Journal of Inflammation Research最新文献

Background: Pepsinogen I and pepsinogen II are widely used as diagnostic markers in gastric mucosal diseases such as gastric atrophy and pangastritis, and in assessing the risk of progression to gastric cancer. This study assesses the relationship between serum pepsinogen levels and changes in the gastric mucosa and stomach lining, stratified by Helicobacter pylori status. We also evaluate the significance of the serum pepsinogen ratio (PGI/PGII ratio) as a biomarker of atrophic gastritis and intestinal metaplasia that may progress to gastric cancer.

Methods: A total of 84 patients presenting with dyspeptic symptoms or indigestion were recruited for the study. The hallmark diagnostic criteria for atrophic gastritis are serum PGI < 70 ng/mL, and for pangastritis, serum PGII > 20 ng/mL. The serum Helicobacter pylori antibody is negative when the concentration is <30 AU/mL (no infection in the gastric mucosa) and positive when the concentration is ≥30 AU/mL (presence of infection in the gastric mucosa) using POCT immunoassay.

Results: Our findings defined the diagnosis of serum Helicobacter pylori infection optimal cut-off points concentration of >25 AU/mL with a sensitivity of 100% and specificity of 95%, atrophic gastritis a PGI < 73 ng/mL, with a sensitivity of 100% and specificity of 97%, and pangastritis a PGII > 18.25 ng/mL with a sensitivity of 100% and specificity of 97.8%, respectively. We defined a PGR ratio ≤ 3 As a risk of precancerous conditions, with a sensitivity of 100% and a specificity of 97.8%. We categorize patients with PGR ≤ 3 as low risk, and those patients with a PGI/PGII ratio < 2.5 (high risk) and < 1.5 (very high risk), who may be at risk of developing gastric precancerous lesions that may progress to gastric cancer.

Conclusion: A low PGI, high PGII, and a PGI/PGII ratio ≤ 3 Sensitive biomarkers to identify patients at risk of developing pangastritis and gastric precancerous lesions in the absence of endoscopic gastric mucosal biopsy.

Background: Endothelial cells play a central role in the pathogenesis of sepsis. Currently, effective therapeutic options for sepsis remain limited. Baicalein (BAI) is a compound with multiple bioactivities. This study aims to investigate the protective effects of BAI against lipopolysaccharide (LPS)-induced endothelial cell injury and to explore the underlying molecular mechanisms.

Methods: Bioinformatics tools, including RNA sequencing (RNA-seq), immune cell infiltration analysis, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses, were utilized to explore the molecular mechanisms of BAI in human umbilical vein endothelial cells (HUVECs) induced by LPS. The LPS-induced HUVECs model was used to assess the effects of BAI through CCK8 assays, cell permeability assays, and RT-qPCR.

Results: RNA-seq analysis revealed a set of differentially expressed genes (DEGs) shared between the Control group vs LPS group and LPS vs Baicalein group, including vascular cell adhesion molecule 1 (VCAM1), phosphoinositide-specific phospholipase C X-domain containing 1 (PLCXD1), and MIR3142 host gene (MIR3142HG), a long non-coding RNA. GO, KEGG, and Reactome enrichment analyses indicated that the DEGs were primarily enriched in TNF signaling, NF-κB signaling, and immune regulation pathways. Molecular docking and molecular dynamics simulation analyses revealed that BAI exhibits a strong binding affinity for key targets VCAM1 and PLCXD1. ROC analysis revealed that these core genes, VCAM1 and PLCXD1, exhibited significant diagnostic potential for sepsis. The cell experimental results demonstrated that BAI significantly alleviated the expression levels of inflammatory markers (such as IL-6 and IL-1β) and reduced endothelial cell permeability induced by LPS in HUVECs.

Conclusion: BAI may alleviate LPS-induced endothelial cell injury by modulating the inflammatory response and immune microenvironment through the regulation of MIR3142HG, VCAM1, and PLCXD1 targets. This study provides new molecular targets and theoretical insights for sepsis therapy.

Purpose: This study aimed to investigate the association between blood inflammatory markers, including C-reactive protein (CRP) and interleukin-6 (IL-6), and the short-term prognosis of pneumoconiosis, and to develop a multifactorial prediction model.

Patients and methods: Clinical data of 813 pneumoconiosis patients admitted to two regional tertiary hospitals from October 2016 to August 2023 were retrospectively collected and randomly divided into a training set (n=568) and an external validation set (n=245). Variables were screened by least absolute shrinkage and selection operator (LASSO) regression, a multifactorial logistic regression column-line graph model was constructed, and the relationship between risk factors and prognosis was analyzed by multifactorial Cox regression and Kaplan-Meier survival curves. The model performance was verified by consistency index (C index), receiver operating characteristic (ROC) curve, calibration curve, decision curve analysis (DCA) and clinical impact curve (CIC).

