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Increased human neutrophil lipocalin and its clinical relevance in adult-onset Still’s disease

Chinese Medical Journal 2023年第23期136卷 2867-2873页

作者： Ji li Yingni li Ru li Xiangbo Ma lianjie Shi Shengguang li Qian Guo Yuan Jia zhanguo li Department of Rheumatology and Immunology Peking University People’s HospitalBeijing Key Laboratory for Rheumatism Mechanism and Immune Diagnosis(BZ0135)Beijing 100044China Department of Rheumatology and Immunology Peking University International HospitalBeijing 102206China Department of Rheumatology and Immunology Handan Central HospitalHandanHebei 056001China Peking-Tsinghua Center for life Sciences Beijing 100044China

Background:Human neutrophil lipocalin(HNL)has been used extensively to differentiate acute bacterial infection from febrile diseases as a biomarker to reflect the activation of the neutrophil.The serum HNL levels in the adult-onset Still’s disease(AOSD)patients with and without infection,as well as the healthy controls(HCs),were analyzed statistically in this study to evaluate the value of HNL for the diagnosis of AOSD.Methods:A total of 129 AOSD patients were enrolled,from whom blood samples were drawn and the AOSD diagnosis was confirmed through the review of the medical records,where the systemic score,demographic characteristics,clinical manifestations,and laboratory parameters were also collected for the patients;in addition,a total of 40 HCs were recruited among the blood donors from the healthcare center with the relevant information collected.The HNL test was done for the blood samples with the enzyme-linked immunosorbent assay and the analyses were done for the correlations of HNL with clinical manifestations and diagnostic effectiveness.Results:The serum HNL increased significantly in the patients with only AOSD as compared with that in the HCs(139.76±8.99 ng/mL vs.55.92±6.12 ng/mL;P<0.001).The serum HNL level was correlated with the white blood cell(WBC)count(r=0.335,P<0.001),neutrophil count(r=0.334,P<0.001),erythrocyte sedimentation rate(r=0.241,P=0.022),C-reactive protein(r=0.442,P<0.0001),and systemic score(r=0.343,P<0.0001)in the AOSD patients significantly.Patients with fever,leukocytosis≥15,000/mm^(3),and myalgia in the HNL-positive group were observed relatively more than those in the HNL-negative group(P=0.009,P=0.023,and P=0.007,respectively).HNL was a more sensitive indicator than ferritin and C-reactive protein(CRP)to differentiate the AOSD patients with bacterial infection from AOSD-only patients,and the Youden index was 0.6 for HNL and 0.29 for CRP.Conclusion:Serum HNL can be used as a biomarker for the diagnosis of the AOSD,and HNL is also observed to be associated with the disease activ

关键词： Adult-onset Still’s disease Human neutrophil lipocalin Diagnosis Biomarker Disease activity

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Additional risk factors associated with thrombosis and pregnancy morbidity in a unique cohort of antiphospholipid antibody-positive patients

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Chinese Medical Journal 2022年第6期135卷 658-664页

作者： Chun li Yu Zuo Song Zhang Una E.Makris David R.Karp zhanguo li Department of Rheumatology and Immunology Peking University People's HospitalBeijing 100044China Division of Rheumatology Department of Internal MedicineUniversity of MichiganAnn ArborMichiganUSA Division of Biostatistics Department of Clinical SciencesUT Southwestern Medical CenterDallasTXUSA Medical Service VA North Texas Health Care SystemDallasTXUSA Division of Rheumatic Disease Department of Internal MedicineThe University of Texas Southwestern Medical CenterDallasTXUSA

