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| 1 | Sintilimab versus docetaxel as second-line treatment in advanced or metastatic squamous non-small-cell lung cancer:an open-label,randomized controlled phase 3 trial(ORIENT-3)显示文摘Background:Treatment options for Chinese patients with locally advanced or metastatic squamous-cell non-small-cell lung cancer(sqNSCLC)after failure of first-line chemotherapy are limited.This study(ORIENT-3)aimed to evaluate the efficacy and safety of sintilimab versus docetaxel as second-line treatment in patients with locally advanced or metastatic sqNSCLC.Methods:ORIENT-3 was an open-label,multicenter,randomized controlled phase 3 trial that recruited patients with stage IIIB/IIIC/IV sqNSCLC after failure with first-line platinum-based chemotherapy.Patients were randomized in a 1:1 ratio to receive either 200 mg of sintilimab or 75 mg/m^(2) of docetaxel intravenously every 3 weeks,stratified by the Eastern Cooperative Oncology Group performance status.The primary endpoint was overall survival(OS)in the full analysis set(FAS).Secondary endpoints included progression-free survival(PFS),objective response rate(ORR),disease control rate(DCR),duration of response(DoR)and safety.Results:Between August 25,2017,and November 7,2018,290 patients were randomized.For FAS,10 patients fromthe docetaxel armwere excluded.Themedian OS was 11.79(n=145;95%confidence interval[CI],10.28-15.57)months with sintilimab versus 8.25(n=135;95%CI,6.47-9.82)months with docetaxel(hazard ratio[HR]:0.74;95%CI,0.56-0.96;P=0.025).Sintilimab treatment significantly prolonged PFS(median 4.30 vs.2.79 months;HR:0.52;95%CI,0.39-0.68;P<0.001)and showed higher ORR(25.50%vs.2.20%,P<0.001)and DCR(65.50%vs.37.80%,P<0.001)than the docetaxel arm.The median DoRwas 12.45(95%CI,4.86-25.33)months in the sintilimab arm and 4.14(95%CI,1.41-7.23)months in the docetaxel arm(P=0.045).Treatment-related adverse events of grade≥3were reported in 26(18.1%)patients in the sintilimab arm and 47(36.2%)patients in the docetaxel arm.Exploratory biomarker analysis showed potential predictive values of expression levels of two transcription factors,including OVOL2(HR:0.35;P<0.001)and CTCF(HR:3.50;P<0.001),for sintilimab treatment.Conclusions:Compared with docetaxel,sintilimab significantly improved the OS,PFS,and ORR of Chinese patients with previously treated locally advanced or metastatic sqNSCLC. | Yuankai Shi Lin Wu Xinmin Yu Puyuan Xing Yan Wang Jianying Zhou Airong Wang Jianhua Shi Yi Hu Ziping Wang Guangyu An Yong Fang Sanyuan Sun Caicun Zhou Changli Wang Feng Ye Xingya Li Junye Wang Mengzhao Wang Yunpeng Liu Yanqiu Zhao Ying Yuan Jifeng Feng Zhendong Chen Jindong Shi Tao Sun Gang Wu Yongqian Shu Qisen Guo Yi Zhang Yong Song Shucai Zhang Yuan Chen Wei Li Hongrui Niu Wenwei Hu Lijun Wang Jianan Huang Yang Zhang Ying Cheng Zhengdong Wu Bo Peng Jiya Sun Christoph Mancao Yanqi Wang Luyao Sun | 2022 | Cancer Communications2022，42，12： | 8 |
| 2 | Long-term treadmill exercise inhibits neuronal cell apoptosis and reduces tau phosphorylation in the cerebral cortex and hippocampus of aged rats显示文摘Aging is an inevitably spontaneous process of the creature.With the increase of age,physical function is degraded in the elderly.One of the most common degradation is memory loss and cognitive impairment in brain function.Neuron loss and neurofibrillary tangles formation contributes to brain dysfunction.Neuron loss is associated with neuronal cell apoptosis.Apoptosis is a process | Guoliang Fang Jiexiu Zhao Pengfei Li Liang Li Tao Yu Xingya Yang Zihong He Ye Tian | 2017 | Science Bulletin2017，62，11： | 7 |
