Clinical and Investigative Medicine最新文献

Background: Radiation-induced lung injury (RILI) is a significant adverse effect of thoracic radiotherapy, potentially impacting patient prognosis. The risk factors for acute radiation pneumonitis (RP) have not been fully clarified. The present study evaluated the predictive value of serum interleukins (ILs) in the occurrence of RP and overall survival in patients with thoracic cancers.

Methods: This single-centre retrospective observational study enrolled 435 thoracic cancer patients who underwent chest radiation therapy. Serum levels of IL-1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12p70, IL-17, TNF-α, IFN-γ, IFN-α were measured by cytometric bead array before radiotherapy. The relationship between clinical characteristics, serum IL levels and the occurrence of RP were analyzed. Cox regression and Kaplan-Meier methods were also performed to investigate the prognostic role of serum IL levels in these patients.

Results: The incidence of RP in these patients was 17.01%. Elevated serum levels of IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, TNF-α, IFN-α were all associated with the occurrence of RP. High levels of IL-1β, IL-4, and IL-12p70 were correlated with more severe pneumonitis. Univariate and multivariate logistic regression analysis identified serum IL-6 level as an independent prognostic factor in patients receiving thoracic radiotherapy.

Conclusions: Serum interleukin levels are linked to the development of acute RP in patients receiving thoracic radiotherapy. Serum IL-6 could serve as a valuable biomarker in identifying patients at high risk for RP, potentially guiding individualized therapeutic strategies and improving patient management in radiotherapy. Future research should focus on validating IL-6's role in larger cohorts and exploring its integration into clinical practice for the early prediction of RILI.

Purpose: To investigate the detection rate of latent autoimmune diabetes in adults (LADA) among newly diagnosed type 2 diabetes mellitus (T2DM) patients and analyze their clinical characteristics, with the aim of guiding treatment and improving prognosis.

Methods: Glutamic acid decarboxylase autoantibody (GADA), islet cell autoantibody (ICA), insulin autoantibody (IAA), blood pressure, height, weight, and BMI, as well as lipid profiles, fasting plasma glucose, insulin, C-peptide, HbA_1c, thyroid-stimulating hormone (TSH), thyroglobulin antibody (TGAb), and thyroid peroxidase antibody (TPOAb) levels were measured in 352 newly diagnosed T2DM patients with disease duration of less than 1 year and non-ketotic onset. The incidence of LADA was calculated, and clinical characteristics of these patients were compared with those of T2DM patients without autoantibodies.

Results: The detection rate of LADA was 7.10%. Among the 25 LADA patients, 22 had GADA, 5 had ICA, 2 had IAA, and 2 were positive for all three antibodies. The percentages of GADA, ICA, and IAA among LADA patients were 88.00%, 20.00%, and 8.00%, respectively. Compared with the autoantibody-negative group, LADA patients had lower BMIs and total cholesterol, lower insulin and C-peptide levels, higher neutrophil counts, and increased abnormal TSH levels and TPOAb positivity (P < 0.05). LADA patients exhibited reduced CD4⁺ T cell expression levels, which were lower than those in patients without autoantibodies, while LADA patients' CD8⁺ T cell levels were within the normal range and slightly higher than those in patients without autoantibodies, reflecting a lower CD4⁺/CD8⁺ ratio in LADA patients.

Conclusion: A proportion of newly diagnosed T2DM patients have LADA. Early screening for GADA, ICA, and IAA should be performed in newly diagnosed T2DM patients with low BMI and poor islet function. LADA patients may have higher expression of inflammatory immune factors, lower total cholesterol, and a lower CD4⁺/CD8⁺ ratio. The decline in [Formula: see text]-cell function in LADA patients may be associated with decreased CD4⁺ T cell expression.

The 2024 Annual Joint Meeting (AJM) and Young Investigators' Forum of the Canadian Society for Clinical Investigation (CSCI) and Clinician Investigator Trainee Association of Canada (CITAC) was held on April 11, 2024, in Vancouver, British Columbia. Hosted in collaboration with the University of British Columbia (UBC) and the International Congress on Academic Medicine (ICAM), this meeting marked a significant opportunity for clinician investigator trainees to present their research and connect with national and international peers. The event included 70 trainees, consisting of 58 MD+ (MD/PhD, MD and PhD, MD-MSc, MD and MSc) and 12 Clinician Investigator Program and/or Surgeon-Scientist Training Program trainees. The keynote speaker, Dr. Marco Marra, delivered a presentation titled "From C. elegans Genetics to Precision Cancer Genomic Medicine, via the Human Genome Project: Reflections on a Collaborative Scientific Journey." Dr. Kenneth Rockwood (Dalhousie University) received the CSCI Distinguished Scientist Award, and Dr. Bertrand Routy (Université de Montréal) received the CSCI Joe Doupe Young Investigator Award. Over 60 abstracts were showcased, most of which are summarized in this review, and six were selected for oral presentations. Following the AJM, trainees participated in ICAM's three-day health research program, where three AJM attendees were recognized among the top four presenters and were invited to the 2024 Canada Gairdner Awards Gala, with one of our AJM attendees winning the competition and being named the next Lindau Nobel Laurate Meetings Nominee.