Background:Antiphospholipid syndrome(APS)is an autoimmune prothrombotic condition with significant morbidity.The objective of this study was to identify additional clinical and epidemiological risks of arterial thrombosis,venous thrombosis,and pregnancy morbidities in a large cohort of persistent antiphospholipid antibodies(aPLs)-positive carriers.Methods:This was a cross-sectional cohort study of 453 consecutive patients with a documented positive aPL who attended Peking University People's Hospital.Among 453 patients screened,297 patients had persistent positive aPL.We compared asymptomatic aPL carriers with thrombotic and obstetric APS patients.And the univariate analysis and multivariable logistic regression were used to evaluate the association between different risk factors and APS clinical manifestations.The levels of circulating markers of neutrophil extracellular traps(NETs)(cell-free DNA and citrullinated histone H3[Cit-H3])were assessed and compared among aPL-positive carriers with or without autoimmune disease and APS patients.Results:Additional risk factors associated with arterial thrombosis among aPL-positive carriers included:smoking(odds ratio[OR]=6.137,95%confidence interval[CI]=2.408-15.637,P=0.0001),hypertension(OR=2.368,95%CI=1.249-4.491,P=0.008),and the presence of underlying autoimmune disease(OR=4.401,95%CI=2.387-8.113,P<0.001).Additional risks associated with venous thrombosis among aPL carriers included:smoking(OR=4.594,95%CI=1.681-12.553,P=0.029)and the presence of underlying autoimmune disease(OR=6.330,95%CI=3.355-11.940,P<0.001).The presence of underlying autoimmune disease(OR=3.301,95%CI=1.407-7.744,P=0.006)is the additional risk,which demonstrated a significant association with APS pregnancy morbidity.Higher circulating levels of cell-free DNA and Cit-H3 were observed among APS patients and aPL patients with autoimmune diseases compared with those aPL carriers without underlying autoimmune diseases.Furthermore,control neutrophils that are conditioned with APS patients'sera have more

关键词： Antiphospholipid antibodies Antiphospholipid syndrome Arterial thrombosis Pregnancy risk Venous thrombosis

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Electrochemical Removal of Chlorophenol Pollutants by Reactive Electrode Membranes: Scale-Up Strategy for Engineered Applications

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Engineering 2022年第2期8卷 77-84页

作者： Shuzhao Pei Yi Wang Shijie You zhanguo li Nanqi Ren State Key Laboratory of Urban Water Resource and Environment School of EnvironmentHarbin Institute of TechnologyHarbin 150090China State Key Laboratory of NBC Protection for Civilian Beijing 102205China

Chlorophenols(CPs)are significant refractory pollutants that are highly toxic to humans and other organ-isms.Reactive electrode membranes(REMs)show considerable potential in the electrochemical removal of refractory pollutants by allowing flow-through operations with convection-enhanced mass transfer.However,relevant studies are commonly performed on the laboratory scale,and there is no straightfor-ward method that guarantees success in scaling up engineered REM reactors.In this study,we demon-strated that a tubular concentric electrode(TCE)configuration with a titanium suboxide ceramic anode and a stainless-steel cathode is suitable for large-scale CPs removal.Both theoretical and experi-mental results showed that the TCE configuration not only allows the electrode surface to be orthogonal to electric field lines everywhere,but also has an ohmic resistance that is inversely proportional to the length of the electrode.In addition,the TCE configuration can be operated in either the anode-to-cathode(AC)or the cathode-to-anode(CA)mode based on the flow direction,creating adjustable condi-tions for selective degradation of CPs.This was confirmed by 98%removal of 2,4-dichlorophenol(2,4-DCP)and 72.5%removal of chemical oxygen demand(COD)in the CA mode,in which the kinetic constant was one order of magnitude higher than that for the AC mode under flow-through single-pass operations.This can be explained by the lower activation energy and free energy in the CA mode,as revealed by the-oretical calculations and experimental measurements.The TCE configuration is also suitable for a numbering-up strategy to scale up the electrochemical reactor without increasing the ohmic resistance or decreasing the specific electrode area,achieving 99.4%removal of 2,4-DCP with an energy consump-tion of 1.5 kW·h·m^(-3) when three TCE modules were employed.This study presents a suitable electrode design configuration for the REM reactor,offering effective strategies to bridge the“Valley of Death”encountered when scaling up the electrochemica

关键词： Chlorophenols Reactive electrode membrane Tubular concentric electrode Scale-up

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Features of hyperintense white matter lesions and clinical relevance in systemic lupus erythematosus

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Chinese Medical Journal 2022年第8期135卷 962-970页

作者： Qian Guo Yang He Xia liu Xuguang Gao Jing Xu Xue li Yue Sun Yajuan Xiang Ru li zhanguo li Department of Rheumatology and Immunology Peking University People's HospitalBeijing 100044China Department of Rheumatology and Immunology Peking University International HospitalBeijing 102206China Department of Neurology Peking University People's HospitalBeijing 100044China Department of Radiology Peking University People's HospitalBeijing 100044China

