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Laboratory Safety of Dupilumab,and Its Effect on Inflammatory Biomarkers,in Chinese Adults With Moderate-to-Severe Atopic Dermatitis:An Analysis of a Randomized,Double-Blind Phase III Study

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International Journal of Dermatology and Venereology 2022年第4期5卷 218-225页

作者： Yan Zhao Li-Ming Wu Qian-Jin Lu Xing-Hua Gao Xiao-Hong Zhu Xu Yao Lin-Feng Li Wei Li Yang-Feng Ding Zhi-Qiang Song ling-ling liu Ning-Ning Dang Chun-Lei Zhang Xiao-Ming liu Jun Gu Jin-Yan Wang Song-Mei Geng Quan-Zhong liu Yi-Feng Guo Li Dong Shelley Li Christine Xu John T.O’Malley Elizabeth Laws Nikhil Amin Ashish Bansal Min Wang Jian-Zhong Zhang Department of Dermatology Peking University People’s HospitalBeijing 100044China Hangzhou First People’s Hospital HangzhouZhejiang 310006China The Second Xiangya Hospital of Central South University ChangshaHunan 410011China The First Hospital of China Medical University ShenyangLiaoning 110001China Wuxi Second People’s Hospital WuxiJiangsu 214002China Hospital for Skin Diseases Institute of DermatologyChinese Academy of Medical SciencesNanjingJiangsu 210042China Beijing Friendship Hospital Capital Medical UniversityBeijing 100050China Huashan Hospital Fudan UniversityShanghai 200040China Shanghai Skin Disease Hospital Shanghai 200040China The Southwest Hospital of AMU Chongqing 400038China Peking University First Hospital Beijing 100034China Jinan Central Hospital JinanShandong 250013China Peking University Third Hospital Beijing 100191China University of Hong Kong-Shenzhen Hospital ShenzhenGuangdong 518040China Changhai Hospital of Shanghai Shanghai 200433China Ningbo No.2 Hospital NingboZhejiang 315099China The Second Affiliated Hospital of Xi’an Jiaotong University Xi’anShaanxi 710004China Tianjin Medical University General Hospital Tianjin 300052China Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine Shanghai 200092China Research&Development SanofiBridgewaterNJ 08807USA Research&Development RegeneronTarrytownNY 10591USA Medical Sanofi ChinaShanghai 200040China.

Objective:Limited information is available on the use of dupilumab for the treatment of atopic dermatitis(AD)in the Chinese ***:We analyzed laboratory data from a previously published randomized,double-blind phase III trial(NCT03912259)to provide further insight into the safety of dupilumab in Chinese adults with moderate to severe *** trial participants received either 300 mg of dupilumab or placebo every 2 weeks for 16 ***,blood chemistry,serum thymus and activation-regulated chemokine(TARC),and total immunoglobulin E(IgE)were ***:In total,82 participants received dupilumab and 83 received *** the exception of eosinophil counts of>0.8×109/L,which were found less frequently with dupilumab(9.8%)than with placebo(18.7%),the hematology and blood chemistry values were generally stable in both treatment *** were no clinically significant differences between the dupilumab and placebo groups,and no participants developed treatment-emergent abnormalities of potential clinical ***,compared with placebo,greater decreases in serum lactate dehydrogenase(mean change,−97.4 vs.−33.5 IU/L),TARC(median percent change,−78.6%vs.−30.8%),and total IgE(median percent change,−53.4%vs.−0.2%)were observed with dupilumab than placebo at week ***:Dupilumab demonstrated a favorable laboratory safety profile in Chinese adults with moderate to severe AD.

关键词： atopic dermatitis dupilumab laboratory safety Chinese

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Bullous pemphigoid associated with acquired hemophilia A: A case report

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World Journal of Clinical Cases 2025年第4期13卷 28-33页

作者： Su-Ye Hu Meng-Can Li Zi-Jia Hao Xu-Ya Chai Pei-Sai Li Yang liu Li-Xia liu Ying Xu Pan-Pan Yang ling-E Li Department of Dermatology Shijiazhuang Traditional Chinese Medicine HospitalShijiazhuang 050051Hebei ProvinceChina Graduate School Hebei University of Traditional Chinese MedicineShijiazhuang 050051Hebei ProvinceChina Department of Pathology Shijiazhuang Traditional Chinese Medicine HospitalShijiazhuang 050051Hebei ProvinceChina

BACKGROUND Acquired hemophilia A (AHA) is a rare and potentially severe bleeding disordercaused by circulating autoantibodies against factor Ⅷ (FⅧ). In approximately50% of the patients, the condition is associated with autoimmune diseases,cancers, medication use, pregnancy, and the post-partum period. Bullous pemphigoid(BP) is a chronic autoimmune subepidermal blistering disease associatedwith tissue-bound and circulating autoantibodies against BP antigens 180 (BP180)and 230 (BP230). AHA-associated BP has a high mortality rate;hence, the understandingof this disease must *** SUMMARY A 69-year-old man presented with erythema, blisters, blood blisters, and crustsaccompanied by severe pruritus for more than 20 days, and ecchymosis andswelling on his left upper arm for 3 days. Pathological examination revealed asubepidermal blister that contained eosinophils. Laboratory tests showed that theBP180 autoantibody levels had increased, isolated activated partial thromboplastintime was notably prolonged (115.6 s), and coagulation FⅧ activity wasextremely low (< 1.0%). Furthermore, the FⅧ inhibitor titer had greatlyincreased (59.2 Bethesda units). Therefore, the patient was diagnosed as having BP associated with AHA, prescribed 0.05% topical halometasone cream, and transferred to a higher-level hospitalfor effective treatment;however, he died after 2 *** AHA associated BP is rare, dangerous, and has a high mortality rate. Therefore, its timely diagnosis and effectivetreatment are necessary.

