BACKGROUND:Allergic rhinitis (AR) is a highly prevalent immunoglobulin E (IgE)-mediated disease that significantly impacts quality of life. While hematological parameters (complete blood count [CBC]) are linked to inflammation in adult AR, their relevance to pediatric populations remains unclear. This study aimed to characterize allergen sensitization profiles, CBC parameters, and immunoglobulin features in pediatric AR patients across demographic subgroups (sex, age, disease duration). METHODS:A retrospective study included 253 children with AR (aged 3-12 years; 176 males, 77 females) who tested positive for specific IgE (sIgE) to one or more inhalant allergens (≥ 0.35 IU/mL). Demographics, symptom scores (nasal/ocular), family history, sIgE, CBC, total immunoglobulin E (tIgE), immunoglobulin A (IgA), immunoglobulin G (IgG), immunoglobulin M (IgM), and complement component 4 (C4) were assessed. Statistical analyses were performed to compare groups based on sex, age (preschool vs. school-age), and disease duration, and to examine correlations between parameters and symptom scores. RESULTS:House dust mites (HDM) (including Dermatophagoides farinae [D. farinae]: 98.81% and Dermatophagoides pteronyssinus [D. pteronyssinus]: 97.63%) were the predominant sensitizing allergens, predominantly with high-grade sensitization (classes 3-6). Males exhibited significantly higher tIgE, D. farinae sIgE, D. pteronyssinus sIgE, German cockroach sIgE, IgA, C4, neutrophils, monocytes, red blood cell (RBC) count, red cell distribution width-coefficient of variation (RDW-CV), and mean corpuscular volume (MCV) compared to females. School-age children and those with longer disease duration had higher HDM sensitization rates (classes 3-6), Total Nasal Symptom Score (TNSS), IgG, IgA, neutrophils, and specific platelet indices (mean platelet volume [MPV], platelet-large cell ratio [P-LCR]), but lower eosinophils compared to preschoolers or those with short disease duration. Eosinophils, basophils, neutrophils, platelets, tIgE, HDM-sIgE, IgA, hematocrit (HCT), and red cell distribution width-standard deviation (RDW-SD) correlated significantly with nasal symptom scores. After adjusting for multiple comparisons and confounding factors, IgA remained independently associated with longer disease duration and showed significant correlations with nasal symptom scores. CONCLUSION:HDM are the primary allergens in the pediatric AR population in Guangzhou. Significant sex-, age-, and duration-related differences exist in sensitization patterns and immune and CBC profiles. After rigorous statistical control for multiple comparisons, only total IgE, absolute basophil count, and eosinophil percentage correlated significantly with symptom severity, highlighting their potential as accessible biomarkers for assessing disease activity.
Clear cell renal cell carcinoma (ccRCC) is an aggressive kidney malignancy with limited prognostic biomarkers. CRKL has been implicated in cancer progression, but its prognostic value and immune associations in ccRCC remain unclear. Using TCGA, GEO, and UALCAN databases, we analyzed CRKL expression. Kaplan-Meier and multivariate Cox regression assessed survival; TIMER and TISIDB evaluated immune infiltration; LinkedOmics databases and GSEA identified enriched pathways. CRKL was significantly overexpressed in ccRCC tissues at both mRNA and protein levels. Surprisingly, high CRKL expression was associated with better overall survival (OS), disease-specific survival (DSS), progression-free interval (PFI), and disease free survival (DFS). Multivariate Cox analysis identified CRKL as an independent favorable prognostic factor (OS: HR = 0.469, 95% CI: 0.302-0.729, P < 0.001). CRKL positively correlated with immune cell infiltration and immune-related pathways. In conclusion, CRKL is overexpressed in ccRCC, paradoxically, higher expression predicts better prognosis and is associated with immune-active tumor microenvironment features. These findings suggest that the favorable prognosis associated with CRKL may be attributable to its immunomodulatory role within the tumor microenvironment, highlighting its potential as a novel prognostic biomarker for ccRCC.
