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Safety and efficacy of T-614 in the treatment of patients with active rheumatoid arthritis： a double blind, randomized, placebo-controlled and multicenter trial

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Chinese Medical Journal 2008年第7期121卷 615-619页

作者： Lu Liang-jing TENGJia-lin BAO Chun-de HAN Xing-hai SUN Ling-yun XU Jiang-hua LI Xing-fu wu hua-xiang Department of Rheumatology Renji Hospital Shanghai Jiao TongUniversity Shanghai 200001 China Department of Rheumatology Changhai Hospital Second MilitaryUniversity Shanghai 200001 China Department of Rheumatology Gulou Hospital Nanjing UniversityNanjing Jiangsu 210000 China Department of Rlaeumatology Frist Alliliated Hospital AnlluiMedical University Hefei Anhui 230000 China Department of Rheumatology Qilu Hospital of ShandongUniversity Jinan Shandong 250012 China Department of Rheumatology Second Affiliated HospitalZhejiang University Hangzhou Zhejiang 510000 China

Background A novel anti-rheumatic drug, T-614, has been shown to have an anti-inflammatory effect and to improve abnormal immunological findings in rheumatoid arthritis （RA）. To assess the safety and efficacy of T-614 versus placebo in patients with active RA we conducted a 24-week clinical study in 280 Chinese patients. Methods In a multicenter, randomized, double blind, placebo controlled study, 280 patients were randomly assigned to receive placebo （n=95） or T-614 at 50 mg （n=93） or 25 mg （n=92） daily. Active disease was defined by 4 of the following 5 criteria：〉5 tender joints, 〉3 swollen joints, morning stiffness lasting for 〉60 minutes, and Westergren erythrocyte sedimentation rate （ESR）〉28 mm/h, the assessment of pain at the rest by patient as moderate or severe. Clinical and laboratory parameters were analyzed at baseline, 2, 4, 6, 12, 18 and 24 weeks. The primary efficacy variable at week 24 was the American College of Rheumatology （ACR） response rate using the intent-to-treat population. Results The ACR response rate was significantly higher in the T-614 treatment group compared with the placebo group within 8 weeks after the initiation of treatment. After 24 weeks, the 25 mg/d and 50 mg/d dosage groups and the placebo group showed 39.13%, 61.29% and 24.21% in ACR20 and 23.91%, 31.18% and 7.37% in ACR50, respectively. A time-response in ACR response was observed, with clear superiority for the 25 mg/d and 50 mg/d dosage groups compared to placebo （P〈0.0001）, and the 50 mg/d dose compared to the 25 mg/d dose （P〈0.05） when using the ACR response analyses after 24 weeks. ESR and c-reactive protein （CRP） were significantly different in the treatment groups after 24 weeks. The incidence of adverse events （AEs） was not significantly higher with T-614 than with placebo, but upper abdominal discomfort, leucopenia, elevated serum alanine aminotransferase （sALT）, skin rash and/or pruritus were more common in the 50 mg and 25 mg dosage groups. Conclusion T-614, a n

关键词： arthritis, rheumatoid T-614 randomized controlled trial

Dual-ion carrier storage through Mg^(2+) addition for high-energy and long-life zinc-ion hybrid capacitor

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International Journal of Minerals,Metallurgy and Materials 2024年第1期31卷 179-185页

作者： Junjie Zhang xiang wu School of Materials Science and Engineering Shenyang University of TechnologyShenyang 110870China

Cation additives can efficiently enhance the total electrochemical capabilities of zinc-ion hybrid capacitors (ZHCs).However their energy storage mechanisms in zinc-based systems are still under ***,we modulate the electrolyte and achieve dual-ion storage by adding magnesium *** we assemble several Zn//activated carbon devices with different electrolyte concentrations and investigate their electrochemical reaction dynamic *** zinc-ion capacitor with Mg^(2+)mixed solution delivers 82 mAh·g^(-1)capacity at 1 A·g^(-1) and maintains 91%of the original capacitance after 10000 *** is superior to the other assembled zinc-ion devices in single-component *** finding demonstrates that the double-ion storage mechanism enables the superior rate performance and long cycle lifetime of ZHCs.

