Journal of Inflammation Research最新文献

Purpose: Mycoplasma pneumoniae (MP)-segmental/lobar pneumonia represents a growing proportion of Mycoplasma pneumoniae pneumonia (MPP) in children. We aimed to identify the clinical characteristics and risk factors for MP-segmental/lobar pneumonia in children to facilitate early diagnosis and intervention.

Methods: We conducted a retrospective cohort study at a tertiary pediatric center in Chongqing, China, involving 1406 children hospitalized for MPP from January to December 2023. Based on imaging findings, patients were categorized into MP-ordinary pneumonia group and MP-segmental/lobar pneumonia group. Clinical data were compared, and univariate and multivariate logistic regression analyses were performed to identify independent risk factors. The predictive performance was assessed using receiver operating characteristic (ROC) curves.

Results: The MP-segmental/lobar pneumonia group exhibited a significantly longer duration of pre-admission fever, longer hospital stays, and higher rates of bronchoscopy, respiratory failure, and pulmonary complications. (all P < 0.05). Logistic regression analysis identified the following independent risk factors for MP-segmental/lobar pneumonia: sex, days with fever prior to admission, C-reactive protein (CRP), D-dimer, lactate dehydrogenase (LDH), platelet-lymphocyte ratio (PLR), and platelet (PLT). ROC curve analysis identified five primary predictive indicators (days with fever prior to admission >5.5 days, D-dimer >0.539mg/L, CRP >11.33mg/L, LDH >309.5U/L, PLR >155.815) and two secondary predictive indicators (PLT >340.5×10⁹/L, female sex) based on predicted efficacy. The combined use of these seven indicators further enhanced predictive performance (AUC = 0.741, 95% CI: 0.715-0.766).

Conclusion: MP-segmental/lobar pneumonia exhibits more pronounced clinical symptoms and elevated inflammatory markers. The seven clinical indicators-days with fever prior to admission, CRP, D-dimer, LDH, PLR, PLT and female sex-serve as useful predictive markers for segmental/lobar pneumonia caused by MP. These indicators aid clinicians in the early diagnosis and intervention of MPP, thereby preventing its progression to segmental/lobar pneumonia.

Purpose: Kawasaki disease (KD) is a systemic vasculitis of unknown etiology. Delayed diagnosis and treatment elevate the risk of coronary artery complications. This study aims to investigate metabolic disorders associated with its potential pathophysiology and to explore novel diagnostic biomarkers.

Patients and methods: Untargeted metabolomics was used to identify significantly dysregulated metabolic pathways in patients with KD. Targeted lipidomic analysis was performed to detect differentially expressed lipid metabolites. Candidate plasma biomarkers were quantified using ELISA. Single-cell RNA sequencing was used to analyze the expression of lipid metabolism-related genes and cellular heterogeneity.

Results: Sphingolipid metabolism was confirmed to be dysregulated in patients with KD. Twelve differentially expressed lipid species were identified: 20:5-carnitine, sphingomyelin 32:2;O2, ceramide d16:0/24:0, glucosylceramide d18:1/26:0, lysophosphatidylcholine (LPC) O-16:0, LPC 17:0, LPC 18:0, and phosphatidylcholine (PC) 32:2, PC 36:3, PC 40:3, PC 40:4, and PC 40:7. ELISA validation confirmed the lipidomics-identified alterations in LPC. As a diagnostic biomarker, LPC achieved an area under the curve (AUC) of 0.768, with 64.7% sensitivity and 88.2% specificity. Single-cell RNA sequencing data revealed a marked accumulation of monocytes in KD, along with upregulated expression of lipid metabolism-associated genes. Notably, the expression levels of inflammatory genes were altered along with those of LPC degradation-related genes in monocytes from patients with KD.

Conclusion: This study demonstrated significant dysregulation of lipid metabolism in KD, potentially driven by inflammatory responses in monocytes. LPC has emerged as a potential biomarker of KD and provides new insights into its early diagnosis.

Background: Dupilumab is generally considered safe and effective for treating bullous pemphigoid (BP). We report the first case of recurrent hypoperfusion-induced cerebral infarction temporally associated with dupilumab administration in an elderly patient.

Case presentation: A 96-year-old male with BP, type 2 diabetes, and a history of stroke developed acute hypotension, depressed consciousness, and reduced oral intake within 24-72 hours after three separate dupilumab injections. Initial neuroimaging revealed watershed infarcts. Proactive volume expansion during one administration successfully averted new infarction, whereas lack of prophylactic hydration on another occasion precipitated a transient ischemic attack (TIA).