| 3 | Real-variable characterizations of anisotropic product Musielak-Orlicz Hardy spaces显示文摘Let A :=(A_1, A_2) be a pair of expansive dilations and φ : R^n×R^m×[0, ∞) → [0, ∞) an anisotropic product Musielak-Orlicz function. In this article, we introduce the anisotropic product Musielak-Orlicz Hardy space H~φ_A(R^n× R^m) via the anisotropic Lusin-area function and establish its atomic characterization, the g-function characterization, the g_λ~*-function characterization and the discrete wavelet characterization via first giving out an anisotropic product Peetre inequality of Musielak-Orlicz type. Moreover, we prove that finite atomic decomposition norm on a dense subspace of H~φ_A(R^n× R^m) is equivalent to the standard infinite atomic decomposition norm. As an application, we show that, for a given admissible triplet(φ, q, s), if T is a sublinear operator and maps all(φ, q, s)-atoms into uniformly bounded elements of some quasi-Banach spaces B, then T uniquely extends to a bounded sublinear operator from H~φ_A(R^n× R^m) to B. Another application is that we obtain the boundedness of anisotropic product singular integral operators from H~φ_A(R^n× R^m) to L~φ(R^n× R^m)and from H~φ_A(R^n×R^m) to itself, whose kernels are adapted to the action of A. The results of this article essentially extend the existing results for weighted product Hardy spaces on R^n× R^m and are new even for classical product Orlicz-Hardy spaces. | FAN XingYa HE JianXun LI BaoDe YANG DaChun | 2017 | Science China Mathematics2017，60，11： | 5 |
| 4 | An Implanted Closed-loop Chip System for Heart Rate Control:System Design and Effects in Conscious Rats显示文摘Objective:To evaluate the efficiency of an implanted chip system for the control of heart rate (HR). Methods: The HR was recorded in six conscious Sprague-Dawley (SD) rats. An implanted chip system was designed to regulate the HR by stimulating the right cervical vagus nerve according to the feedback of real time HR. Each rat was subjected to 30-min regulation and 30-min recovery. The change of HR during the regulation period was compared with the control. The ECG was recorded during the experiment for 24 h. Results: The ECG signals were successfully recorded during the experiment. The HR was significantly decreased during the period of regulation compared with control (-79.3±34.5, P<0.01, n=6) and then recovered to normal after regulation. Conclusion: The described implanted chip system can regulate the HR to a designated set point. | Yuxuan Zhou Yuan Yuan Juan Gao Ling Yang Feng Zhang Guoqing Zhu Xingya Gao | 2010 | The Journal of Biomedical Research2010，24，2： | 3 |
| 5 | Blockade of deubiquitinase YOD1 degrades oncogenic PML/RARα and eradicates acute promyelocytic leukemia cells显示文摘In most acute promyelocytic leukemia(APL)cells,promyelocytic leukemia(PML)fuses to retinoic acid receptor α (RARα)due to chromosomal translocation,thus generating PML/RARαoncoprotein,which is a relatively stable oncoprotein for degradation in APL.Elucidating the mechanism regulating the stability of PML/RARαmay help to degrade PML/RARαand eradicate APL cells.Here,we describe a deubiquitinase(DUB)-involved regulatory mechanism for the maintenance of PML/RARαstability and develop a novel pharmacological approach to degrading PML/RARαby inhibiting DUB.We utilized a DUB siRNA library to identify the ovarian tumor protease(OTU)family member deubiquitinase YOD1 as a critical DUB of PML/RARα.Suppression of YOD1 promoted the degradation of PML/RARα,thus inhibiting APL cells and prolonging the survival time of APL cell-bearing mice.Subsequent phenotypic screening of small molecules allowed us to identify ubiquitin isopeptidase inhibitor I(G5)as the first YOD1 pharmacological inhibitor.As expected,G5 notably degraded PML/RARαprotein and eradicated APL,particularly drug-resistant APL cells.Importantly,G5 also showed a strong killing effect on primary patient-derived APL blasts.Overall,our study not only reveals the DUB-involved regulatory mechanism on PML/RARαstability and validates YOD1 as a potential therapeutic target for APL,but also identifies G5 as a YOD1 inhibitor and a promising candidate for APL,particularly drug-resistant APL treatment. | Xuejing Shao Yingqian Chen Wei Wang Wenxin Du Xingya Zhang Minyi Cai Shaowei Bing Ji Cao Xiaojun Xu Bo Yang Qiaojun He Meidan Ying | 2022 | Acta Pharmaceutica Sinica B2022，12，4： | 1 |
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