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关键词： Mental Health Continuum-Short Form   Subjective Vitality   Measurement Invariance   Arabic-speaking populations  

摘要： This study aimed to assess the validity of the Mental Health Continuum-Short Form (MHC-SF) as a measure of mental health among Arabic-speaking North African populations. The study had three objectives: (1) to evaluate the structural validity of the MHC-SF and the Subjective Vitality Scale (SVS);(2) to examine measurement invariance across gender and between Moroccan and Egyptian participants;and (3) to assess whether emotional, social, and psychological well-being dimensions predict subjective vitality. A total of 301 psychology students were recruited from Morocco and Egypt. Using CFA, a three-factor model for the MHC-SF demonstrated good structural validity and the SVS showed good fit, as well. Significant correlations between subjective vitality and mental health were observed, and the regression analysis revealed that mental health factors predicted subjective vitality. The findings support the use of the MHC-SF in Arabic-speaking populations and underscore the relevance of cultural context in assessing mental health.

关键词： 孟德尔随机化分析   虚弱指数   炎症介质   细胞因子   全基因组关联研究   C-X-C基序趋化因子10   成纤维细胞生长因子5   白血病抑制因子受体  

摘要： 目的 基于双样本孟德尔随机化（MR）分析来明确哪些炎症细胞因子与虚弱指数（FI）存在因果关系。方法 从8 293名芬兰血统个体的全基因组关联研究（GWAS）荟萃分析研究中获取91种炎症细胞因子遗传变异数据；FI数据集来自IEU-GWAS数据库。以逆方差加权（IVW）为核心MR分析方法，辅以MR-Egger回归、加权中位数、普通模式、增强模式进行多维度检验。用MR-PRESSO等方法评估异质性和多效性。结果 IVW分析结果显示，C-X-C基序趋化因子10（CXCL10）（OR=1.052，95% CI：1.022～1.083，P=0.001）和成纤维细胞生长因子5（FGF5）（OR=1.017，95% CI：1.006～1.029，P=0.003）与FI风险增加正相关；而白血病抑制因子受体（LIFR）（OR=0.975，95% CI：0.955～0.995，P=0.013）、肿瘤坏死因子β（TNF-β）（OR=0.987，95% CI：0.979～0.996，P=0.004）和胸腺基质淋巴细胞生成素（TSLP）（OR=0.968，95% CI：0.942～0.995，P=0.022）则与FI负相关。反向MR分析进一步表明，FI与CD40L（OR=1.273，95% CI：1.051～1.542，P=0.014）、巨噬细胞集落刺激因子1（M-CSF1）（OR=1.267，95% CI：1.013～1.586，P=0.038）、转化生长因子-α（TGF-α）（OR=1.313，95% CI：1.081～1.593，P=0.006）及肿瘤坏死因子配体超家族成员14（TNFSF14）（OR=1.402，95% CI：1.124～1.749，P=0.003）呈正相关，与Delta和Notch样表皮生长因子相关受体（DNER）（OR=0.815，95% CI：0.674～0.985，P=0.034）显著负相关。此外，CXCL10水平表现出异质性和多效性。结论 正向MR分析表明，CXCL10和FGF5是FI的危险因素，而LIFR、TNF-β及TSLP则为保护因素；反向MR分析显示，FI与CD40L、M-CSF1、TGF-α及TNFSF14呈正相关，与DNER呈负相关。本研究锁定了与FI存在因果关联的炎症细胞因子，为临床通过调控炎症细胞因子来改善和治疗虚弱提供了新的靶点和思路。

摘要： Calreticulin (CRT) is important for human leukocyte antigen (HLA) class I assembly. Somatic mutations of the CRT gene ( ) in hematopoietic lineage cells cause myeloproliferative neoplasms (MPNs). Typically, MPN patient cells have one copy each of the wild-type and mutant allele. We find that heterozygous knock-in of a MPN mutation into human cell lines maintains or slightly induces surface expression of HLA class I allotypes. However, full deficiency of wild-type CRT variably reduces the surface expression of HLA class I allotypes, and MPN CRT mutants fail to restore expression for all tested allotypes. Consistent with the largely heterozygous nature of mutations in MPN, surface HLA class I expression in platelets and monocytes from MPN patients with mutations generally falls within the normal range, with higher average expression measured in monocytes from patients treated with interferon alpha compared with other treatments. Overall, the studies indicate that loss of HLA class I expression in cells deficient in wild-type CRT (the CRT dependency) is allele-dependent and correlates with known effects of the assembly factor tapasin. Furthermore, heterozygous knock-in of a MPN-linked mutation has no effect on some allotypes and slightly induces HLA class I expression for CRT-dependent allotypes.

