Journal of Inflammation Research最新文献

Background: The predictors associated with clinical outcomes in patients with tuberculous meningitis (TBM) remain unclear. We aimed to analyse the relationship between systemic inflammation and clinical outcomes, as well as to explore whether systemic inflammation level influences the effectiveness of dexamethasone on treatment.

Methods: Between January 2011 and December 2021, TBM patients admitted to five hospitals were observed consecutively. Baseline and post-treatment systemic inflammation levels were calculated using the neutrophil-lymphocyte-ratio (NLR). Generalized linear mixed models were employed to identify predictors of clinical outcomes. Propensity score matching and subgroup analyses were conducted to evaluate the effect of dexamethasone on treatment outcomes across different NLR levels.

Results: A total of 1203 TBM patients were included in the study. During the follow-up, 144 (13.6%) participants experienced early neurological deterioration within 7 days after admission, and 345 (28.67%) exhibited poor functional outcome at the 12-month follow-up. Multivariate analysis revealed that post-treatment NLR was significantly associated with early neurological deterioration (OR=1.25; 95% CI, 1.14-1.33; P<0.001), and poor outcome (OR=1.34; 95% CI, 1.26-1.45; P<0.001). After propensity score matching, dexamethasone treatment was not associated with early neurological deterioration (OR=0.83; 95% CI, 0.42-1.66; P=0.610) or poor outcome (OR=1.22; 95% CI, 0.49-2.11; P=0.490) in the highest quartile of post-treatment NLR. The effect of dexamethasone on treatment outcomes did not significantly vary with disease severity stratification.

Conclusion: Elevated systemic inflammation is an independent risk factor for neurological outcome in TBM patients. Further studies are required to investigate systemic inflammation in more severely affected population to better predict the outcomes following anti-inflammatory therapies.

Purpose: The pathogenesis of CRSwNP is complex and not yet fully explored, so we aimed to identify the pivotal hub genes and associated pathways of CRSwNP, to facilitate the detection of novel diagnostic or therapeutic targets.

Methods: Utilizing two CRSwNP sequencing datasets from GEO, differential expression gene analysis, WGCNA, and three machine learning methods (LASSO, RF and SVM-RFE) were applied to screen for hub genes. A diagnostic model was then formulated utilizing hub genes, and the AUC was generated to evaluate the performance of the prognostic model and candidate genes. Hub genes were validated through the validation set and qPCR performed on normal mice and CRSwNP mouse model. Lastly, the ssGSEA algorithm was employed to assess the differences in immune infiltration levels.

Results: A total of 239 DEGs were identified, with 170 upregulated and 69 downregulated in CRSwNP. Enrichment analysis revealed that these DEGs were primarily enriched in pathways related to nucleocytoplasmic transport and HIF-1 signaling pathway. Data yielded by WGCNA analysis contained 183 DEGs. The application of three machine learning algorithms identified 11 hub genes. Following concurrent validation analysis with the validation set and qPCR performed after establishing the mouse model confirmed the overexpression of BTBD10, ERAP1, GIPC1, and PEX6 in CRSwNP. The examination of immune cell infiltration suggested that the infiltration rate of type 2 T helper cell and memory B cell experienced a decline in the CRSwNP group. Conversely, the infiltration rates of Immature dendritic cell and Effector memory CD8 T cell were positive correlation.

Conclusion: This study successfully identified and validated BTBD10, ERAP1, GIPC1, and PEX6 as potential novel diagnostic or therapeutic targets for CRSwNP, which offers a fresh perspective and a theoretical foundation for the diagnostic prediction and therapeutic approach to CRSwNP.

Objective: Despite the substantial advancements in imaging techniques for the diagnosis and differential diagnosis of acute appendicitis (AA) over recent decades, the specificity and sensitivity of widely utilized laboratory biomarkers in clinical practice remain inadequate.This study aimed to investigate the diagnostic utility of commonly employed blood inflammatory markers for AA.

Methods: A total of 399 participants who either sought medical care or underwent health examinations were enrolled in this prospective study. The cohort comprised 200 patients diagnosed with AA (AA group), 100 patients presenting with abdominal pain but without AA (AP group), and 99 healthy individuals undergoing routine health check-ups (HC group). For all subjects, the following biomarkers were measured: plasma neutrophil gelatinase-associated lipocalin (NGAL), white blood cell count (WBC), neutrophil count (NEU), percentage of neutrophils (NEU%), neutrophil-to-lymphocyte ratio (NLR), and C-reactive protein (CRP). The diagnostic performance of the observed indicators, both individually and in combination, was assessed for the diagnosis of AA using Receiver Operating Characteristic (ROC) curves analysis and Delong's test.

