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5. Association of Mitochondrial Pyruvate Carrier with the Clinical and Histological Features in Lupus Nephritis

Author

Zhu,Huanhuan, Chen,Chen, Geng,Luhan, Li,Qing, Zhang,Chengning, Wu,Lin, Zhang,Bo, Duan,Suyan, Xing,Changying, Yuan,Yanggang, Zhu,Huanhuan, Chen,Chen, Geng,Luhan, Li,Qing, Zhang,Chengning, Wu,Lin, Zhang,Bo, Duan,Suyan, Xing,Changying, and Yuan,Yanggang

Abstract

Huanhuan Zhu, Chen Chen, Luhan Geng, Qing Li, Chengning Zhang, Lin Wu, Bo Zhang, Suyan Duan,* Changying Xing,* Yanggang Yuan* Department of Nephrology, the First Affiliated Hospital of Nanjing Medical University, Nanjing Medical University, Nanjing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yanggang Yuan, Department of Nephrology, the First Affiliated Hospital of Nanjing Medical University, Nanjing Medical University, 300 Guangzhou Road, Nanjing, Jiangsu Province, 210029, People’s Republic of China, Tel/Fax +86-25-6813-6462, Email ygyuan@njmu.edu.cnBackground: Mounting evidence suggests that mitochondrial dysfunction contributes to lupus nephritis (LN) pathogenesis. Mitochondrial pyruvate carrier 1 (MPC1) and mitochondrial pyruvate carrier 2 (MPC2) mediating pyruvate transport from the cytoplasm to the mitochondrial matrix, determines the cell survival and cellular energy supply. Here, we aimed to investigate the association of mitochondrial pyruvate carrier expression with the clinical and histological features in LN.Methods: Patients with biopsy-proven proliferative LN (class III and class IV, n=18) and membranous LN (class V, n=18) were included. Expression of MPC1 and MPC2 were examined by immunohistochemistry. MPC protein levels in the two groups were evaluated by the Student’s t-test. Correlation analysis between MPC levels and clinicopathological features was performed by Spearman’s rank correlation.Results: Both MPC1 and MPC2 were exclusively expressed in renal tubules of enrolled LN. Significantly lower MPC1 and MPC2 were observed in patients with proliferative LN compared to membranous LN. In addition, the MPC1 and MPC2 were negatively correlated with SLEDAI-2K score, renal function, and renal pathology activity index.Conclusion: Both MPC1 and MPC2 were localized in renal tubules, and decreased MPC content was more pronounced in proliferative LN than membranous LN. MPC l

Published
2024

20. The thickness of glomerular basement membrane predicts complete remission in primary membranous nephropathy.

Author

Duan, Suyan, Sun, Lianqin, Zhang, Chengning, Zeng, Ming, Sun, Bin, Yuan, Yanggang, Mao, Huijuan, Xing, Changying, and Zhang, Bo

Subjects
BASAL lamina, KIDNEY diseases, GLOMERULAR filtration rate, CUBIC curves, ELECTRON microscopes
Abstract