关键词： venous sinus stenosis   venous sinus stenting   idiopathic intracranial hypertension   headache   papilledema   BMI   body mass index   CSF   cerebrospinal fluid   ICP   intracranial pressure   IIH   idiopathic intracranial hypertension   IJV   internal jugular vein   IL   Illinois   IQR   interquartile range   IU   international unit   mg/d   milligram per day   mg/dL   milligram pro deciliter   MRI   magnetic resonance imaging   MRV   magnetic resonance venography   SD   standard deviation   SPSS   Statistical Package for Social Sciences   USA   united states of America  

摘要： Background and purpose Most patients with idiopathic intracranial hypertension (IIH) have venous sinus stenosis. In the previous decade, venous sinus stenting has emerged as an ultimate treatment for resistant or refractory cases with IIH. However, studies in this regard are relatively few, especially from lower income countries. We aimed to evaluate the feasibility and efficacy of venous sinus stenting in our tertiary center. Methods We retrospectively reviewed our prospectively collected database from January 2021 to January 2023 and recruited eligible patients with IIH and venous sinus stenosis who underwent stenting. Results We recruited 113 patients, all of them were females with a mean age of 30 ± 8 years and mean BMI of 30 ± 3.1. Stenting was technically successful in all our patients. Post stenting angioplasty was warranted in three cases (2.6%). Complications occurred in one case (0.9%) in the form of a rim of subdural hematoma without any clinical sequelae. At 3 months follow-up, 93 patients (82.3%) experienced complete relief of their symptoms, whereas 11 patients (9.7%) still had headache without papilledema and 9 patients (8%) had papilledema. Seven patients (6.2%) received ventriculoperitoneal shunting and two patients (1.8%) experienced restenosis and received another stenting procedure. Conclusions Stenting of the venous sinus stenosis in IIH patients is effective and safe treatment and can be accomplished with a very low complication rate and relatively higher success rate.

关键词： bioinformatics analysis   IL4R   immune infiltration   ovarian clear cell carcinoma  

摘要： Objective: Ovarian clear cell carcinoma (OCCC) is characterized by poor prognosis and limited early diagnostic markers. Identifying molecular distinctions between OCCC and the more common high-grade serous ovarian cancer (HGSC) is critical to developing targeted diagnostic and therapeutic strategies for improved clinical outcomes. Methods: We retrieved the mRNA expression profiles of OCCC and HGSC from the Gene Expression Omnibus (GEO) database. To identify differentially immune-related genes (DIRGs) linked to OCCC. We assessed DIRGs functional enrichment and built a protein-protein interaction (PPI) to explore DIRGs interactions. Least Absolute Shrinkage and Selection Operator (LASSO) regression model and Multiple Support Vector Machine Recursive Feature Elimination (mSVM-RFE) methods were applied to identify predictive genes. The diagnostic performance of these candidate genes was evaluated using receiver operating characteristic (ROC) curves. A nomogram was constructed to predict OCCC. We further validated key DIRGs' diagnostic ability via a validation set and immunohistochemistry (IHC). The CIBERSORT algorithm was used to analyze correlations between DIRGs and immune cell types in OCCC. Results: We detected 10 DIRGs in OCCC compared to HGSC. These genes were mainly linked to collagen-rich extracellular matrix, Phosphoinositide-3 Kinase- Protein Kinase B (PI3K-AKT) pathway, and transcriptional dysregulation in cancer. Nuclear receptor subfamily 1 group H member 4 (NR1H4) and Interleukin-4 Receptor (IL4R) emerged as potential biomarkers for OCCC (AUC(NR1H4) = 0.809;AUC(IL4R) = 0.840). In the validation cohort, AUC(NR1H4) = 0.848 and AUC(IL4R) = 0.821, respectively. IHC revealed higher expression levels of NR1H4 and IL4R in OCCC (P < 0.05). Additionally, NR1H4 correlated positively with resting memory T cells and neutrophils, while IL4R correlated with resting Natural Killer (NK) cells and neutrophils. Conclusion: NR1H4 and IL4R are promising immune-related diagnos

摘要： Clinical studies of T cells engineered with chimeric antigen receptor (CAR) targeting CD19 in B-cell malignancies have demonstrated that relapse due to target antigen (CD19) loss or limited CAR T cell persistence is a common occurrence. The possibility of such events is greater in solid tumors, which typically display more heterogeneous antigen expression patterns and are known to directly suppress effector cell proliferation and persistence. T cell engineering strategies to overcome these barriers are being explored. However, strategies to simultaneously address both antigen heterogeneity and T cell longevity, while localizing anti-tumor effects at disease sites, remain limited. In this study we explore a dual antigen targeting strategy by directing independent CARs against the solid tumor targets PSCA and MUC1. To enhance functional persistence in a tumor-localized manner, we expressed the transgenic IL-7 cytokine and receptor (IL-7Rα) in respective CAR products. We now demonstrate the potency and durable antitumor effects of this binary strategy in a pancreatic tumor model.