Results: The laboratory indicators demonstrated a progressive increase from the HC group to the AP group, and further to the AA group (all p<0.05). Multifactorial logistic regression analysis identified NEU% and plasma NGAL as significant risk factors for the occurrence of AA. ROC curve analysis and Delong's test indicated that, in distinguishing the AA group from the HC group, the diagnostic performance of plasma NGAL, CRP, and NLR was equally substantial and superior to that of NEU and WBC. Within the AP group, plasma NGAL and CRP exhibited comparable diagnostic efficacy, outperforming NEU, WBC, and NLR. When differentiating AA in the non-appendicitis group (ie HC group + AP group), NGAL and CRP demonstrated comparable diagnostic efficacy, surpassing that of NEU, white WBC, and NLR. While the integration of multiple diagnostic tests can potentially improve overall diagnostic accuracy, the observed enhancement in the AUC is not statistically significant.

Conclusion: NGAL, CRP, WBC, NEU% and NLR were significantly increased in patients with acute abdomen. NGAL and NEU% may function as independent risk factors for predicting the incidence of AA, with NGAL and CRP demonstrating similar and favorable diagnostic performance. While the combined evaluation of these biomarkers may enhance the diagnostic value for AA, the improvement in the area under the curve (AUC) is not substantial.

Background: To assess the relationship between soluble interleukin-17 receptor (sIL-7R) levels and CD3-positive t cells and lymphocytes in patients with sepsis and their predictive clinical significance.

Methods: The study cohort comprised individuals diagnosed with sepsis based on the Third International Consensus Definitions for Sepsis and Septic Shock, treated in the emergency and critical care medicine departments at Beijing Chuiyangliu Hospital and Baoding No. 1 Central Hospital between December 2020 and June 2022. Patient outcomes were classified based on survival or mortality. Biomarkers, including sIL-7R levels and illness severity scores, were documented. All statistical analyses, including predictive modeling and comparisons were carried out using SPSS v.23.0 software and R software.

Results: On the fifth day post-admission, sIL-7R levels significantly decreased in both the survival and death groups, compared with levels on day one (2.09 ± 0.65 vs 1.07 ± 0.53 ng/mL, P < 0.01). There was a significant correlation between the sIL-7R level and the CD3+ T-lymphocyte count (CD3+) (r = 0.44) and lymphocyte count (LYM) (r = 0.42). The combination of the sIL-7R level with the Sequential Organ Failure Assessment (SOFA) score demonstrated optimal predictive value for clinical outcomes in patients with sepsis, demonstrated by an area under the receiver operating characteristic curve of 0.998.

Conclusion: sIL-7R levels are correlated with CD3+ and LYM counts. Additionally, the combination of serum sIL-7R level and SOFA score provides a robust method for predicting sepsis outcomes.

Background: Acute lung injury (ALI) is a life-threatening clinical syndrome with high mortality. Currently, the safe and effective therapies for ALI patients are still limited. Qingfei Huoxue decoction (QFHXD) is a hospital agreement prescription for treating pulmonary diseases and displays a remarkable efficacy. However, the pharmacological effect of QFHXD on preventing lipopolysaccharide (LPS)-induced ALI has yet to be reported, let alone questions of potential molecular mechanisms and anti-ALI active substances.

Methods: To answer the above-mentioned questions, histopathological observation and kit detection were performed to estimate the protective effect of QFHXD pretreatment against LPS-induced ALI. Based on comprehensive chemical profiling of QFHXD, a network pharmacology strategy and experimental validation were integrated to elucidate the underlying functional mechanisms. The potential anti-ALI active components were identified by molecular docking. The anti-ALI activity of narirutin and its anti-inflammatory mechanism were further validated using animal and molecular experiments.

Results: Pretreatment with different doses of QFHXD effectively mitigated histopathological lesions and systemic inflammation caused by LPS stimulation. A detailed analysis of established compound-target-disease network revealed the strong correlation between anti-ALI action of QFHXD and inflammatory mechanisms. Compared with the model group, QFHXD intervention markedly restrained the abnormally increased transcription and protein levels of pro-inflammatory factors (TLR4, NF-κB, IL-6, IL-1β, and TNF-α) in lung tissues of ALI mice. The results of molecular docking highlighted the anti-ALI potential of narirutin targeting to TLR4 and NF-κB p65. In addition to the protective effect of narirutin on suppressing LPS-induced pathological changes, we found that narirutin pretreatment effectively normalized the disordered protein levels of above pro-inflammatory factors of ALI mice.

