BACKGROUND:Mounting research has proven that microRNAs (miRNAs) exert critical regulatory functions in the pathological progression of pediatric pneumonia. AIMS:To investigate the expression levels and clinical significance of miR-493-5p in children with severe pneumonia. METHODS:A total of 125 children diagnosed with severe pneumonia, 100 children with mild pneumonia, and 100 healthy children as normal controls were enrolled in this study. RT-qPCR was adopted to quantify serum miR-493-5p expression levels. ROC curves were plotted to assess its diagnostic efficiency; Kaplan-Meier survival analysis combined with Log-rank test evaluated 28-day prognostic value. LPS-stimulated MRC-5 human lung fibroblast cell model was constructed for in vitro functional experiments to uncover the underlying molecular mechanism of miR-493-5p. RESULTS:Serum miR-493-5p expression was markedly elevated in children with severe pneumonia. ROC analysis validated that serum miR-493-5p possessed satisfactory accuracy for distinguishing severe pneumonia from mild cases. miR-493-5p may target Interferon Regulatory Factor 1 (IRF1) to affect the functions and inflammatory responses of cells in the pneumonia model. CONCLUSIONS:Serum miR-493-5p level has significant diagnostic and prognostic value in children with severe pneumonia.
OBJECTIVE:This study aimed to identify novel circular RNA (circRNA) biomarkers in peripheral blood mononuclear cells (PBMCs) for the diagnosis of ankylosing spondylitis (AS) and to explore their potential pathogenic mechanisms. METHODS:High-throughput circRNA sequencing was performed on PBMCs from 3 AS patients and 3 healthy controls. Differentially expressed circRNAs were validated by RT-qPCR in an independent cohort (64 AS patients and 24 healthy individuals). Diagnostic performance was evaluated via ROC curve analysis. Correlations between circRNA expression and clinical inflammatory markers were assessed. Bioinformatics analysis was employed to predict target miRNAs and enriched signaling pathways. RESULTS:A total of 53 circRNAs were differentially expressed in AS PBMCs. Among these, circ_0024085 and circ_0000339 were significantly upregulated in AS (41.6-fold and 27.0-fold, p < 0.05), and demonstrated good diagnostic performance (AUC = 0.815 for the combination). The expression of Circ_0024085 was inversely correlated with erythrocyte sedimentation rate (ESR, p = 0.005) and monocyte count (p = 0.027). Bioinformatic analysis indicated that the target miRNAs of circ_0024085 were significantly enriched in the IL‑4/IL‑13 signaling pathway, while those of circ_0000339 were enriched in the SEMA4D signaling pathway. CONCLUSION:Our findings identify circ_0024085 and circ_0000339 as potential diagnostic biomarkers for AS. With bioinformatics predictions indicating that Circ_0024085 may exert an anti-inflammatory effect via M2 macrophage polarization, whereas circ_0000339 might contribute to bone damage through SEMA4D signaling.
OBJECTIVE:To compare the coagulation factor levels in acute respiratory distress syndrome caused by pulmonary infection (ARDSp) and ARDS caused by extrapulmonary sepsis (ARDSexp) patients. METHODS:This study included 112 ARDSp and 88 ARDSexp patients. Coagulation factor levels were compared within 24 hours after the diagnosis of ARDS. RESULTS:In the ARDSexp group, prothrombin time (PT) and activated partial thromboplastin time (APTT) were significantly prolonged, fibrinogen (FIB) levels were significantly decreased, and D-dimer (D-D) levels were significantly increased. Coagulation factors V and VII levels were significantly lower, while factor VIII levels and the degree of thrombocytopenia were substantially higher in the ARDSexp group, in contrast to the ARDSp group. In terms of prognosis, the ARDSexp group had longer mechanical ventilation duration and ICU stay duration, and higher 28-d and 90-d mortality (all p < 0.05). D-D > 7 mg/L, coagulation factor V < 70%, elevated sequential organ failure assessment (SOFA) score, and antithrombin III <60% were independent predictors of 28-d mortality. CONCLUSION:This study demonstrates that there are visible coagulation phenotypic distinctions between ARDSp patients and ARDSexp patients. Coagulation factor levels can serve as biomarkers for prognostic assessment and provide a theoretical basis for the development of individualized anticoagulation strategies in clinical practice.
