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| 1 | Small molecule inhibitors reveal allosteric regulation of USP14 via steric blockade显示文摘The ubiquitin system is important for drug discovery,and the discovery of selective small-molecule inhibitors of deubiquitinating enzymes (DUBs) remains an active yet extremely challenging task. With a few exceptions,previously developed inhibitors have been found to bind the evolutionarily conserved catalytic centers of DUBs,resulting in poor selectivity. The small molecule IU1 was the first-ever specific inhibitor identified and exhibited surprisingly excellent selectivity for USP14 over other DUBs. However,the molecular mechanism for this selectivity was elusive. Herein,we report the high-resolution co-crystal structures of the catalytic domain of USP14 bound to IU1 and three IU1 derivatives. All the structures of these complexes indicate that IU1 and its analogs bind to a previously unknown steric binding site in USP14,thus blocking the access of the C-terminus of ubiquitin to the active site of USP14 and abrogating USP14 activity. Importantly,this steric site in USP14 is very unique,as suggested by structural alignments of USP14 with several known DUB X-ray structures. These results,in conjunction with biochemical characterization,Indicate a coherent steric blockade mechanism for U5P14 inhibition by compounds of the IU series. In light of the recent report of steric blockade of USP7 by FT671,this work suggests a potential generally applicable allosteric mechanism for the regulation of DUBs via steric blockade,as showcased by our discovery of IU1-248 which is 10-fold more potent than IU1. | Yiwei Wang Yuxuan Jiang Shan Ding Jiawang Li Ningjing Song Yujing Ren Danning Hong Cai Wu Bin Li Feng Wang Wei He Jiawei Wang Ziqing Mei | 2018 | Cell Research2018，28，12： | 15 |
| 2 | Prognostic value of interim ^(18)F-FDG PET/CT in diffuse large B-cell lymphoma显示文摘Objective: Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous disease. The prognostic factor currently used is not accurate enough to predict the outcomes of patients with DLBCL. The prognostic significance of interim PET/CT in DLBCL remains controversial. The aim of this study is to determine the predictive value of interim 18F-FDG PET/CT after first-line treatment in patients with DLBCL. Methods: Thirty-two patients with DLBCL underwent baseline, interim and post-treatment 18F-FDG PET/CT scans. Imaging results were analyzed for the survival of patients via software SPSS 13.0, retrospectively. Results: Thirty-one of the 32 patients were treated with R-CHOP regimen, and interim 18F-FDG PET/CT of 24 patients was performed after 2 cycles of treatment. After a median follow-up period of 16.7 months, the 2-year progression-free survival (PFS) rates were significantly different between the groups above and below SUV max cut-off value of 2.5 (P=0.039). No significant differences were found in the 2-year PFS rates if SUV max cut-off values were set as 2.0 and 3.0, respectively (P=0.360; P=0.113). Conclusions: Interim PET/CT could predict the prognosis of DLBCL patients with the SUV max cut-off value of 2.5, but more clinical data should be concluded to confirm this conclusion. | Zhitao Ying Xuejuan Wang Yuqin Song Wen Zheng Xiaopei Wang Yan Xie Ningjing Lin Meifeng Tu Lingyan Ping Weiping Liu Lijuan Deng Chen Zhang Zhi Yang Jun Zhu | 2013 | Chinese Journal of Cancer Research2013，25，1： | 4 |
| 3 | Prognostic value of pre-and post-transplantation 18F-fluorodeoxyglucose positron emission tomography results in non-Hodgkin lymphoma patients receiving autologous stem cell transplantation显示文摘Objective: High-dose chemotherapy(HDC) followed by autologous stem cell transplantation(ASCT) is the standard of care in the upfront or relapsed/refractory setting in some patients with non-Hodgkin lymphoma(NHL).However,a proportion of patients do not respond to ASCT.