关键词： zinc-ion hybrid capacitor MgSO_(4) electrolyte rate performance storage mechanism

Development of antibody-drug conjugates in cancer:Overview and prospects

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Cancer Communications 2024年第1期44卷 3-22页

作者： Dan-Yun Ruan Hao-xiang wu Qi Meng Rui-hua Xu Department of Clinical Research Sun Yat-sen University Cancer CenterState Key Laboratory of Oncology in South ChinaGuangdong Provincial Clinical Research Center for CancerSun Yat-sen UniversityGuangzhouGuangdongP.R.China Research Unit of Precision Diagnosis and Treatment for Gastrointestinal Cancer Chinese Academy of Medical SciencesGuangzhouGuangdongP.R.China Department of Medical Oncology Sun Yat-sen University Cancer CenterState Key Laboratory of Oncology in South ChinaGuangdong Provincial Clinical Research Center for CancerSun Yat-sen UniversityGuangzhouGuangdongP.R.China

In recent years,remarkable breakthroughs have been reported on antibody-drug conjugates(ADCs),with 15 ADCs successfully entering the market over the past *** substantial development has positioned ADCs as one of the fastest-growing domains in the realm of anticancer drugs,demonstrating their efficacy in treating awide array of ***,there is still an unmet clin-ical need forwider application,better efficacy,and fewer side effects of *** ADC generally comprises an antibody,a linker and a payload,and the combina-tion has profound effects on drug structure,pharmacokinetic profile and ***,optimization of the key components provides an opportunity to develop ADCs with higher potency and fewer side *** this review,we comprehen-sively reviewed the current development and the prospects of ADC,provided an analysis of marketed ADCs and the ongoing pipelines globally as well as in China,highlighted several ADC platforms and technologies specific to different pharmaceutical enterprises and biotech companies,and also discussed the new related technologies,possibility of next-generation ADCs and the directions of clinical research.

关键词： companies breakthrough payload

Differentiation and immunosuppressive function of CD19^(+)CD24^(hi)CD27^(+) regulatory B cells are regulated through the miR-29a-3p/NFAT5 pathway

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Hepatobiliary & Pancreatic Diseases International 2024年第5期23卷 472-480页

作者： Jin-Yang Li Tian-Shuo Feng Ji Gao Xin-xiang Yang xiang-Cheng Li Zhen-hua Deng Yong-xiang Xia Zheng-Shan wu Hepatobiliary Center the First Affiliated Hospital of Nanjing Medical UniversityNanjing 210029China Key Laboratory of Liver Transplantation Chinese Academy of Medical SciencesNanjing 210029China NHC Key Laboratory of Living Donor Liver Transplantation Nanjing Medical UniversityNanjing 210029China

Background: Regulatory B cells(Bregs) is an indispensable element in inducing immune tolerance after liver transplantation. As one of the microRNAs(miRNAs), mi R-29a-3p also inhibits translation by degrading the target mRNA, and yet the relationship between Bregs and mi R-29a-3p has not yet been fully explored. This study aimed to investigate the impact of miR-29a-3p on the regulation of differentiation and immunosuppressive functions of memory Bregs(m Bregs) and ultimately provide potentially effective therapies in inducing immune tolerance after liver transplantation. Methods: Flow cytometry was employed to determine the levels of Bregs in peripheral blood mononuclear cells. TaqMan low-density array miRNA assays were used to identify the expression of different miRNAs, electroporation transfection was used to induce mi R-29a-3p overexpression and knockdown, and dual luciferase reporter assay was used to verify the target gene of miR-29a-3p. Results: In patients experiencing acute rejection after liver transplantation, the proportions and immunosuppressive function of m Bregs in the circulating blood were significantly impaired. mi R-29a-3p was found to be a regulator of m Bregs differentiation. Inhibition of miR-29a-3p, which targeted nuclear factor of activated T cells 5(NFAT5), resulted in a conspicuous boost in the differentiation and immunosuppressive function of m Bregs. The inhibition of mi R-29a-3p in CD19~+ B cells was capable of raising the expression levels of NFAT5, thereby promoting B cells to differentiate into m Bregs. In addition, the observed enhancement of differentiation and immunosuppressive function of m Bregs upon mi R-29a-3p inhibition was abolished by the knockdown of NFAT5 in B cells. Conclusions: mi R-29a-3p was found to be a crucial regulator for m Bregs differentiation and immunosuppressive function. Silencing mi R-29a-3p could be a potentially effective therapeutic strategy for inducing immune tolerance after liver transplantation.

