Journal of Inflammation Research最新文献

Background: The Naples prognostic score (NPS) and its relation to the prognosis of oral squamous cell carcinoma (OSCC) have been inconclusive. This study aimed to investigate the correlation between NPS and the prognosis of postoperative OSCC patients. Additionally, the study sought to develop a new nomogram for predicting disease-free survival (DFS) and overall survival (OS).

Methods: The study included 576 OSCC patients who underwent surgical treatment at two hospitals between August 2008 and June 2018. Univariate and multivariate Cox regression analyses were conducted to identify independent prognostic factors. Subsequently, two nomograms were developed to predict DFS and OS based on these factors and underwent rigorous validation.

Results: The median DFS and OS were 31.5 months and 36.5 months, respectively. Significant differences in DFS and OS were observed among patients with different NPS scores. Adjuvant radiotherapy, age-adjusted Charlson comorbidity index (ACCI), extranodal extension (ENE), NPS, American Joint Committee on Cancer (AJCC) stage, surgical safety margin, eastern cooperative oncology group performance status (ECOG PS), and systemic inflammation score (SIS) were identified as independent predictors of DFS and OS. In the training cohort, the nomogram's concordance index (C-index) for predicting DFS and OS was 0.701 and 0.693, respectively. In the validation group, the corresponding values were 0.642 and 0.635, respectively. Calibration plots confirmed a high level of agreement between the model's predictions and actual outcomes. Decision curve analysis (DCA) demonstrated the nomogram's good clinical utility. Additionally, patients in the low-risk group did not benefit from adjuvant radiotherapy, while those in the medium-risk and high-risk group could benefit from adjuvant radiotherapy.

Conclusion: NPS significantly influences the prognosis of OSCC patients following surgery. The nomogram developed in this study holds significant clinical application potential. The low-risk subgroup of patients was not required to undergo postoperative radiotherapy.

Background: Lichen sclerosus (LS) is a chronic inflammatory disease affecting skin and mucosal tissues, particularly external genitalia, with a risk of cancer. Its etiology is unknown, possibly involving immune dysregulation and inflammation.

Methods: Study used DNA methylation (DNAme) and single-cell RNA sequencing (scRNA-seq) to compare LS with normal skin. A detailed DNAme profile of LS was created, analyzing differentially methylated probes (DMPs) and cell type-specific DMPs. EpiSCORE deconvolution and immune infiltration analyses identified altered cell types in LS. Immunohistochemistry confirmed cellular changes. Enrichment analysis identified significantly altered pathways, and cell communication analysis described interactions among altered cell types in LS.

Results: DNA methylation patterns generally distinguished LS from normal skin, with a few exceptions. Data analysis showed that T cells significantly increased and fibroblasts decreased in LS. Immunohistochemical staining confirmed the changes in T cells. Enrichment analysis of DMPs indicated significant impacts on fibroblast-related processes and key immune pathways. The COLLAGEN signal was the most prominent in the cell communication. The CD99-CD99 interaction was the strongest between T cells and fibroblasts.

Conclusion: Combining DNAme and scRNA-seq data revealed changes in cellular composition and immune pathways in LS, enhancing understanding of its pathogenesis and highlighting potential therapeutic targets and diagnostic markers.

Purpose: Myocardial infarction (MI) is a prevalent cardiovascular disorder affecting individuals worldwide. There is a need to identify more effective therapeutic agents to minimize cardiomyocyte damage and enhance cardioprotection. Ginkgo biloba extract is extensively used to treat neurological disorders and peripheral vascular diseases. The aim of this study was to determine the protective effects and mechanisms of ginkgetin on postinfarction cardiomyocytes through bioinformatics and experimental validation.

Methods: Bioinformatics analysis was performed to predict the underlying biological mechanisms of ginkgetin in the treatment of MI. Next, we performed further validation through experiments. For in vivo studies, we used coronary ligation to construct an MI rat model. In vitro, oxygen and glucose deprivation (OGD) was performed to simulate ischemia in H9c2 cardiomyocytes.

