Clinical and Experimental Medicine最新文献

The REBECCA project taps into the potential of using real-world data (RWD) for supporting groundbreaking clinical research on complex chronic conditions as a complement to Randomised Controlled Trials. REBECCA moves beyond the analysis of clinical data from Electronic health records, by combining it with detailed monitoring data from multiple wearables, online behaviour and self-reported data to monitor patients's quality of life in terms of their functional and emotional status. The project focuses on the detection of cancer-related fatigue, developed during breast cancer recovery, using digital biomarker profiles for early detection of the disease and assessing the value of detailed and longitudinal patient monitoring as a means of improving patient care. The project also demonstrates the extensibility of REBECCA monitoring to other forms of cancer, such as prostate cancer. We describe the three clinical trials being conducted in Norway and the use of the REBECCA platform, capable of detailed monitoring and privacy preserving federated cross-country data analysis. The RWD will be analyzed in the context of data from questionnaires (Patient Reported Outcome Measures) and results from analysis of biological samples. Through this approach we expect that the REBECCA project will produce new knowledge on clinical management of cancer patients and contribute to new biological knowledge on cancer-related fatigue. Status and perspectives: The REBECCA project is ongoing, and patient follow-up will be completed during February 2026. The initial analyses of RWD, PROMs and biological samples have started together with the partners in the REBECCA consortium. The REBECCA trials are approved by the Regional Ethics Committee of the Western Health Authority (REK Vest) under the IDs 225,855 (REBECCA-1), 242,088 (REBECCA-2) and 619,903 (REBECCA-3). All trials have also been registered at clinicaltrials.gov (NCT05587777, NCT06120595 and NCT06435091). Trial registration: NCT05587777, Retrospectively registered 19th of October 2022, https://clinicaltrials.gov/study/ NCT05587777; NCT05587777, Retrospectively registered 6th of November 2023, https://clinicaltrials.gov/study/ NCT06120595; NCT05587777, Retrospectively registered 23rd of May 2024, https://clinicaltrials.gov/study/ NCT06435091.

Cytokines are pivotal regulators of immune responses and inflammation, and their dysregulation is implicated in cancer initiation and progression. A deeper understanding of cytokine-mediated modulation of tumor cell behavior may uncover novel therapeutic targets for cancer treatment.A comprehensive literature search was conducted across PubMed, Scopus, and Web of Science databases using keywords such as "cytokines," "tumor sensitization," "immune regulation," and "cancer therapy." Peer-reviewed articles published between 2002 and 2025 were evaluated and synthesized to provide an updated overview of cytokine-related therapeutic strategies.This review highlights the complex roles of key cytokines-including interleukins (IL-1, IL-6, IL-8, IL-10, IL-17), interferons (types I and II), tumor necrosis factor-α (TNF-α), and transforming growth factor-β (TGF-β)-in modulating tumor cell susceptibility to therapeutic interventions. While cytokines exhibit both tumor-promoting and tumor-suppressive properties, recent advances in cytokine engineering, targeted delivery systems, and combination immunotherapies have enhanced their clinical potential.Integrating cytokine modulation into oncology may improve personalized immunotherapy outcomes.

Female-related cancers, including breast, ovarian, endometrial, and cervical malignancies, are among the most prevalent and clinically significant health challenges worldwide. Their development involves a complex interplay of genetic mutations, environmental factors, lifestyle influences, and therapeutic interventions. Long non-coding RNAs (lncRNAs) have emerged as critical regulators in these cancers, modulating epigenetic mechanisms, transcriptional programs, and post-transcriptional processes. Aberrant lncRNA expression promotes tumor initiation, drives progression and metastasis, and facilitates epithelial-mesenchymal transition (EMT) and angiogenesis. Among these, colon cancer-associated transcript 2 (CCAT2) has been identified as an oncogenic lncRNA across multiple tumor types. CCAT2 primarily activates the Wnt/β-catenin signaling pathway, enhancing β-catenin transcriptional activity and upregulating downstream targets such as MYC and cyclin D1, which are essential for cancer cell proliferation and survival. Despite growing evidence of its oncogenic role, the specific contribution of CCAT2 to female-related cancers remains incompletely understood. This study systematically reviews recent findings on CCAT2's role in the development and progression of breast, ovarian, endometrial, and cervical cancers, elucidates the underlying molecular mechanisms, and evaluates its potential as a diagnostic and prognostic biomarker. Furthermore, the translational potential of CCAT2 as a therapeutic target is discussed, highlighting opportunities for improving clinical outcomes in these malignancies.

