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关键词： gastric cancer   esophageal cancer   immune checkpoint inhibitor   interleukin-6   immune-related adverse events   prognosis  

摘要： Purpose Immune checkpoint inhibitors (ICIs) significantly prolong the survival of cancer patients. including gastric adenocarcinoma (GAC) and esophageal squamous cell carcinoma (ESCC) patients. Immune-related adverse events (irAEs) are inevitably involved in ICIs treatment sometimes with severe consequences. Extreme caution is necessary for predicting irAEs and precisely screening of appropriate patients. We evaluated the association of interleukin-6 (IL-6) with irAEs and their impacts on ICIs treatment effectiveness in advanced GAC and ESCC *** This retrospective study analyzed 121 patients treated with ICIs between March 1, 2020 and August 31, 2023 to evaluate the association between serum IL-6 and ICIs treatment effectiveness. The occurrence of irAEs, including grade and category, and effectiveness of immunotherapy, including objective remission rate (ORR), disease control rate (DCR), progression-free survival (PFS) and overall survival (OS), was evaluated. Categorical count data were tested by chi-square test. Nonparametric rank sum tests were performed using Wilcoxon and Kruskal-Wallis test. Survival rate estimation and survival curves were generated using Kaplan-Meier curve and Log-rank test. Univariate and multivariable COX regression analyses were performed to identify independent prognostic *** A total of 121 patients including 79 with GAC and 42 with ESCC patients were randomly divided into TC (n=81) and VC (n=40) groups. Higher serum IL-6 levels were associated with increased incidence of irAEs, the outcome analysis also indicated its association with lower DCR, shorter PFS and shorter OS in TC group. The higher IL-6 related irAEs occurrence and poor prognosis (DCR, PFS) was confirmed in the VC group. Individual tumor analysis showed that higher IL-6 was associated with both irAEs occurrence and poor prognosis (DCR, PFS, OS) in ESCC patients, and with irAEs occurrence and poor prognosis (DCR, PFS) in GAC patients. No statistically

关键词： Chronic lymphocytic leukemia   Type 2 innate lymphoid cells (ILC2s)   IL-9   Regulatory T cells (Treg)   CD8(+) T cells  

摘要： Objective This study investigated the impact of innate lymphoid cell type 2 (ILC2s) on the function of regulatory T cells (Treg) and CD8(+) T cells in chronic lymphocytic leukemia (CLL) through IL-9. Methods Peripheral blood samples were collected from CLL patients (n = 52) and healthy controls (n = 30). ILC2 proportions and IL-9 levels were assessed using flow cytometry and ELISA. Immunofluorescence staining was performed to stain GATA3, CRTH2, and IL-9 in cervical lymph nodes from CLL patients (n = 10) and control subjects with reactive lymphadenitis (n = 10). Correlation analysis between ILC2s and IL-9 was conducted using the Spearman test. ILC2s were sorted and cultured from CLL patients, followed by co-culture experiments with PBMCs of healthy controls and MEC-1 cells, with or without anti-IL-9 antibody intervention. Flow cytometry was used to measure the proportions of ILC2s, Treg cells, PD-1(+)/TIGIT(+)/CTLA-4(+) Treg subsets, and granzyme B+/perforin(+) CD8(+) T cells, along with MEC-1 cell apoptosis. Results The proportions of ILC2s and Treg, along with serum IL-9 levels, were significantly elevated in CLL patients (P < 0.05). Peripheral blood ILC2s were positively correlated with IL-9 (r = 0.609, P < 0.001). The average fluorescence intensity of GATA3, CRTH2, and IL-9 in the cervical lymph nodes of CLL patients increased significantly (P < 0.001), and IL-9 showed colocalization with GATA3 and CRTH2. In vitro, IL-9 levels in the supernatant of sorted ILC2s from CLL patients increased. Treatment with anti-IL-9 antibody significantly reduced the PD-1(+) Treg and TIGIT(+) Treg cells while increasing granzyme B+ CD8(+) T cells (P < 0.05). However, there was no significant effect on Treg, CTLA-4(+) Treg, and perforin(+) CD8(+) T cells (P > 0.05). Additionally, anti-IL-9 antibody significantly increased early apoptosis (P < 0.05). Conclusion ILC2s affect CD8(+) T cells and Treg cells through IL-9, weakening the anti-tumor effects of CD8(+) T cells and enhancing t

关键词： psoriasis   hand eczema   palmoplantar   tape stripping   endotype   overlap dermatitis  

关键词： Atopic dermatitis   Clonal mesenchymal stem cell   Galectin-9   IFN-alpha   Priming   Vitamin B6  