Results: The mean age was 62.1 years in the training set and 63.3 years in the validation set, with mortality rates of 11.1% and 11.9%, respectively. LASSO regression identified age, dust exposure duration, dyspnea, blood oxygen saturation (SpO₂), neutrophil count, CRP, and IL-6 as predictors. CRP (OR=1.028, 95% CI: 1.016-1.040) and IL-6 (OR=1.020, 95% CI: 1.010-1.030) were independent risk factors for poor short-term prognosis (both P<0.001), consistent with Cox analysis. The model demonstrated excellent discrimination with AUCs of 0.905 in the training set and 0.920 in the validation set. Calibration showed good agreement between predicted and observed risks (Hosmer-Lemeshow P>0.05). DCA and CIC indicated high clinical value. High CRP/IL-6 levels were associated with significantly reduced survival (log-rank P<0.001).

Conclusion: The prediction model based on CRP, IL-6, and clinical characteristics effectively identifies pneumoconiosis patients at high risk of short-term poor prognosis, providing a reliable basis for early intervention due to its high discriminatory power and clinical applicability.

Background: Acute generalized exanthematous pustulosis (AGEP) is a drug-induced severe cutaneous adverse reaction (SCAR) characterized by an acute extensive erythematous pustular eruption. Integrated analyses including Asian cohorts remain scarce.

Methods: A total of 503 AGEP cases were analyzed by combining two distinct, routinely-collected data cohorts: (1) a literature-derived cohort (PubMed, Embase, Web of Science, and CNKI) and (2) a hospital-based clinical cohort from a tertiary-care center in China. The hospital cohort data were collected retrospectively from January 2015 to July 2025. Demographic, etiologic, clinical, laboratory and therapeutic characteristics were summarized. Drugs were stratified by median latency (3 days) into short- versus long-latency groups to explore class-specific patterns.

Results: Drugs triggered 94.6% of cases, mainly β-lactam antibiotics (20.7%), non-β-lactam antibiotics (16.3%), and hydroxychloroquine (10.4%). With a 3-day median latency threshold, antibiotic-related reactions showed short latency, whereas antimalarials, analgesics, and antifungals exhibited longer latency. Hospitalization occurred in 75.1%, and systemic involvement in 20.2% (mostly hepatic or renal). Mucosal lesions were infrequent (oral 8.7%, genital 1.8%). Among those tested, patch tests were positive in 71.6%. Systemic corticosteroids were the mainstay (63.8%) of treatment, with cyclosporine (3.7%) and intravenous immunoglobulin (2.5%) used as adjuncts. A few refractory cases received biologics, including IL-17 inhibitors (eg secukinumab, brodalumab) and IL-36 receptor blockade (spesolimab), achieving partial or complete response. Eight deaths (1.6%) were documented, mainly among older, comorbid, polymedicated patients.

Conclusion: AGEP displays distinct drug class-specific latency signatures and occasional systemic morbidity. We propose a conceptual AGEP causality triage framework integrating latency and allergologic evidence to enhance culprit identification in polypharmacy settings. Given the mechanistic involvement of the IL-36-Th17/IL-17 axis, biologic agents targeting IL-17 or IL-36 pathways show promise in severe or corticosteroid-refractory AGEP, warranting confirmation in larger prospective studies.

Introduction: The ability of honey varieties to both prevent infection and prevent a dysregulated immune reaction to an implanted biomaterial provides a strong case for their viability as biomaterial additives. However, the mechanisms, components, and concentration ranges underlying honey's anti-inflammatory activity remain incompletely understood. The present study sought to screen serial concentrations of the common flavonoid and phenolic components: pinobanksin, pinocembrin, chrysin, and methyl syringate to determine concentrations best to reduce intracellular reactive oxygen species (ROS) activity and neutrophil extracellular trap (NET) release (NETosis) in a differentiated HL60 (dHL60) model.

Methods: HL60s were differentiated into neutrophil-like cells (dHL60s) using a validated protocol, and were cultured with concentrations ranging from 1 nM to 1 mM of each flavonoid and from 10 μM to 2 mM of methyl syringate. NETosis and ROS were measured via Sytox Orange staining and DCFH-DA assay.

Results: ROS activity was moderately inhibited by chrysin but increased by methyl syringate. Flavonoids failed to reduce NET levels. Methyl syringate significantly reduced NETosis in a dose-dependent manner, but increased ROS.