Results: Bioinformatics analysis revealed that the key targets of ginkgetin for MI treatment were MMP2, MMP9, and VEGFA. Immune infiltration analysis revealed that ginkgetin might be involved in immune regulation by acting on the TCR signaling pathway. The results of the GO enrichment analysis revealed that ginkgetin might protect the heart by acting on the cell membrane to alleviate the senescent apoptosis of cardiomyocytes after MI. In vivo studies revealed that ginkgetin ameliorated myocardial pathological damage and cardiac decompensation after MI. It also alleviated the inflammatory infiltration and senescent apoptosis of cardiomyocytes after MI. Additionally, ginkgetin can downregulate the activation signals of the TCR signaling pathway by dephosphorylating CD3 and CD28. In vitro studies revealed that ginkgetin attenuated elevated OGD-induced cytotoxicity, increased cell viability, and alleviated OGD-induced senescent apoptosis, thus protecting cardiomyocytes.

Conclusion: Ginkgetin inhibits postinfarction myocardial fibrosis and cardiomyocyte hypertrophy, scavenges oxygen free radicals, decreases postinfarction limbic cell inflammatory infiltration, suppresses activation of the inflammatory-immune pathway, and delays postinfarction peripheral cells from undergoing senescent apoptosis, thus protecting the heart.

Background: Acupuncture is an effective treatment for knee osteoarthritis (KOA), reducing pain and improving function. While melatonin (MLT) has notable pain relief benefits, the analgesic mechanism of acupuncture in KOA and its relationship with melatonin are still unknown. This study aims to explore this mechanism.

Methods: In this work, the KOA rabbit model was constructed using the traditional Hulth method, and the therapeutic effect was assessed by the Lequesne MG score and Pain assessment by hot plate test. The pathological alterations of cartilage tissue were observed using hematoxylin and eosin (H&E) staining, Safranin O-fast green and MASSON staining to observe the pathological changes in cartilage tissue, and the efficacy was evaluated according to the principles of Mankin score and Osteoarthritis Research Society International (OARSI) score. Meanwhile, MLT in serum, cyclic adenosine monophosphate (cAMP) in cartilage, and matrix metalloproteinase-3 (MMP-3) in joint fluid were detected by enzyme-linked immunosorbent assay. In addition, the expression of aromatic L-amino acid N-acetyltransferase (AANAT), melatonin receptor 1 (MT1) and 2 (MT2) mRNAs in cartilage was determined by real-time quantitative reverse transcription-polymerase chain reaction, and the levels of proteins related to PKA/CREB signaling pathway were detected by Western blotting.

Results: Based on the results of Lequesne MG score and Pain assessment by hot plate test experimental data, the treatment group presented significant improvements in knee pain and overall function relative to OA (Osteoarthritis) group. Besides, according to results of histologic staining, Mankin and OARSI scores, articular cartilage degeneration of treatment group remarkably improved. In addition, acupuncture significantly reduced the expression of the inflammatory factor MMP-3 in knee joint fluid and significantly increased the levels of MLT, AANAT, MT1, MT2, cAMP, PKA and CREB.

Conclusion: By regulating sympathetic excitability, acupuncture may activate the MLT/cAMP/PKA/CREB signaling pathway, decrease inflammatory factor expression and slow down degradation of articular cartilage, resulting in the relief of knee pain.

Background: Systemic immune-inflammation index (SII) and neutrophil-to-lymphocyte ratio (NLR) are novel inflammatory markers based on neutrophil, platelet and lymphocyte counts. Atherosclerosis is a chronic inflammatory vascular disease. This study aimed to verify the predictive value of the clinical parameters such as systemic immune-inflammation index (SII) and neutrophil-to-lymphocyte ratio (NLR) for the severity in Large Artery Atherosclerosis (LAA) stroke patients.

Methods: The SII is defined as platelet × (neutrophil count/lymphocyte count), the NLR is defined as neutrophil count/lymphocyte count. Univariate logistic regression was used to analyze the association between SII and NLR and NIHSS score in patients with LAA stroke. Multiple logistic regression was used to analyze the risk factors for the severity of LAA stroke. We plotted receiver operating characteristic curves to determine the diagnostic role of SII and NLR in differentiating stroke disease severity.

Results: We included 283 LAA stroke patients, the SII and NLR in the moderate-to-severe stroke group were significantly higher than the mild stroke group. Multiple logistic regression analysis showed that SII (OR 1.051 95% CI (1.035-1.066), P < 0.001), NLR (OR 1.077,95% CI (1.032-1.123), P < 0.001) were significantly associated with stroke severity. The SII values under the receiver operating characteristic curve (0.701, 95% CI (0.649-0.791, P < 0.001, cut-off value 912.97) and NLR values under the receiver operating characteristic curve (0.604,5% CI (0.519-0.689), P < 0.01, cut-off value 1.461), and SII values had high discrimination ability. Both SII and NLR had high diagnostic and predictive value for stroke severity, and SII was better than NLR.