AIMS:This study investigated the association between Epstein-Barr virus (EBV) infection and breast cancer (BC) susceptibility and evaluated the role of interferon-gamma (IFN-γ) rs2069705 polymorphism in disease risk and clinicopathological characteristics among Egyptian women. MATERIALS AND METHODS:A case-control study was conducted on 96 histologically confirmed BC patients and 50 age-matched healthy controls. EBV serostatus was assessed by ELISA detection of anti-viral capsid antigen IgG antibodies. IFN-γ rs2069705 (A/G) genotyping was performed using TaqMan real-time PCR assays. RESULTS:EBV seropositivity was significantly higher in BC patients (93.75%) than controls (p = 0.008). Significant associations were observed between IFN-γ rs2069705 polymorphism and BC susceptibility, particularly for AA and AG genotypes and A and G alleles (p < 0.001), whereas the GG genotype showed no significant association. AA and AG genotypes were also associated with unfavorable clinicopathological features. CONCLUSION:EBV infection and IFN-γ rs2069705 polymorphism may contribute to BC susceptibility and progression among Egyptian women and could serve as potential combined biomarkers for risk assessment and prognosis.
BACKGROUND:Clinical utility of biomarker-based treatment depends on both analytical and clinical validity. CD20+ B-lymphocytes often form nodular lymphoid structures within tumors, presenting potential analytical issues if using tissue microarrays (TMA). We compared CD20 expression in TMAs and whole-slide sections (WS) using digital image analysis. MATERIALS AND METHODS:Immunohistochemical CD20+ expression was assessed on 1 TMA core/patient and corresponding WS from 221 breast cancer patients. CD20+ area fractions were quantified within four spatial tissue compartments: (1) tumor epithelium; (2) tumor margin; (3) tumor-related stroma; (4) total tumor area. Bland-Altman analysis and t-test compared CD20+ area fractions of WS and TMA. RESULTS:CD20+ cells were predominantly located in the stroma and often formed nodules. Across all compartments, the absolute area fraction of CD20+ was significantly lower in TMAs than in WS. Mean ratios of CD20+ area fractions (WS vs. TMA) ranged from 2.5 (95% confidence interval: 1.7-3.6; p < 0.001) to 6.4 (4.7-8.9; p < 0.001) within the four spatial regions. CONCLUSIONS:These findings indicate that TMAs may underestimate the presence of CD20+ cells in breast cancer, presumably due to the formation of nodules. This heterogeneity in distribution is important to consider when exploring the use of CD20 as a potential clinical biomarker.
BACKGROUND:The Inflammatory Burden Index (IBI) has been identified as a significant prognostic factor in various gastrointestinal (GI) malignancies. However, despite extensive research, its prognostic value remains inconsistent. To clarify this association, we conducted a systematic meta-analysis following rigorous methodological standards. METHODS:A comprehensive literature search was performed across PubMed, Web of Science, Embase, Scopus, and Cochrane databases. Ultimately, nine studies were included, covering multiple gastrointestinal cancer subtypes. RESULTS:Our analysis demonstrated that an elevated IBI was significantly associated with poorer overall survival (OS) (HR = 2.14, 95% CI: 1.38-3.31, p = 0.001), disease-free survival (DFS) (HR = 1.75, 95% CI: 1.35-2.26, p < 0.001), and recurrence-free survival (RFS) (HR = 2.15, 95% CI: 1.59-2.92, p < 0.001). Furthermore, IBI levels were significantly correlated with several key clinicopathological factors including age, tumor size, lymph node metastases, lymph-vascular invasion, and neoadjuvant chemotherapy. CONCLUSION:This meta-analysis suggests that elevated IBI might be a robust predictor for poor survival in GI cancer patients and correlates closely with advanced disease features including larger tumor size, lymph node metastases, and lymph-vascular invasion. These findings underscore IBI as a clinically relevant prognostic biomarker for GI malignancies.