^(18)F-fluorodeoxyglucose(FDG) positron emission tomography(PET)/computed tomography(CT) has been widely used for staging,response evaluation,and prognosis prediction.Here,we investigated the prognostic role of PET/CT in NHL patients before and after ASCT.Methods: A retrospective study was conducted at Peking University Cancer Hospital.All NHL patients who underwent ASCT between March 2010 and July 2016 were identified.Patients who had PET/CT scan before and after ASCT were included.Deauville criteria(5-point scale) were used to interpret PET scans.Univariate and multivariate survival analyses were performed using Cox regression.The predictive value of PET scanning was estimated by comparing the area under the receiver operating characteristic(ROC) curve.Results: In total,79 patients were enrolled in this study.In univariate analysis,pre-and post-ASCT PET result was identified as prognostic factors for 3-year progression-free survival(PFS) and overall survival(OS).Patients with negative pre-ASCT PET result demonstrated significantly better PFS(84.2% vs.54.2%) and OS(89.2% vs.63.6%) than patients with positive pre-ASCT PET result.PFS(91.6% vs.25.3%) and OS(96.5% vs.36.8%) were also significantly different between patients with negative and positive post-ASCT PET result.Multivariate analysis also showed a significant association between survival and post-ASCT PET result.ROC analysis revealed that the predictive value of post-ASCT PET result was superior to that of pre-ASCT PET result alone.Combined pre-and post-ASCT PET result is better for predicting outcomes in patients with NHL receiving transplantation.Deauville criteria score >3 was identified as the best cutoff value for post-ASCT PET.Conclusions: Post-ASCT PET result was more important than pre-ASCT PET result in predicting outcomes for NHL patients who underwent ASCT.The prognostic significance can be improved when combining preASCT PET result with post-ASCT PET result.Deauville criteria can be used for interpreting PET scans in this scenario. | Zhitao Ying Lan Mi Xuejuan Wang Yuewei Zhang Zhi Yang Yuqin Song Xiaopei Wang WenZheng Ningjing Lin Meifeng Tu Yan Xie Lingyan Ping Chen Zhang Weiping Liu LijuanDeng Jun Zhu | 2017 | Chinese Journal of Cancer Research2017，29，6： | 3 |
| 4 | Immune checkpoint inhibitors in malignant lymphoma: Advances and perspectives显示文摘Classical Hodgkin lymphoma(cHL) has been identified with universal genetic alterations of chromosome 9p24.1,which contains PD-L1/PD-L2 genes.The amplification of 9p24.1 is associated with the increased expression of PDL1 and PD-L2 on RS cells, which promotes their immune evasion, and subsequently makes cHL sensitive to PD-1 blockade.Several PD-1 inhibitors have shown significant efficacies with overall response rate(ORR) of 70%-90% in relapse/refractory(r/r) cHL and have acquired the approvals for this indication.Recently, more and more studies are conducted to investigate PD-1 blockade in earlier disease course and in combination with neo-agents or chemotherapy.Unlike cHL, non-Hodgkin lymphoma(NHL) consists of numerous subtypes harboring highly biological heterogeneity.Only a few subtypes have been shown to have genetic alteration of 9p24.1 including primary mediastinal B cell lymphoma(PMBL), gray zone lymphoma(GZL) with features intermediate between diffuse large B cell lymphoma(DLBCL) and cHL, primary central nervous system lymphoma(PCNSL) and primary testicular lymphoma(PTL).Epstein-Barr virus(EBV)-associated lymphomas have a virally mediated overexpression of PD-L1, also making them sensitive to PD-1 blockade.Therefore, PD-1 inhibitors are less effective in most r/r NHL than in r/r cHL.Further understanding of the biological features of NHL and immune checkpoint inhibitors(ICPi) combined therapy is the research focus in the future.In this review, we outlined the recent progress of ICPi in lymphoma originating from clinical studies. | Ningjing Lin Yuqin Song Jun Zhu | 2020 | Chinese Journal of Cancer Research2020，32，3： | 3 |
| 5 | PEG-asparaginase in BFM-90 regimen improves outcomes in adults with newly diagnosed lymphoblastic lymphoma显示文摘Objective: Although L-asparaginase(L-ASP) is a standard treatment for lymphoblastic lymphoma(LBL),hypersensitivity reactions by some patients limit its application. Polyethylene glycol-conjugated asparaginase(PEGASP) has a lower immunogenicity and is a standard treatment in all pediatric acute lymphoblastic leukemia(ALL).In this study, we investigated the efficacy and toxicity of PEG-ASP instead of L-ASP as used in the BFM-90regimen(PEG-ASP-BFM-90) for adult LBL.Methods: Between June 2012 and July 2015, we treated 30 adult patients with newly diagnosed LBL, using PEGASP-BFM-90 in a prospective, multicenter and single-arm clinical study at 5 participating institutions in China.Results: All the 30 patients, including 19 males and 11 females with a median age of 30(range: 18–62) years,completed 128 times of the PEG-ASP, with the median of 4(range: 2–6) times. Patients did not receive radiotherapy at this time. The overall response rate was 86.7%(26/30), with 50.0%(15/30) complete response