Systemic inflammation and hypercoagulability are two major characteristics of rheumatoid arthritis (RA), both contributing to atherosclerosis development. This study aims to evaluate their joint and mutual associations with early atherosclerosis risk in RA patients via the systemic inflammation response index (SIRI) and thromboelastography maximum amplitude (TEG-MA). The study encompassed 335 RA patients who fulfilled the specified inclusion criteria. Logistic regression assessed SIRI, TEG-MA, and their combined link to early atherosclerosis risk. Both multiplicative and additive interactions were evaluated, and a bidirectional mediation model explored their reciprocal impacts on early atherosclerosis. After full confounder adjustment, SIRI and TEG-MA both showed significant positive links to early atherosclerosis risk, whether analyzed as continuous or categorical variables (P < 0.05). In joint analyses, RA patients with both high SIRI and TEG-MA had a 10.06-fold higher risk than those with low levels of both (odds ratio [OR]: 10.06, 95% confidence interval [CI]: 3.75-25.90). SIRI and TEG-MA showed notable additive interaction in affecting atherosclerosis risk, with relative excess risk of interaction (RERI) at 4.03 (95% CI: 1.25-9.36), attributable proportion of interaction (API) at 0.42 (95% CI: 0.03-0.79), and synergy index (SI) at 1.73 (95% CI: 1.03-2.96). No significant multiplicative interaction was detected (P > 0.05). Mutual mediation analysis showed SIRI mediated 40.6% of TEG-MA's effect, while TEG-MA mediated 27.6% of SIRI's effect on atherosclerosis risk. These results suggest that there is an intertwined and mutually reinforcing relationship between inflammation and hypercoagulability in the occurrence and progression of atherosclerosis in RA.

Aplastic anaemia (AA) is a disease that shows complex pathogenesis involving multiple immune factors. While immunosuppressive therapies such as cyclosporine can effectively control AA, they may be ineffective in certain patients or those with relapse. Therefore, new treatments are needed. Among the targets for these treatments, the Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway regulates inflammatory cytokines and immune activation. Ruxolitinib, a JAK1/2 inhibitor, reduces T-cell activation and the associated inflammatory response and improves AA disease status in mice. However, its mechanism of action is unclear; thus, further research is needed before its clinical use. We previously showed increased pyroptosis in patients with severe AA (SAA) and that macrophage pyroptosis is an important factor in immune activation. The current study investigated the interaction of ruxolitinib with macrophages and whether the drug could treat SAA by improving pyroptosis levels. We induced differentiation of the THP-1 human monocyte cell line into macrophages in vitro and then induced pyroptosis. After constructing a macrophage pyroptosis model, treatment with different concentrations of ruxolitinib was administered. The results showed that ruxolitinib reduced the levels of pyroptosis and inflammatory-related factors. We then used the SAA mouse model to validate this conclusion. In conclusion, ruxolitinib may affect SAA by reducing the level of macrophage pyroptosis.