Background: Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease characterized by complex and various clinical manifestations. The study aimed to analyze clinical features and cerebral magnetic resonance imaging (MRI) changes of hyperintense white matter (WM) lesions in SLE patients.Methods: This was a retrospective study based on a consecutive cohort of 1191 SLE patients;273 patients for whom cerebral MRI data were available were enrolled to assess hyperintense WM lesions associated with SLE. Patients were assigned to two groups, ie, with or without hyperintense WM lesions. The MRI assessment showed that the hyperintense WM lesions could be classified into three categories: type A, periventricular hyperintense WM lesions;type B, subcortical hyperintense WM lesions;and type C, multiple discrete hyperintense WM lesions. The clinical and MRI characteristics were analyzed. Factors related to hyperintense WM lesions were identified by multivariate logistic regression analysis.Results: Among the 273 SLE patients with available cerebral MRI scans, 35.9% (98/273) had hyperintense WM lesions associated with SLE. The proportions of types A, B, and C were 54.1% (53/98), 11.2% (11/98), and 92.9% (91/98), respectively. Fifty-one percents of the patients showed an overlap of two or three types. Type C was the most common subgroup to be combined with other types. Compared with those without hyperintense WM lesions, the patients with hyperintense WM lesions were associated with neuropsychiatric SLE (NPSLE), lupus nephritis (LN), hypertension, and hyperuricemia (P = 0.002,P = 0.018,P = 0.045, andP = 0.036, respectively). Significantly higher rates of polyserous effusions and cardiac involvement were found in the patients with hyperintense WM lesions (P = 0.029 andP = 0.027, respectively), and these patients were more likely to present with disease damage (P < 0.001). In addition, the patients with hyperintense WM lesions exhibited a higher frequency of proteinuria (P = 0.009) and higher levels of CD8+ T cells (

关键词： Systemic lupus erythematosus Hyperintense white matter lesions Magnetic resonance imaging

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Low-dose IL-2 mitigates glucocorticoid-induced Treg impairment and promotes improvement of SLE

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Signal Transduction and Targeted Therapy 2023年第5期8卷 2041-2043页

作者： Haotian Zhou Xiaozhen Zhao Ruijun Zhang Miao Miao Wenwen Pei Zijun li Yimin li Jing He zhanguo li Xiaolin Sun Department of Rheumatology and Immunology Clinical Immunology CenterBeijing Key Laboratory for Rheumatism Mechanism and Immune Diagnosis(BZ0135)Peking University People’s HospitalNo.11 Xizhimen South Street100044BeijingChina Department of Rheumatology Beijing Children’s HospitalCapital Medical UniversityNational Centre for Children’s Health100045BeijingChina Peking-Tsinghua Center for life Science BeijingChina

Dear Editor,Previous studies have proved that regulatory T cell(Treg)insufficiency contributed to the development of autoimmune conditions including systemic lupus erythematosus(SLE).Conventional immunosuppressive treatment was reported to downregulate beneficial Tregs together with pathogenic effector immune cells,which may impede a rapid achievement of optimal therapeutic effects.

关键词： glucocorticoid lupus erythematosus SLE

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Decorating rare-earth fluoride upconversion nanoparticles on AuNRs@Ag core-shell structure for NIR light-mediated photothermal therapy and bioimaging

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Journal of Rare Earths 2022年第2期40卷 193-200,I0001页

作者： Jingzhi Dou Bei Chen Guixia liu Xiangting Dong Wensheng Yu Jinxian Wang Yunxiao Zhang zhanguo li Jiang Zhu Key Laboratory of Applied Chemistry and Nanotechnology at Universities of Jilin Province Changchun University of Science and TechnologyChangchun 130022China Key Laboratory of Artificial Micro-and Nano-Structures of Ministry of Education School of Physics and TechnologyWuhan UniversityWuhan 430072China Tianjin Jinhang Technical Physics Institute Tianjin 300070China School of Optoelectronic Engineering Changchun University of Science and TechnologyChangchun 130022China School of Foreign Languages Changchun University of Science and TechnologyChangchun 130022China