and36.7%(11/30) partial response. The 3-year overall survival was 46.0% [95% confidence interval(95% CI),28.2%–64.8%], and the 3-year progression-free survival was 43.0%(95% CI, 25.7%–62.0%). Major adverse events were myelosuppression, reduced fibrinogen, liver dysfunction and digestive tract toxicities. No allergic reaction and no treatment-related mortality or severe complications were recorded.Conclusions: Our clinical data and observed outcomes indicate that 1 dose of PEG-ASP can replace multiple doses of native L-ASP in BFM-90, with predominantly grade 3–4 neutropenia for adult LBL, and no therapyrelated deaths. The effect is similar to previous reports of PEG-ASP-containing regimens for adult ALL. Major advantages include less serious allergic reactions, 2–3 weeks of action duration, and convenience for patients and physicians. | Wen Zheng Hanyun Ren Xiaoyan Ke Mei Xue Yongqing Zhang Yan Xie Ningjing Lin Meifeng Tu Weiping Liu Lingyan Ping Zhitao Ying Chen Zhang Lijuan Deng Xiaopei Wang Yuqin Song Jun Zhu | 2017 | Chinese Journal of Cancer Research2017，29，1： | 2 |
| 6 | A durable 4-1BB-based CD19 CAR-T cell for treatment of relapsed or refractory non-Hodgkin lymphoma显示文摘Objective:Previous studies reported that 4-1BB-based CD19 chimeric antigen receptor(CAR)-T cells were more beneficial for the clinical outcomes than CD28-based CAR-T cells,especially the lower incidence rate of severe adverse events.However,the median progression-free survival(mPFS)of 4-1BB-based product Kymriah was shorter than that of CD28-based Yescarta(2.9 months vs.5.9 months),suggesting that Kymriah was limited in the long-term efficacy.Thus,a safe and durable 4-1BB-based CD19 CAR-T needs to be developed.Methods:We designed a CD19-targeted CAR-T(named as IM19)which consisted of an FMC63 scFv,4-1BB and CD3ζintracellular domain and was manufactured into a memory T-enriched formulation.A phase I/II clinical trial was launched to evaluate the clinical outcomes of IM19 in relapsed or refractory(r/r)B cell non-Hodgkin lymphoma(B-NHL).Dose-escalation investigation(at a dose of 5×10^(5)/kg,1×10^(6)/kg and 3×106/kg)was performed in 22 r/r B-NHL patients.All patients received a single infusion of IM19 after 3-day conditional regimen.Results:At month 3,the overall response rate(ORR)was 59.1%,the complete response rate(CRR)was 50.0%.The mPFS was 6 months and the 1-year overall survival rate was 77.8%.Cytokine release syndrome(CRS)occurred in 13 patients(59.1%),with 54.5%of grade 1−2 CRS.Only one patient(4.5%)experienced grade 3 CRS and grade 3 neurotoxicity.Conclusions:These results demonstrated the safety and durable efficacy of a 4-1BB-based CD19 CAR-T,IM19,which is promising for further development and clinical investigation. | Zhitao Ying Ting He Shanzhao Jin Xiaopei Wang Wen Zheng Ningjing Lin Meifeng Tu Yan Xie Lingyan Ping Weiping Liu Lijuan Deng Yanping Ding Xuelian Hu Bing Bu Xin’an Lu Yuqin Song Jun Zhu | 2022 | Chinese Journal of Cancer Research2022，34，1： | 2 |
| 7 | Prognostic value of ^(18)F-fluorodeoxyglucose positron emission tomography using Deauville criteria in diffuse large B cell lymphoma treated with autologous hematopoietic stem cell transplantation显示文摘Objective: High-dose chemotherapy(HDC) followed by autologous hematopoietic stem cell transplantation(auto-HSCT) plays an important role in improving outcomes of diffuse large B cell lymphoma(DLBCL) patients.18 F-fluorodeoxyglucose(18 F-FDG) positron emission tomography(PET)/computed tomography(CT) has been widely accepted in response assessment and prediction of prognosis in DLBCL. Here, we report the value of 18 FFDG PET/CT pre-and post-HSCT in predicting outcomes of patients with DLBCL.Methods: DLBCL patients who had PET/CT scan before and after HSCT were included. PET results were interpreted based upon Deauville criteria. The prognostic value of 18 F-FDG PET/CT in auto-HSCT was evaluated.Results: Eighty-four patients were enrolled. In univariate analysis, pre-and post-HSCT PET findings were correlated with 3-year progression-free survival(PFS) [hazard ratio(HR)=4.391, P=0.001; HR=7.607, P<0.001] and overall survival(OS)(HR=4.792, P=0.008; HR=26.138, P<0.001). Patients receiving upfront auto-HSCT after firstline treatment had better outcomes than relapsed/refractory DLBCL patients(3-year PFS, P<0.001; 3-year OS,P<0.001). In the relapsed/refractory patients, pre-and post-HSCT PET findings were also associated with 3-year PFS(P=0.003 vs. P<0.001) and OS(P=0.027 vs. P<0.001). A significant correlation was