MicroRNAs (miRNAs) are key post-transcriptional regulators frequently dysregulated in cancer, yet how somatic mutational patterns influence miRNA regulatory regions remains unclear. In this study, we integrated mutation profiles, transition-transversion (Ti/Tv) ratios, and miRNA-gene interaction analyses across multiple TCGA cancer subtypes to investigate how mutation patterns may affect miRNA binding regions. miRNA interactions were strongly enriched in 3' untranslated regions (3'UTRs), with fewer interactions observed in coding sequences (CDS). Across cancers, miRNA regions exhibited moderate GC content (~51%), which typically predicts elevated Ti/Tv ratios; however, most cancer cohorts showed markedly reduced Ti/Tv ratios, indicating a shift toward transversion-heavy mutational processes. Because transversions generally produce greater nucleotide class changes than transitions, this shift may increase the likelihood of disrupting sequence-specific miRNA binding. Supporting this, we identified missense mutations overlapping predicted miRNA binding sites within coding regions, highlighting a potential intersection between somatic mutations and post-transcriptional regulation. Together, these findings suggest that cancer-associated mutational patterns may reshape miRNA regulatory regions and alter miRNA-gene interactions, providing insight into how somatic mutations impact gene regulation beyond protein-coding changes.
Psoriasis is a chronic immune-mediated inflammatory skin disease caused by dysregulated interaction between innate and adaptive immune cells. Of note, the IL-23/Th17 axiom is new central circuit amongst known pathways, while TNF-alpha, IL-17 family cytokines and IL-36 mediate the dysfunction of keratinocyte and tissue in inflammation. An interconnecting inflammatory network involves dendritic cells, T-cell populations, keratinocytes, neutrophils and fibroblasts that plate epidermal hyperproliferation and lesional immune-cell recruitment. Biologics targeting TNF-alpha and IL-17 and IL-23 are clinically transformative in the treatment of disease, but a large cohort of patients are left with incomplete response, resistance or challenges in long-term management. Other novel targets such IL-36R and AHR may extend the window of therapeutic opportunity. Molecular stratification and biomarker-driven treatment selection also merit investigation in parallel with further delineation of a specific therapeutic strategy.
Multiple sclerosis (MS) is a chronic autoimmune disorder of the central nervous system characterized by demyelination, inflammation, and progressive neurodegeneration. Cannabinoid receptor 1 (CB1) plays a role in neuroprotection and modulation of inflammatory responses, making it a potential therapeutic target in MS. This study evaluated selected natural compounds as CB1 modulators using an integrated computational approach. Compounds were screened based on ADMET properties, followed by molecular docking and 100 ns molecular dynamics simulations. Berberine and curcumin demonstrated binding affinities of -7.9 kcal/mol and -9.4 kcal/ mol, respectively. Key binding interactions involved residues VAL137, LEU404, PHE408, ARG405, and ARG409 for berberine, and MET363, LEU193, LEU359, TRP356, PHE189, PHE177, HIS178, PHE174, PHE379, ALA380, and SER383 for curcumin. Stability analyzes including RMSD, RMSF, secondary structure elements, and protein-ligand contacts, indicated stable complex formation. These findings suggest that berberine and curcumin may serve as potential lead candidates targeting CB1 and warrant further experimental validation in multiple sclerosis research.
Immune checkpoint inhibitors (ICIs) play a key role in cancer immunotherapy, enhancing outcomes for patients with multiple malignancies by blocking the programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) pathways. Nevertheless, their application is limited due to immune-related adverse events (irAEs), which comprise various manifestations, among which cardiovascular toxicities - primarily myocarditis, arrhythmias, pericarditis, and heart failure - are a major clinical challenge. While relatively rare, myocarditis has a fatality rate as high as 50%. The mechanisms underlying ICI-induced cardiovascular toxicity remain not fully understood, especially regarding how immune dysregulation translates into myocardial fibrosis. Herein, the immune dysregulation-inflammation-fibrosis axis is reviewed, and the mechanisms by which immune checkpoint blockade breaks cardiac immune tolerance, inducing T-cell activation, cytokine storms, and the subsequent production of anti-cardiac antibodies, are discussed. Moreover, the important function of non-coding RNAs (ncRNAs) in immunomodulatory and fibrotic pathways is then revealed as a key player in ICI-associated cardiac injury. It also discusses therapeutic strategies involving immune modulation and anti-fibrotic mechanisms, which may be suitable to reduce cardiovascular toxicity as well as improve the overall prognosis of patients. An improved mechanistic understanding underlying these processes will offer new theoretical insights into how to most effectively utilize ICIs safely.
