Capital Medical University

About: Capital Medical University is a education organization based out in Beijing, China. It is known for research contribution in the topics: Population & Medicine. The organization has 56150 authors who have published 47290 publications receiving 811249 citations.

Evaluation of the Chronic Kidney Disease Epidemiology Collaboration equation for estimating glomerular filtration rate in the Chinese population

Abstract: Background. Previous studies have indicated that the performance of glomerular filtration rate (GFR) estimation equations vary according to the races of the target population. The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation has not been validated in the Chinese population including patients with chronic kidney disease (CKD) and healthy controls. Methods. A total of 977 adult persons (682 patients with CKD and 295 healthy volunteers) from nine renal institutes of university hospitals located in nine geographic regions of China were enrolled in the study. A diagnostic test study comparing the CKD-EPI two-level and fourlevel race equation, the Modification of Diet in Renal Disease (MDRD) Study equation and the modified MDRD equation for Chinese (the Chinese equation). The 99m Tc- diethylenetriamine pentaacetic acid dual plasma clearance was used as a reference method for measuring GFR. Results. The mean age of participants was 48.3 ± 16.0 years and 479 (49.0%) were male. The CKD-EPI twolevel race equation and the Chinese equation performed better than the MDRD Study equation and CKD-EPI four-level race equation, with less bias (median difference between estimated GFR and reference GFR, 0.2 and 0.3 versus −2.4 and 3.0 mL/min/1.73 m 2 ), improved precision (interquartile range of the difference, 20.5 and 20.8 versus 23.4 and 20.5 mL/min/1.73 m 2 ) and greater accuracy (percentage of estimated GFR within 30% of reference GFR, 73.4 and 73.0% versus 69.8 and 70.1%). Conclusions. The CKD-EPI two-level race equation and the Chinese equation performed similarly in the Chinese population, and both performed better than the MDRD Study equation and the CKD-EPI four-level race equation.

Suppression of the SLC7A11/glutathione axis causes synthetic lethality in KRAS-mutant lung adenocarcinoma

Abstract: Oncogenic KRAS is a major driver in lung adenocarcinoma (LUAD) that has yet to be therapeutically conquered. Here we report that the SLC7A11/glutathione axis displays metabolic synthetic lethality with oncogenic KRAS. Through metabolomics approaches, we found that mutationally activated KRAS strikingly increased intracellular cystine levels and glutathione biosynthesis. SLC7A11, a cystine/glutamate antiporter conferring specificity for cystine uptake, was overexpressed in patients with KRAS-mutant LUAD and showed positive association with tumor progression. Furthermore, SLC7A11 inhibition by either genetic depletion or pharmacological inhibition with sulfasalazine resulted in selective killing across a panel of KRAS-mutant cancer cells in vitro and tumor growth inhibition in vivo, suggesting the functionality and specificity of SLC7A11 as a therapeutic target. Importantly, we further identified a potent SLC7A11 inhibitor, HG106, that markedly decreased cystine uptake and intracellular glutathione biosynthesis. Furthermore, HG106 exhibited selective cytotoxicity toward KRAS-mutant cells by increasing oxidative stress- and ER stress-mediated cell apoptosis. Of note, treatment of KRAS-mutant LUAD with HG106 in several preclinical lung cancer mouse models led to marked tumor suppression and prolonged survival. Overall, our findings reveal that KRAS-mutant LUAD cells are vulnerable to SLC7A11 inhibition, offering potential therapeutic approaches for this currently incurable disease.