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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 | Unsteady aerodynamic characteristics of a horizontal wind turbine under yaw and dynamic yawing显示文摘Horizontal axis wind turbine(HAWT)often works under yaw due to the stochastic variation of wind direction.Yaw also can be used as one of control methods for load reduction and wake redirection of HAWT.Thus,the aerodynamic performance under yaw is very important to the design of HAWT.For further insight into the highly unsteady characteristics aerodynamics of HAWT under yaw,this paper investigates the unsteady variations of the aerodynamic performance of a small wind turbine under static yawed and yawing process with sliding grid method,as well as the there-dimensional effect on the unsteady characteristics,using unsteady Reynolds-averaged Navier-Stokes(URANS)simulations.The simulation results are validated with experimental data and blade element momentum(BEM)results.The comparisons show that the CFD results have better agreement with the experimental data than both BEM results.The wind turbine power decreases according to a cosine law with the increase of yaw angle.The torque under yaw shows lower frequency fluctuations than the non-yawed condition due to velocity component of rotation and the influence of spinner.Dynamic yawing causes larger fluctuate than static yaw,and the reason is analyzed.The aerodynamic fluctuation becomes more prominent in the retreating side than that in the advancing side for dynamic yawing case.Variations of effective angle of attack and aerodynamic forces along the blade span are analyzed.The biggest loading position moves from middle span to outer span with the increase of yaw angle.Three-dimensional stall effect presents load fluctuations at the inner board of blade,and becomes stronger with the increase of yaw angle. | Zhaoliang Ye Xiaodong Wang Ziwen Chen Luyao Wang | 2020 | Acta Mechanica Sinica2020，36，2： | 8 |
| 3 | Engineering self-healing adhesive hydrogels with antioxidant properties for intrauterine adhesion prevention显示文摘Intrauterine adhesion (IUA) is the fibrosis within the uterine cavity. It is the second most common cause of female infertility, significantly affecting women’s physical and mental health. Current treatment strategies fail to provide a satisfactory therapeutic outcome for IUA patients, leaving an enormous challenge for reproductive science. A self-healing adhesive hydrogel with antioxidant properties will be highly helpful in IUA prevention. In this work, we prepare a series of self-healing hydrogels (P10G15, P10G20, and P10G25) with antioxidant and adhesive properties. Those hydrogels exhibit good self-healing properties and can adapt themselves to different structures. They possess good injectability and fit the shape of the human uterus. Moreover, the hydrogels exhibit good tissue adhesiveness, which is desirable for stable retention and therapeutic efficacy. The in vitro experiments using P10G20 show that the adhesive effectively scavenges ABTS+, DPPH, and hydroxyl radicals, rescuing cells from oxidative stress. In addition, P10G20 offers good hemocompatibility and in vitro and in vivo biocompatibility. Furthermore, P10G20 lowers down the in vivo oxidative stress and prevents IUA with less fibrotic tissue and better endometrial regeneration in the animal model. It can effectively downregulate fibrosis-related transforming growth factor beta 1 (TGF-β1) and vascular endothelial growth factor (VEGF). Altogether, these adhesives may be a good alternative for the clinical treatment of intrauterine adhesion. | Luyao Feng Liqun Wang Yao Ma Wanglin Duan Sergio Martin-Saldana Ye Zhu Xianpeng Zhang Bin Zhu Chaowei Li Shibo Hu Mingjie Bao Ting Wang Yuan Zhu Fei Yang Yazhong Bu | 2023 | Bioactive Materials2023，，9： | 3 |
| 4 | Dependence of sperm structural and functional integrity on testicular calcineurin isoform PPP3R2 expression显示文摘After leaving the testis,mammalian sperm undergo a sequential maturation process in the epididymis followed by capacitation during their movement through the female reproductive tract.These phenotypic changes are associated with modification of protein phosphorylation and membrane remodeling,which is requisite for sperm to acquire forward motility and induce fertilization.However,the molecular mechanisms underlying sperm maturation and capacitation are still not fully understood.Herein,we show that PPP3R2,a testis-specific regulatory subunit of protein phosphatase 3(an isoform of calcineurin in the testis),is essential for sperm maturation and capacitation.Knockout of Ppp3r2 in mice leads to male sterility due to sperm motility impairment and morphological defects.One very noteworthy change includes increases in sperm membrane stiffness.Moreover,PPP3R2 regulates sperm maturation and capacitation via(i)modulation of membrane diffusion barrier function at the annulus and(ii)facilitation of cholesterol efflux during sperm capacitation.Taken together,PPP3R2 plays a critical role in modulating cholesterol efflux and mediating the dynamic control of membrane remodeling during sperm maturation and capacitation. | Yue Liu Chujun Zhang Shiyao Wang Yanqin Hu Jia Jing Luyao Ye Ran Jing Zhide Ding | 2020 | Journal of Molecular Cell Biology2020，12，7： | 1 |