Cardiovascular disease (CVD) is a major source of morbidity and mortality across the globe. Effective screening and risk stratification of patients can improve long‑term outcomes by allowing physicians to offer fine-tuned advice and treatments. Advances in technology have enabled the study of various biomarkers associated with CVD, allowing researchers to study the molecular processes underlying illness. In this study, we sampled recent advances in the application of Machine Learning (ML) techniques to transcriptome datasets of CVD patients in the hopes of progressing our understanding of underlying pathophysiology, improving our ability to detect disease, and refining our methods of risk stratification of patients. These studies suggest that ML algorithms may help identify complex relationships within high-dimensional datasets to isolate relationships within datasets that were previously missed, enhancing our understanding of disease. However, there are several challenges that need to be addressed before these innovations can reach the clinic. Researchers must verify their results via means that are readily obtainable for physicians and must adequately identify the indications for a particular test so they can integrate into preexisting workflows. We offer potential solutions and suggestions to these issues so that these approaches may eventually contribute to improved patient care.
AIMS:Varicocele (VC) remains a leading correctable cause of male infertility, yet standardized multimodal biomarkers are lacking for clinical stratification and outcome prediction. PATIENTS AND METHODS:This prospective observational study enrolled 131 primary VC patients and 20 healthy controls, evaluating semen parameters, sperm DNA fragmentation index (DFI), testicular shear wave elastography (SWE), hormonal profiles, and inflammatory/metabolic markers. RESULTS:VC patients showed reduced sperm progressive motility (sperm PM) (p < 0.001), elevated DFI (p = 0.002), increased abnormal sperm morphology (p < 0.001); smaller left (p = 0.002) and right (p = 0.029) testis, volume difference (p = 0.030); bilateral testicular stiffness (left p < 0.001, right p < 0.001); higher homocysteine (p = 0.001); and a lower T/E2 ratio (p = 0.030). DFI correlated negatively with sperm PM (r = -0.367, p < 0.001). Postoperative improvements were observed in sperm PM (p < 0.001), sperm morphology (p < 0.001), DFI (p < 0.001), left testicular elasticity (p < 0.001), right testicular elasticity (p < 0.001), homocysteine (p = 0.001), testosterone (p = 0.011), and the T/E2 ratio (p = 0.011). Preoperative DFI (OR =1.045), abnormal sperm morphology rate (OR =1.604), and sperm PM (OR =0.951) independently predicted complete semen parameter recovery at 3 months (AUC = 0.863, sensitivity 67.9%, specificity 89.5%). CONCLUSION:An integrated multimodal framework incorporating imaging, molecular, and functional biomarkers facilitates prognostic stratification and personalized management of varicocele-associated infertility.
BACKGROUND:Polycystic ovary syndrome (PCOS) is a prevalent endocrinopathy in reproductive-aged women having both gynecological and metabolic comorbidities. PCOS increases the risk of cardiovascular and thromboembolic diseases due to heightened prothrombotic states, suggesting shared genetic determinants with thrombophilia. In addition, convergence of these polymorphisms to insulin resistance, a hallmark feature of PCOS, may exacerbate PCOS risk and further intensify hypercoagulability-associated metabolic and reproductive manifestations. METHODS:This case-control study explores the association between MTHFR (C677T), FGB (-148C/T, -249C/T, -455G/A), FXIII (V34L), and FV (FVL, rs6020) and risk of PCOS development and its related traits in PCOS (n = 475) and control (n = 245) women. Clinical, biochemical, and hormonal parameters were estimated for all study participants and genotyping was carried out by direct sequencing. RESULTS:To the best of our knowledge, this is the first time that FGB promoter polymorphisms (-148C/T and -455G/A) were investigated and showed nominal association with reduced risk of PCOS prior to multiple testing correction. Additionally, potential genotype-phenotype trends with metabolic and hormonal parameters were noted in both controls and women with PCOS, with and without insulin resistance. CONCLUSION:Genetic profiling of thrombophilia-related gene polymorphisms could help monitoring and management of PCOS and its related reproductive and metabolic complications.
