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Peficitinib suppresses diffuse-type tenosynovial giant cell tumor by targeting TYK2 and JAK/STAT signaling

Science China Life Sciences 2025年

作者： Shan Lu Chenxi Cao Wenjia Zhang Jiayi Li Jingli Yang Zisheng Huang Zhijun Wu Baitao Liu Hongjie Huang Haijun Wang Yongjian Wang Dingge Liu Zhihua Zhang Kaiping Liu Gang Yang xi gong Hui Dai Yingjia Li Erdan Dong xin Zhang Yan Zhang Haihe Laboratory of Cell Ecosystem Institute of Cardiovascular Diseases The First Affiliated Hospital of Dalian Medical University Institute of Cardiovascular Sciences School of Basic Medical Sciences Peking University Health Science Center Department of Cardiology and Institute of Vascular Medicine Peking University Third HospitalState Key Laboratory of Vascular Homeostasis and Remodeling Peking University Department of Sports Medicine Peking University Third Hospital Institute of Sports Medicine of Peking University Beijing Key Laboratory of Sports Injuries Engineering Research Center of Sports Trauma Treatment Technology and Devices Ministry of Education State Key Laboratory of Membrane Biology Institute of Molecular Medicine College of Future Technology Peking University Peking University Health Science Centre Peking University Department of Immunology School of Basic Medical Sciences NHC Key Laboratory of Medical Immunology Peking University Research Center for Cardiopulmonary Rehabilitation University of Health and Rehabilitation Sciences Qingdao Hospital (Qingdao Municipal Hospital) School of Health and Life Sciences University of Health and Rehabilitation Sciences Research Unit of Medical Science Research Management/Basic and Clinical Research of Metabolic Cardiovascular Diseases Chinese Academy of Medical Sciences

Diffuse-type tenosynovial giant cell tumor(dTGCT) is a destructive but rare benign proliferative synovial neoplasm. Although surgery is currently the main treatment modality for dTGCT, the recurrence risk is up to 50%. Therefore, there is a great need for effective drugs against dTGCT with minor side effects. The Janus kinase(JAK)/signal transducer and activator of transcription(STAT) signaling plays a central role in rheumatoid arthritis(RA), a disease with similar characteristics as dTGCT, but its function in dTGCT remains *** fibroblast-like synoviocytes(FLS) and macrophages were isolated from 10 synovial tissue samples from dTGCT patients for the screening and validation of the five clinically approved JAK inhibitors to treat RA against dTGCT. Cell viability, cell death, inflammation and the activity of the JAK family members of cultured dTGCT FLS(both 2-D and 3-D) and macrophages were investigated for the efficacy of the JAK inhibitors. Here, we found that similar to RA, JAK/STAT signaling was markedly activated in the dTGCT synovium. Of the 5 JAK inhibitors, peficitinib was shown to have the most potency in addressing some of the pathological responses of dTGCT FLS and *** potency of peficitinib was much higher than pexidartinib, which is the only FDA-approved drug for dTGCT. Mechanistically, peficitinib inhibited tyrosine kinase 2(TYK2), a JAK family member necessary for the pathological progression of dTGCT FLS and macrophages. In summary, we not only revealed JAK/STAT(especially TYK2) signaling as the major mechanism underlying dTGCT, but also identified peficitinib as a promising drug against dTGCT.

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Characteristics of Near Surface Winds over Different Underlying Surfaces in China: Implications for Wind Power Development

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Journal of Meteorological Research 2019年第2期33卷 349-362页

作者： xi gong Rong ZHU Lianshou CHEN Nanjing University of Information Science & Technology Chinese Academy of Meteorological Sciences National Climate Center China Meteorological Administration