Conclusion: The higher SII and NLR, the more severity in LAA stroke patients. SII and NLR are independent risk factors for LAA stroke, and they can also effectively predict stroke severity; moreover, SII has a higher diagnostic efficacy than NLR. However, multicenter studies with large sample size are still needed to confirm this conclusion.

Background: Acute respiratory distress syndrome (ARDS) is a severe form of organ dysfunction and a common postoperative complication. This study aims to develop a predictive model for ARDS in postoperative patients with gastrointestinal perforation to facilitate early detection and effective prevention.

Methods: In this single-center retrospective study, clinical data were collected from postoperative patients with gastrointestinal perforation admitted to the ICU in Hebei Provincial People's Hospital from October 2017 to May 2024. Univariate analysis and multifactorial logistic regression analysis were used to determine the independent risk factors for developing ARDS. Nomograms were developed to show predictive models, and the discrimination, calibration, and clinical usefulness of the models were assessed using the C-index, calibration plots, and decision curve analysis (DCA).

Results: Two hundred patients were ultimately included for analysis. In the development cohort, 38 (27.1%) of 140 patients developed ARDS, and in the internal validation cohort, 13 (21.7%) of 60 patients developed ARDS. The multivariate logistic regression analysis revealed the site of perforation (OR = 0.164, P = 0.006), the duration of surgery (OR = 0.986, P = 0.008), BMI (OR = 1.197, P = 0.015), SOFA (OR = 1.443, P = 0.001), lactate (OR = 1.500, P = 0.017), and albumin (OR = 0.889, P = 0.007) as the independent risk factors for ARDS development. The area under the curve (AUC) was 0.921 (95% CI: 0.869, 0.973) for the development cohort and 0.894 (95% CI: 0.809, 0.978) for the validation cohort. The calibration curve and decision curve analysis (DCA) demonstrate that the nomogram possesses good predictive value and clinical practicability.

Conclusion: Our research introduced a nomogram that integrates six independent risk factors, facilitating the precise prediction of ARDS risk in postoperative patients following gastrointestinal perforation.

Background: Accurately assessing the activity of Crohn's disease (CD) is crucial for determining prognosis and guiding treatment strategies for CD patients.

Objective: This study aimed to develop and validate a nomogram for assessing CD activity.

Methods: The semi-automatic segmentation method and PyRadiomics software were employed to segment and extract radiomics features from the spectral CT enterography images of lesions in 107 CD patients. The radiomic score (rad-score) was calculated using the radiomic signature formula. Multivariate logistic regression analysis identified the independent risk factors of erythrocyte sedimentation rate, fecal calprotectin, and Inflammatory Bowel Disease Questionnaire (IBDQ), and a nomogram was constructed in combination with rad-score. The nomogram underwent evaluation and testing in the training set (n = 84) and validation set (n = 23), respectively.

Results: The discrimination performance of the combined (AUC 0.877) was marginally superior to that of IBDQ + clinical (AUC 0.854). However, there was no significant difference in AUC between the two models in the validation set (P = 0.206). IBDQ + clinical outperformed clinical (AUC 0.808), clinical outperformed IBDQ (AUC 0.746), and IBDQ outperformed radiomic signature (AUC 0.688). Significant differences in AUC were observed between the two models (radiomic signature vs clinical, P = 0.026; radiomic signature vs IBDQ + clinical, P = 0.011; radiomic signature vs combined, P = 0.008; in the validation set).

Conclusion: The nomogram, combined with laboratory data, IBDQ and rad-score, presents an accurate and reliable method for assessing CD activity.

Clinical impact: The nomogram enhances the potential for personalized treatment plans and better disease management, making it a valuable tool for clinical practice.

Patients with selective IgA deficiency could have various clinical presentations ranging from asymptomatic to severe respiratory or gastrointestinal tract infection, as well as autoimmune disease and allergic reactions. Selective IgA deficiency is relatively common in Caucasians, but it is rare in the Asian population, meaning it could be easily missed in the clinic. In this study, we report a 26-year-old man with a history of asthma and nephrotic syndrome. He presented with symptoms of pulmonary infection, and his condition quickly deteriorated to respiratory failure that required endotracheal intubation and mechanical ventilation. Sputum smear; sputum, blood, and bronchoalveolar lavage fluid culture; and metagenomic sequencing examination identified multiple mixed pathogens, including Mycobacterium chelonae-abscessus, Pseudomonas aeruginosa, Candida parapsilosis, Acinetobacter baumannii, and Klebsiella cepacia. Finally, he was diagnosed with selective IgA deficiency after a laboratory test detected an extremely low serum IgA level (<0.06 g/L). The patient died of septic shock and multiorgan failure despite aggressive management with a combination of antibiotics and supportive care. We report this case to remind clinicians about this rare disease in the Asian population. Patients with multisystem illnesses that are related to immune dysregulation, such as asthma or nephrotic syndrome, should be tested for immune system disorder. Rare and mixed pathogens should be considered during antibiotic selection in patients with selective IgA deficiency.

