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关键词： Periodontal disease   Menstrual cycle   Interleukin-1 beta   Interleukin-6   Tumor necrosis factor-alpha   Gingival crevicular fluid  

摘要： Purpose: Hormonal fluctuations, primarily in progesterone and estrogen during the menstrual cycle, may influence periodontal tissues, with inflammatory cytokines playing a crucial role. Therefore, our primary objective was to assess clinical periodontal parameters and measure levels of interleukin (IL)-1 beta, IL-6, and tumor necrosis factor (TNF)-alpha in gingival crevicular fluid (GCF) throughout the menstrual cycle. Methods: This longitudinal prospective study was conducted from February to April 2022 and included 50 participants. We assessed clinical periodontal parameters-plaque index (PI), gingival index (GI), pocket depth (PD), clinical attachment loss (CAL), and tooth mobility-at three stages of the menstrual cycle: menstruation day, ovulation day, and premenstrual day. Additionally, GCF samples were collected using paper points. These samples were then stored and analyzed for levels of IL-1 beta, IL-6, and TNF-alpha using enzyme-linked immunosorbent assays. Results: There were 25 participants in our study. The GI, PD, and CAL increased significantly during the menstrual cycle and were significantly higher during the premenstrual phase than in the ovulation phase (P<0.05). The levels of GCF IL-1 beta (P=0.012), IL-6 (P=0.002), and TNF-alpha (P=0.015) showed statistically significant throughout the menstrual cycle compared to baseline which was the menstrual (follicular) phase. Furthermore, the GCF levels of IL-1 beta and IL-6 reached their peak during the luteal or premenstrual phase, whereas TNF-alpha peaked during the ovulation phase. The increase in biological markers was more pronounced between the menstruation phases than the clinical periodontal markers. Conclusions: All clinical periodontal parameters, except for the PI, showed a slight increase from the follicular phase to the luteal phase, with significant differences observed between each phase. The levels of GCF IL-1 beta (P=0.012), IL-6 (P=0.002), and TNF-alpha (P=0.015) were statistically signif

关键词： biological DMARD   Safety  

关键词： Psoriasis   Psoriatic arthritis   Tumor necrosis factor-alpha   Biosimilar pharmaceuticals  

摘要： BACKGROUND: In the current landscape of psoriasis therapeutic management, despite the more recent market introduction of highly targeted molecules such as anti-interleukins, anti-tumor necrosis factor alpha (anti-TNF-a) biologic agents still play a key role, partly due to the availability of cost-effective biosimilar alternatives. Retention rate, long-term safety and effectiveness of these drugs have rarely been investigated. METHODS: We carried out a retrospective monocentric study including patients treated with biosimilar adalimumab, biosimilar etanercept, and biosimilar infliximab to assess drug survival, safety and effectiveness of these drugs over an extended period. RESULTS: A total of 93 patients were included in this study, with a median treatment duration of 86 months. Drug survival at 12 months was 91.4%, declining to <50% at 86 months. Interestingly, no significant differences were observed among the three anti-TNF-a biosimilars in terms of drug survival. The presence of psoriatic arthritis (PsA) correlated with increased drug survival. Adverse drug reactions were reported in 61.3% of patients, with infections being the most common issue. Treatment discontinuation was predominantly due to loss of efficacy. CONCLUSIONS: Despite certain limitations, such as the retrospective design and the monocentric nature of the study, our findings underscore the long-term effectiveness and safety of anti-TNF-a biosimilars in psoriasis and PsA management, emphasizing the importance of considering disease characteristics in treatment decisions.

关键词： Rare/orphan diseases   Lungs   Prognostic factors   Descriptive Studies   Observational studies/registry  

关键词： Targeted synthetic drugs   biological DMARD   Autoantibodies  

关键词： biological DMARD   omics   Targeted synthetic drugs  

摘要： Background: Previous studies on cellular immunity in rheumatoid arthritis (RA) treatment have mostly targeted synovial tissue (ST). The synovium has long been recognized as an important target organ in RA involvement joint, but it can usually be obtained during surgery and is not suitable as a routine method for disease diagnosis and evaluation of efficacy. Therefore, we have turned our attention to synovial fluid (SF), which is co-located with ST in the inflammatory environment of the joint cavity. Additionally, cytological investigations relying on traditional approaches have hampered the ability to systematically explore the damaging role of immune cells in RA at the single-cell level due to the low throughput. With the development of single-cell RNA sequencing (scRNA-seq), multiple studies have delineated the cellular transcriptional profile of different cell components of ST from RA patients [1, 2], but a complete single-cell immunoprofile of RA synovial fluid, along with its variations before and after treatment remains elusive to this day. Objectives: This study aims to construct a single-cell atlas of RA synovial fluid, explore the dynamic immunoprofiles of cell components impacted by the treatment with adalimumab/tofacitinib, and expect to screen key cell subpopulations involved in RA pathogenesis from SF. Methods: Six RA patients and three osteoarthritis (OA) patients were included. RA patients were randomized to receive either the TNF-α inhibitor adalimumab (n=3) or the JAK inhibitor tofacitinib (n=3) after enrollment. Knee SF from 6 RA patients before treatment (referred to as RA-BT) and 1 month after receiving treatment (referred to as RA-AT), as well as SF from 3 OA patients, was collected for scRNA-seq to map the single-cell immunoprofiles of RA synovial fluid. Based on scRNA-seq data, appropriate flow cytometry sorting strategies are devised. Flow cytometry was used to sort pathogenic cell subpopulations, which are subsequently co-cultured in vitro w

关键词： Innate immunity   Epitranscriptomics   epigenetics   genetics  

关键词： Cytokines and Chemokines   Biomarkers   Diagnostic test