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OBJECTIVE: Immune checkpoint inhibitors (ICIs), specifically targeting the programmed cell death protein-1 or its ligand (PD-1/PD-L1), have been extensively used in the treatment of a spectrum of malignancies, although the predictive biomarkers remain to be elucidated. This study aims to investigate the association between baseline circulating levels of cytokines and the creatinine/cystatin C ratio (CCR) with the treatment outcomes of ICIs in patients with advanced cancer. METHODS: The pre-treatment circulating levels of 10 cytokines (PD-L1, CTLA4, CXCL10, LAG3, HGF, CCL2, MIG, GRANB, IL-18, and IL-6) were measured via automated capillary-based immunoassay platform in the serum of 65 advanced cancer patients treated with anti-PD-1/PD-L1-based systemic therapy and 10 healthy volunteers. The levels of cytokines and CCR were quantified and categorized into high and low groups based on the median value. The associations of serum cytokines and CCR with response to treatment, survival, and immune-related adverse events were assessed. RESULTS: Elevated circulating levels of 6 cytokines (PD-L1, CXCL10, HGF, CCL2, MIG, and IL-6) were observed in cancer patients compared with that in healthy volunteers. The correlation coefficients between cytokines, CCR and nutritional risk index were also calculated. In the cancer cohort (N = 65), low circulating HGF (P = 0.023, P = 0.029), low IL-6 (P = 0.002, P < 0.001), and high CCR (P = 0.031, P = 0.008) were associated with significantly improved progression-free survival (PFS) and overall survival (OS). Multi-variable COX analyses adjusted for clinicopathological factors revealed that low HGF, low IL-6, and high CCR were independent favorable prognostic factors for PFS (P = 0.028, P = 0.010, and P = 0.015, respectively) and OS (P = 0.043, P = 0.003, and P = 0.026, respectively). Grade 2 irAEs occurred more frequently in patients with low levels of circulating CCL2 and LAG3. CONCLUSIONS: Pre-treatment circulating levels of serum IL-6, HGF, and CCR may serve as independent predictive and prognostic biomarkers in advanced cancer patients treated with ICIs-based systemic therapy. These findings might help to identify potential patients who would benefit from these therapies.
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Biomarcadores Tumorais , Creatinina , Citocinas , Inibidores de Checkpoint Imunológico , Neoplasias , Humanos , Masculino , Feminino , Neoplasias/tratamento farmacológico , Neoplasias/sangue , Pessoa de Meia-Idade , Idoso , Citocinas/sangue , Prognóstico , Inibidores de Checkpoint Imunológico/uso terapêutico , Inibidores de Checkpoint Imunológico/farmacologia , Creatinina/sangue , Biomarcadores Tumorais/sangue , Adulto , Idoso de 80 Anos ou mais , Antígeno B7-H1/sangue , Estudos de Casos e ControlesRESUMO
BACKGROUND: Recent reviews have outlined the main nanomaterials used in relation to gastrointestinal tumors and described the basic properties of these materials. However, the research hotspots and trends in the application of nanomaterials in gastric cancer (GC) remain obscure. AIM: To demonstrate the knowledge structure and evolutionary trends of research into the application of nanomaterials in GC. METHODS: Publications related to the application of nanomaterials in GC were retrieved from the Web of Science Core Collection for this systematic review and bibliometric study. VOSviewer and CiteSpace were used for bibliometric and visualization analyses. RESULTS: From 2000 to 2022, the application of nanomaterials in GC developed rapidly. The keyword co-occurrence analysis showed that the related research topics were divided into three clusters: (1) The application of nanomaterials in GC treatment; (2) The application and toxicity of nanomaterials in GC diagnosis; and (3) The effects of nanomaterials on the biological behavior of GC cells. Complexes, silver nanoparticles, and green synthesis are the latest high-frequency keywords that represent promising future research directions. CONCLUSION: The application of nanomaterials in GC diagnosis and treatment and the mechanisms of their effects on GC cells have been major themes in this field over the past 23 years.
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OBJECTIVE: A link between periodontitis and chronic obstructive pulmonary disease (COPD) has been identified, and interleukin-33 (IL-33) may play an important role in the common inflammatory mechanisms of these diseases. This study analyzed the associations of the serum IL-33 level with the occurrence and severity of periodontitis and COPD. METHODS: A total of 161 participants were divided into four groups: healthy volunteers, periodontitis patients, COPD patients, and patients with both COPD and periodontitis. Associations between serum IL-33 levels were measured by enzyme-linked immunosorbent assay, and clinical factors as well as the risks and severity of periodontitis and COPD were analyzed. RESULTS: Serum IL-33 levels were lower in all patient groups than in healthy controls. A trend toward lower IL-33 levels was observed among patients with both diseases compared with patients with either disease alone. The serum IL-33 level was also inversely associated with the severity of periodontitis and COPD. The serum IL-33 level was negatively associated with risks of periodontitis and COPD, indicating that IL-33 is likely involved in the pathophysiologic mechanism of the relationship between COPD and periodontitis. CONCLUSION: This study advances our understanding of the association between COPD and periodontitis and provides new bases for COPD prevention and treatment.
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Interleucina-33 , Periodontite , Doença Pulmonar Obstrutiva Crônica , Humanos , Doença Pulmonar Obstrutiva Crônica/sangue , Interleucina-33/sangue , Masculino , Feminino , Pessoa de Meia-Idade , Periodontite/sangue , Periodontite/complicações , Idoso , Índice de Gravidade de Doença , Adulto , Estudos de Casos e Controles , Biomarcadores/sangueRESUMO
Triterpenoid saponins, a major bioactive component of liquorice, possess high hydrophilicity and often co-occur with other impurities of similar polarity. Additionally, subtle structural differences of some triterpenoid saponins bring challenges to comprehensive characterisation. In this study, triterpenoid saponins of three Glycyrrhiza species were systematically analysed using rapid resolution liquid chromatography quadrupole time-of-flight mass spectrometry (RRLC-Q-TOF-MS) coupled with mass defect filtering (MDF). Firstly, comprehensive date acquisition was achieved using RRLC-Q-TOF-MS. Secondly, a polygonal MDF method was established by summarizing known and speculated substituents and modifications based on the core structure to rapidly screen potential triterpenoid saponins. Thirdly, based on the fragmentation patterns of reference compounds, an identification strategy for characterisation of triterpenoid saponins was proposed. The strategy divided triterpenoid saponins into three distinct classes. By this strategy, 98 triterpenoid saponins including 10 potential new ones were tentatively characterised. Finally, triterpenoid saponins of three Glycyrrhiza species were further analysed using principle component analysis (PCA) and orthogonality partial least squares discriminant analysis (OPLS-DA). Among these, 18 compounds with variable importance in projections (VIP) > 1.0 and P values < 0.05 were selected to distinguish three Glycyrrhiza species. Overall, our study provided a reference for quality control and rational use of the three species.