Conclusion: These interesting findings indicate the beneficial effects of QFHXD and its active component narirutin against ALI partly via regulating TLR4/NF-κB mediated inflammation. This work contributes to the development of novel medications for ALI patients.

Objective: This study aimed to investigate the risk factors for immune checkpoint inhibitor (ICI)-related colitis and its impact on prognosis in the treatment of lung cancer.

Methods: This retrospective, single-center, observational study included lung cancer patients who received ICIs treatment between January 2016 and January 2022. The correlation between immune-related colitis and prognosis was evaluated. Kaplan-Meier analysis was used to compare the median overall survival (OS).

Results: Among the lung cancer patients treated with ICIs, the incidence of colitis was 5.88% (35/595). The severity of colitis was graded as follows: grade 1 (8 cases), grade 2 (15 cases), grade 3 (9 cases), and grade 4 (3 cases). Except for the 1 case that resulted in death due to grade 4 adverse events, the remaining patients showed significant improvement after corticosteroid intervention. Among the 35 patients with ICI-related colitis, complete remission was not achieved. Partial remission was observed in 11 cases, disease stability in 16 cases, disease progression in 7 cases, and death in 1 case. Among the included patients, 19 chose to continue ICI treatment after symptom relief. The overall survival for all participants was 34 months (IQR: 24-36), while the overall survival for those who received ICI treatment again was 36 months (IQR: 32-NA), and for those who did not receive ICI treatment again was 32 months (IQR: 21-35). Kaplan-Meier survival curve analysis showed that patients who received ICI treatment again had significantly better overall survival compared to other patients.

Conclusion: Immune-related colitis remains a significant concern in lung cancer patients treated with ICIs and requires close monitoring and timely intervention. Restarting treatment after symptom relief can provide additional benefits for patients.

Exosomes have grown as promising carriers for noncoding RNAs (ncRNAs) in the treatment of inflammation, particularly in conditions like ischemic stroke and myocardial infarction. These ncRNAs, which include microRNAs (miRNAs) and long noncoding RNAs (lncRNAs), play a crucial role in regulating inflammatory pathways, presenting new therapeutic opportunities. In both ischemic stroke and myocardial infarction, inflammation significantly influences disease progression and severity. Exosomes can deliver ncRNAs directly to specific cells and tissues, providing a targeted approach to modulate gene expression and reduce inflammation. Their biocompatibility and low risk of inducing immune responses make exosomes ideal therapeutic vehicles. Ongoing research is focused on optimizing the loading of ncRNAs into exosomes, ensuring efficient delivery, and understanding the mechanisms by which these ncRNAs mitigate inflammation. In ischemic stroke, exosome-derived ncRNAs originate from various cell types, including neurons, M2 microglia, patient serum, genetically engineered HEK293T cells, and mesenchymal stromal cells. In the case of myocardial infarction, these ncRNAs are sourced from mesenchymal stem cells, endothelial cells, and patient plasma. These exosome-loaded ncRNAs play a significant role in modulating inflammation in both ischemic stroke and myocardial infarction. As this research advances, therapies based on exosomes may completely change how diseases linked to inflammation are treated, offering new avenues for patient care and recovery. This review explores the latest advancements in understanding how exosomes impact specific inflammatory components, with a particular emphasis on the role of ncRNAs contained in exosomes. The review concludes by highlighting the clinical potential of exosome-derived ncRNAs as innovative therapeutic and diagnostic tools.

Objective: To assess the efficacy of methotrexate (MTX) and hydroxychloroquine (HCQ) in improving fatigue symptoms in patients with primary Sjögren's syndrome (pSS).

Methods: A single-center retrospective study was conducted on pSS patients experiencing fatigue symptoms. All patients received either MTX, HCQ, or a combination of MTX + HCQ for a period of six months. Clinical efficacy was measured using the European League Against Rheumatism (EULAR) Sjögren's Syndrome Disease Activity Index (ESSDAI), EULAR Sjögren's Syndrome Patient Reported Index (ESSPRI), Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F), fatigue severity scale (FSS), and visual analog scale (VAS) score. These measures were assessed at baseline and at 1, 2, 3, and 6 months.