Observations & analysis: A significant temporal association was documented. The Naranjo Adverse Drug Reaction Probability Scale score was 8, indicating a probable association. The patient's advanced age, compromised cerebrovascular reserve, and mandatory discontinuation of antithrombotics created a hypervulnerable substrate. The hypotensive mechanism is hypothesized to involve IL-4/IL-13 pathway blockade, potentially disrupting endothelial function and vascular tone regulation.

Conclusion & clinical implications: This case report describes a potential, albeit rare, serious adverse effect associated with dupilumab in an elderly individual at high risk. Based on this single experience, we suggest at least 72 hours of post-injection blood pressure monitoring for high-risk patients. Management could include administering prophylactic fluid replacement based on the patient's actual condition and critically reassessing concomitant antihypertensive regimens. This finding highlights the need for heightened clinical vigilance and suggests that the drug's safety profile in advanced-age patients may warrant further investigation.

Background: Lumbar infectious spondylodiscitis is a severe spinal condition traditionally managed with antibiotics, though some patients require surgical intervention. The heterogeneity in infection sites, causative pathogens, and clinical presentations leads to significant variability in surgical approaches, and optimal surgical strategies remain controversial. This study aims to evaluate the feasibility, safety, and preliminary efficacy of endoscopic retroperitoneal debridement combined with posterior percutaneous pedicle screw fixation for the treatment of lumbar infectious spondylodiscitis.

Methods: This retrospective study analyzed patients diagnosed with lumbar infectious spondylodiscitis and treated with endoscopic retroperitoneal debridement at our institution from June 2023 to June 2024. Baseline patient characteristics, operative time, intraoperative blood loss, postoperative lesion clearance, changes in inflammatory markers (eg, C-reactive protein[CRP] and erythrocyte sedimentation rate[ESR]), complication rates, Visual analog scale (VAS) scores for back pain, Oswestry Disability Index (ODI) scores, kyphotic angle changes at the infected level, and radiological follow-up outcomes were recorded.

Results: Of the 30 patients, 28 (28/30, 93.33%) showed improvement in clinical symptoms. During follow-up, all patients demonstrated significant improvements in VAS scores and ODI scores compared to preoperative values (p<0.05). At the final follow-up, all patients exhibited a kyphotic angle change of less than 8°, and no spinal instability was observed. Computed tomography (CT) at the 12-month follow-up demonstrated intervertebral bone fusion in 27 cases (27/29, 93.10%). Postoperative inflammatory markers showed improved compared with preoperative levels (p<0.001). No infection recurrence or serious surgery-related complications were observed during the postoperative follow-up period.

Conclusion: Endoscopic retroperitoneal debridement combined with posterior percutaneous pedicle screw fixation appears to be a safe and effective minimally invasive approach for treating lumbar infectious spondylodiscitis. However, long-term efficacy requires further validation through prospective studies with larger sample sizes and extended follow-up periods.

Background: Lactylation has emerged as a novel post-translational modification, and genes linked to both lactylation and macrophage polarization may play a role in inflammatory bowel disease (IBD). However, the connection between these genes and TNF-α inhibitor response in IBD remained unclear.

Methods: This study used bioinformatic tools including weighted gene co-expression network analysis (WGCNA), immune infiltration analysis, and machine learning algorithms to identify correlations between lactylation and macrophage-related genes and TNF-α inhibitor response in IBD.

Results: Significant differential expression of MNDA, CALD1, RECQL, and RBM10 was identified between the remission and non-remission groups in the pre-treatment data. Based on these findings, we established a predictive model for TNF-α inhibitor response, achieving an ROC performance with training AUC reaching 0.894 and validation AUC reaching 0.883. Furthermore, MNDA, LGALS1, ZYX, ADAR, and WAS were significantly elevated in the non-remission group 4-6 weeks after initial treatment. Immune infiltration analysis further indicated strong correlations between hub genes expression and immune cell proportions. In addition, GSEA identified signaling pathways associated with TNF-α inhibitor response. To validate these observations, TNF-α inhibitor was administered to mice with TNBS-induced colitis, and the expression of hub genes was confirmed by RT-qPCR. Importantly, combination therapy with lactate supplementation enhanced the efficacy of TNF-α inhibitor treatment compared with monotherapy. Finally, analysis of lactylation levels indicated intergroup differences associated with TNF-α inhibitor treatment in IBD.