observed between clinical response to chemotherapy before auto-HSCT and outcomes of patients in the entire cohort(3-year PFS, P<0.001;3-year OS, P<0.001) and in the subgroup of 21 patients with positive pre-HSCT PET(3-year PFS, P=0.084; 3-year OS, P=0.240). A significant association between survival and post-HSCT PET findings was observed in multivariate analysis(HR=5.168, P<0.001).Conclusions: PET results before and after HSCT are useful prognostic factors for DLBCL patients receiving HSCT. Patients who responded to chemotherapy, even those with positive pre-HSCT PET, are appropriate candidates for auto-HSCT. | Zhitao Ying Lan Mi Nina Zhou Xuejuan Wang Zhi Yang Yuqin Song Xiaopei Wang Wen Zheng Ningjing Lin Meifeng Tu Yan Xie Lingyan Ping Chen Zhang Weiping Liu Lijuan Deng Jun Zhu | 2019 | Chinese Journal of Cancer Research2019，31，1： | 2 |
| 8 | Tracking lead origin in the Yellow River Estuary and nearby Bohai Sea based on its isotopic composition显示文摘 | Hu Ningjing Huang Peng Liu Jihua | 2015 | Estuarine Coastal and Shelf Science2015，163，： | 1 |
| 9 | Flame retardancy and synergistic flame retardant mechanisms of aerylonitrile-butadiene-styrene emnposites based on aluminum hypophosphite 显示文摘 | Wu Ningjing Li Xiangting | 2014 | Polymer Degradation and Stability2014，105，1： | 1 |
| 10 | Thermogravimetric analysis and pyrolysis kinetic of cotton fabrics finished with Pyrovatex CP显示文摘 | NINGJ IANGUO QIU RONG | 1986 | Journal of Fire Sciences1986，，4： | 1 |
| 11 | apoptotis endometrial glandular and stromai cells inWomen with and With- out endometriosis 显示文摘 | Dmowski WP NINGJ SHENJ | 2006 | Hum Reprod2006，16，9： | 1 |
| 12 | HnRNP AI/A2 and SF2/ASF proteins regulate alternative splicing of interferon regulatory factor-3 and ef- fect immunomodulatory functions in human non-small cell lung cancer cells显示文摘 | Guo R Li Y NingJ | 2013 | Plos One2013，8，4： | 1 |
| 13 | Over - expression of PKGIa inhibits hypoxia - induced proliferation, Akt activation, and phenotype modulation of human PASMCs: the role of phenotype modulation of PASMCs in pulmonary vascular remodeling显示文摘 | Yi B CuiJ NingJ et at | 2012 | Gene2012，492，2： | 1 |
| 14 | Anovelhybriddifferentialevolutionandparticleswarm optimizationalgorithm forunconstrainedoptimization显示文摘 | ZhangC NingJ LuS etal | 2009 | OperationsResearchLet-ters2009，37，2： | 1 |
| 15 | Characterization and source apportionment of polycyclic aromatic hydrocarbons (PAHs) in sediments in the Yellow River Estuary,China显示文摘 | Hu Ningjing Huang Peng Liu Jihua | 2014 | Environmental Earth Sciences2014，71，2： | 1 |
| 16 | The influence of different wave green process for oolong tea quality显示文摘 | ZHENG P C NINGJ M ZHAO C R FANGS H XIA T | 2009 | Journal of Anhui Agricultural University2009，36，1： | 1 |
| 17 | A field lysimeter study of heavy metal movement down the profile of soils with multiple metal pollution during chelate-enhanced phytoremediation 显示文摘 | HU Ningjing LUO Yongming WU Longhua | 2007 | International Journal of Phytoremediation2007，99，： | 1 |
| 18 | Statistic of a Gaussian beam from an arbitrary rough target in the single passage atmospheric turbulence显示文摘The extended Huygens-Fresnel principle and Goodman model was utilized for target surface to derive the mutual coherence function(MCF) of a Gaussian beam reflected from an arbitrary rough target in atmospheric turbulence. According to the MCF, expressions of the mean irradiance and average speckle size at the receiver were obtained. The analysis indicated that the mean intensity is closely related to the ratio of root mean square(rms) height to the lateral correlation length. In addition, the speckle size at the receiver is associated with turbulence strength, propagation distance and roughness of the target. The results can be reduced to the result of a Gaussian beam illuminating rough target and scattering from a target in free space. | XIANG NingJing WU ZhenSen WANG MingJun | 2014 | Science China(Physics,Mechanics & Astronomy)2014，57，10： | 1 |
| 19 | Mechanical properties and crystallization of Poly(L-lactide) films with several percents of ACR nanoparticles显示文摘 | Ningjing Wu Meichun Ding Jianming Zhang Runxiong Lin | 2012 | Materials Letters2012，，： | 1 |
| 20 | Peroxiredoxin 1 is a tumor-associated antigen in esophageal squamouscell carcinoma显示文摘 | Pengfei Ren Hua Ye Liping Dai Mei Liu Xinxin Liu Yurong Chai Qing Shao Yang Li Ningjing Lei Bo Peng Wu Yao Jianying Zhang | 2013 | Oncology Reports2013，，5： | 1 |
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