Objective: Motor Neuron Disease (MND) is an increasing social health issue, in the cases of adults above 50 years of age, which requires the examination of its multidimensional burden, the spatiotemporal patterns, and the factors that contribute to it. Methods: We estimated age-standardized prevalence (ASPR), incidence (ASIR), mortality (ASMR), disability-adjusted life years (ASDR), and years lived with disability (ASYLDs) and years of life lost (ASYLLs) in adults aged 50 and older based on Global Burden of Disease (GBD) data 1990-2021. The correlation between Socio-demographic Index (SDI) and disease burden was sought through the analysis of correlation; the relationship between temporal changes and the gave way to joinpoint regression and the Bayesian age-period-cohort (BAPC) models to determine future disease burden. Results: The number of MND cases and age-standardized rates (ASRs) increased substantially over the period 1990-2021 with YLLs making up over 95 percent of DALYs. The highest burden was 75-84 years, with the males having a skewed burden. There were positive relationships between SDI where high-SDI regions (such as Australasia, North America, Western Europe) had the greatest burdens. The burdens were highest in Finland, Ireland and Sweden; the smallest countries recorded steep increases in Lithuania and Costa Rica. The analysis of joinpoint showed that global ASIR on the increase (1995-2005) then decreased (2019-2021), high-SDI areas recorded consistent growth. BAPC forecasted the increase in the number of cases even after minimal decrease in ASRs by 2040. Interpretation: The problem of the increasing burden of MND fueled by the aging population and negative prognosis highlights the inequalities between the strata in terms of SDI. The ability to treat increases the burdens in high-income regions. The focus on surveillance, fair prevention, and resources distribution is important. The paper has emphasized the importance of international cooperation to help reduce disparities associated with SDI and maximize interventions.
Platelet-Derived Growth Factor (PDGF)/Platelet-Derived Growth Factor Receptor (PDGFR) are key regulators in the complex network of signaling from Receptor Tyrosine Kinases (RTKs). PDGFR has historically been considered an attractive therapeutic target given its association with oncogenic mutations, gene fusions and altered signaling. However, growing evidence suggests that PDGFR functions beyond these traditional roles as a single therapeutic target and into a broader role as a central coordinator of oncogenic signaling. PDGFR mediates cross-talk among multiple oncogenic pathways such as EGFR, VEGFR and IGF-1R thus supporting redundancy in oncogenic signaling, resistance to therapy and adaptive changes in tumors. The biologic effects of PDGFR signaling do not end at tumor cell borders but rather include the regulation of the tumor microenvironment. Specifically, PDGFR directs the recruitment of pericytes, remodeling of the extracellular matrix and influences interstitial fluid pressure (IFP); each effect ultimately impacts both drug delivery and therapeutic efficacy. Studies have demonstrated that inhibition of PDGFR reduces stromal tension and normalizes tumor vasculature resulting in enhanced penetration of chemotherapy, targeted and radiation therapy. As such, these studies provide rationale for using PDGFR directed strategies in order to enhance treatment outcome via rational combinations of drugs. This review aims to integrate current knowledge of PDGF/PDGFR biology based on molecular interactions, tumor microenvironment dynamics and therapeutic approaches. It will highlight how PDGFR directed therapeutic strategies may serve to circumvent drug resistance, enhance drug delivery, enable use of biomarkers to drive combination therapeutics and promote a systems-level understanding of PDGFR function as a basis for advancing its translational application in precision oncology.