Discussion: The present study provides proof of concept for the honey-derived phenolic compound methyl syringate as a therapeutic candidate to reduce neutrophil-mediated inflammation, specifically NETosis, in response to implanted biomaterials. Methyl syringate is highlighted because NETosis can profoundly affect the progression of downstream inflammatory responses in neutrophils arriving at the site and in other cell types within the microenvironment. Furthermore, it proposes a high-throughput method to screen for potential therapeutic compounds prior to primary neutrophil investigations, thereby addressing the current lack of neutrophil-targeted drug discovery efforts.

Background: Pulmonary tuberculosis (PTB) may coexist with non-small cell lung cancer (NSCLC), yet the clinical implications of this coexistence, including its prognostic impact, remain understudied.

Methods: We performed a retrospective 1:1 matched cohort study of 132 patients (66 PTB-NSCLC cases and 66 NSCLC-only controls) diagnosed between 2017 and 2023. Cases and controls were matched on age (±5 years) and TNM stage. Kaplan-Meier analysis evaluated survival differences, with hazard ratios derived from Cox proportional hazards regression.

Results: Between 2017 and 2023, patients with simultaneously diagnosed PTB and NSCLC (PTB-NSCLC) cases constituted approximately 4.7% of all diagnosed NSCLC patients. PTB-NSCLC patients exhibited higher erythrocyte sedimentation rates (p = 0.002) and lower serum albumin levels (p = 0.032) than controls. Elevated erythrocyte sedimentation rate was associated with poor survival in univariate analysis (p = 0.037), while a high modified Glasgow Prognostic Score (mGPS) remained an independent predictor of adverse outcomes in multivariable analysis (HR: 2.55, 95% CI: 1.12-5.84; p = 0.026). Kaplan-Meier analysis revealed that patients with PTB-NSCLC coexistence had significantly worse overall survival compared to matched controls (median OS: 32 vs 72 months; HR: 2.879, 95% CI: 1.728-4.797; p < 0.001). Furthermore, in multivariable analysis, surgical intervention was associated with significantly improved survival (HR: 0.34, 95% CI: 0.14-0.81; p = 0.015).

Conclusion: PTB-NSCLC confers worse survival outcomes. The mGPS provides independent prognostic value, while surgical intervention was associated with a significant survival benefit, highlighting the importance of integrated management.

Purpose: Membranous nephropathy (MN) is a common glomerular disease characterized by high relapse rates and heterogeneous outcomes. This study aimed to develop a genetic risk score (GRS) based on five MN-associated single nucleotide polymorphisms (SNPs) and assess its predictive value for disease relapse.

Methods: In this prospective study, we analyzed data from 234 patients with phospholipase A2 receptor (PLA2R)-associated MN between January 2020 and December 2023. Genotyping for five SNPs associated with MN risk (rs28383345, rs2187668, rs35771982, rs3749117, and rs4664308) was performed. A GRS was constructed and Cox regression models were used to assess risk factors for remission and relapse. Predictive performance was evaluated using Cox regression, time-dependent receiver operating characteristic (tROC) curves, net reclassification improvement (NRI), integrated discrimination improvement (IDI), Akaike information criterion (AIC), Bayesian information criterion (BIC), likelihood ratio test (LRT), and cross-validation.

Results: Over a median follow-up duration of 28.0 (IQR 20.0, 39.0) months, the cumulative remission rate was 85.5%, with 47% relapsing. A high GRS was significantly associated with the risk of relapse (HR = 1.885, 95% CI: 1.331-2.585; P < 0.001). Adding GRS to the base model consistently increased the time-dependent AUC at years 2, 4, and 5 (all P < 0.05). Notably, assessments using risk reclassification metrics (IDI/NRI) and model fit metrics (LRT/AIC/BIC) also verified significant improvements in model performance across multiple years. Critically, rigorous repeated cross-validation demonstrated that the overall C-index gain provided by the GRS was both stable and significant (P < 0.05), and further year-by-year cross-validation confirmed that this advantage persisted across all evaluated years (all P < 0.05). Furthermore, sensitivity analysis further confirmed the robustness of the GRS.

Conclusion: This study is the first to apply a GRS in predicting relapse in PLA2R-associated MN. GRS significantly enhances predictive accuracy, offering a valuable tool for personalized risk assessment.