Conclusion: Overall, we identified lactylation and macrophage-related genes as potential biomarkers for TNF-α inhibitor response. Lactate supplementation was found to enhance the efficacy of TNF-α inhibitor based on animal experimental validation. Nevertheless, the findings were based on secondary analyses of public datasets, and the animal experiments remained preliminary. Further studies should be conducted to validate these findings and explore the molecular pathways involved.

Purpose: Atrial fibrillation (AF) is a leading cause of stroke, heart failure, and mortality, yet the molecular mechanisms remain incompletely defined.

Patients and methods: We integrated bulk transcriptomes from GEO with weighted gene co-expression network analysis, consensus clustering, and a 12-algorithm machine-learning pipeline (66 model combinations) to map programmed cell death (PCD) pathways and pinpoint diagnostic genes. Immune infiltration was profiled by CIBERSORT, xCell, and ssGSEA. Hub-gene expression was validated in an HL-1 atrial pacing model and in peripheral blood mononuclear cells (PBMCs) from patients with persistent AF.

Results: Four hub genes-SGPL1, NPC2, PTGDS, and RCAN1-were identified and incorporated into a nomogram and a PCD-based risk score (PCDscore). The nomogram showed robust discrimination in the training cohort and two independent validation datasets. Patients with a high PCDscore exhibited markedly increased immune-cell infiltration and dysregulated immune modulators, with macrophages consistently enriched across algorithms. qRT-PCR confirmed up-regulation of SGPL1, NPC2, and RCAN1 and down-regulation of PTGDS in AF cell models; NPC2 and SGPL1 were further elevated in PBMCs from AF patients.

Conclusion: Our integrative framework reveals PCD-linked remodeling in AF and nominates SGPL1, NPC2, PTGDS, and RCAN1 as candidate diagnostic biomarkers, providing a PCD-based nomogram and risk score that may inform patient stratification and hypothesis-generating targeted interventions.

Background: Ulcerative colitis (UC), a chronic inflammatory bowel disease with rising global incidence, involves neutrophil-driven mucosal damage. The precise mechanisms remain elusive, hindering targeted therapies. Therefore, this study aims to integrate single-cell transcriptomics with in vivo experiments to reveal the key signaling axes driving pathogenic neutrophil activation in UC.

Methods: Single-cell transcriptomics characterized UC inflammatory microenvironments, focusing on neutrophil functional states and intercellular interactions. Based on key findings from bioinformatics analysis, we hypothesize that the eNAMPT-integrin α5β1 signaling axis drives abnormal neutrophil-endothelial cell communication and functionally validate this hypothesis in in vivo models.

Results: Neutrophils exhibited aberrant activation and significant NAMPT overexpression in UC. Extracellular eNAMPT functioned as a signaling molecule binding endothelial integrin α5β1, mediating pathological neutrophil-endothelial crosstalk. Pharmacological blockade of the eNAMPT/integrin α5β1 axis inhibited neutrophil mucosal infiltration, reducing inflammation and tissue damage in UC mouse models.

Conclusion: The eNAMPT-integrin α5β1-mediated neutrophil-endothelial communication axis represents a novel pathogenic pathway in UC, providing a foundation for precision therapies targeting this mechanism.

Background: Allergic rhinitis (AR) is a prevalent chronic inflammatory disease characterized by immune dysregulation and epithelial barrier dysfunction. Conventional therapies are often limited by side effects and insufficient efficacy in addressing the underlying pathophysiology. To explore alternative approaches, this study investigated the potential of YuPingTongQiao (YPTQ), a novel Traditional Chinese Medicine (TCM) formulation, as a multi-target treatment for AR.

Methods: An ovalbumin-induced AR rat model was established. Nasal allergic symptoms were assessed using a standardized scoring system. Histopathology, FC, RT-qPCR, and ELISA were performed to assess epithelial integrity, cell infiltration, cytokine expression, and immune cell phenotypes.