| 5 | The associations of lens power with age,axial length and type 2 diabetes mellitus in Chinese adults aged 50 and above显示文摘Background:To investigate the associations of lens power with age,axial length(AL),and Type 2 diabetes mellitus(DM)in Chinese adults aged 50 and above.Methods:Random clustering sampling was used to identify adults aged 50 years and above in urban regions of Shanghai.The participants underwent a comprehensive ophthalmic examination including subjective refraction,autorefraction,and IOL-Master.The crystalline lens power was calculated using Bennett’s formula.Results:A total of 4177 adults were included.A linear decrease in lens power was observed both with age and with AL,followed by a stop of lens power loss after the age of 70 or when AL≥25 mm,respectively.Participants with Type 2 DM presented higher lens power(0.43 diopter(D),p<0.001)and thicker lens thickness(0.06 mm,p<0.001).In multivariate regression models,there was a positive correlation between lens power and Type 2 DM when age<75 years(p<0.001)or AL<25 mm(p<0.001)after adjusting for other factors,while no significant association was found in participants aged≥75 years(p=0.122)or with AL≥25 mm(p=0.172).Conclusions:The lens power in adults aged 50 and above exhibited two stages with age and with AL.Type 2 DM caused an increase in lens power,which was not seen in participants aged≥75 years or with AL≥25 mm. | Luyao Ye Jiangnan He Xinji Zhang Yi Xu Qiuying Chen Yao Yin Ying Fan Lina Lu Jianfeng Zhu Haidong Zou Xun Xu | 2020 | Eye and Vision2020，7，1： | 0 |
| 6 | Repurposing diacerein to suppress colorectal cancer growth by inhibiting the DCLK1/STAT3 signaling pathway显示文摘Double cortin-like kinase 1(DCLK1)exhibits high expression levels across various cancers,notably in human colorectal cancer(CRC).Diacerein,a clinically approved interleukin(IL)-1βinhibitor for osteoarthritis treatment,was evaluated for its impact on CRC proliferation and migration,alongside its underlying mechanisms,through both in vitro and in vivo analyses.The study employed MTT assay,colony formation,wound healing,transwell assays,flow cytometry,and Hoechst 33342 staining to assess cell proliferation,migration,and apoptosis.Additionally,proteome microarray assay and western blotting analyses were conducted to elucidate diacerein’s specific mechanism of action.Our findings indicate that diacerein significantly inhibits DCLK1-dependent CRC growth in vitro and in vivo.Through high-throughput proteomics microarray and molecular docking studies,we identified that diacerein directly interacts with DCLK1.Mechanistically,the suppression of p-STAT3 expression following DCLK1 inhibition by diacerein or specific DCLK1 siRNA was observed.Furthermore,diacerein effectively disrupted the DCLK1/STAT3 signaling pathway and its downstream targets,including MCL-1,VEGF,and survivin,thereby inhibiting CRC progression in a mouse model,thereby inhibiting CRC progression in a mouse model. | YE Qiaobei ZHU Yu SHI Meng LV Linxi GONG Yuyan ZHANG Luyao YANG Lehe ZHAO Haiyang ZHAO Chengguang XU Huanhai | 2024 | Chinese Journal of Natural Medicines2024，22，4： | 0 |
| 7 | The associations of lens power with age, axial length and type 2 diabetes mellitus in Chinese adults aged 50 years and above显示文摘Background:To investigate the associations of lens power with age,axial length(AL),and type 2 diabetes mellitus(DM)inChineseadultsaged5oandabove.Methods:Random clustering sampling was used to identify adults aged 50 years and above in urban regions of Shanghai.The participants underwent a comprehensive ophthalmic examination including subjective refraction,autorefraction,and IOL-Master.The crystalline lens power was calculated using Bennett's formula.Results:A total of 4177 adults were included.A linear decrease in lens power was observed both with age and with AL,followed by a stop of lens power loss after the age of 70 or when AL≥25 mm,respectively.Participants with type 2 DM presented higher lens power(0.43 diopter(D),P<0.001)and thicker lens thickness(0.06 mm,P<0.001).In multivariate regression models,there was a positive correlation between lens power and type 2 DM when age<75 years(P<0.001)or AL<25 mm(P<0.001)after adjusting for other factors,while no significant association was found in participants aged≥75 years(P=0.122)or with AL≥25 mm(P=0.172).Conclusions:The lens power in adults aged 50 and above exhibited two stages with age and with AL.Type 2 DM caused an increase in lens power,which was not seen in participants aged≥75 years or with AL≥25 mm. | Luyao Ye Jjangnan He Xinji Zhang Yi Xu Qiuying Chen Yao Yin Ying Fan Lina Lu Jianfeng Zhu Haidong Zou Xun Xu | 2022 | Eye and Vision2022，8，6： | 0 |