Glomerular basement membrane (GBM) thickening is a typical and essential histopathological characteristic for the diagnosis of primary membranous nephropathy (PMN). The present study aimed to explore the relationship between GBM thickness and treatment response in PMN patients. A total of 128 patients with nephrotic syndrome concurrent with PMN were studied. The highest GBM thickness was measured from at least five glomerular capillary loops using an electron microscope, and the mean value was obtained. Patients were categorized into three groups according to the tertiles of GBM thickness as follows: Group 1 (GBM thickness ≤ 1100 nm, n = 48), Group 2 (1100 nm < GBM thickness ≤ 1300 nm, n = 40), Group 3 (GBM thickness >1300 nm, n = 40). Clinicopathological features and treatment response were compared among the three groups. The associations of GBM thickness with complete remission (CR) were assessed by Cox proportional hazard analyses and a cubic spline curve. During a median follow-up period of 25.80 months, 69 (53.9%) patients achieved CR. Kaplan–Meier analysis showed that the non-CR probability was significantly higher in the highest tertile of GBM thickness (p˂0.001). Univariate Cox proportional hazard analysis indicated that GBM thickness was associated with CR (HR per SD 0.617, 95% CI [0.471–0.809], p˂0.001). After adjusting for age, duration of PMN, estimated glomerular filtration rate (eGFR), urinary protein excretion, grade of C3 deposition, and titer of serum anti-phospholipase A2 receptor (PLA2R) antibody, GBM thickness remained an independent predictor of CR (HR per SD 0.580, 95% CI [0.436–0.772], p˂0.001). Further multivariable-adjusted restricted cubic spline analysis confirmed a significant reverse linear association between GBM thickness and CR (p for nonlinear = 0.1261). GBM thickness is an independent risk factor of CR. PMN patients with an increased level of GBM thickening at diagnosis have a lower probability of achieving CR. [ABSTRACT FROM AUTHOR]

Published
2023
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21. Serum 25-hydroxyvitamin D as a predictive biomarker of clinical outcomes in patients with primary membranous nephropathy

Author

Duan, Suyan, primary, Chen, Si, additional, Lu, Fang, additional, Zhou, Meng, additional, Jiang, Ling, additional, Chen, Chen, additional, Geng, Luhan, additional, Sun, Rui, additional, Xu, Yili, additional, Huang, Zhimin, additional, Zhang, Chengning, additional, Zhang, Bo, additional, Mao, Huijuan, additional, Xing, Changying, additional, and Yuan, Yanggang, additional

Published
2023
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25. Torque-Ripple Reduction of Permanent Magnet Synchronous Machine Drives Based on Novel Speed Harmonic Control at Low-Speed Operation

Author

Qu, Jianzhen, Zhang, Pinjia, Jatskevich, Juri, and Zhang, Chengning

Abstract

Torque-ripple reduction methods based on harmonic current injection for permanent magnet synchronous machine (PMSM) drives have been widely discussed, while the performance of torque-ripple-model-based methods is limited due to model accuracy as well as the rotor position errors, and the speed harmonic control-based methods still cannot get rid of the impact of the phase information of speed harmonics, which results in remaining torque ripples and the difficulty in designing speed harmonic controller. In this article, the unique relationships between the quadrature magnitudes of speed harmonics and harmonic currents are derived considering the minimal conduction copper loss by the harmonic currents. Based on that, a novel torque-ripple reduction method based on the speed harmonic control is proposed, wherein a novel speed harmonic controller is presented to regulate the quadrature magnitudes of speed harmonics so that the phase of speed harmonics is avoided in the speed harmonic controller. Also, the proposed speed harmonic controller aims to generate harmonic current references. The proposed methodology is evaluated by experiments and is verified to reduce torque ripples of PMSM drives effectively.

Published
2023
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32. Impact of Overhydration on Left Ventricular Hypertrophy in Patients With Chronic Kidney Disease

Author

Sun, Lianqin, primary, Li, Qing, additional, Sun, Zhiying, additional, Duan, Suyan, additional, Nie, Guangyan, additional, Dong, Jiaxin, additional, Zhang, Chengning, additional, Zeng, Ming, additional, Sun, Bin, additional, Yuan, Yanggang, additional, Wang, Ningning, additional, Mao, Huijuan, additional, Xing, Changying, additional, and Zhang, Bo, additional

Published
2022
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40. A Computationally Efficient Surrogate Model Based Robust Optimization for Permanent Magnet Synchronous Machines.