Pediatric obesity is one of the foremost global chronic medical conditions. It affects almost every organ system via mechanisms that tend to be organ-specific. Obesity-related asthma is one such pediatric comorbidity that is rising in incidence such that obesity is now considered the foremost modifiable risk factor for asthma. Immune dysregulation of both innate and adaptive responses is one of the best understood pathobiologic mechanisms underlying obesity-related asthma. From the perspective of innate immune dysregulation, there are higher proportions of pro-inflammatory M1 macrophages in systemic circulation and in the airway in pediatric studies; the underlying mechanisms are only studied among adults wherein airway M1 macrophages impaired efferocytosis and induced neutrophil recruitment in the airway. From the perspective of adaptive immune responses, there are higher proportion of T helper 1 cells that are associated with lower lung function supporting the non-allergic phenotype of pediatric obesity-related asthma. There is also substantial new literature from bulk and single cell transcriptomic T cell analyses that have identified novel pathways and distinct differentiation of Th cells in obese children as compared to healthy-weight children with asthma. CDC42 pathway is one such pathway that is upregulated in Th cells from obese children with asthma and is associated with Th cell chemotaxis and adhesion to airway smooth muscle (ASM), activating pathways that promote ASM contractility and proliferation. There is also increased recognition of the role of neutrophils, as compared to eosinophils, in pediatric obesity-related asthma but the mechanistic pathways that are functional relevance in disease phenotype have not yet been investigated. Finally, obesity-mediated metabolic abnormalities, including insulin resistance and dyslipidemia, have been epidemiologically linked with pediatric asthma but their underlying mechanisms are not known. In summary, there have been several strides in understanding the immune pathobiology of pediatric obesity-related asthma which have firmly established it as a distinct asthma phenotype, which have highlighted the need for further scientific investigation of mechanisms that underlie the contribution of immunometabolism.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a curative treatment for thalassemia major but carries a high risk of post-transplant complications. We report a pediatric case with β-thalassemia major who developed steroid-refractory grade III acute graft-versus-host disease (aGVHD) after HLA-9/10 mismatched unrelated donor allo-HSCT. This was followed by cytomegalovirus (CMV) reactivation that progressed to severe CMV pneumonia complicated by diffuse alveolar hemorrhage (DAH). Notably, after failure of first-line antiviral therapy, a combination of ganciclovir and letermovir was employed, resulting in complete virologic clearance and marked respiratory improvement. During follow-up, bronchiolitis obliterans syndrome (BOS) was diagnosed on day +154. The patient received repeated infusions of umbilical cord-derived mesenchymal stromal cells (UC-MSCs), initially for refractory intestinal aGVHD and later in conjunction with the FAM regimen (fluticasone, azithromycin, montelukast) for BOS, ultimately achieving full clinical recovery. This case highlights two key management insights: (1) the ganciclovir-letermovir combination can be effective in pediatric refractory CMV pneumonia, and (2) sequential UC-MSC administration may contribute to controlling both acute GVHD and late pulmonary complications. Finally, multidisciplinary collaboration and individualized strategies are essential in managing such complex post-transplant pulmonary syndromes in children.

Background: Risk stratification in sepsis remains a major clinical challenge in hospital settings, where timely recognition of disease progression can critically influence outcomes. Traditional scoring systems, such as SOFA and APACHE II, are frequently applied but are limited by their complexity and inconsistent predictive accuracy. Integrating biological markers with clinical scores may enhance the early identification of patients with an unfavorable prognosis.

Objective: The objective of this investigation was to determine the prognostic performance of two composite scoring systems, BIO-S and BIO-SC, in predicting 28-day mortality among patients with sepsis or septic shock.

Methods: We conducted a retrospective single-center study including 125 adult surgical patients with sepsis or septic shock. BIO-S was calculated using procalcitonin (PCT), neutrophil-to-lymphocyte ratio (NLR), INR, and SOFA score, whereas BIO-SC extended this model by incorporating the Charlson Comorbidity Index (CCI). Both bioscores were calculated at admission and analyzed in relation to 28-day mortality and discharge status.

Results: Among the 125 patients included, 28-day all-cause mortality was 36% (n = 45). The BIO-SC score achieved the highest predictive accuracy for 28-day mortality (AUC = 0.942), surpassing BIO-S (AUC = 0.930), SOFA (AUC = 0.928), and APACHE II (AUC = 0.918). Both bioscores correlated strongly with discharge outcomes and were independent predictors of 28-day mortality (p < 0.001).

Conclusion: Integrating inflammatory biomarkers, organ dysfunction, and comorbidity burden into composite prognostic models such as BIO-S and BIO-SC significantly improves early mortality risk assessment and outcome prediction in sepsis, although external validation remains necessary.