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270 results on '"Zhao, Hongyuan"'

8. Durable clinical response to the multidisciplinary management of neurosurgery, radiation and chemoimmunotherapy in a patient with PD-L1/PD-L2/JAK2 (PDJ)-amplified, refractory triple-negative breast cancer.

Author

Zhao, Hongyuan, Ma, Weijie, Fragoso, Ruben, Iv, Griffith, Ashok, Arya, and Li, Tianhong

Subjects
Brain metastasis, Immune checkpoint inhibitor, Multidisciplinary, Pdj amplification, Triple-negative breast cancer
Abstract

Patients with refractory metastatic triple-negative breast cancer (mTNBC) and symptomatic brain metastases have poor prognosis and are challenging to treat. The addition of an programmed cell death-1 (PD-1)/programmed cell death-ligand 1 (PD-L1) inhibitor (pembrolizumab or atezolizumab) to first line chemotherapy has prolonged survivals in mTNBC patients with PD-L1-positive tumor and/or tumor-infiltrating immune cells. The clinical efficacy of the chemoimmunotherapy combination in patients with refractory mTNBC, especially brain metastasis, is unknown. Co-amplification of PD-L1, PD-L2, and Janus kinase 2 (PD-L1/PD-L2/JAK2) genes (PDJ amplification) is associated with high PD-L1 protein expression and a 65-87% response rate to PD-1/PD-L1 inhibitors in patients with lymphomas. But the utility of PDJ amplification as a biomarker predictive of response to PD-1/PD-L1 inhibitors is unknown for mTNBC patients. Here, we report a 46-year-old woman who had rapid tumor progression in the brain and lung within 3 months after chemotherapy, neurosurgery, and gamma knife stereotactic radiosurgery for brain metastasis. Next-generation sequencing of her brain metastasis specimen revealed 9 copies of PDJ amplification and a tumor mutational burden of 5 mutations per megabase. Although high PDJ mRNA expression levels were detected, PD-L1 protein expression was negative on tumor cells and 10% on tumor-associated immune cells. After the debulking brain tumor resection, she received pembrolizumab monotherapy, whole brain radiation, and then atezolizumab and nab-paclitaxel with good intracranial and extracranial responses for >16 months. To the best of our knowledge, this is the first report that PDJ amplification is associated with durable clinical response to the PD-1/PD-L1 inhibitor-containing, multidisciplinary management in a patient with refractory, PD-L1 protein-negative, PDJ-amplified mTNBC. Further study is warranted to understand the underlying mechanism and validate PDJ amplification as a biomarker for clinical response to PD-1/PD-L1 inhibitor-containing therapy in patients with mTNBC.

Published
2021

45. Lacticaseibacillus rhamnosusFmb14 ameliorates hyperuricemia-induced hepatocyte pyroptosis via NLRP3 inflammasome cascade inhibition

Author

Zhao, Hongyuan, Chen, Xiaoyu, Zhang, Li, Meng, Fanqiang, Zhou, Libang, Lu, Zhaoxin, and Lu, Yingjian

Abstract

Hyperuricemia is a high-risk factor for the development of gout and renal fibrosis, but the adverse effects of hyperuricemia on the liver have been seriously neglected. This research investigated the ameliorating effect of Lacticaseibacillus rhamnosusFmb14 on hyperuricemia induced liver dysfunction both in vitroand in vivo. Cell free extracts of high dose L. rhamnosusFmb14 treatment reduced the death rate of HepG2 cell lines from 24.1 % to 14.9 % by inhibiting NLRP3 recruitment, which was mainly activated by reactive oxygen species release and mitochondrial membrane potential disorder. In purine dietary induced hyperuricemia (PDIH) mice model, liver oedema and pyroptosis were ameliorated after L. rhamnosusFmb14 administration through downregulating the expression levels of NLRP3, caspase-1 and gasdermin-D from 1.61 to 0.86, 3.15 to 1.01 and 5.63 to 2.02, respectively. L. rhamnosusFmb14 administration restored mitochondrial inner membrane protein (MPV17) and connexin 43 from 2.83 and 0.73 to 0.80 and 0.98 respectively in PDIH mice, indicating that dysbiosis of mitochondrial membrane potential was restored in liver. Intriguingly, PDIH pyroptosis stimulates the process of apoptosis, which leads to severe leakage of hepatocytes, and both of pyroptosis and apoptosis were decreased after L. rhamnosusFmb14 treatment. Therefore, L. rhamnosusFmb14 is a promising biological resource to maintain homeostasis of the liver in hyperuricemia and the prevention of subsequent complications.

Published
2024
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50. A Hierarchical Control Scheme for Adaptive Cruise Control System Based on Model Predictive Control

Author

Zhao, Hongyuan Mu, Liang Li, Mingming Mei, and Yongtao

Subjects
adaptive cruise control, model predictive control, brake-by-wire, deceleration control
Abstract

An adaptive cruise control (ACC) system can improve safety and comfort during driving by taking over longitudinal control of the vehicle. It requires the coordination between the upper-layer controller and the lower-layer actuators. In this paper, a hierarchical anti-disturbance cruise control architecture based on electronic stability control (ESC) system is proposed. The upper-layer controller outputs the desired longitudinal acceleration or deceleration to the lower-layer actuators. In order to improve the accuracy of model prediction and achieve the coordinated control of multiple objectives, an upper-layer model prediction cruise controller is established based on feedback control and disturbance compensation. In addition, based on the hydraulic control unit (HCU) model and the vehicle longitudinal dynamics model, a lower-layer nonlinear model predictive deceleration controller is proposed in order to solve the problems of pressure fluctuations and the low accuracy of small decelerations when ESC is used as the actuator for the ACC system. Finally, the simulation and experimental tests were carried out. The results show that the proposed control architecture can improve the stability and comfort of the cruise control process. Moreover, compared with the traditional PID deceleration controller, it effectively improves the deceleration control accuracy.

Published
2023
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