BACKGROUND:Chronic rhinosinusitis with nasal polyps (CRSwNP) frequently recurs after functional endoscopic sinus surgery (FESS), particularly in patients with eosinophilic inflammation or aspirin-exacerbated respiratory disease (AERD). Optimizing postoperative medical regimens based on disease severity may reduce recurrence rates. The aim of this study was to evaluate the impact of severity-based postoperative medical regimens on recurrence rates following FESS in patients with CRSwNP. METHODS:This prospective multicentric cohort study included 144 patients with CRSwNP who underwent FESS between 2021 and 2023. Patients were stratified into five groups based on eosinophilia, AERD status, and radiologic/endoscopic severity using the Modified Lund-Mackay (MLM) and Modified Lund-Kennedy (MLK) scores. Each group received a tailored postoperative medical regimen. Patients were followed for two years, with recurrence assessed via nasal endoscopy and scored using MLK. RESULTS:The overall recurrence rate at two years was 10.4%. Recurrence rates increased progressively from 0% in Group 1 (non-eosinophilic) to 33.3% in Group 5 (AERD). The trend was statistically significant (Cochran-Armitage test, Z = 3.48, P < 0.001). A significant association between follow-up group and recurrence was found (Chi-square, P = 0.006, Cramér's V = 0.316). Blood eosinophilia and elevated IgE levels were strongly correlated (P < 0.001, OR = 3.15). CONCLUSION:Postoperative recurrence in CRSwNP can be significantly reduced by tailoring medical regimens based on clinical, radiologic, and immunologic severity. Group-based stratification provides a feasible model for personalizing care, especially in settings where biologics are unavailable.
BACKGROUND:Acetylcholinesterase inhibitors (AChEIs) remain the standard therapy for Alzheimer's disease (AD), yet their cognitive and functional benefits are limited, creating a strong need for effective adjunctive treatments. Aerobic exercise and acupuncture have been proposed as promising complements to AChEIs because of their potentially synergistic neurotrophic and cholinergic effects. To compare these treatment combinations, we carried out a Bayesian network meta-analysis (BNMA) of randomized controlled trials (RCTs). These studies were sourced from major English and Chinese databases and examined cognitive and functional outcomes. In total, 37 RCTs were included, covering 2,188 participants. Among all, combined acupuncture (SUCRA = 78.92%) and fire needle therapy (SUCRA = 78%) demonstrated the highest probability of improving Mini Mental State Examination scores, while moderate intensity aerobic exercise ranked best for the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog, SUCRA = 23.3%) and the Barthel Index (SUCRA = 71.1%). Combined acupuncture was ranked highest for the Alzheimer's Disease Assessment Scale-Activities of Daily Living (ADAS-ADL, SUCRA = 94.3%), although its effects did not reach statistical significance. Across analyses, heterogeneity was minimal (I2 ≤ 4%), model convergence was stable, and no publication bias was detected. Overall, this BNMA suggests that combined or thermal acupuncture offers the strongest cognitive gains alongside AChEIs, whereas moderate-intensity aerobic exercise provides the most reliable functional support. Because overall functional improvements were modest and evidence for some interventions remains limited, the benefits appear selective rather than broad. Larger, standardized trials are needed to clarify these patterns and guide their use in practice.
Rheumatoid arthritis (RA) is a chronic autoimmune disease that can lead to multiple complications. Sjögren's syndrome (SS) is another autoimmune condition that may occur as a primary disorder or in conjunction with other autoimmune diseases, including RA. This study aimed to investigate the shared gene signatures between RA and SS. Gene expression datasets for RA (GSE15573, GSE93776) and SS (GSE48378, GSE94510, GSE93683) were obtained and analyzed to identify differentially expressed genes (DEGs) in peripheral blood mononuclear cells (PBMCs) and T cells. Gene ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed on the DEGs identified. Quantitative real-time PCR (qRT-PCR) was used to validate the expression levels of DEGs in PBMCs from patients with RA and SS. A total of 244 DEGs were identified from the RA PBMC dataset, comprising 142 upregulated genes and 102 downregulated genes. These DEGs were significantly enriched in biological processes related to immune responses, including cellular response to lipopolysaccharide, defense response against fungi, inflammatory responses, and antibacterial humoral responses. In contrast, 335 DEGs were identified from the SS PBMC dataset; among these, 320 genes were upregulated, while 15 were downregulated. The DEGs associated with SS showed strong involvement in defense responses against viruses, innate immune responses, viral responses, as well as cellular reactions to lipopolysaccharide. Moreover, we identified 12 shared DEGs between RA and SS PBMCs: RNASE2, NDUFB3, LY96, ANKRD22, EIF2AK2, RNASE3, CLEC4D, TNFAIP6, DYNLT1, RPS27L, LILRA5, and F5. Validation through qRT-PCR confirmed increased expression levels of RNASE2, RNASE3, NDUFB3, and EIF2AK2 in PBMCs. This study successfully delineated key DEGs along with their associated biological processes within the context of RA and SS PBMCs. Through bioinformatics analyses combined with qRT-PCR validation, we have identified four critical genes that may serve as potential biomarkers or therapeutic targets for further investigation.