AIM:To evaluate the combined predictive value of serum neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and macular neovascularization (MNV) characteristics for treatment efficacy in neovascular age-related macular degeneration (nAMD) patients receiving anti-VEGF plus glucocorticoid therapy. PATIENTS AND METHODS:This retrospective study included 145 patients (153 eyes) with nAMD receiving conbercept combined with dexamethasone implant. Patients were categorized as Inactive (n = 89) or Active (n = 64) based on post-treatment MNV activity. Baseline NLR, PLR, and MNV morphology were assessed. Multivariate logistic regression identified independent predictors, and ROC analyses evaluated predictive value. RESULTS:Patients with persistent MNV activity showed significantly higher baseline NLR, PLR, MNV area, and fractal dimension (all p < 0.001). Multivariate analysis identified baseline visual acuity, MNV type, fluid volumes, MNV morphological parameters, and inflammatory markers as independent predictors. The combined model incorporating inflammatory markers and MNV characteristics demonstrated superior performance (AUC = 0.92, 95% CI: 0.87-0.96) with 79.69% sensitivity and 91.01% specificity. CONCLUSION:Combining serum inflammatory markers with MNV morphological characteristics enhanced predictive value for treatment response in nAMD patients receiving combination therapy. This integrated approach may facilitate personalized treatment strategies in nAMD management.
BACKGROUND:Risk stratification in acute myocardial infarction (AMI) remains a critical challenge in clinical practice. Traditional prognostic markers often require complex or costly assessments, underscoring the need for simple, accessible indicators. This study, conducted with the aim of evaluating the relationship between the blood urea nitrogen (BUN) and creatinine (Cr) ratio and rehospitalization following AMI. METHODS:This retrospective cohort study, conducted at a single center, patients diagnosed with AMI. BUN and Cr levels at the time of initial admission were collected to calculate the BUN/Cr ratio, which was categorized into two groups: ≤16.23 and >16.23. Statistical analyses were carried out using IBM SPSS software (version 22). RESULTS:Among 1147 AMI patients, 53% had BUN/Cr ≤16.23 and 42.1% >16.23. Over four years, rehospitalization rates were slightly higher in the high BUN/Cr group but not statistically significant (p > 0.05). Primary outcomes differed significantly, with mortality notably higher in patients with elevated BUN/Cr ratios (3.7% vs. 1.1%) (p < 0.05). CONCLUSION:While rehospitalization rates over a four‑year period were slightly higher among those with elevated ratios, the difference was not statistically significant. However, patients with a BUN/Cr ratio >16.23 demonstrated markedly increased rates of major adverse cardiac events (MACE) compared to those with lower ratios.
AIMS:Patients undergoing transcatheter tricuspid valve intervention (TTVI) frequently present with advanced right-sided heart failure and multiorgan dysfunction, limiting the interpretability of conventional biomarkers such as natriuretic peptides. Soluble suppression of tumorigenicity 2 (sST2), a marker of myocardial strain, inflammation, and fibrosis, may provide complementary insight into biological response following intervention. PATIENTS & METHODS:In this prospective single-center cohort study, 135 patients undergoing TTVI were included. Plasma concentrations of sST2 were measured at baseline, discharge, 3 months, and 12 months. Longitudinal changes were analyzed using non-parametric repeated measures testing and compared with established biomarkers, including GDF-15, suPAR, H-FABP, NT-proANP and supplementary NT-proBNP analyses. RESULTS:sST2 demonstrated a distinct biphasic trajectory, with an early increase at discharge followed by a significant decline at 3 and 12 months below baseline levels (overall p < 0.001). This pattern remained consistent in sensitivity analyses. In contrast, GDF-15, suPAR, H-FABP, NT-proANP, and supplementary NT-proBNP analyses showed heterogeneous longitudinal profiles without the sustained treatment-related trajectory observed for sST2. CONCLUSIONS:In patients undergoing TTVI, sST2 exhibits a characteristic longitudinal profile reflecting biological response to intervention. These findings identify sST2 as a candidate dynamic biomarker and support a framework distinguishing prognostic baseline-risk biomarkers from dynamic treatment-response biomarkers.