摘要： Background Mesenchymal stem cells (MSCs) possess a variety of immunomodulatory functions that can vary depending on the MSC line. Investigating priming strategies is essential for increasing the immunomodulatory potential of MSCs. Methods Human clonal MSCs (cMSCs) were primed with TNF-alpha, IFN-gamma, IL-1 beta, IFN-alpha, and vitamin B6. Their immunomodulatory functions, including T-cell proliferation and cytokine production, were analyzed. The primed cMSCs were injected intravenously into a mouse model of ovalbumin-induced atopic dermatitis (AD), and their therapeutic effects were evaluated. Results We identified IFN-alpha and vitamin B6 as promising priming agents when they are combined with TNF-alpha and IFN-gamma. The primed cMSCs showed expression of galectin-9 (Gal-9), IL-1Ra, and PDL-1. Gal-9 facilitates the induction of regulatory T cells (Tregs) and apoptosis. Treatment with primed cMSCs significantly alleviated pathological changes in an AD mouse model. Notable improvements included a reduction in epidermal thickness (p < 0.05), a decreased number of mast cells and eosinophils in the dermis (p < 0.01), restored expression of claudin-1 in the epidermis (p < 0.0001), and lower serum levels of IgE (p < 0.05). Conclusions This novel combination of priming factors significantly promotes the immunomodulatory functions of cMSCs by inducing Gal-9. Consequently, Gal-9 may serve as an excellent biomarker for screening primed cMSCs for their immunomodulatory capabilities, facilitating a more accurate assessment of their therapeutic effectiveness.

关键词： Interleukin-11 receptor alpha ( (IL11RA (IL11RA   methylation   prognostic biomarker   immune infiltration   lung adenocarcinoma (LUAD)  

摘要： Background: Interleukin-11 receptor alpha (IL11RA) involves in numerous biological processes of malignant tumor. Nevertheless, the precise role of IL11RA in lung adenocarcinoma (LUAD) remains unknown. This research aimed to elucidate the differential expression, methylation, prognosis significance and immune infiltration of IL11RA in LUAD. Methods: Using the University of Alabama at Birmingham Cancer Data Analysis Portal (UALCAN), Profiling Interactive Analysis (GEPIA), and Human Protein Atlas (HPA) databases, the varied expression of IL11RA in LUAD was confirmed. The level of IL11RA methylation was investigated by UALCAN database. Spearman method was utilized to analyze the relevance between IL11RA expression and its methylation. The prognostic significance of IL11RA methylation was assessed using the Kaplan-Meier method. Furthermore, a meta-analysis based on TCGA and GEO databases was executed to judge the prognostic significance of IL11RA in LUAD. Immune infiltration was evaluated by Gene set enrichment analysis (GSEA) analysis, single-sample gene set enrichment analysis (ssGSEA) analysis and Tumor Immune Estimation Resource Results: Our research demonstrated that IL11RA expression was markedly diminished in LUAD. The low expression of IL11RA was tightly linked with stage, T stage, N stage and cancer status. IL11RA gene was inversely regulated by hypermethylation, resulting in its low expression in LUAD. The hypermethylation of IL11RA implied poor prognosis in LUAD. Moreover, a meta-analysis of 2,964 LUAD patients from 23 studies demonstrated that low IL11RA expression was positively associated with dismal overall survival (OS). Subsequently, we demonstrated that low expression of IL11RA was closely linked to diverse immune cells, Conclusions: Our work demonstrates that IL11RA might be an underlying prognostic biomarker and an innovative molecular therapeutic target for individuals with LUAD.

关键词： 柳氮磺吡啶肠溶片   药物超敏反应综合征   肝功能损害   皮疹   淋巴结肿大   药品不良反应  

摘要： 目的 探究柳氮磺吡啶肠溶片致药物超敏反应综合征的病例，为临床安全用药提供参考。方法 分析1例结肠炎患者服用柳氮磺吡啶肠溶片致药物超敏反应综合征的病例，探讨药物超敏反应综合征的可能机制、临床表现和防治措施。结果 患者使用柳氮磺吡啶肠溶片治疗1个月，出现肝功能损害、全身多发散在皮疹、多发淋巴结肿大、外周血异型淋巴细胞明显升高，考虑为柳氮磺吡啶肠溶片致药物超敏反应综合征为“很可能”，给予糖皮质激素、肿瘤坏死因子α抑制剂、护肝、抗过敏等治疗后，病情好转。结论 药物超敏反应综合征是柳氮磺吡啶的罕见不良反应，潜伏期长，临床表现多样，使用柳氮磺吡啶后若出现肝功能异常、皮疹、淋巴结肿大、血液学检查异常等应高度警惕药物超敏反应综合征的发生。