Accurate wind and turbulence information are essential to wind energy research and utilization, among which wind shear and turbulence intensity/scale have seldom been investigated. In this paper, the observational data from the100-m high wind towers in xilinhot in Inner Mongolia(2009–10; grassland region), Huanghua in Hebei Province(2009–10; coastal flat region), and xingzi County in Jiangxi Province(2010–11; mountain–lake region) are used to study the variations in near surface winds and turbulence characteristics related to the development of local wind energy over different underlying surfaces. The results indicate that(1) the percentage of the observed wind shear exponents exceeding 0.3 for the grassland region is 6%, while the percentage is 13% for the coastal flat region and 10%for the mountain–lake region. In other words, if the wind speed at 10 m is 10 ms^(–1), the percentage of the wind speed at 100 m exceeding 20 ms^(–1) for the grassland region is 6%, while the percentage is 13% for the coastal flat region and 10% for the mountain–lake region.(2) In terms of the turbulent intensity in the zonal, meridional, and vertical directions(I_u, I_v, and I_w, respectively), the frequencies of I_v/I_u < 0.8 in the grassland, coastal flat, and mountain–lake regions are 23%–29%, 32%–38%, and 30%–37%, respectively. Additionally, the frequencies of I_w/I_u < 0.5 in the grassland, coastal flat, and mountain–lake regions are 45%–75%, 52%–70%, and 43%–53%, respectively. The frequencies of I_v/I_u < 0.8 and Iw/I_u < 0.5 in each region mean that I_u is large and the air flow is unstable and fluctuating,which will damage the wind turbines. Therefore, these conditions do not meet the wind turbine design requirements,which must be considered separately.(3) At 50-and 70-m heights, the value of the turbulence scale parameter Λ in the grassland region is greater than that in the coastal flat region, and the latter is greater than that in the mountain–lake region. Therefore, under

关键词： wind energy underlying surface wind shear exponent turbulence turbulent intensity

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A New Route for the Synthesis of N-Substituted Diketopiperazine Derivatives

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Chinese Chemical Letters 2006年第4期17卷 469-472页

作者： xi gong xiao xiao YANG De xin WANG Institute of Materia Medica Chinese Academy of Medical Sciences ＆ Peking Union Medical College Beijing 100050

Eight N-substituted diketopiperazines （DKPs） were synthesized by solid-phase protocols. The introduction of iminodiacetic acid （Ida） and followed another a-amino acid residue as the precursor of DKP framework made... 详细信息

关键词： Diketopiperazine iminodiacetic acid solid-phase synthesis.

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Bone metastases from hepatocellular carcinoma:clinical features and prognostic factors

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Hepatobiliary & Pancreatic Diseases International 2017年第5期16卷 499-505页

作者： Yang Lu Jin-Gen Hu xiang-Jin Lin xi-gong Li Department of Orthopedics First Affiliated HospitalZhejiang University School of Medicine Hangzhou 310003 China

BACKGROUND: Bone metastases (BMs) from hepatocellular carcinoma (HCC) is an increasingly common disease in Asia. We assessed the clinical features, prognostic factors, and differences in outcomes related to BMs among patients with different treatments for HCC. METHODS: Forty-three consecutive patients who were diagnosed with BMs from HCC between January 2010 and December 2014 were retrospectively enrolled. The clinical features were identified, the impacts of prognostic factors on survival were statistically analyzed, and clinical data were compared. RESULTS: The median patient age was 54 years; 38 patients were male and 5 female. The most common site for BMs was the trunk (69.3%). BMs with extension to the soft tissue were found in 14 patients (32.5%). Most (90.7%) of the lesions were mixed osteolytic and osteoblastic, and most (69.8%) patients presented with multiple BMs. The median survival after BMs diagnosis was 11 months. In multivariate analyses, survival after BM diagnosis was correlated with Karnofsky performance status (P=0.008) and the Child-Pugh classification (P<0.001); BM-free survival was correlated with progression beyond the University of California San Francisco criteria (P<0.001) and treatment of primary tumors (P<0.001). BMs with extension to soft tissue were less common in liver transplantation patients. During metastasis, the control of intrahepatic tumors was improved in liver transplantation and hepatectomy patients, compared to conservatively treated patients. CONCLUSIONS: The independent prognostic factors of survival after diagnosis of BMs were the Karnofsky performance status and Child-Pugh classification. HCC patients developed BMs may also benefit from liver transplantation or hepatectomy.

关键词： hepatocellular carcinoma bone metastases survival prognostic factors

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A Brief Overview of the Development and Significance of Modern Scientific Medicine in China:Take Chinese Academy of Medical Science and Peking Union Medical College as an Example

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Chinese Medical Sciences Journal 2024年第2期39卷 140-143页

作者： Pu-An Cui Zhe-xi gong Zhong He School of Humanities and Social Sciences Chinese Academy of Medical Science&Peking Union Medical CollegeBeijing 100730China

Since the early 20th century,China has gradually established a clinical,educational,and research system centered around modern scientific medicine,which has now become the dominant force in China's medical and health system and services,with the construction and development of the Chinese Academy of Medical Sciences and Peking Union Medical College as the most prominent *** scientific medicine in the new era requires close cooperation across multiple disciplines and fields to build a high-quality and efficient medical and health service *** also involves combining the excellent traditional Chinese culture with Western medicine to explore a unique path of modern scientific medicine with Chinese characteristics.