Photothermal therapy(PTT)has presented its inherent application value in cancer treatment.Nevertheless,single-functional photothermal materials cannot meet the precise diagnosis and treatment of cance r.Therefo re,it is important to design a nanocomposite that has both high therapeutic efficiency and multimodal imaging capabilities.In our work,a new nanostructure of gold nanorods(AuNRs)with silver shells decorated by BaGdF5:Yb^(3+),Er^(3+)nanoparticle was synthesized by a simple way.The biostability of AuNRs is increased by coating with silver shells,and the AuNR@Ag nanoparticles can be used as excellent surface enhanced Raman scattering(SERS)probe.Moreover,the modification of BaGdF5:Yb^(3+),Er^(3+)nanoparticles provides the possibility of real-time optical imaging of the tumor area.Under the irradiation of NIR laser,the AuNR@Ag/BaGdF5:Yb^(3+),Er^(3+)nanocomposites(NCs)have strong upconversion emission and excellent photothermal conversion efficiency.Meanwhile,the NCs show low cytotoxicity and good biocompatibility in MTT cytotoxicity test.Moreover,the NCs are also exceptional contrast agents for CT imaging.For in vitro photothermal therapy test,NCs show excellent killing efficiency on tumor cells.Therefore,the multifaceted research of AuNR@Ag/BaGdF5:Yb^(3+),Er^(3+)multifunctional nanomaterials provides a break for high-efficiency tumor photothermal therapy and multimodal imaging.

关键词： Multifunctional nanocomposites Photothermal therapy Multimodal imaging Rare earths

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Development of in situ characterization techniques in molecular beam epitaxy

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Journal of Semiconductors 2024年第3期45卷 9-32页

作者： Chao Shen Wenkang Zhan Manyang li Zhenyu Sun Jian Tang Zhaofeng Wu Chi Xu Bo Xu Chao Zhao zhanguo Wang Laboratory of Solid State Optoelectronics Information Technology Institute of SemiconductorsChinese Academy of SciencesBeijing 100083China College of Materials Science and Opto-Electronic Technology University of Chinese Academy of SciencesBeijing 101804China School of Physics Science and Technology Xinjiang UniversityUrumqi 830046China School of New Energy and Electronics Yancheng Teachers UniversityYancheng 224002China Key Laboratory of Optoelectronic Materials and Devices Institute of SemiconductorsChinese Academy of SciencesBeijing 100083China

Ex situ characterization techniques in molecular beam epitaxy(MBE)have inherent limitations,such as being prone to sample contamination and unstable surfaces during sample transfer from the MBE chamber.In recent years,the need for improved accuracy and reliability in measurement has driven the increasing adoption of in situ characterization techniques.These techniques,such as reflection high-energy electron diffraction,scanning tunneling microscopy,and X-ray photoelectron spectroscopy,allow direct observation of film growth processes in real time without exposing the sample to air,hence offering insights into the growth mechanisms of epitaxial films with controlled properties.By combining multiple in situ characterization techniques with MBE,researchers can better understand film growth processes,realizing novel materials with customized properties and extensive applications.This review aims to overview the benefits and achievements of in situ characterization techniques in MBE and their applications for material science research.In addition,through further analysis of these techniques regarding their challenges and potential solutions,particularly highlighting the assistance of machine learning to correlate in situ characterization with other material information,we hope to provide a guideline for future efforts in the development of novel monitoring and control schemes for MBE growth processes with improved material properties.

关键词： epitaxial growth thin film in situ characterization molecular beam epitaxy(MBE)

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Identification of lipopolysaccharide-binding protein as a novel citrullinated autoantigen in rheumatoid arthritis

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Rheumatology & Autoimmunity 2022年第1期2卷 5-14页

作者： Xiaozhen Zhao Yuling Chen Wen Wen Yongjing Cheng Ru li Xu liu Yuhui li Rulin Jia Haiteng Deng zhanguo li Xiaolin Sun Clinical Immunology Center Department of Rheumatology and ImmunologyPeking University People's Hospital BeijingChina 2Department of RheumatologyBeijing Children's Hospital Affiliated to Capital Medical UniversityBeijingChina MOE Key Laboratory of Bioinformatics School of Life SciencesTsinghua UniversityBeijingChina Beijing Tsinghua Changgung Hospital Tsinghua UniversityBeijingChina National Center of Gerontology Department of Rheumatology and ImmunologyBeijing HospitalBeijingChina Peking-Tsinghua Center for life Science BeijingChina