关键词： immunosuppression   sensitization   HLA   PRA   vascular thrombosis  

关键词： Interaction   interleukin 10   obesity   polycystic ovary syndrome   single nucleotide polymorphisms  

摘要： Objectives The pathogenesis of polycystic ovary syndrome (PCOS) was complex, and the incident PCOS involves both genetic and environmental factors. However, no study focused on the synergistic effect between interleukin 10 (IL-10) gene and obesity on PCOS risk yet. This study aimed to evaluate the correlation between IL-10 gene single nucleotide polymorphisms (SNPs) and PCOS susceptibility and impact of the interaction between IL-10 gene and obesity on PCOS risk. Methods A total of 540 participants consisted of 180 PCOS patients and 360 normal controls were enrolled in this study. Logistic regression model was employed to evaluate the association between IL-10 gene polymorphisms and PCOS susceptibility, odds ratios (ORs) and 95% confidence interval (CI) were calculated. Generalized multifactor dimensionality reduction (GMDR) was employed to screen the IL-10 gene-obesity interaction. Results Logistic regression also indicated that rs1800896-G allele was statistically significant correlated with increased risk of PCOS, the ORs (rs (95%CI) for AG, GG and AG+GG genotype was 1.75 (1.21-2.33), 1.93 (1.17-2.72) and 1.79 (1.26-2.35), respectively. However, no significant difference was observed on the distribution of genotypes and alleles within rs1800890, rs1800871, rs1800872 between PCOS patients and normal controls (all p values > 0.05). GMDR model found a significant interaction combination (two-locus model with p = 0.001) between rs1800896 and obesity, the cross-validation consistency was 10/10 and the prediction error was 0.641. Compared with those non-obese participants with rs1800896-AA genotype, OR (95% CI) was 1.62 (1.14-2.12), 1.46 (1.02-1.95) for non-obese participants with rs1800896-AG or GG genotype, obese participants with rs1800896-AA genotype, and obese participants with rs1800896-AG or GG genotype have the highest PCOS risk, OR (95% CI) = 3.58 (1.81-5.41), after covariates adjusting. Conclusions We found that rs1800896-G allele, gene-environment interactio

关键词： IL-17   inflammation   psoriatic arthritis   Th17   secukinumab   ixekizumab   bimekizumab   brodalumab  

摘要： IntroductionPsoriatic arthritis (PsA) is an immune-inflammatory disease involving skin and synovial-entheseal compartments. The understanding of IL-17 biological function has revolutionized the understanding of PsA pathogenesis and, consequently, its therapeutic *** coveredIn this review article, we have outlined the primary evidence regarding the biological functions of IL-17A in PsA, and summarized data from randomized controlled trials (RCTs) on PsA and psoriasis approved secukinumab, ixekizumab, bimekizumab, brodalumab, and emerging IL-17 *** opinionThe biologic disease-modifying antirheumatic drugs (bDMARDs), secukinumab, and ixekizumab target interleukin-17A (IL-17A), and bimekizumab, which simultaneously neutralizes IL-17A and IL-17F, have demonstrated efficacy in treating both peripheral and axial articular manifestations of PsA, as well in improving skin involvement, enthesitis and dactylitis. Brodalumab, which inhibits the IL-17 receptor A (IL-17RA), represent an efficacious strategy for *** research into the role of IL-17s in PsA pathogenesis is crucial for improving our understanding of the disease and developing more effective therapeutic strategies. Further research and advancements in biologic therapies will refine IL-17 inhibitory strategies, potentially improving outcomes for PsA patients, and other immune-mediated *** opinionThe biologic disease-modifying antirheumatic drugs (bDMARDs), secukinumab, and ixekizumab target interleukin-17A (IL-17A), and bimekizumab, which simultaneously neutralizes IL-17A and IL-17F, have demonstrated efficacy in treating both peripheral and axial articular manifestations of PsA, as well in improving skin involvement, enthesitis and dactylitis. Brodalumab, which inhibits the IL-17 receptor A (IL-17RA), represent an efficacious strategy for *** research into the role of IL-17s in PsA pathogenesis is crucial for improving our understanding of the diseas