Background: Posttraumatic elbow stiffness is a complex complication with two characteristics of capsular contracture and heterotopic ossification. Currently, genomic mechanisms and pathogenesis of posttraumatic elbow stiffness remain inadequately understood. This study aims to identify differentially expressed genes (DEGs) and elucidate molecular networks of posttraumatic elbow stiffness, providing novel insights into disease mechanisms at transcriptome level.

Methods: Global transcriptome sequencing was conducted on six capsular samples from individuals with posttraumatic elbow stiffness and three control capsular samples from individuals with elbow fractures. Differentially expressed genes (DEGs), microRNAs, and long non-coding RNAs (LncRNAs) were identified and analyzed. Functional enrichment analysis was performed, and the associated protein-protein interaction (PPI) network was constructed. MicroRNAs targeting these DEGs were identified, and transcription factors (TFs) targeting DEGs were predicted using the ENCODE database. Finally, key DEGs were validated by quantitative real-time polymerase chain reaction (qRT-PCR).

Results: A total of 4909 DEGs associated with protein-coding, LncRNA and microRNA were detected, including 2124 upregulated and 2785 downregulated. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed that the DEGs were significantly enriched in 36 signaling pathways, notably involving inflammatory responses and extracellular matrix (ECM) receptor interactions. The protein-protein interaction (PPI) network analysis highlighted genes such as SPP1, IBSP, MMP13 and MYO1A as having higher degrees of connectivity. Key microRNAs (hsa-miR-186-5p, hsa-miR-515-5p, and hsa-miR-590-3p) and transcription factors (TFDP1 and STAT3) were predicted to be implicated in the pathogenesis of posttraumatic elbow stiffness through the microRNA-transcription factor regulatory network analysis.

Conclusion: The study provided insights into the molecular mechanisms underlying the changes in the contracted capsules associated with posttraumatic elbow stiffness. Hub genes including SPP1, IBSP, MMP13, and MYO1A, key microRNAs (has-miR-186-5p, has-miR-515-5p, hsa-miR-590-3p) and TFs (TFDP1 and STAT3) may serve as prognostic and therapeutic targets of posttraumatic elbow stiffness, and provide a new idea for the future research direction of clinical treatment.

Objective: To explore the neuroprotective effect of Eugenol Acetate (EA) on post-stroke neuroinflammation and investigate the underlying mechanisms.

Methods: For in vitro experiments, primary microglia were pre-incubated with EA for 2 hours, followed by lipopolysaccharide (LPS) stimulation for 24 hours or Oxygen-Glucose Deprivation (OGD) treatment for 4 hours. Real-time quantitative PCR, enzyme-linked immunosorbent assay (ELISA) and Western blot were performed to examine the expression levels of inflammatory cytokines in primary microglia. The activation of NF-κB signaling pathway was evaluated by immunofluorescence staining and Western blot. For in vivo experiments, middle cerebral artery occlusion (MCAO) was constructed to mimic ischemic brain injury on 8-week-old male C57BL/6J mice. The mice were continuously injected intraperitoneally with EA or vehicle after MCAO. Neurobehavioral tests and TTC staining were conducted to estimate the neurological deficits and infarct area. Moreover, the white matter integrity after MCAO was observed via immunofluorescence staining.

Results: EA significantly reduced the expression of pro-inflammatory cytokines in LPS or OGD treated primary microglia, and inhibited LPS-induced activation of the NF-κB signaling pathway. In addition, EA alleviated ischemic brain injury and improved neuromotor function of MCAO mice. Furthermore, long-term neurological deficits and white matter integrity were improved by EA treatment after MCAO.

Conclusion: EA alleviated ischemic injury and restored white matter integrity in MCAO mice, which might be associated with the inhibition of NF-κB signaling pathway in microglia. Therefore, EA might be a promising candidate for the treatment of ischemic stroke.