关键词： modern scientific medicine cultural confidence multiple view

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Neuroprotective effects of rapamycin on spinal cord injury in rats by increasing autophagy and Akt signaling

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Neural Regeneration Research 2019年第4期14卷 721-727页

作者： xi-gong Li Jun-Hua Du Yang Lu xiang-Jin Lin Department of Orthopedic Surgery The First Affiliated Hospital School of Medicine Zhejiang University

Rapamycin treatment has been shown to increase autophagy activity and activate Akt phosphorylation, suppressing apoptosis in several models of ischemia reperfusion injury. However, little has been studied on the neuroprotective effects on spinal cord injury by activating Akt phosphorylation. We hypothesized that both effects of rapamycin, the increased autophagy activity and Akt signaling, would contribute to its neuroprotective properties. In this study, a compressive spinal cord injury model of rat was created by an aneurysm clip with a 30 g closing force. Rat models were intraperitoneally injected with rapamycin 1 mg/kg, followed by autophagy inhibitor 3-methyladenine 2.5 mg/kg and Akt inhibitor IV 1 μg/kg. Western blot assay, immunofluorescence staining and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay were used to observe the expression of neuronal autophagy molecule Beclin 1, apoptosis-related molecules Bcl-2, Bax, cytochrome c, casp ase-3 and Akt signaling. Our results demonstrated that rapamycin inhibited the expression of mTOR in injured spinal cord tissue and up-regulated the expression of Beclin 1 and phosphorylated-Akt. Rapamycin prevented the decrease of bcl-2 expression in injured spinal cord tissue, reduced Bax, cytochrome c and caspase-3 expression levels and reduced the number of apoptotic neurons in injured spinal cord tissue 24 hours after spinal cord injury. 3-Methyladenine and Akt inhibitor IV intervention suppressed the expression of Beclin-1 and phosphorylated-Akt in injured spinal cord tissue and reduced the protective effect of rapamycin on apoptotic neurons. The above results indicate that the neuroprotective effect of rapamycin on spinal cord injury rats can be achieved by activating autophagy and the Akt signaling pathway.

关键词： nerve regeneration rapamycin mammalian target of rapamycin,mTOR autophagy Beclin 1 3-methyladenine acute spinal cord injury apoptosis Bax Akt neural regeneration

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A STUDY OF NEAR SURFACE WIND PROFILES IN THE HEBEI COASTAL AREA BASED ON OBSERVATIONAL EXPERIMENTS

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Journal of Tropical Meteorology 2018年第4期24卷 508-514页

作者： gong xi ZHU Rong LI Ze-chun Nanjing University of Information Science and Technology Nanjing 210044 China China Academy of Meteorological Sciences Beijing 100081 China National Climate Center Beijing 100081 China National Meteorological Center Beijing 100081 China

In order to provide wind profiles for the microscale numerical simulation of wind farm with complex terrain,using the 100 m tower atmospheric turbulence observation experiment data in 2010 in Hebei Province offered by National Climate Center, the variation characteristics of wind profile under the different atmospheric stability conditions are analyzed, and the wind profile expression based on the local similarity theory is established. The results show that:(1) In spring, the occurrence probability of unstable stratification in the Hebei coastal area is as high as 28%, and the probability of stable stratification is more than 43% while, in summer, the probability of occurrence of unstable stratification is as high as 80% with a lower probability for stable stratification; and(2) for stable stratification, the characteristics of atmosphere change is dramatic in terms of the vertical direction, which need to be treated layer by *** to the atmospheric turbulence observation experiment data above, under stable stratification, the relationship between the dimensionless velocity gradient and the stability ζ can be expressed as 1 +βmζ, with βm changing with the height: βm takes 4.1-4.3 under 30 m, βm takes 4.6-4.7 between 30-50 m, and βm takes 6.3-6.7 over 50 m.