AIMS:Although dietary glycemic index (GI) and glycemic load (GL) are known to affect inflammation and oxidative balance, their roles in OA are unclear. This study aims to investigate the relationship between dietary GI and GL with inflammation, oxidative stress, and clinical symptoms in patients with knee osteoarthritis (KOA). PATIENTS AND METHODS:In a cross-sectional study, 160 patients diagnosed with KOA were included. Dietary intake was assessed using a validated food frequency questionnaire, and daily GI and GL values were calculated. Clinical symptoms were assessed using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). RESULTS:Higher dietary GI and GL were significantly associated with increased serum levels of malondialdehyde (MDA), total oxidant status (TOS), tumor necrosis factor-alpha (TNF-α), and high-sensitivity C-reactive protein (hs-CRP), as well as with decreased total antioxidant capacity (TAC). Dietary GI and GL were positively correlated with the total WOMAC score, as well as with the WOMAC physical activity and stiffness. CONCLUSION:High dietary GI and GL may be associated with oxidative stress and inflammatory responses, and may worsen clinical symptoms in KOA patients. Nutritional strategies emphasizing low-GI/GL diets may contribute to better symptom control and disease management in KOA.
AIMS:The C-reactive protein-albumin-lymphocyte (CALLY) index is a composite biomarker reflecting inflammation, nutritional status, and immune response. This study evaluated the association of the CALLY index with all-cause mortality in patients undergoing transcatheter aortic valve implantation (TAVI). METHODS:In this retrospective study, 733 consecutive TAVI patients were classified as Low-CALLY (≤0.95) or High-CALLY (>0.95) using an ROC-derived cutoff. The primary endpoint was all-cause mortality during follow-up. Predictors of mortality were assessed using Cox proportional hazards regression, while discriminative performance and survival were evaluated by ROC and Kaplan-Meier analyses. RESULTS:Mortality was higher in the Low-CALLY group than in the High-CALLY group (57.1% vs. 19.3%; p < 0.001). The CALLY index showed moderate discrimination for mortality (AUC 0.719; 95% CI 0.681-0.757; p < 0.001). In multivariable Cox regression, Low CALLY remained independently associated with mortality in the clinical model (HR 3.31; 95% CI 2.49-4.39), STS-PROM-adjusted model (HR 3.16; 95% CI 2.37-4.22), and EuroSCORE II-adjusted model (HR 3.72; 95% CI 2.84-4.88) (all p < 0.001). Kaplan-Meier analysis showed lower survival in the Low-CALLY group (log-rank p < 0.001). CONCLUSION:The CALLY index was independently associated with mortality after TAVI and may complement established risk scores in pre-procedural risk stratification.
OBJECTIVE:Biomarkers that accurately reflect disease activity and inflammatory burden are needed, particularly in the early stages of spondyloarthropathy (SpA). This study aimed to evaluate the association between serum neopterin levels and disease activity indices in patients with SpA. METHODS:This cross-sectional study included 84 participants based on a priori sample size estimation: 21 patients with axial SpA (axSpA), 21 with peripheral SpA (pSpA), 21 with active rheumatoid arthritis (RA) and 21 healthy controls (HC). Disease activity in SpA was assessed using the Axial Spondyloarthritis Disease Activity Score (ASDAS) and the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI). A disease activity was assessed using the Disease Activity Score in 28 Joints (DAS28). Serum neopterin levels were measured by Enzyme-Linked Immunosorbent Assay. RESULTS:Serum neopterin levels differed significantly among the groups (post-hoc, p = 0.007), with higher levels observed in patients with active RA than in those with axSpA, and no significant associations were found between neopterin levels and disease activity indices in either axial or peripheral SpA. CONCLUSION:In the present study cohort, no significant association was observed between serum neopterin levels and disease activity in patients with axial or peripheral SpA.