Results: A total of 86 pSS patients with fatigue symptoms were enrolled (27 received MTX, 29 received HCQ, and 30 received MTX + HCQ). Patients receiving MTX and MTX + HCQ showed significant improvements at 6^th month in ESSDAI, ESSPRI, FSS, FACIT-F, and VAS scores (all P < 0.01) compared with baseline. Repeated-measures analysis of variance revealed that patients treated with MTX and MTX + HCQ experienced significant improvements in ESSDAI, FSS, FACIT-F, and VAS scores (all P < 0.01) from baseline to the 6^th month. The HCQ group did not show significant improvement in FSS, FACIT-F, and VAS scores (all P > 0.05), although their ESSDAI and ESSPRI scores did improve significantly (all P < 0.01). Patients in the MTX group showed the most improvement in mean changes of ESSDAI score, FSS score, FACIT-F score, and VAS score from baseline to the 6^th month. And patients received MTX treatment significantly had more fatigue remission numbers (all P < 0.05).

Conclusion: In clinical practice, methotrexate is more effective than hydroxychloroquine in improving fatigue symptoms, as measured by patient-reported fatigue scales (FSS, FACIT-F, and VAS scores) in patients with pSS.

Purpose: Vascular dementia (VaD) is the second most common dementia in the world. An increasing number of studies have demonstrated the important role of long non-coding RNAs (lncRNAs) in VaD. Our previous investigation demonstrated that Trimethylamine-N-oxide (TMAO) exacerbates cognitive impairment and neuropathological alterations in VaD rats. Thus, we hypothesized that TMAO could play an injury role in VaD by regulating lncRNAs.

Materials and methods: The rats using the bilateral common carotid artery (2VO) model were administered TMAO (120 mg/kg) for 8 consecutive weeks, 4 weeks preoperatively and 4 weeks postoperatively. High-throughput sequencing was conducted to investigate the effects of TMAO treatment on lncRNA expression in rat hippocampus and bioinformatics analysis was performed to identify potential downstream targets. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to detect the levels of lncRNA fetal-lethal noncoding developmental regulatory RNA (Fendrr), miR-145-5p, and paxillin (PXN). Learning and spatial memory capacities were measured, as well as inflammatory factors. Nissl staining was used to observe neuronal injury in the CA1 area of the hippocampus. Furthermore, we used the Fendrr loss-of-function assay, miR-145-5p gain-of-function assays and PXN loss-of-function assay to explore the mechanisms by which TMAO acts on VaD.

Results: TMAO administration upregulated lncRNA Fendrr expression in the rat hippocampus, while the damaging effects of TMAO were counteracted after knockdown of Fendrr. Fendrr exhibits highly expressed in 2VO rats and sponged miR-145-5p, which targets PXN. Silencing of Fendrr or PXN, or promotion of miR-145-5p improved neurological function injury, reduced neuronal damage, as well as repressed inflammation response. Inhibition of miR-145-5p abrogated up Fendrr knockdown mediated influence on 2VO rats.

Conclusion: The results of this study indicated that TMAO inhibits the miR-145-5p/PXN axis by increasing the Fendrr expression, thus exacerbating the development of VaD.

Background: Fecal incontinence (FI) is the inability to control bowel movements, resulting in fecal leakage. If left untreated, FI can seriously impact the long-term well-being of individuals affected. Recently, using secretome has become a promising new treatment method. The secretome combines growth factors released outside cells during stem cell development, such as mesenchymal stem cells. It consists of soluble proteins, nucleic acids, fats, and extracellular vesicles, which contribute to different cell processes. The primary aim is to assess the impact of hypoxic secretome administration on accelerating wound healing through the HIF-1α pathway in a post-sphincterotomy rat model.

Methods: The study was conducted with two distinct groups of 10 rats each, the control and treatment groups, which were injected with hypoxic secretome at 0.3 mL. The inclusion criteria for the rats were as follows: male gender, belonging to the Sprague-Dawley strain, aged between 12 to 16 weeks, with an average body weight ranging from 240 to 250 grams.

Results: There was an increase in HIF-1α gene expression in both groups. The treatment group 37 was significantly higher on day 42 (p = 0.001). VEGF increased significantly in the treatment 38 group on day 42 (p = 0.015). The neovascularization score increased significantly in the treatment 39 group during the first 24 hours (p = 0.004). The fibroblast score increased significantly in the 40 treatment group in the first 24 hours (p = 0.000) and 42 days (p = 0.035). After being given secretome, there was a higher increase in % collagen area and collagen area (µm²) in the treatment group compared to the control group (27,77 vs 11.01) and (419.027,66 vs 186.694,16).

Conclusion: The use of hypoxic secretome has a significant effect as a choice for the treatment of anal sphincter injury after sphincterotomy through the HIF-1α-VEGF-Fibroblast pathway.