The pathological process of rheumatoid arthritis is not only driven by immune inflammation but is more profoundly shaped by abnormal remodeling of the extracellular matrix. This study systematically reviews the core manifestations of abnormal extracellular matrix remodeling in RA: matrix sclerosis, excessive degradation mediated by matrix metalloproteinase/a disintegrin and metalloproteinase with thrombospondin motifs, and degradation fragments as damage-associated molecular patterns activating the TLR4/RAGE pathway, thereby forming a self-perpetuating vicious cycle of "sclerosis-degradation-inflammation amplification-resclerosis," significantly exacerbating inflammatory reactions and joint damage. It proposes a dual framework of "mechanism loop-clinical loop," emphasizing the integration of the biomarkers C1M, C3M, COMP, HA, and other ECM-degradation fragments for dynamic disease monitoring, progression prediction, and precise efficacy evaluation. By combining biomarker panels with imaging data, it is expected to optimize the stratification of high-risk populations and individualized treatment adjustments, which may enhance the precision of diagnostic and therapeutic strategies and provide a new direction for RA to progress from inflammation control to structural protection.

Although prior research has established sex and menopausal status-based differences in immune response, susceptibility, and severity to a variety of pathogens, their relevance in early Lyme disease is understudied. We examined the clinical and serologic presentation of patients with early Lyme disease, stratified first by sex then by menopausal status. We also explored the hypothesis that males would present with more severe early Lyme disease. In this prospective cohort study from the Mid-Atlantic US, 243 adult, antibiotic-naïve patients were enrolled with a diagnostic erythema migrans rash present. Demographic, physical exam, symptom, laboratory, and two-tier serology data were collected at a baseline, and a post-treatment visit 3 weeks later. Lyme disease severity was operationalized through six indicators: rash size, number of acute symptoms, dermatologic dissemination, positive serology, liver function elevation, and elevated neutrophil-lymphocyte ratio. Unadjusted group comparisons and multivariate regression adjusting for potential confounders were used to assess difference. In logistic models adjusted for age, Lyme disease duration, systemic steroid use, and co-morbid thyroid disease, males had higher odds of testing two-tier positive (OR = 1.77 [1.03, 3.04], p = 0.039). This difference was more pronounced between males and pre-menopausal females (OR = 2.93 [1.26-6.79], p = 0.012) and no significant difference was found comparing males to post-menopausal females. In ordinal logistic models with Lyme disease severity as the outcome adjusted for age and Lyme disease duration, males had higher odds of being in a higher disease severity score category (OR = 1.94 [1.20,3.15], p = 0.028); again, particularly in comparison to pre-menopausal females (OR = 2.26 [1.13,4.58], p = 0.044). Heart palpitations (p = 0.023), vomiting (p = 0.007), and photophobia (p = 0.057) trended towards higher reporting among females, while sleep difficulty (p = 0.010) was higher among males. No differences were found on non-dermatologic components of the physical exam. We found sex and menopausal status to be relevant in accounting for variability in two-tier serologic status and severity of early Lyme disease in a well-characterized group of patients. Lower rates of seroreactivity among females is unexpected but may be consistent with lower acute severity of disease. Our clinical findings underscore the need for additional research to understand possible contributing biologic and/or social behavioral factors, as well as their impact on timely diagnosis and post-treatment conditions.

Whipple's disease is a sporadic infectious condition, with an incidence rate of approximately 1 per million individuals. The causative agent is the gram-positive bacterium Tropheryma whipplei. The disease manifests with a wide range of clinical symptoms, including non-specific presentations such as diarrhea, arthralgia, and fever, as well as the more pathognomonic lipodystrophy. This diversity in presentation poses a significant diagnostic challenge even for experienced clinicians. Our review aims to provide an updated overview encompassing the latest insights into Whipple's disease, focusing on epidemiology, pathophysiology, genetic predisposition, clinical manifestations, diagnosis, immune reconstitution inflammatory syndrome, and treatment. Herein, we have additionally explored many of the confounding factors in the diagnosis and management of Whipple's disease, including the variable presentations among patients colonized by Trophyrema whipplei as well as the limitations of current treatment options, and underscore the need for further research and guidelines related to this complex disease process.