关键词： Regulatory B cells miR-29a-3p NFAT5 Liver transplantation

Ballistic performances of the hourglass lattice sandwich structures under high-velocity fragments

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Defence Technology（防务技术） 2024年第1期31卷 312-325页

作者： He-xiang wu Jia Qu Lin-zhi wu Key Laboratory of Advanced Ship Materials and Mechanics College of Aerospace and Civil EngineeringHarbin Engineering UniversityHarbin150001China School of Civil Engineering Northeast Forestry UniversityHarbin150040China

In this paper,the numerical simulation method is used to study the ballistic performances of hourglass lattice sandwich structures with the same mass under the vertical incidence of *** is paid to elucidating the influences of rod cross-section dimensions,structure height,structure layer,and rod inclination angle on the deformation mode,ballistic performances,and ability to change the ballistic direction of *** results show that the ballistic performances of hourglass lattice sandwich structures are mainly affected by their structural *** this respect,structural parameters optimization of the hourglass lattice sandwich structures enable one to effectively improve their ballistic limit velocity and,consequently,ballistic performances.

关键词： Hourglass lattice sandwich structures Ballistic performances high-velocity Finite element analysis

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房地产经纪机构的电子商务运作模式

重庆建筑大学学报 2005年第4期27卷 93-96页

作者：吴翔华胡桓河海大学商学院江苏南京210013

对于房地产经纪企业而言,建立企业内部网INTRANET及企业的WEB站点的巨大投入阻碍了电子商务发展,其中大多数仅停留在“网上黄页”的层面。因此,必须结合中小房地产经纪企业发展实际,建立以公共信息平台为基础,以电子商务系统为依托,以... 详细信息

对于房地产经纪企业而言,建立企业内部网INTRANET及企业的WEB站点的巨大投入阻碍了电子商务发展,其中大多数仅停留在“网上黄页”的层面。因此,必须结合中小房地产经纪企业发展实际,建立以公共信息平台为基础,以电子商务系统为依托,以电子商务技术为核心,兼顾传统的电子商务运作模式,构建具有中小型房地产经纪企业特色的电子商务系统。

关键词：房地产经纪电子商务

Microstructure and mechanical properties of a cast TRIP-assisted multiphase stainless steel

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China Foundry 2024年第3期21卷 221-228页

作者： Meng-xin Wang Zi-xiang wu Jing-yu He xiang Chen School of Materials Science and Engineering Tsinghua UniversityBeijing 100084China Key Laboratory for Advanced Materials Processing Technology Ministry of EducationBeijing 100084China

Stainless steels are used in a wide range of complex environments due to their excellent corrosion *** stainless steels can offer an excellent combination of strength,toughness and corrosion resistance due to the coexistence of different *** microstructure and mechanical properties of a novel cast multiphase stainless steel,composed of martensite,ferrite,and austenite,were investigated following appropriate heat treatment processes:solution treatment at 1,050℃ for 0.5 h followed by water quenching to room temperature,and aging treatment at 500℃ for 4 h followed by water quenching to room *** show reversed austenite is formed by diffusion of Ni element during aging process,and the enrichment of Ni atoms directly determines the mechanical stability of *** austenite with a lower Ni content undergoes a martensitic transformation during plastic *** tensile strength of the specimen exceeds 1,100 MPa and the elongation exceeds 24%after solid solution,and further increases to 1,247 MPa and 25%after aging *** enhancement is due to the TRIP effect of austenite and the precipitation of the nanoscale G-phase pinning dislocations in ferrite and martensite.

