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| 1 | Efficacy and safety of low-dose interleukin-2 in combination with methotrexate in patients with active rheumatoid arthritis:a randomized,double-blind,placebo-controlled phase 2 trial显示文摘Rheumatoid arthritis(RA)is an aggressive autoimmune arthritis,and current therapies remain unsatisfactory due to low remission rate and substantially adverse effects.Low-dose interleukin-2(Ld-IL2)is potentially a therapeutic approach to further improve the disease.This randomized,double-blind,placebo-controlled trial was undertaken to evaluate the efficacy and safety of Ld-IL2 in patients with active RA.Patients were randomly assigned(1:1)to receive Ld-IL2,defined as a dose of 1 million IU,or placebo in a 12-week trial with a 12-week follow-up.Three cycles of Ld-IL2 or placebo were administered subcutaneously every other day for 2 weeks(a total of 7 doses),followed by a 2-week break.All patients received a stable dose of methotrexate(MTX).The primary outcomes were the proportion of patients achieving the ACR20,DAS28-ESR<2.6,and the change from baseline in CDAI or SDAI at week 24.Secondary endpoints included other clinical responses and safety.The primary outcomes were achieved in the perprotocol population.The improvements from baseline in CDAI and SDAI were significantly greater across time points for the LdIL2+MTX group(n=17)than for the placebo+MTX group(n=23)(P=0.018 and P=0.015,respectively).More patients achieved ACR20 response in the Ld-IL2+MTX group than those in the placebo+MTX group at week 12(70.6%vs 43.5%)and at week 24(76.5%vs 56.5%)(P=0.014).In addition,low Treg and high IL-21 were associated with good responses to Ld-IL2.Ld-IL-2 treatment was well-tolerated in this study.These results suggested that Ld-IL2 was effective and safe in RA.ClinicalTrials.gov number:NCT 02467504. | Xiaoying Zhang Miao Miao Ruijun Zhang Xu Liu Xiaozhen Zhao Miao Shao Tian Liu Yuebo Jin Jiali Chen Huixin Liu Xia Zhang Yun Li Yunshan Zhou Yue Yang Ru Li Haihong Yao Yanying Liu Chun Li Yuhui Li Limin Ren Yin Su Xiaolin Sun Jing He Zhanguo Li | 2022 | Signal Transduction and Targeted Therapy2022，7，4： | 7 |
| 2 | Rac1 Modulates Excitatory Synaptic Transmission in Mouse Retinal Ganglion Cells显示文摘Ras-related C3 botulinum toxin substrate 1(Racl),a member of the Rho GTPase family which plays important roles in dendritic spine morphology and plasticity,is a key regulator of cytoskeletal reorganization in dendrites and spines.Here,we investigated whether and how Racl modulates synaptic transmission in mouse retinal ganglion cells(RGCs)using selective conditional knockout of Racl(Racl-cKO).Racl-cKO significantly reduced the frequency of AMPA receptor-mediated miniature excitatory postsynaptic currents,while glycine/GABA_A receptor-mediated miniature inhibitory postsynaptic currents were not affected.Although the total GluA1 protein level was increased in Racl-cKO mice,its expression in the membrane component was unchanged.RaclcKO did not affect spine-like branch density in single dendrites,but significantly reduced the dendritic complexity,which resulted in a decrease in the total number of dendritic spine-like branches.These results suggest that Racl selectively affects excitatory synaptic transmission in RGCs by modulating dendritic complexity. | Ling-Zhu Li Ning Yin Xue-Yan Li Yanying Miao Shuo Cheng Fang Li Guo-Li Zhao Shu-Min Zhong Xin Wang Xiong-Li Yang Zhongfeng Wang | 2019 | Neuroscience Bulletin2019，35，4： | 2 |
| 3 | Dopamine D2 Receptor-Mediated Modulation of Rat Retinal Ganglion Cell Excitability显示文摘Ganglion cells(RGCs) are the sole output neurons of the retinal circuity. Here, we investigated whether and how dopamine D2 receptors modulate the excitability of dissociated rat RGCs. Application of the selective D2 receptor agonist quinpirole inhibited outward K^+ currents, which were mainly mediated by glybenclamide-and 4-aminopyridine-sensitive channels, but not the tetraethylammonium-sensitive channel. In addition,quinpirole selectively enhanced Nav1.6 voltage-gated Na^+ currents. The intracellular c AMP/protein kinase A,Ca^2+/calmodulin-dependent protein kinase Ⅱ, and mitogen-activated protein kinase/extracellular signal-regulated kinase signaling pathways were responsible for the effects of quinpirole on K^+ and Na^+ currents, while phospholipase C/protein kinase C signaling was not involved. Under current-clamp conditions, the number of action potentials evoked by positive current injection was increased by quinpirole. Our results suggest that D2 receptor activation increases RGC excitability by suppressing outward K+currents and enhancing Nav1.6 currents, which may affect retinal visual information processing. | Ning Yin Yu-Long Yang Shuo Cheng Hong-Ning Wang Xin Hu Yanying Miao Fang Li Zhongfeng Wang | 2020 | Neuroscience Bulletin2020，36，3： | 2 |
| 4 | High birefringence low-dispersion of nonlinear photonic crystal fiber显示文摘 | Xu Qiang Miao Runcai Zhang Yani | 2013 | Op tik-International Journal for Light and Electron Optics2013，124，15： | 1 |
| 5 | P2X7/P2X4 Receptors Mediate Proliferation and Migration of Retinal Microglia in Experimental Glaucoma in Mice显示文摘Microglia are involved in the inflammatory response and retinal ganglion cell damage in glaucoma.Here,we investigated how microglia proliferate and migrate in a mouse model of chronic ocular hypertension(COH).In COH retinas,the microglial proliferation that occurred was inhibited by the P2X7 receptor(P2X7R)blocker BBG or P2X7R knockout,but not by the P2X4R blocker 5-BDBD.Treatment of primary cultured microglia with BzATP,a P2X7R agonist,mimicked the effects of cell proliferation and migration in COH retinas through the intracellular MEK/ERK signaling pathway.Transwell migration assays showed that the P2X4R agonist CTP induced microglial migration,which was completely blocked by 5-BDBD.In vivo and in vitro experiments demonstrated that ATP,released from activated Müller cells through connexin43 hemichannels,acted on P2X7R to induce microglial proliferation,and acted on P2X4R/P2X7R(mainly P2X4R)to induce microglial migration.Our results suggest that inhibiting the interaction of Müller cells and microglia may attenuate microglial proliferation and migration in glaucoma. | Meng-Xi Xu Guo-Li Zhao Xin Hu Han Zhou Shu-Ying Li Fang Li Yanying Miao Bo Lei Zhongfeng Wang | 2022 | Neuroscience Bulletin2022，38，8： | 0 |
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