关键词： acute lymphoid leukemia   children   HLA-A   HLA-B   DRB1   DQB1   Morocco  

摘要： Leukemia constitutes approximately one-third of all pediatric cancers, with acute lymphoblastic leukemia (ALL) comprising roughly 80% of pediatric leukemia instances. This study sought to ascertain the prevalence of HLA A, B, DR, and DQ allele groups linked with pediatric acute leukemia. We recruited 70 Moroccan children diagnosed with acute lymphoblastic leukemia (ALL), 39 of whom had BCP-ALL and were eligible for hematopoietic stem cell transplantation, compared to a control group of 136 healthy children. Patients and controls were subjected to HLA class I and II typing, utilizing either sequence-specific primers (SSPs) or sequence-specific oligonucleotides (SSOs) in polymerase chain reaction-based techniques. The findings indicated significantly elevated frequencies of HLA-A*68 and B*14 in pediatric patients with ALL relative to the control group (p = 0.001 and p = 0.02, respectively). The frequencies of HLA-DRB1*01 and DQB1*05 allele groups were considerably elevated in children with ALL and BCP-ALL compared to the controls (p < 0.01 for both). The findings of our study indicate that HLA-A*68, -B*14, -DRB1*01, and DQB1*05 may serve as potential predisposing immunogenetic variables for the development of juvenile acute lymphoblastic leukemia (ALL). Nonetheless, additional research including a bigger sample considering other regions of Morocco would be beneficial to more accurately delineate the association between the HLA system and ALL.

摘要： CD4+ T cells are indispensable for optimal immunity to Mycobacterium tuberculosis (***), a pathogen that triggers tuberculosis (TB) in humans. ***-specific human CD4+ T cells are known to polarize toward an interferon-gamma (IFN-gamma)-producing, CCR4-CCR6+CXCR3+T-bet+ROR gamma T+ T helper 1* cell (TH1*cell) memory phenotype. We report that autosomal recessive deficiency of the human lymphocytic surface receptor LY9 (SLAMF3 and CD229), which is found in less than 10-5 individuals in the general population, underlies TB in three unrelated patients due to selective impairment in IFN-gamma production by TH1* cells. TH1* cells express higher levels of LY9 than other CD4+ T cells. Mechanistically, LY9 polarizes na & iuml;ve CD4+ T cells toward memory TH1* cells by inducing T-bet via signaling lymphocytic activation molecule (SLAM)-associated protein (SAP) and ROR gamma T (thymus-specific retinoid-related orphan receptor gamma) without SAP. LY9 costimulation enhances TCR-driven IFN-gamma production of memory TH1*, but not TH1, cells in a T cell-intrinsic manner via NFAT1 (nuclear factor of activated T cells 1) and ROR gamma T. LY9 is likely to govern an optimal TH1* cell- and IFN-gamma-dependent protective immunity to *** in humans.

关键词： CircRNA-DLGAP4   interleukin 6   rheumatoid arthritis   DAS28  

摘要： Rheumatoid arthritis (RA) as a systemic autoimmune disease is often misdiagnosed in its early stages due to vague symptoms, delaying treatment and increasing the likelihood of severe complications including cardiovascular mortality. The main aim of this work is to evaluate the serum levels of interleukin 6 (IL-6) and circular RNA DLGAP4 (circRNA-DLGAP4) in RA patients and healthy controls, also analyzing the correlations between all biomarkers to indicate whether those can be used as predictors for early diagnoses of RA. One hundred subjects were included, they were divided into two equal groups, 50-healthy matched individuals and 50 RA patients. For all participants, a venous blood sample for serum isolation was taken and analyzed for the serum level of IL-6 and circRNA-DLGAP4 as well as laboratory tests. For all patients, full clinical investigations have been performed as well as Disease Activity Score (DAS28) and modified Larsen radiological scoring have been calculated. Results revealed that there was a significant up-regulation of the concentration level of IL-6 (p = 0.0001) and circRNA-DLGAP4 expression (p = 0.0001) in the RA group as compared to healthy controls. Moreover, altered expression of circRNA-DLGAP4 showed a slight significant difference between patients with positive deformities with p = 0.05. Serum levels of both IL-6 and circRNA-DLGAP4 increased with the severity of RA. Various correlations were detected of both IL-6 and circRNA-DLGAP4 with the associated RA parameters. It can be concluded that IL-6 and circRNA-DLGAP4 could have a potential role in RA pathogenesis and could act as possible biomarkers of RA for further studies to be applied for RA diagnostic purposes.

关键词： Beclin1   duck Tembusu virus   ILF2   IRF7  

摘要： Interleukin enhancer-binding factor 2 (ILF2) has been reported to act as either a positive or negative regulator of viral infection by directly affecting viral RNA replication. In this study, mallard ILF2 was found to impair type I IFN production, thereby facilitating the replication of duck Tembusu virus (DTMUV). The overexpression of ILF2 in duck embryo fibroblast (DEF) cells resulted in suppression of polyI: C- and DTMUV-induced production of three type I interferons (IFNs), IFN-alpha, IFN-beta, IFN-kappa-like, whereas the knockdown of ILF2 expression in DEF cells enhanced type I IFN production and inhibited DTMUV infection. It is also found that the zinc finger-related domain (DZF) of ILF2 interacts with the IRF association domain (IAD) of IRF7, and ILF2 may cause autophagic degradation of IRF7 at the protein level. Furthermore, ILF2 was found to interact also with Beclin1, and Beclin1 is necessary for ILF2-induced IRF7 degradation as ILF2-induced IRF7 degradation was significantly restored after knockdown of Beclin1. These results provide obvious evidence that ILF2 recruits Beclin1 to degrade IRF7, resulting in the suppression of type I IFN production in DEF cells.