Results: YPTQ significantly alleviated AR symptoms, including nasal rubbing, sneezing, and rhinorrhea, in a dose-dependent manner. The high-dose YPTQ (YPTQ-H) group demonstrated superior efficacy compared to Loratadine. Mechanistically, YPTQ suppressed T_H2 cytokines (IL-4, IL-5, IL-13) and IL-33, restored follicular regulatory T (T_FR) cell balance, and increased CTLA4 expression, thus mitigating IgE-mediated immune responses. Additionally, YPTQ enhanced epithelial barrier integrity by upregulating Claudin1 and reduced mucus hypersecretion by suppressing MUC2 expression. Histological analysis revealed decreased infiltration of eosinophils, mast cells, and goblet cells in the nasal mucosa.

Conclusion: YPTQ offers a safe, effective, and multi-target therapeutic option for AR, addressing both immune dysregulation and epithelial dysfunction. Its superior efficacy compared to Loratadine and excellent safety profile highlight its potential as a novel alternative or adjunct to conventional treatments for AR.

Background: Acute lung injury (ALI), as a respiratory condition triggered by various internal and external factors, is characterized clinically by high rates of incidence and mortality. In the current context where respiratory system diseases are on the rise, the incidence of ALI has been increasing annually. Previous research has established the efficacy of traditional Chinese medicine (TCM) in inhibiting ALI. Siji Kangbingdu Mixture (SJM), has demonstrated a clear clinical therapeutic effect in managing respiratory infections. Nevertheless, its mechanism of action in treating ALI is still lacking.

Purpose: To clarify the mechanism by which SJM exerts its therapeutic effects in the treatment of ALI.

Materials and methods: In our study, we initially elucidated the chemical constituents of SJM by the UHPLC-Q-Orbitrap HRMS (LC-MS), and established an ALI model. Next, we evaluated how SJM inhibited ALI by measuring the weight curve of mice, the wet-to-dry lung weight ratio (W/D), the HE lung tissue pathological change score, along with the inflammatory factor expression. Then, by employing transcriptomics and network pharmacology approaches, the mechanism of SJM acting on ALI were predicted and analyzed. Finally, the expression and regulatory interactions of the differentially expressed target proteins in the key pathways were verified by qRT-PCR analysis, Western blotting (WB), immunofluorescence and immunohistochemistry.

Results: The LC-MS analysis identified 148 active ingredients. In vitro experiments indicated that SJM could significantly reduce the W/D index, pulmonary tissue pathological score, and the inflammatory factor levels. The findings from transcriptomics and network pharmacology suggested that SJM may alleviate ALI as a TNF and IL-17 signaling pathway. Further, through WB, immunofluorescence and immunohistochemistry, we noted significant downregulations in the pulmonary tissue expression of keys proteins in the SJM-H group.

Conclusion: SJM has the potential to inhibit the progression of ALI, and its mechanism of action may involve the TNF and IL-17 signaling downregulation.

Purpose: A common complication observed in septic patients under intensive care is acute kidney injury (AKI), which is characterized by acute onset and strong inflammation, resulting in poor clinical outcomes for patients. This study aims to explore the expression status of PCED1B-AS1 in sepsis-induced AKI and to preliminarily investigate the molecular mechanism by which PCED1B-AS1 affects AKI.

Patients and methods: This study included 105 healthy individuals and 220 patients with sepsis (110 patients with AKI and 110 non-AKI patients). The levels of PCED1B-AS1 were examined by RT-qPCR. Macrophage polarization was induced by LPS treatment of RAW264.7 cells, and an in vitro renal injury model was established using HK-2 cells. Cell proliferation ability was evaluated by CCK-8 assay, apoptosis was detected by flow cytometry, and the levels of inflammatory factors were assessed using ELISA kits. The dual-luciferase assay was used to verify the interrelationship among the PCED1B-AS1/miR-361-3p/SOCS1 axis.

Results: PCED1B-AS1 was downregulated in sepsis patients without AKI and further reduced in AKI patients. PCED1B-AS1 could differentiate healthy individuals from non-AKI sepsis patients and identify AKI patients. Additionally, low PCED1B-AS1 expression correlated with poor AKI prognosis. Overexpression of PCED1B-AS1 promoted the polarization of M1 macrophages to M2 by regulating the miR-361-3p/SOCS1 axis, thereby inhibiting apoptosis and inflammatory responses in HK-2 cells.

Conclusion: PCED1B-AS1 may serve as a potential diagnostic and prognostic marker and inhibit sepsis-induced AKI by promoting transformation of macrophages from M1 to M2 type via regulating the miR-361-3p/SOCS1 axis.