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关键词： biological DMARD   Targeted synthetic drugs   Remission  

关键词： GRAVIT-D   IL-1 beta   Inflammation   Obesity   Pregnancy   Vitamin D3  

摘要： Background: Maternal and placental inflammatory activity is carefully regulated during pregnancy and changes in inflammatory status are associated with pregnancy complications and health deficits in the offspring including adverse effects on ***/obesity is associated with chronic inflammation, thereby contributing to adverse effects. Disturbingly, overweight and obesity are highly prevalent among pregnant women worldwide. Vitamin D (vitD) possess immunomodulatory effects and is believed to support healthy pregnancy. Endocrinological societies recommend empiric vitD supplementation in pregnancy but there is no consensus on the minimal supplementation dose Methods: An adjacent study to GRAVIT-D (no. NCT04291313, ***), a double-blinded randomized trial investigating the clinical benefits of increasing vitD supplementation in pregnancy from 400IU to 3600IU/ day from gestational week 11-16 onwards. In a subgroup, (n = 156), multiplex ELISA targeting third-semester serum levels of IL-1 beta, IL-6, IL-10, TNF alpha, MCP-1, and IL-17A was performed. Inflammation signals were correlated with the vitD dose given, subsequently analysing the effect of vitD in relation to the pre-pregnancy body mass index (BMI) within each treatment arm comparing the inflammatory response in WHO-defined BMI groups, < 25, 25-30 and > 30 kg/m(2). Main Results: High pre-pregnancy BMI was associated with increased IL6 and MCP1 in both the 400IU and the 3600 IU exposed group. IL1 beta levels increased with BMI if using a 400IU/day supplement. High dose vitD supplementation ameliorated BMI effects on IL1 beta. Conclusion and Perspectives: Increased vitD supplementation during pregnancy may ameliorate some overweight/ obesity-induced inflammatory activity. Further studies are needed to determine the vitD need in pregnancies complicated by obesity and overweight.

关键词： Real-world evidence   biological DMARD   Observational studies/ registry  

关键词： omics   Biomarkers   Anti-Inflammatory Agents   Non-Steroidal  

关键词： biological DMARD   Real-world evidence   Observational studies/registry   Quality of care   Health services research  

摘要： We read with interest the article by Kuhner LM et al, which investigated the association between plasma levels of the soluble forms of HLA-G (sHLA-G) and HLA-E with both CLAD development and HCMV viremia in a cohort of 76 lung transplant (LTx) rec...

关键词： Uveitis   Enthesitis  

关键词： POI   COCs   ovarian granulosa cells   IL-11/PI3K/AKT   apoptosis  

摘要： Background: Premature ovarian insufficiency (POI) is characterized by a reduction in primary follicle count along with abnormal follicle development. This study aims to explore the impact of combined oral contraceptives (COCs) on the apoptosis of ovarian granulosa cells, which are instrumental for follicular development, in POI and the underlying mechanisms, to provide theoretical guidance for the treatment of POI. Methods: A rat model of POI was established using tripterygium glycoside tablets. After treatment with COCs, the therapeutic effect of the animals was verified by means of hematoxylin-eosin staining, immunohistochemistry, and enzyme-linked immunosorbent assay (ELISA). Flow cytometry, cell counting kit-8 (CCK-8), quantitative polymerase chain reaction, and Western blotting were utilized to investigate the impact of COCs on granulosa cell apoptosis, as well as the function of the interleukin (IL)-11/phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway. Further experiments were also conducted to verify whether COCs could inhibit granulosa cell apoptosis through this pathway. Results: COCs treatment was effective in improving ovarian granulosa cell status, reducing luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels, and increasing estradiol levels in the POI rats (p G 0.01). IL-11 silencing promoted apoptosis in POI granulosa cells by inhibiting the PI3K/AKT pathway. COCs treatment partially reversed these effects by upregulating IL-11 expression and restoring PI3K/AKT pathway activity. This resulted in increased levels of B-cell lymphoma 2 (Bcl-2) (p G 0.05) and cytochrome P450 family 19 subfamily A member 1 (CYP19A1) (p G 0.01), while suppressing the expression of Bax and cleaved-cysteine-aspartic acid protease 3 (cleaved-caspase 3) (p G 0.001). Conclusion: Our findings demonstrated that COCs protect ovarian granulosa cells from apoptosis in rats with POI, an effect mediated through the IL-11/PI3K/AKT signaling casca

关键词： HLA typing   HLA-DQA1*06 NEW   next generation sequencing  

摘要： HLA-DQA1*06:09 differs from HLA-DQA1*06:01:01:02 by one nucleotide substitution in Exon 2, codon 23 GGC > AGC.