Background: Allergic rhinitis (AR) is an inflammatory disorder involving immunoglobulin E (IgE)-mediated immune response. Interleukin (IL)-21 IL-21 can regulate immune cell functions and IgE production. We aimed to explore the modulation of IL-21 expression before and after sublingual immunotherapy (SLIT) in AR patients and its correlation with IgE and Th2 cytokines. Methods: Fifty AR patients were enrolled and treated with HDM allergen extract via SLIT. Serum levels of IL-21 and Th2 cytokines as well as IgE were determined using enzyme-linked immunosorbent assay (ELISA). Statistical analysis was performed to compare changes in cytokine levels and assess correlations. Results: After 3 years of SLIT, serum levels of IL-21, Th2 cytokines and IgE were significantly reduced. Greater decreases were found in the effective treatment group compared to the ineffective group. The expression of IL-21 was correlated to IL-4 and IgE levels. Conclusion: SLIT downregulates the expression of IL-21 and other Th2 cytokines, with IL-21 potentially serving as a biomarker for SLIT efficacy in AR patients.
Aim: Macrophage-mesenchymal stem cell (MSC) interactions critically influence bone regeneration during periodontitis resolution. While macrophage polarization under strong inflammatory conditions has been well studied, the functional role of macrophages exposed to low-grade inflammatory stimulation and their impact on MSC osteogenesis remain poorly understood. Methods: RAW264.7 macrophages were stimulated with reduced doses of classical M1 inducers to generate a low-inflammatory transitional phenotype (M1semi). Macrophage polarization and inflammatory cytokine expression were assessed by quantitative real-time PCR. M1semi macrophages were co-cultured with bone marrow mesenchymal stem cells (BMSCs) using conditioned medium, Transwell indirect co-culture, or direct cell-cell contact, with or without oxidative stress induction by hydrogen peroxide. Intracellular reactive oxygen species (ROS) levels in BMSCs were evaluated by fluorescence staining, and osteogenic differentiation was assessed by alkaline phosphatase (ALP) staining, ALP activity, and osteogenic gene expression. Results: Compared with classically activated M1 macrophages, M1semi macrophages exhibited reduced expression of pro-inflammatory cytokines and a polarization profile intermediate between M1 and M2 phenotypes. Among the co-culture systems tested, only direct contact with M1semi macrophages significantly enhanced osteogenic and angiogenic marker expression and increased ALP activity in BMSCs. This osteogenic enhancement was accompanied by a marked reduction in intracellular ROS levels. Importantly, exogenous induction of oxidative stress attenuated both ROS suppression and the osteogenic effects observed in direct co-culture. Conclusion: Macrophages exposed to low-grade inflammatory stimulation acquire a transitional phenotype with distinct immunomodulatory properties. Direct interaction with these macrophages enhances BMSC osteogenic differentiation, which is associated with reduced intracellular ROS accumulation. These findings suggest that modulation of oxidative stress contributes to macrophage-mediated osteogenesis in low-inflammatory environments, providing insight into immune-regulated bone regeneration during periodontal healing.