Introduction: Ischemic stroke (IS) is a global health concern, often tied to dyslipidemia and vascular endothelial dysfunction. MicroRNA-34a (miR-34a) was reported to be up-regulated in the blood samples of patients with IS, but the specific role of miR-34a and methylenetetrahydrofolate reductase (MTHFR) in IS remains to be elucidated.

Methods: We studied 143 subjects: 71 IS patients, and 72 healthy controls. Human umbilical vein endothelial cells (HUVECs) were cultured and transfected with a miR-34a mimic, inhibitor, or negative control. The miR-34a expression in serum and HUVECs was quantified via quantitative reverse transcription polymerase chain reaction (qRT-PCR). Viability and apoptosis of HUVECs were assessed using CCK-8 assay and flow cytometry. The expression levels of bcl-2, bax, cyt-c, cleaved caspase 3, MTHFR, and homocysteine were measured by Western blot or enzyme-linked immunosorbent assay (ELISA). The relationship between miR-34a and MTHFR was verified by luciferase reporter assay. The levels of MTHFR and homocysteine in serum were examined by ELISA.

Results: MiR-34a expression was increased in IS patients and inhibited viability of HUVECs while promoting their apoptosis. Overexpression of miR-34a up-regulated pro-apoptotic proteins (bax, cyt-c and cleaved caspase 3) and down-regulated anti-apoptotic protein bcl-2 in HUVECs. MTHFR was identified as the downstream target of miR-34a and its expression was reduced by miR-34a overexpression, while homocysteine levels increased. Consistently, MTHFR levels were lower and homocysteine levels were higher in IS patients compared with controls.

Discussion: Our results suggest that up-regulated miR-34a plays a role in the pathogenesis of IS, potentially through inhibiting MTHFR expression and increasing homocysteine in endothelial cells. Therefore, miR-34a might be a therapeutic target for IS.

Purpose: This study aimed to establish a CT imaging grading system and explore its value in evaluating upper urinary tract calculi associated with kidney infections.

Methods: CT images of 126 patients with kidney infections caused by upper urinary tract calculi were retrospectively analyzed. The CT grading system was developed based on CT images. CT images were classified into 4 grades. General information, symptoms, and clinical findings of patients in different CT grades were analyzed. With the occurrence of systemic inflammatory response syndrome (SIRS) as the endpoint, univariate and multivariate analysis was conducted to analyze the risk factors of SIRS.

Results: Patients with fever or diabetes had higher CT grades, and the following examination data revealed significant differences across the various CT grades (P < 0.05): the white blood cell count, urine leucocytes count, CT1, CT2, maximum body temperature, duration of disease, the proportion of blood neutrophils, the size of stones, and levels of the C-reactive protein and procalcitonin. Only CT grading was statistically significant after multivariate analysis. According to the values of the partial regression coefficient (B), the higher the CT grade, the greater the risk of SIRS. The risk of SIRS was 4.472 times higher with each increment of the CT grade.

Conclusions: The CT grade is directly associated with clinical symptoms and the risk of SIRS.

[Figure: see text] Dr. Kenneth Rockwood is a Professor of Medicine in the Division of Geriatric Medicine and Neurology and Clinical Research Professor of Frailty and Aging at Dalhousie University, as well as an actively practising geriatric physician. Dr. Rockwood has made significant contributions to geriatric medicine and research, including his involvement in developing the Clinical Frailty Scale. He has been recognized with countless prestigious awards, the most recent being the Distinguished Scientist Award from the Canadian Society for Clinical Investigation.

Purpose: Over the past 20 years, much of the research on diabetes has focused on pancreatic beta cells. In the last 10 years, interest in the important role of pancreatic alpha cells in the pathogenesis of diabetes, which had previously received little attention, has grown. We aimed to summarize and visualize the hotspot and development trends of pancreatic alpha cells through bibliometric analysis and to provide research direction and future ideas for the treatment of diabetes and other islet-related diseases.

Methods: We used two scientometric software packages (CiteSpace 6.1.R6 and VOSviewer1.6.18) to visualize the information and connection of countries, institutions, authors, and keywords in this field.

Results: A total of 532 publications, published in 752 institutions in 46 countries and regions, were included in this analysis. The United States showed the highest output, accounting for 39.3% of the total number of published papers. The most active institution was Vanderbilt University, and the authors with highest productivity came from Ulster University. In recent years, research hotspots have concentrated on transdifferentiation, gene expression, and GLP-1 regulatory function. Visualization analysis shows that research hotspots mainly focus on clinical diseases as well as physiological and pathological mechanisms and related biochemical indicators.

Conclusions: This study provides a review and summary of the literature on pancreatic alpha cells through bibliometric and visual methods and shows research hotspot and development trends, which can guide future directions for research.