Journal of investigative medicine : the official publication of the American Federation for Clinical Research
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Spinal cord ischemia-reperfusion injury (SCIRI) is a major contributor to neurological damage and mortality associated with spinal cord dysfunction. This study aims to explore the possible mechanism of Propofol and G-protein-coupled receptor-interacting protein 1 (GIT1) in regulating SCIRI in rat models. SCIRI rat models were established and injected with Propofol, over expression of GIT1 (OE-GIT1), or PI3K inhibitor (LY294002). ⋯ LY294002 can also decrease GIT1 expression levels in SCIRI rats. Propofol can attenuate neurological dysfunction induced by SCIRI, decrease spinal cord tissue injury and BSCB permeability in addition to suppressing cell apoptosis and inflammatory cytokines, whereas further treatment by LY294002 can partially reverse the protective effect of Propofol on SCIRI. Propofol can activate PI3K/AKT signal pathway to increase GIT1 expression level, thus attenuating SCIRI in rat models.
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Advances in human immunodeficiency virus (HIV) treatment, including combination antiretroviral therapy (cART), have transformed HIV into a chronic condition. Kidney diseases cause morbidity and mortality in patients living with HIV (PLWH), though cART has permitted kidney transplants with acceptable post-transplant graft and patient survival. Risk of allograft rejection remains high, which may be related to interactions between cART, specifically protease inhibitors (PI), and immunosuppressants prescribed post-transplant. ⋯ Two studies found significant patient survival benefit to non-PI-based therapy. For each outcome measure, remaining data suggested improved outcomes with non-PI-based therapies without achieving statistical significance. The results demonstrate superior outcomes in PLWH taking non-PI-based cART, though the paucity of significant results suggests that PLWH who require PI-based cART for virological control may continue their regimen safely post-kidney transplant.
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To explore the causal relationship between obesity and hypothyroidism and identify risk factors and the predictive value of subclinical hypothyroidism (SCH) in obese patients using Mendelian randomization, this study employed five Mendelian randomization methods (MR Egger, Weighted Median, Inverse Variance Weighted, Simple Mode, and Weighted Mode) to analyze clinical data from 308 obese patients at the People's Hospital of Xinjiang Uygur Autonomous Region, from January 2015 to June 2023. Patients were divided based on thyroid function tests into normal (n = 173) and SCH groups (n = 56). Comparative analyses, along with univariate and multivariate logistic regression, were conducted to identify risk factors for SCH in obese patients. ⋯ The predictive value of FT4 levels for SCH in obesity was significant, with an Area Under the Curve (AUC) of 0.632. The study supports a potential causal link between obesity and hypothyroidism, identifying specific risk factors for SCH in obese patients. FT4 level stands out as an independent predictive factor, suggesting its utility in early diagnosis and preventive strategies for SCH.
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Patients with heart failure with reduced ejection fraction (HFrEF) are at risk for chronic kidney disease (CKD). Elevated levels of circulating biomarkers soluble urokinase plasminogen activator receptor (suPAR), galectin-3, soluble suppression of tumorigenicity 2 (ST2), and N-terminal prohormone B-type natriuretic peptide (NT-proBNP) are associated with CKD progression and mortality. The predictive value of these biomarkers in a population with HFrEF and kidney disease is relatively unknown. ⋯ Higher baseline suPAR, galectin-3, and NT-proBNP are associated with eGFR decline in patients with HFrEF. Only ST2 and NT-proBNP are associated with greater mortality after controlling for other factors including change in eGFR. These biomarkers may provide prognostic value for kidney disease progression in HFrEF and inform candidacy for advanced heart failure therapies.
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Multiple myeloma (MM), constituting 10% of hematological malignancies, poses significant morbidity and mortality, especially with skeletal involvement. Bisphosphonate use in MM may lead to severe hypocalcemia due to vitamin D deficiency (VDD), exacerbating bone-marrow plasma cell burden. We aimed to assess VDD prevalence and its impact on outcomes in MM patients. ⋯ In regression analysis, VDD in MM patients correlated with higher morbidity (adjusted odds ratio (aOR): 1.24, 95% confidence interval (95% CI): 1.14-1.36) and major disability (aOR: 1.26, 95% CI: 1.20-1.30). MM patients with VDD exhibit worse outcomes, underscoring the importance of recognizing and managing VDD promptly. Further prospective studies are needed to validate our findings and explore the impact of vitamin D supplementation on MM patient outcomes.