BACKGROUND:Rheumatoid arthritis (RA) is a chronic inflammatory condition defined by synovitis and progressive joint damage. The connection between inflammatory cytokines, molecules, and RA is still poorly understood despite the information combining both immune dysregulation and metabolic reprogramming to its pathophysiology. METHODS:A two-sample Mendelian randomization (MR) analysis was carried out using summary statistics from the largest-scale genome-wide association study (GWAS) to examine the link between 91 inflammatory cytokines and RA risk. Metabolite pathways were identified through mediation analysis. Multiple MR Methods including inverse variance weighting (IVW) were used for causal estimation and the hypothesis was verified by sensitivity analysis. RESULTS:The analysis results showed that there was a causal association between six inflammatory cytokines and RA. Among them, HGF and IL-10RA increased the risk of RA, while CXCL9, EN-RAGE, IFN-γ and CCL8 showed protective effects. These associations were validated using multiple MR methodologies, including inverse-variance weighting, MR-Egger regression, and leave-one-out sensitivity analyses. Further mediation MR analysis revealed seven metabolite-mediated pathways of inflammatory cytokines and RA. Specifically, the protective effect of CXCL9 was achieved in part by reducing plasma eicosapentaenoic acid (EPA; 20:5n3) levels (mediating effect = -0.007; proportion mediated = 8.10%). The protective effect of EN-RAGE was mediated by a decrease in the level of salicyluric glucuronide (mediating effect = -0.015; 12.70%). IFN-γ reduced the risk of RA through two independent metabolic pathways: reducing the level of 1-arachidonoyl-glycerol-3-phosphocholine (20:4n6) levels (mediating effect = -0.005; 4.67%), and increasing the ratio of glycine-to-pyridoxal (mediating effect = -0.020; 19.60%). In contrast, IL-10RA increases the risk of RA by increasing 3,7-dimethylurate (mediating effect = 0.011; 12.50%) and decreasing N, N-dimethylalanine levels (mediating effect = 0.010; 11.70%). The protective effect of CCL8 was mediated by the reduction of specific sphingomyelin species (d17:2/16:0, d18:2/15:0) (mediating effect = -0.012; 12.30%). CONCLUSIONS:The results of this study not only confirmed the causal role of specific inflammatory cytokines in the pathogenesis of RA from a genetic perspective, but more importantly, for the first time, systematically revealed the specific plasma metabolite mediating pathways that connect these inflammatory cytokines to RA. These findings more specifically link the immune dysregulation of RA to metabolic remodeling, especially the protective role of IFN-γ through glycine/pyridoxal balance, and the pathway of IL-10RA through purine metabolites to affect risk, providing novel and mechanistic insights into the immunometabolic network of RA. We believe that these specific intermediate metabolites are expected to be potential candidate targets for future targeted therapies or intervention strategies, aiming to precisely regulate the interaction between inflammation and metabolism.
Objective: Sepsis shock is characterized by endothelial damage and coagulation abnormalities. However, the relationship between von Willebrand factor (vWF), microthrombosis, and various clinical phenotypes such as thrombotic thrombocytopenic purpura (TTP) and sepsis-induced coagulopathy (SIC) has not been fully elucidated. Methods: This retrospective study enrolled 147 patients with septic shock admitted to the ICU in 2023, all of whom underwent vWF antigen testing. The patients were divided into three groups: the TTP-like group, the SIC group, and the control group. Platelet (PLT) indices, vWF levels, SOFA subscores, incidence of organ dysfunction, and 28-day mortality were compared. Correlation analyses and non-parametric tests were performed. Results: The SIC group showed significantly lower nadir PLT counts and higher PLT decline rates compared with the TTP-like and control groups (P < 0.05). vWF levels were elevated across all groups and were significantly higher in the TTP-like and SIC groups versus controls (P < 0.05). vWF levels correlated negatively with nadir PLT (r = -0.20, P = 0.018). Both TTP-like syndrome and SIC were associated with high rates of MODS; however, hepatic and renal injury, number of dysfunctional organs, and 28-day mortality were significantly worse in the SIC group (P < 0.05). Conclusion: Elevated vWF is associated with diffuse microthrombus formation in septic shock and may serve as a marker of endothelial injury. While both TTP-like syndrome and SIC contribute to organ dysfunction, SIC is associated with more severe organ injury and higher mortality. Prospective studies are needed to validate these findings.
