Journal of investigative medicine : the official publication of the American Federation for Clinical Research
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NKG2D chimeric antigen receptor (CAR)-modified T cells (NKG2D CAR-T cells) have been reported to be preclinically efficient in several tumors, but little is known whether NKG2D CAR-T cells co-expressing IL21 (IL21-NKG2D CAR-T cells) display greater antitumor activity in multiple myeloma (MM). In this study, the lentivirus has been produced for expression of the IL21 sequence linked to the extracellular NKG2D sequence with the signal peptide linked through the CD8α hinge-transmembrane domain to the 4-1BB molecule fused with the CD3-ζ chain signaling domain, and the engineered IL21-NKG2D CAR-T cells and NKG2D CAR-T cells were constructed. The CAR expression on CAR-T cells was assessed by flow cytometry, and the killing effects of CAR-T cells on MM were assessed by the cytotoxicity assay and ELISA assay. ⋯ Remarkably, we found that dexamethasone enhanced the cytotoxicity of IL21-NKG2D CAR-T cells on MM cells. Furthermore, IL21-NKG2D CAR-T cells also displayed significant anti-myeloma activity in vivo. In conclusion, IL21-NKG2D CAR-T cells had dramatic cytotoxicity on MM cells in vitro and in vivo, and a system to apply IL21-NKG2D CAR-T cells and low dosage of dexamethasone for the future study of the targeted therapy for MM has been established.
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Translational research moves scientific discoveries and innovations across the development spectrum for a particular target or disease, trying to bridge in a multidisciplinary fashion the gap between laboratory scientific discoveries and practical, real-world applications in medicine and in healthcare. Translational research aims to move research findings across settings, specific languages, methodologies, and study designs, from laboratory to clinical practice and ultimately into community- and population-level health benefits. In contrast, translational science is a distinct field, which evolved over time toward a systematic study and practice of operationalizing the translation of content from one language, ecosystem, environment, contextual landscape, culture, discipline, area, or domain into another. ⋯ Translational science often uses knowledge, operational frameworks, and specific capabilities borrowed from other specialties, disciplines, and fields such as operations management, implementation and dissemination science, quality improvement and management, project management, public health, intervention science, change management and leadership, decision science, design thinking, functional design, data science, communication and marketing science, etc. The main goal of this article is to open a series of thematic reviews in this journal, introducing the reader to the main definitions, contingencies, touchpoints, and overlapping areas between translational science and these related specialties, disciplines, and fields of study. Transdisciplinary capabilities borrowing from these related specialties can create a robust translational science machinery for health systems, research organizations, and innovation hubs.
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To investigate the impact of vaccines on sociodemographic characteristics, clinical profiles, and outcomes of SARS-CoV-2 infection among healthcare workers in South China during the period of Omicron variant dominance, a retrospective, analytical cross-sectional study was conducted. The findings revealed that while full vaccination could not prevent Omicron variant infection efficiently (26.51% uninfected vs 14.29% uninfected between vaccinated and unvaccinated participants, p = 0.506), it did substantially reduce the length of viral clearance significantly (p < 0.05), potentially facilitating quicker patient recovery. Unvaccination was found to be an independent risk factor for slow clearance when a linear regression analysis model was used (Coefficient: -3.516; 95% CI: -6.425 to -0.607; p = 0.020). Therefore, all eligible individuals should be fully vaccinated to get prepared for a potential wave of epidemic in the future.
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Immunothrombosis has emerged as a potential mechanistic link underlying the development and progression of acute respiratory distress syndrome (ARDS), but understanding its specific profile in patients, both locally and systemically, is limited. The objective of this study was to characterize and compare the immunothrombotic signatures in patients diagnosed with pneumonia-related ARDS (p-ARDS) at both the pulmonary and systemic levels and to evaluate their clinical relevance. The study included 23 consecutive patients diagnosed with p-ARDS admitted to the intensive care unit at a tertiary university hospital from July 2022 to May 2023, alongside 40 concurrently hospitalized patients with common pneumonia as controls. ⋯ These observations were maintained after adjustment for severity of illness (Acute Physiology and Chronic Health Evaluation II scores). In terms of clinical relevance, inflammatory biomarkers (interleukin [IL]-6, IL-8) in BALF were found to correlate with PaO2/FiO2 ratio, while serum levels of a disintegrin and metalloproteinase with thrombospondin type 1 motif 13 (ADAMTS-13) and thrombomodulin showed associations with Sequential Organ Failure Assessment and Disseminated Intravascular Coagulation scores. In conclusion, this preliminary investigation identified compartment-specific variations in the immunothrombotic signature between patients with p-ARDS and those with pneumonia alone, with inflammatory responses predominantly localized in the alveolar compartments and coagulation/endothelial injury biomarkers more pronounced in peripheral blood.
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The current study was conducted aimed at exploring the clinical characteristics and distinguishing factors of patients with the novel coronavirus pneumonia (COVID-19) complicated with active pulmonary tuberculosis. A total of 354 patients with COVID-19 in our hospital from November 2022 to February 2023 were included in the present study, of whom 87 patients were also combined with active pulmonary tuberculosis. Significant differences were found in fever, fatigue, nasal congestion, nasal discharge, sore throat, expectoration, and weight loss between the two groups (p < 0.05). ⋯ There were significant differences in pulmonary consolidation, multifocal ground-glass opacities in both lungs and infiltrating shadows, "cavity" by CT imaging between the two groups (p < 0.05). The independent variables were set as the indicators with different results of clinical characteristics and CT imaging, including fever, fatigue, nasal congestion, nasal discharge, sore throat, expectoration, weight loss, leukocytes, count neutrophils and lymphocytes, monocytes, hemoglobin, C-reactive protein, CD4/CD8, pulmonary consolidation, multifocal ground-glass opacities in both lungs and infiltration shadows. Our findings have revealed that fever, fatigue, expectoration, leukocytes, neutrophils, monocytes, hemoglobin, C-reactive protein, lymphocytes, CD4/CD8, pulmonary consolidation, multifocal ground-glass opacities in both lungs, and infiltration shadows were the risk factors responsible for the patients with COVID-19 complicated with active pulmonary tuberculosis.