关键词： multiphase stainless steel mechanical properties TRIP effect reversed austenite G-phase

Performance improvements in complementary metal oxide semiconductor devices and circuits based on fin field-effect transistors using 3-nm ferroelectric Hf_(0.5)Zr_(0.5)O_(2)

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Rare Metals 2024年第7期43卷 3242-3249页

作者： Zhao-Hao Zhang Yan-Na Luo Gao-Bo Xu Jia-Xin Yao Zhen-hua wu Hong-Bin Zhao Qing-Zhu Zhang hua-xiang Yin Jun Luo Wen-wu Wang Hai-Ling Tu Integrated Circuit Advanced R&D Center Institute of Microelectronics of Chinese Academy of SciencesBeijing 100029China School of Integrated Circuits University of Chinese Academy of SciencesBeijing 100049China State Key Laboratory of Advanced Materials for Smart Sensing General Research Institute for Nonferrous MetalsBeijing 100088China

In this work,a conventional HfO_(2) gate dielectric layer is replaced with a 3-nm ferroelectric(Fe) HZO layer in the gate stacks of advanced fin field-effect transistors(FinFETs).Fe-induced characteristics,e.g.,negative drain induced barrier lowering(N-DIBL) and negative differential resistance(NDR),are clearly observed for both p-and n-type HZO-based *** characteristics are attributed to the enhanced ferroelectricity of the 3-nm hafnium zirconium oxide(HZO) film,caused by Al doping from the TiAlC capping *** mechanism is verified for capacitors with structures similar to the *** to the enhanced ferroelectricity and N-DIBL phenomenon,the drain current(I_(DS))of the HZO-FinFETs is greater than that of HfO_(2)-FinFETs and obtained at a lower operating ***,circuits based on HZO-FinFET achieve higher performance than those based on HfO_(2)-FinFET at a low voltage drain(V_(DD)),which indicates the application feasibility of the HZO-FinFETs in the ultralow power integrated circuits.

关键词： FinFET Ferroelectric Hafnium zirconium oxide Subthreshold swing Low power

Multi-performance evaluation of high-throughput accelerated corrosion test for high-strength low-alloy 921A steel

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Journal of Iron and Steel Research International 2024年第5期31卷 1260-1278页

作者： Cong-cong Du Ming-hua Qin Zhan-fang wu Dong-ling Li Lei Zhao xiang-yang Li Hai-zhou Wang Beijing Advanced Innovation Center for Materials Genome Engineering National Center for Materials Service SafetyUniversity of Science and Technology BeijingBeijing100083China China Iron and Steel Research Institute Group Co. Ltd.Beijing100081China Beijing Advanced Innovation Center for Materials Genome Engineering Central Iron and Steel Research InstituteBeijing100081China

The corrosion behavior of high-strength low-alloy 921A steel in a simulated marine atmospheric environment was studied using a high-throughput experimental *** corrosion behavior,corrosion morphology,and corrosion products of 921A steels were analyzed using various techniques,including corrosion mass loss method,polarization curve,white-light interferometry,scanning electron microscopy,energy-dispersive spectrometry,microbeam X-ray fluorescence spectrometry,X-ray diffraction technique,and X-ray photoelectron *** test results indicated that 921A steel exhibits better corrosion resistance than Q450NQR1 steel in simulated harsh atmospheric environments,as evidenced by a lower corrosion mass loss rate throughout the corrosion *** corrosion products of both steels consisted ofα-FeOOH,Fe_(3)O_(4),andγ-FeOOH,withα-FeOOH being more prevalent in the rust layer of 921A steel than in Q450NQR1 *** inner rust layer of 921A steel also exhibited an appositional enrichment region of Cr,Ni,Mo,and V,leading to its superior corrosion resistance compared to that of Q450NQR1 *** efficacy of high-throughput accelerated corrosion experimental methods was highlighted for evaluating the corrosion resistance of steel materials in harsh environmental *** findings suggest that 921A steel exhibits better corrosion resistance compared to Q450NQR1 steel and has the potential to be more suitable in harsh marine atmospheric *** characterization of the rust layer structures and composition reveals the parallel enrichment of certain elements in the inner rust layer of 921A steel,which enhances its corrosion resistance.

关键词： Atmospheric corrosion High-throughput experimental method High-strength low-alloy steel Corrosion characteristics Rust layer Element enrichment