BACKGROUND:Renal artery aneurysm (RAA) is a rare but potentially life-threatening condition. The definition of giant RAA is ≥ 50 mm. Although often asymptomatic, the risk of rupture increases significantly with size, posing a substantial threat. Giant RAAs have historically tended to be repaired using open surgery. At present, intravascular technology has become an alternative solution due to its advantage of less invasiveness. OBJECTIVE:This study seeks to present a rare case of successful endovascular embolization for a giant renal aneurysm (RAA), while also systematically reviewing recent literature to compare the outcomes of surgical and endovascular treatments for giant RAA, and to describe management strategies for giant renal hemangiomas. METHODS:We describe a case of a young man treated by endovascular coil embolization and had a large RAA. After the PRISMA guidelines were followed, a systematic literature review was carried out, initially identifying 347 studies. After screening and full-text review, 35 studies met the inclusion criteria for comparative analysis of patient demographics, treatment modalities, and outcomes. RESULTS:A total of 35 studies, encompassing 35 patients with giant renal artery aneurysms, were included. The mean age was 53 years (15-88 years). Endovascular therapy was performed in 12 cases, while 20 patients underwent surgical management; 2 patients received combined treatment and 1 was treated conservatively. Overall, symptom improvement and complication profiles were reported descriptively across both surgical and endovascular treatments. CONCLUSION:Managing giant renal artery aneurysms necessitates a personalized, multifaceted approach. Intravascular therapy represents a feasible and minimally invasive option for selected patients with suitable anatomical structures and stable hemodynamics, while open surgery remains indispensable for complex anatomy or rupture. A multidisciplinary approach, guided by precise assessment of aneurysm morphology and renal function, is essential for optimal outcomes.
Idiopathic pulmonary fibrosis (IPF) is a chronic, relentlessly progressive interstitial lung disease with limited treatment options and poor survival. Existing antifibrotic agents slow functional decline but do not halt or reverse established fibrosis, highlighting the need for IPF specific mechanistic understanding and new therapeutic targets. This review summarizes epigenetic regulatory mechanisms that are implicated in IPF, including DNA methylation, histone modifications, non-coding RNAs, and RNA modifications. These mechanisms can be viewed as interacting networks that reprogramme gene expression in alveolar epithelial cells, macrophages and fibroblasts, leading to impaired epithelial repair, profibrotic immune activation and maintenance of a chronically activated myofibroblast state. The contribution of cell type specific epigenetic signatures to chronic inflammation, disordered tissue remodelling and progressive extracellular matrix accumulation in IPF is underscored. Recent work that translates epigenetic insights into applications for IPF is also reviewed, with a focus on epigenetic marks and regulators as biomarkers for diagnosis, prognosis and treatment response, and as targets for small molecule drugs, nucleic acid based therapies and epigenome editing strategies. Overall the evidence assembled here provides a framework that focuses on IPF epigenetic regulation and can inform experimental design and support the development of more precise therapeutic approaches for patients with IPF.
Diabetic foot (DF), is called "foot gangrene" (gangrene) or "nerve gangrene" (gangrene of the nerve area) in traditional Chinese medicine. It is a severe complication of diabetes, whose incidence rate is high, and the consequences is serious. Acupuncture is a promising therapy, it is effective, it can alleviate symptoms, accelerate the wound healing and reduce the risk of amputation. This consensus includes clinical evidence and expert practical experience, it shows acupuncture is an effective supportive treatment methods. Its main purpose is to provide practical, standardized, and safe instructions for clinicians. It can promote the use of acupuncture in evidence-based treatment of diabetic foot ulcers. The innovation points of this consensus are: 1. Stage guidance: It includes the indications, contraindications and Wagner classification system, which adjusts the treatment measures for different conditions. 2. Integrated diagnosis: It includes modern vascular assessment, neurological examinations, and TCM syndrome, such as ankle-brachial index, arterial oxygen partial pressure and nerve conduction studies, finally formulating different treatment plans. 3. Focus on strict operating procedures: Formulating safe and controlling infection measures for patients with diabetic foot to conduct acupuncture treatment, and figuring out the risk factors.
