highlights that programmed cell death (PCD) plays a central role in GN, linking disordered urate metabolism to inflammation and renal functional decline. In GN, multiple PCD modalities, including apoptosis, necroptosis, pyroptosis, ferroptosis, and autophagy, are aberrantly activated. These death pathways contribute to tubular epithelial cell loss, interstitial inflammation, and fibrosis, forming an interactive pathological network rather than isolated phenomena. Apoptosis quietly depletes nephrons; necroptosis and pyroptosis mediate membranolytic cell rupture and sterile inflammation; ferroptosis inflicts iron-dependent lipid peroxidation injury; and autophagy, a double-edged sword, can both mitigate and exacerbate damage through its crosstalk with other PCD pathways. Recognizing the PCD network as a core driver of GN opens new avenues for therapy beyond conventional urate-lowering. Targeting key nodes of cell death holds promise to interrupt the self-perpetuating cycle in GN, for example: restoring mitochondrial redox balance to limit apoptosis, inhibiting the RIPK3/MLKL necroptosis cascade, suppressing NLRP3 inflammasome-mediated pyroptosis, modulating iron homeostasis to prevent ferroptosis, or fine-tuning autophagy. In sum, deciphering the molecular interplay of PCD in gouty nephropathy not only deepens our understanding of its pathology but also reveals novel therapeutic opportunities to protect the kidney beyond simply lowering uric acid levels.

Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease characterized by persistent synovitis, progressive joint destruction, and diverse extra-articular complications. Increasing evidence indicates that RA pathogenesis is not driven by isolated inflammatory events, but by a tightly interconnected network involving immune dysregulation, metabolic reprogramming, and aberrant mechanotransduction. This review synthesizes recent advances in these three pathogenic dimensions and proposes an integrated framework for understanding RA as a systemic, self-reinforcing disease process. We highlight how inflammatory circuits, particularly the IL-6/STAT3 and TNF-α/NF-κB axes, interact with autoantibody- and neutrophil extracellular trap-mediated immune propagation beyond the synovium. We further discuss how glycolytic rewiring, succinate accumulation, and microbiota-derived metabolites amplify inflammatory signaling and tissue remodeling. In parallel, altered extracellular matrix stiffness and activation of the integrin-FAK-YAP/TAZ pathway sustain pathogenic fibroblast behavior through mechano-epigenetic coupling. Collectively, these pathways form a feed-forward loop that links local synovial inflammation with systemic organ involvement. A systems-level understanding of these interactions may provide a stronger foundation for biomarker-guided stratification and the development of multi-target, mechanism-based therapeutic strategies in RA.

Gouty arthritis (GA) falls within the category of metabolic arthropathies. Its onset stems from abnormal uric acid metabolism, which subsequently leads to the deposition of monosodium urate (MSU) crystals and ultimately triggers a robust inflammatory response. Currently, the global prevalence rate of GA is on the rise, gradually increasing the societal disease burden it imposes. This review comprehensively examines the pathogenesis of GA. The content encompasses uric acid metabolic disorders, the innate immune activation process induced by MSU crystals, as well as various subsequently triggered programmed cell death (PCD) modalities, including pyroptosis, NETosis, apoptosis, necroptosis and ferroptosis. We then evaluate in vivo and in vitro experimental models according to the disease stage and pathogenic processes they best recapitulate. Exogenous MSU models are highly suitable for studying acute inflammatory flares; hyperuricemia models capture the metabolic basis of disease initiation; and composite models more closely reflect the chronic and multifactorial course of human gout. In vitro systems ranging from macrophage monocultures to co-culture and organoid platforms provide complementary tools for mechanistic studies and drug screening. However, current models still cannot fully reproduce the complexity of human gout, particularly with respect to metabolic initiation, tissue hierarchy, systemic context, and species-specific differences. We therefore propose a model-selection approach in which the choice of platform should be guided by the specific pathogenic process under investigation. Future model development should integrate innovative technologies to enhance the authenticity of pathological features, address the shortcomings of existing systems, and facilitate the clinical translation of GA research.

Progressive bone destruction in rheumatoid arthritis (RA) represents a core pathological mechanism leading to joint dysfunction. Its pathogenesis involves multiple critical pathways, including abnormal activation of immune and synovial cells, excessive pro-inflammatory cytokine secretion, and disrupted bone remodeling balance. Recent advancements in research techniques and academic exploration have progressively refined our understanding of RA-related bone destruction regulatory mechanisms. Programmed cell death (PCD), long noncoding RNAs (lncRNAs), and the significantly enhanced glycolytic metabolism observed in RA patients all mediate the onset and progression of RA bone destruction by targeting these pathological pathways. These findings collectively reveal a complex regulatory network intertwining cell demise processes, epigenetic regulation, and metabolic reprogramming. This not only deepens our understanding of the pathological mechanisms underlying RA bone destruction but also provides novel theoretical support and potential therapeutic targets for developing multi-targeted intervention strategies against this pathological process.

Background: The exact pathogenesis of gouty arthritis (GA) is unclear. However, it is believed that GA is characterized by recurrent episodes and a self-limiting nature. During episodes, the disease primarily manifests locally, making local omics research particularly relevant. Objective: Based on the local proteomic analysis of GA patients during the chronic phase (with tophi) and acute phase (with joint cavity effusion), this study systematically screened for inflammation-related differentially expressed proteins to provide specific biomarkers and potential intervention targets for disease prevention and treatment. Methods: Through a cross-sectional study, the baseline data were collected from the GA patients with chronic phase (with tophi) and acute phase (with joint cavity effusion)(n = 100 per group). Five cases were randomly selected from each group for local proteomics analysis to determine the biological functions and enriched signaling pathways of differentially expressed proteins. Based on the differential results, 30 additional cases were randomly selected from each group for validation using Western blot analysis. Results: The quantitative proteomics analysis identified a total of 810 differentially expressed proteins between the two groups, including 548 upregulated and 262 downregulated proteins. The GO and KEGG pathway enrichment analysis showed that the differential proteins were associated with ferroptosis. Ultimately, three ferroptosis-related differential proteins, including glutathione peroxidase 4 (GPX4), ferritin heavy chain 1 (FTH1), arachidonate and 15-lipoxygenase (ALOX15) were identified in GA patients. The differential expression of these proteins was validated using Western blot, showing statistically significant differences ( P < 0.05). Conclusions: The comprehensive analysis of proteomics and Western blot validation experiments showed that local lesions in the chronic phase of GA exhibited increased expression levels of GPX4 and FTH1, while local lesions in the acute phase of GA exhibited increased expression of ALOX15. Therefore, it was speculated that ferroptosis-inhibiting factors in the chronic phase of GA might participate in the chronic progression of the disease by limiting the toxicity of free iron. In the acute phase of GA, ferroptosis-promoting factors were activated in the joint microenvironment. This study revealed the differential expression of ferroptosis-related proteins at different stages of GA, providing a theoretical basis for developing GA staging and treatment strategies based on ferroptosis regulation.