| 8 | Reconfigurable Vortex-like Paramagnetic Nanoparticle Swarm with Upstream Motility and High Body-length Ratio Velocity显示文摘Drug delivery systems with high-targeted doses can minimize excipients,reduce side effects,and improve efficacy.Human blood circulation is a complex circulatory system,and the motion control of microrobots in the static flow field in vitro is completely different from in vivo.How to achieve precise counterflow motion for targeted drug delivery without vascular blockage and immune rejection is the biggest challenge for micro-nano robots.Here,we propose a control method that enables vortex-like paramagnetic nanoparticle swarm(VPNS)to move upstream against the flow.By mimicking the clustering motion of wild herring schools and the rolling of leukocytes,VPNS are incredibly stable even when subjected to high-intensity jet impacts in the blood environment,can travel upstream,anchor at the target location,and dissipate when the magnetic field is withdrawn,which greatly reduces the risk of thrombosis.VPNS can also upstream along the vessel wall without an additional energy source and has a marked targeted therapeutic effect on subcutaneous tumors. | Luyao Wang Han Gao Hongyan Sun Yiming Ji Li Song Lina Jia Chutian Wang Chan Li Deyuan Zhang Ye Xu Huawei Chen Lin Feng | 2023 | Research2023，，4： | 0 |
| 9 | Targeting the ferroptosis crosstalk:novel alternative strategies for the treatment of major depressive disorder显示文摘Depression is a major contributor to poor global health and disability,with a recently increasing incidence.Although drug therapy is commonly used to treat depression,conventional antidepressant drugs have several disadvantages,including slow onset,low response rates and severe adverse effects.Therefore,developing effective therapies for depression remains challenging.Although various aetiological theories of depression exist,the underlying mechanisms of depression are complex,and further research is crucial.Moreover,oxidative stress(OS)-induced lipid peroxidation has been demonstrated to trigger ferroptosis.Both OS and ferroptosis are pivotal mechanisms implicated in the pathogenesis of neurological disorders,and investigation of the mediators involved in these processes has emerged as a prominent and active research direction.One previous study revealed that regulatory proteins involved in ferroptosis are implicated in the pathogenesis of depression,and antidepressant drugs could reverse depressive symptoms by inhibiting ferroptosis in vivo,suggesting an important role of ferroptosis in the pathogenesis of depression.Hence,our current comprehensive review offers an up-to-date perspective on the intricate mechanisms involved,specifically concerning ferroptosis and OS in the context of depression,along with promising prospects for using molecular mediators to target ferroptosis.We delineate the key targets of molecular mediators involved in OS and ferroptosis implicated in depression,most notably reactive oxygen species and iron overload.Considering the pivotal role of OS-induced ferroptosis in the pathogenesis of neurological disorders,delving deeper into the underlying subsequent mechanisms will contribute significantly to the identification of novel therapeutic targets for depression. | Luyao Wang Rongyang Xu Chengying Huang Guozhong Yi Zhiyong Li Huayang Zhang Rongxu Ye Songtao Qi Guanglong Huang Shanqiang Qu | 2023 | General Psychiatry2023，36，5： | 0 |
| 10 | Differential regulation of JAK1 expression by ETS1 associated with predisposition to primary biliary cholangitis显示文摘Primary biliary cholangitis(PBC)is an autoimmune liver disease characterized by the destruction of intrahepatic small bile ducts and progressive cholestasis,eventually leading to liver cirrhosis and hepatic failure without appropriate treatment(Terziroli Beretta-Piccoli et al.,2019). | Peng Jiang Chan Wang Mingming Zhang Ye Tian Weifeng Zhao Junyi Xin Yexi Huang Zhibin Zhao Wenjuan Sun Jie Long Ruqi Tang Fang Qiu Xingjuan Shi Yi Zhao Li Zhu Na Dai Lei Liu Xudong Wu Jinshan Nie Bo Jiang Youlin Shao Yueqiu Gao Jianjiang Yu Zhigang Hu Zhidong Zang Yuhua Gong Yaping Dai Lan Wang Ningling Ding Ping Xu Sufang Chen Lu Wang Jing Xu Luyao Zhang Junyan Hong Ruonan Qian Hu Li Xuan Jiang Congwei Chen Wenyan Tian Jian Wu Yuzhang Jiang Chongxu Han Kui Zhang Hong Qiu Li Li Hong Fan Liming Chen Jianqiong Zhang Zhongsheng Sun Xiao Han Zhenhua Dai Erguang Li M.Eric Gershwin Zhexiong Lian Xiong Ma Michael F.Seldin Weichang Chen Meilin Wang Xiangdong Liu | 2023 | Journal of Genetics and Genomics2023，50，10： | 0 |
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