Background:A specific feature of the autoimmune response in rheumatoid arthritis(RA)is the presence of anti-citrullinated protein antibodies(ACPAs)in patient sera.These antibodies can appear several years before disease onset and are involved in the development of RA.Objective:We performed proteomic analysis by mass spectroscopy to identify novel citrullinated antigens and autoantibodies in RA patients.Methods:Polypeptides isolated from the sera of RA patients were identified by Orbitrap high-precision mass spectrometry and then citrulline-containing proteins were selected.The levels of ACPAs against these newly identified citrullinated autoantigens in sera of 100 RA patients and 50 healthy controls were determined by enzyme-linked immunosorbent assays.Results:A total of 135 proteins were identified in RA patients and the protein profile included 11 citrulline-containing antigens.Three of the 11 citrullinated proteins had been reported in previous studies.ACPAs against the novel citrullinated epitopes from these proteins were increased in sera from the RA patients compared with those from healthy controls.Autoantibodies against one of the citrullinated antigens,lipopolysaccharide-binding protein(LBP),was significantly increased in RA patients and associated with disease activities.The titer of anti-citrullinated LBP antibodies(anti-cLBP)was closely related to the infection incidence in RA patients.Conclusion:Serum protein analysis by high-precision proteomic technology is a feasible method to identify novel citrullinated epitopes in RA patients.Anti-cLBP antibodies are associated with disease severity and infection in RA patients.

关键词： ACPA lipopolysaccharide-binding protein rheumatoid arthritis

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Mid-wavelength nBn photodetector with high operating temperature and low dark current based on InAs/InAsSb superlattice absorber

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Chinese Optics Letters 2024年第1期22卷 123-127页

作者：曹澎王天财彭红玲李占国 Qiandong Zhuang 郑婉华 Laboratory of Solid-State Optoelectronics Information Technology Institute of SemiconductorsChinese Academy of SciencesBeijing 100083China Center of Materials Science and Optoelectronics Engineering University of Chinese Academy of SciencesBeijing 100049China College of Electronic and Communication Engineering University of Chinese Academy of SciencesBeijing 100049China State Key Laboratory on Integrated Optoelectronics Institute of SemiconductorsChinese Academy of SciencesBeijing 100083China School of Physics Changchun Normal UniversityChangchun 130022China Physics Department Lancaster UniversityLancaster LA14YBUK

In this paper,we demonstrate nBn InAs/InAsSb type II superlattice(T2SL)photodetectors with AlAsSb as the barrier that targets mid-wavelength infrared(MWIR)detection.To improve operating temperature and suppress dark current,a specific Sb soaking technique was employed to improve the interface abruptness of the superlattice with device passivation using a SiO_(2) layer.These result in ultralow dark current density of 6.28×10^(-6)A/cm^(2)and 0.31 A/cm^(2)under-600 mV at 97 K and297 K,respectively,which is lower than most reported InAs/InAsSb-based MWIR photodetectors.Corresponding resistance area product values of 3.20×10^(4)Ω·cm^(2)and 1.32Ω·cm^(2)were obtained at 97 K and 297 K.A peak responsivity of 0.39 A/W with a cutoff wavelength around 5.5μm and a peak detectivity of 2.1×10^(9)cm·Hz^(1/2)/W were obtained at a high operating temperature up to 237 K.

关键词： mid-wavelength infrared photodetector InAs/InAsSb superlattice high operating temperature dark current

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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

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Signal Transduction and Targeted Therapy 2022年第4期7卷 1194-1201页

作者： 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 Department of Rheumatology and Immunology Peking University People’s Hospital100044 BeijingChina Department of Rheumatology and Immunology The First Affiliated Hospital of Wannan Medical College241000 WuhuAnhuiChina Department of Clinical Epidemiology and Biostatistics Peking University People’s Hospital100044 BeijingChina Beijing Key Laboratory for Rheumatism Mechanism and Immune Diagnosis(BZ0135) BeijingChina Peking-Tsinghua Center for life Sciences BeijingChina State Key Laboratory of Natural and Biomimetic Drugs School of Pharmaceutical SciencesPeking UniversityBeijingChina

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-ESRline 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.

关键词： patients placebo methotrexate

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