OBJECTIVE:To evaluate the plasma-based methylated Septin9 (mSEPT9) diagnostic accuracy for gastric cancer (GC) and analyze its performance across different subgroups. METHODS:Through comprehensive computer searching, we systematically collected clinical trials on the diagnostic efficacy of plasma mSEPT9 in GC. The search scope covered PubMed, Web of Science, the Cochrane Library, Embase, CNKI, WanFang Data and VIP databases from their establishments to 31 August 2025. Study quality was rigorously assessed with the assistance of Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2). Meta-analysis via Stata 17.0 and Meta-Disc 1.4 was performed. RESULTS:This study included 9 articles containing 10 studies, encompassing 3,120 participants. Meta-analysis revealed a pooled sensitivity of 0.40 (95%CI: 0.34-0.47), specificity of 0.94 (95%CI: 0.91-0.96), diagnostic odds ratio of 11.10 (95%CI: 6.42-19.18), area under the curve of 0.78 (95%CI: 0.74-0.82). Meta-regression identified sample size and positive criteria algorithm as potential contributors to heterogeneity in sensitivity, although the associations were only of borderline statistical significance. Other covariables were not significantly associated with heterogeneity. CONCLUSION:Plasma mSEPT9 demonstrated high specificity and relatively low sensitivity in GC. The assay may be unsuitable for general population screening but showed promise as an adjunctive marker in high-risk patients. Heterogeneity and geographical concentration may influence the assessment of mSEPT9. PROTOCOL REGISTRATION:www.crd.york.ac.uk/prospero identifier is CRD420251140125.
BACKGROUND:Gastric cancer (GC) remains the fifth most common and lethal cancer worldwide, often diagnosed at advanced stages, with limited treatment options and poor survival. Beyond established risk factors, the ABO blood group system has been suggested as a potential prognostic factor, but evidence remains inconclusive. METHODS:Medline, Scopus, and Web of Science were searched to 27 July 2025, for studies including GC patients with reported overall survival (OS) stratified by blood types O, A, B, and AB. Kaplan-Meier curves from eligible studies were digitized to reconstruct individual patient data, which were pooled to estimate median OS and hazard ratios (HR) using Cox regression. RESULTS:Seven studies comprising 8,726 GC patients were included (O: 3,693; A: 946; B: 605; AB: 315). Median OS was highest for type O (85.1 months, 95% CI 77.5-86.4) and AB (78.2 months, 95% CI 73.9-NA), and lowest for type A (20.0 months, 95% CI 17.9-21.9) and B (35.5 months, 95% CI 27.9-78.5). Compared with non-O, type O had a significantly better prognosis (HR 0.63; p < 0.0001). Type A (HR 1.85; p < 0.0001) and type B (HR 1.20; p = 0.0018) were associated with worse survival, while type AB showed a favorable prognosis compared to non-AB (HR 0.83; p = 0.039). CONCLUSION:ABO blood group is a significant prognostic factor in GC, with types A and B linked to poorer survival.
BACKGROUND:Although polycystic ovary syndrome (PCOS) is an endocrine and metabolic disorder among reproductive-aged women, the integrated role of adipokines in linking metabolic and hormonal dysfunction remains incompletely understood. OBJECTIVE:The study aims to evaluate the associations between lipid profile alterations, selected adipokines (resistin, galectin-3, and apelin), oxidative stress markers, and the insulin resistance index (HOMA-IR) in women with PCOS compared to controls. METHODS:This case-control study included 85 women with PCOS and 55 age-matched controls. Anthropometric and clinical data were collected. Levels of lipid profiles, adipokines, oxidative stress markers, and HOMA-IR were measured. Group comparisons and correlation analyses were performed. RESULTS:Women with PCOS demonstrated elevated levels of resistin, galectin-3, and apelin compared to the controls, with respective measurements of 3.55 ± 0.52 vs 1.07 ± 0.34, 10.01 ± 1.76 vs 3.49 ± 1.03, and 289.23 ± 20.08 vs 191.31 ± 31.30), respectively. MDA exhibited a significant increase, whereas TAC was significantly reduced in the PCOS group. HOMA-IR showed significant positive associations with lipid profiles, adipokines, and levels of MDA, and an inverse correlation with HDL and TAC. CONCLUSION:The findings support the concept that altered adipokine levels and oxidative stress indices may reflect underlying metabolic dysfunction in women with PCOS.
