Search

Diabetic kidney disease (DKD) represents the predominant and severe microvascular complication associated with diabetes, frequently culminating in End-Stage Kidney Disease (ESKD). The escalating prevalence of diabetes has correspondingly led to a rise in DKD incidence, imposing significant challenges on both individuals and society. The etiology of DKD is multifaceted and remains devoid of definitive therapeutic interventions. This article examines the pharmacological actions and mechanisms of different drugs used for the prevention and treatment of DKD that are currently in clinical use or undergoing development. The goal is to offer insights for early intervention based on therapeutic combinations to potentially slow kidney disease progression. [ABSTRACT FROM AUTHOR]

Background: Breast cancer is the prevailing malignancy among women, exhibiting a discernible escalation in incidence within our nation; hormone receptor‐positive (HR+) human epidermal growth factor receptor 2‐negative (HER2−) breast cancer is the most common subtype. In this study, we aimed to search for a non‐invasive, specific, blood‐based biomarker for the early detection of luminal A breast cancer through proteomic studies. Methods: To explore new potential plasma biomarkers, we applied data‐independent acquisition (DIA), a technique combining liquid chromatography and tandem mass spectrometry, to quantify breast cancer‐associated plasma protein abundance from a small number of plasma samples in 10 patients with luminal A breast cancer, 10 patients with benign breast tumors, and 10 healthy controls. Results: The proteomes of 30 participants in all cohorts were analyzed using the DIA method, and a total of 517 proteins and 3584 peptides were quantified. We found that there were significant differences in plasma protein expression profiles between breast cancer patients and non‐breast cancer patients, and breast cancer was mainly related to lipid metabolism pathways. Finally, the optimal protein combinations for the diagnosis of breast cancer were PON3, IGLV3‐10, and IGHV3‐73 through multi‐model analysis, which had a high prediction accuracy for breast cancer (AUC = 0.92), and the model could also distinguish breast cancer from HC (AUC = 0.92) and breast cancer from benign breast tumor (AUC = 0.91). Conclusions: The study revealed proteomic signatures of patients with luminal A breast cancer, identified multiple differential proteins, and identified three plasma proteins as potential diagnostic biomarkers for breast cancer. It provides a reference for the screening of biomarkers for breast cancer. [ABSTRACT FROM AUTHOR]

Aims: To determine if estimated glucose disposal rate (eGDR) can predict cardiovascular disease mortality risk at different levels of glycaemic tolerance. Materials and Methods: The eGDR levels of 11 656 individuals aged 45–79 years from the National Health and Nutrition Examination Survey cycles 1999 to 2010 were analysed. Associations between eGDR levels and all‐cause and cardiovascular mortality were examined using Cox proportional hazards and Fine and Gray models, respectively. Results: After a median follow‐up of 12.8 years, a total of 2852 participants died, with 777 of those deaths attributed to cardiovascular causes. When comparing participants with eGDR values of ≤4 mg/kg/min to those with eGDR values falling within the ranges of 4–6, 6–8 and >8 mg/kg/min, it was found that the latter groups exhibited lower hazard ratios for both all‐cause mortality (0.61 [0.52–0.72], 0.61 [0.52–0.72] and 0.46 [0.39–0.55]) and cardiovascular mortality (0.44 [0.33–0.57], 0.45 [0.34–0.59] and 0.30 [0.23–0.40]). A U‐shaped relationship between eGDR and all‐cause mortality was observed, with an inflection point at an eGDR of 9.54 mg/kg/min. Conclusions: In the general population, the association between reduced eGDR and all‐cause and cardiovascular mortality was independently significant, contributing to the identification of individuals at high risk for different levels of glucose tolerances. [ABSTRACT FROM AUTHOR]

Severe autoimmune hemolytic anemia complicating hereditary spherocytosis is life threatening and has not been described in a case report. Here, we report a case in which this intractable disease was treated successfully with glucocorticoids and cyclosporine. A 25-year-old female patient with hereditary spherocytosis developed severe autoimmune hemolytic anemia after respiratory syncytial virus infection. Her hemoglobin level was 26 g/L and various anti-red blood cell antibodies were detected in her serum, making blood matching difficult. Glucocorticoid monotherapy was ineffective. With the addition of cyclosporine (50 mg/12 h), the patient's hemoglobin level increased significantly and the symptoms associated with anemia were greatly relieved. In patients with severe autoimmune hemolytic anemia, especially when the presence of multiple anti-red blood cell antibodies and alloantibodies interferes with blood matching, a glucocorticoid-cyclosporine regimen may be tried. [ABSTRACT FROM AUTHOR]

Measurement of the serum levels of vitamin B12 (VB12) is key for evaluating VB12 deficiency-dependent anemia. Immunoassay, the major method for determining VB12, tends to give false-normal results because of the presence of anti-intrinsic factor (IF-Ab) or other factors such as heterophilic antibodies et al. This study aimed to develop a liquid chromatography tandem mass spectrometry (LC-MS/MS) method that is helpful for distinguish false normal VB12 results measured by the immunoassay. Different forms of VB12 were derivatized into CN-B12, which was collected through solid-phase extraction and analyzed via LC-MS/MS. 236 serum samples were measured both by LC-MS/MS and immunoassay, results were compared, and the IF-Ab effect was evaluated. The LC-MS/MS assay afforded a linear slope from 20 to 4,000 pmol/L for CN-B12. OH-VB12, methyl-VB12, and CoA-VB12 showed recovery within 89.3–109.5%. The intra-assay CV of VB12 was 2.6–4.1%, whereas the total CV was 9.3–9.8%. Passing–Bablok regression between LC-MS/MS and immunoassay results showed that the slope was 1.085 and the intercept was −15.691. The Bland–Altman plot showed that the mean difference and difference% were −34.6 pmol/L and 0.3%, respectively. Inter-rater agreement analysis showed that the linear weighted kappa value was 0.885, implying good agreement between the two methods. However, two samples were falsely elevated and one sample was falsely normal in the immunoassay compared with LC-MS/MS. The LC-MS/MS method helped in the distinction of false-normal VB12 results shown by the immunoassay. The VB12 LC-MS/MS method can be used as an arbiter of clinically discordant immunoassay results. [ABSTRACT FROM AUTHOR]