关键词： wind profile atmospheric stability classification similarity theory Monin-Obukhov length local similarity theory

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千里光通过抑制肥大细胞P2X7受体缓解炎性疼痛

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中国药理学通报 2025年第1期41卷 131-137页

作者：叶凡廖利辉唐婧玥陈佳慧成江陈功锡唐宗湘吉首大学药学院湖南吉首416000 武陵山区药用资源化学与药理湖南省高校重点实验室湖南吉首416000 南京中医药大学医学院·整合医学学院江苏南京210000

目的探讨千里光对肥大细胞P2X7受体介导的炎症性疼痛的影响。方法采用高浓度ATP诱导脚掌炎症性疼痛模型,利用免疫荧光染色技术,甲苯胺蓝染色技术,探究千里光对肥大细胞上P2X7受体是否有抑制作用。利用钙离子成像实验技术,探究千里光是... 详细信息

目的探讨千里光对肥大细胞P2X7受体介导的炎症性疼痛的影响。方法采用高浓度ATP诱导脚掌炎症性疼痛模型,利用免疫荧光染色技术,甲苯胺蓝染色技术,探究千里光对肥大细胞上P2X7受体是否有抑制作用。利用钙离子成像实验技术,探究千里光是否可以抑制小鼠腹膜肥大细胞上P2X7受体激活引起的细胞内钙离子富集。利用全细胞膜片钳技术,探究千里光是否可以抑制小鼠腹膜肥大细胞上P2X7受体激活后引起的内向电流。结果体内实验结果显示,千里光(3.9 g·kg^(-1))明显缓解ATP诱导的炎性疼痛(P<0.05);千里光(3.9 g·kg^(-1))明显抑制P2X7受体阳性肥大细胞的浸润(P<0.01);敲除肥大细胞可以消减千里光(3.9 g·kg^(-1))的镇痛效果(P=0.645)。体外实验结果显示,千里光明显抑制肥大细胞P2X7受体介导的钙离子内流(300 mg·L^(-1),P<0.05;1 g·L^(-1),P<0.01;3 g·L^(-1):P<0.01);千里光(1 g·L^(-1))明显抑制肥大细胞P2X7受体介导的内向电流(P<0.01)。结论千里光通过抑制肥大细胞P2X7受体功能缓解ATP诱导的炎性疼痛。

关键词：千里光疼痛肥大细胞 P2X7受体炎症 ATP

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Note on rare Z-boson decays to double heavy quarkonia

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Chinese Physics C 2023年第4期47卷 89-93页

作者：高道能龚玺 Interdisciplinary Center for Theoretical Study University of Science and Technology of ChinaHefei 230026China Peng Huanwu Center for Fundamental Theory Hefei 230026China

Within the standard model,we have investigated rare Z-boson decays into double heavy quarkonia,Z→VV and Z→VP,with V and P denoting vector and pseudo scalar quarkonia,*** is assumed that the leading-order QCD diagrams would give the dominant contributions to these processes,and the corresponding branching fractions,for instance,B(Z→J/ΨJ/Ψ),have been estimated to be approximately 10^(-13)in ***,these decays could also happen through electromagnetic transitions Z→Vγ^(*)and Z→Pγ^(*),with the virtual photon transforming into ***,the smallness of the vector quarkonium mass can give rise to a large factor m_(Z)^(2)/m_(V)^(2)relative to the QCD contributions,which thus counteracts the suppression from the electromagnetic *** systematically include these two types of contributions in our calculation to predict branching fractions for these ***,owing to the virtual photon effects,it is found that B(Z→J/ΨJ/Ψ)will be significantly enhanced,up to 10^(-10).

关键词： rare decays Z-boson heavy quarkonia

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Remnant-preserving posterior cruciate ligament reconstruction with graft tension-relieving： a comparative study with conventional technique

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Chinese Medical Journal 2013年第6期126卷 1155-1158页

作者： gong xi YU Jia-kuo AO Ying-fang Institute of Sports Medicine Peking University Third HospitalBeijing 100191 China

Background Posterior cruciate ligament （PCL） tear is a severe injury to the knee joint and often requires surgical reconstruction. A number of PCL reconstruction techniques have been reported. However, the problem of residual laxity after surgery is not unusual with conventional techniques. This study aims to introduce a modified PCL reconstruction with remnant preservation and graft tension relieving. Meltlods Between December 2008 and June 2011, 36 cases of PCL reconstruction were performed in our institute, 20 with conventional technique （Group I） and 16 with modified technique （Group II）. Pre- and post-operative results of the international knee documentation committee knee evaluation form （IKDC）, Lysholm, Tegner, and KT2000 side-to-side difference were obtained. Results Significant improvements of IKDC, Lysholm, Tegner, and KT2000 results after surgery were found in both groups. Group II showed better improvement in all subjective examinations and significantly more decrease of KT 2000 side-to-side difference. Conclusion Modified PCL reconstruction with remnant preservation and graft tension relieving showed better results in restoration of posterior stability compared to conventional technique.

关键词： posterior cruciate ligament reconstruction remnant preservation tension-relieving

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