Author

Yang, Yongxi, Zhang, Chengning, Bramerdorfer, Gerd, Bianchi, Nicola, Qu, Jianzhen, Zhao, Jing, and Zhang, Shuo

Subjects
*ROBUST optimization, *PERMANENT magnets, *FINITE element method, *MANUFACTURING processes, *PROCESS optimization, *PERMANENT magnet motors
Abstract

One of the main obstacles to the robust optimization for permanent magnet machines is the high computational burden, which is mainly caused by the robustness evaluation process considering the manufacturing uncertainties. In this paper, a sequential sampling Kriging model is adopted to estimate the design robustness, and the problem of high-dimensional variables for the surrogate model due to uncertainties is avoided through adopting the worst-case based approach. To further reduce the number of finite element analyses (FEA) required for constructing a metamodel, a multi-points sequential sampling process with a two-step optimization oriented surrogate model updating algorithm is proposed. Compared with the FEA directly based robust optimization in previous work, similar Pareto Fronts are achieved by adopting the meta-model proposed algorithm but the overall run time reduced by 75%. In the end, an optimization problem for a 1.2 kW motor is considered by applying the proposed algorithm, and two prototypes with deliberately designed tolerances, imitating the worst-case scenarios in the real world, are manufactured. The worst-case torque ripple is reduced from 7.6% to 4.8% after optimizing, and this verifies the efficacy of the proposed algorithm. [ABSTRACT FROM AUTHOR]

Published
2022
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48. Effects of CYP3A5 Polymorphisms on Efficacy and Safety of Tacrolimus Therapy in Patients with Idiopathic Membranous Nephropathy

Author

Zhang,Chengning, Duan,Suyan, Guo,Miao, Yuan,Yanggang, Huang,Zhimin, Zhu,Jingfeng, Sun,Bin, Zhang,Bo, and Xing,Changying

Subjects
Pharmacogenomics and Personalized Medicine
Abstract

Chengning Zhang,1,* Suyan Duan,1,* Miao Guo,2 Yanggang Yuan,1 Zhimin Huang,1 Jingfeng Zhu,1 Bin Sun,1 Bo Zhang,1 Changying Xing1 1Departments of Nephrology; 2Department of Pharmacy, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, People’s Republic of China*These authors contributed equally to this workCorrespondence: Changying XingDepartment of Nephrology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, 300 Guangzhou Road, Nanjing 210029, Jiangsu Province, People’s Republic of ChinaTel/Fax +86-25-6830-6462Email cyxing62@126.comBackground: Tacrolimus (TAC) is beneficial for patients with idiopathic membranous nephropathy (IMN). It has a narrow therapeutic concentration range and many factors influence TAC blood concentration. CYP3A5 is the most important enzyme in TAC metabolism. The aim of this study was to analyze the effects of CYP3A5 gene polymorphisms on the efficacy and safety of TAC in IMN patients.PatientsandMethods: Patients with IMN who received oral TAC (0.05– 0.075mg/kg/day) combined with prednisone (0.5mg/kg/day) from March 2016 to October 2018 were included. The data of clinical characteristics, therapeutic drugs and adverse reactions of patients were collected at baseline and during 24 weeks of treatment. Patients were divided into two groups according to different CYP3A5 genetic polymorphisms. The significant differences in the efficacy and side effects between the two groups were analyzed.Results: A total of 76 patients who completed follow-up were divided into CYP3A5 nonexpresser (CYP3A5*3/*3) group and CYP3A5 expresser (CYP3A5 *1/*3) group. The significant association between the CYP3A5 phenotype and TAC metabolism was observed. A total of 43 case-times patients exhibited adverse effects. The infection rate in CYP3A5 nonexpresser group (21.95%) was remarkably higher than the rate in CYP3A5 expresser group (5.71%). Blood concentration and C0/D levels were risk factors for adverse events through logistic regression analysis. There was no statistical difference between the study groups with respect to the efficacy.Conclusion: Our results demonstrated that CYP3A5 polymorphisms had important guiding roles in the treatment of IMN with tacrolimus. CYP3A5 expressers required higher daily doses of TAC to achieve the target drug concentration, but with fewer side effects. CYP3A5 genetic polymorphism might be used for TAC dosing adjustment to optimize the treatment for patients with IMN.Keywords: CYP3A5 polymorphisms, idiopathic membranous nephropathy, tacrolimus, side effects

Published
2020

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