OBJECTIVE:To perform a meta-analysis on the sedative effects of midazolam and dexmedetomidine in patients undergoing bronchoscopy. METHODS:Relevant literature on the sedative effects of midazolam and dexmedetomidine in patients undergoing bronchoscopy was searched in both Chinese and English databases. RESULTS:A total of 19 studies published between 2012 and 2024 were included, involving 38 groups and 2,339 patients. Meta-analysis of continuous variables from fifteen studies reported no statistically significant difference in systolic blood pressure between the study group and the control group (MD = -0.27, 95% CI: -2.16 to 1.61, Z = -0.28, P = 0.78). Similarly, eight studies showed no significant difference in heart rate between the study group and the control group (MD = -0.62, 95% CI: -2.67 to 1.43, Z = -0.59, P = 0.55). Twelve studies demonstrated significantly higher oxygen saturation (SaO2) levels in the study group compared to the control group (MD = 1.88, 95% CI: 0.56 to 3.20, Z = 2.79, P = 0.01). Nine studies indicated that sedation satisfaction was significantly higher in the study group than in the control group (MD = 2.93, 95% CI: 1.16 to 4.70, Z = 3.25, P < 0.01). Ten studies assessed sedation scores, showing no statistically significant difference between groups (MD = 0.32, 95% CI: -0.02 to 0.67, Z = 1.82, P = 0.07). Awakening time, reported in eight studies, also showed no significant difference (MD = -2.70, 95% CI: -5.50 to 0.09, Z = -1.89, P = 0.06). Six studies reported VAS (Visual Analogue Scale) scores, showing a statistically significant difference (MD = -0.46, 95% CI: -0.83 to -0.08, Z = -2.39, P = 0.02). Meta-analysis of dichotomous variables from fourteen studies showed no significant difference in the incidence of adverse events between the groups (OR = -0.10, 95% CI: -0.49 to 0.29, Z = -0.49, P = 0.62). Meta-regression analysis suggested that heterogeneity mainly originated from differences in study type and methodology (P < 0.05). CONCLUSION:Both midazolam and dexmedetomidine demonstrate good sedative effects during bronchoscopy, and their use should be tailored to individual patient conditions.
BACKGROUND:Previous studies have found associations between dietary habits, physical activity (PA) and a variety of renal/urinary disorders. However, only a few studies have used Mendelian randomisation analyses to explore the causal relationship between dietary habits, physical activity and a range of renal/urinary diseases. METHODS:The exposure and outcome datasets were sourced from the BioBank, FinnGen, and the NHGRI-EBI databases. The exposure dataset comprised of 20 dietary patterns and 4 PA modalities, while the outcome dataset included 19 renal/urological disorders. The primary methods employed for MR analyses were inverse variance weighted. Heterogeneity and multiplicity analyses were conducted to ensure the validity of the results. RESULTS:In terms of dietary habits, studies have found that consumption of soya-based sweets reduces the risk of chronic kidney disease (CKD). Consumption of fresh fruits prevented benign adrenal tumours and immunoglobulin A nephropathy (IgA-N). Consumption of paneer helps to reduce the risk of developing type 2 diabetes (T2D) nephropathy and immunoglobulin A nephropathy (IgA-N). In addition, consumption of nuts is a protective factor against type 2 diabetic nephropathy. Consumption of nuts, lean fish and fatty fish reduces the incidence of acute tubulointerstitial nephritis (ATIN). Among various forms of physical activity, recreational hiking was inversely associated with IgA-N nephritis and T2D nephritis. Other physical activities, including swimming, cycling, fitness and bowling, also reduced the risk of developing IgA-N. In contrast, leisure screen time (LST) was considered a risk factor. CONCLUSION:This study suggests that a sensible diet and increased leisure time walking may prevent chronic kidney diseases such as chronic renal insufficiency, chronic renal failure, type 2 kidney disease and IgA nephropathy. This study deepens the understanding of the association between diet, physical activity and renal/urinary abnormalities and provides practical recommendations for reducing the risk of developing these diseases.