关键词： Bullous pemphigoid Acquired hemophilia A Acquired hemophilia A FactorⅧ Case report

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胰岛素对高糖条件下体外培养的大鼠牙囊细胞增殖、分化的影响

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上海口腔医学 2008年第4期17卷 425-429页

作者：鄂玲玲刘洪臣徐璐璐王东胜吕娇解放军总医院口腔医学研究所北京100853

目的:探讨胰岛素对高糖条件下体外培养的大鼠牙囊细胞(dental follicle cells,DFC_s)增殖、分化的影响。方法:取出生7d的SD大鼠上、下颌磨牙牙囊,原代培养牙囊细胞,选取生长状态良好的第4代细胞,在糖生理浓度(5.5mmol/L)和高糖条件下(16... 详细信息

目的:探讨胰岛素对高糖条件下体外培养的大鼠牙囊细胞(dental follicle cells,DFC_s)增殖、分化的影响。方法:取出生7d的SD大鼠上、下颌磨牙牙囊,原代培养牙囊细胞,选取生长状态良好的第4代细胞,在糖生理浓度(5.5mmol/L)和高糖条件下(16.5 mmol/L和49.5 mmol/L)与6μg/mL胰岛素共同孵育,分别于培养1、3、7、9d时采用MTT法和1～7d采用碱性磷酸酶试剂盒检测胰岛素对高糖条件下体外培养的大鼠牙囊细胞增殖、分化的影响。采用SPSS13.0软件包对数据进行统计学分析。结果:所培养的细胞波形丝蛋白阳性,角蛋白阴性。在第l、3天,16.5mmol/L葡萄糖促进第4代大鼠牙囊细胞的增殖,而49.5 mmol/L葡萄糖抑制牙囊细胞的增殖,胰岛素下调16.5 mmol/L葡萄糖下牙囊细胞的增殖,上调49.5 mmol/L葡萄糖下牙囊细胞增殖;在第7、9天,高糖促进牙囊细胞增殖,胰岛素上调高精下牙囊细胞的增殖。在1～7d内,高糖提高第4代大鼠牙囊细胞碱性磷酸酶活性,胰岛素下调高糖下牙囊细胞的碱性磷酸酶活性(P<0.05)。结论:本实验培养的细胞是来源于外胚层间充质的牙囊细胞。实验结果表明,胰岛素能纠正急性高糖对大鼠牙囊细胞增殖和分化的影响。

关键词：牙囊细胞葡萄糖胰岛素细胞培养大鼠

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积雪草醇提物对2型糖尿病ZDF大鼠肝脏胰岛素抵抗的影响

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中国实验方剂学杂志 2017年第10期23卷 104-110页

作者：吴莉娟孙文吴丽丽高健穆晓红秦灵灵刘铜华成都中医药大学临床医学院成都610072 北京中医药大学中医养生所北京100029 对外经济贸易大学信息学院北京100029 北京中医药大学东直门医院北京100700 北京中医药大学北京100029

目的:探讨积雪草醇提物对2型糖尿病(type 2 diabetes mellitus,T2DM)ZDF(Zucker diabetic fatty)大鼠肝脏胰岛素抵抗的作用机制。方法:6只雄性ZDF(fa/+)大鼠设为正常组,成模的雄性ZDF(fa/fa)大鼠18只根据体重及随机血糖分层随机分为3组... 详细信息

目的:探讨积雪草醇提物对2型糖尿病(type 2 diabetes mellitus,T2DM)ZDF(Zucker diabetic fatty)大鼠肝脏胰岛素抵抗的作用机制。方法:6只雄性ZDF(fa/+)大鼠设为正常组,成模的雄性ZDF(fa/fa)大鼠18只根据体重及随机血糖分层随机分为3组,模型组(生理盐水10 m L·kg^(-1)),二甲双胍(二甲双胍片0.18 g·kg^(-1)·d^(-1))组,积雪草(积雪草醇提物0.1 g·kg^(-1)·d^(-1))组。每2周监测大鼠体重,随机血糖(random blood glucose,RBG),空腹血糖(fasting blood glucose,FBG);给药6周后取材,检测大鼠空腹血糖及空腹血清胰岛素(fasting serum insulin,FINS),并计算胰岛素抵抗指数(homeostasis model of assessment for insulin resistence index,HOMA-IR)。采用实时荧光定量聚合酶链式反应(Real-time polymerase chain reaction,Real-time PCR)法检测各组大鼠肝脏组织中胰岛素受体2(insulin receptor substrate 2,IRS2),3-磷酸肌醇依赖性蛋白激酶1(3-phosphoinositide-dependent protein kinase1,PDK1)及葡萄糖转运蛋白2(glucose transporter 2,GLUT2)mRNA的表达情况;免疫组化法观察肝脏中PDK1,IRS2蛋白表达情况。结果:与模型组比较,积雪草组及二甲双胍组均可显著改善ZDF大鼠体重,RBG,FBG水平及HOMA-IR(P<0.01);积雪草组IRS2,PDK1及GLUT2 mRNA相对表达量及PDK1,IRS2蛋白表达水平显著增加(P<0.01)。结论:积雪草醇提物能有效改善2型糖尿病ZDF大鼠肝脏胰岛素抵抗,其作用机制可能与胰岛素信号传导通路中IRS2,PDK1的表达及葡萄糖转运中GLUT2的表达相关。

关键词：积雪草醇提物 2型糖尿病 ZDF大鼠肝脏胰岛素抵抗

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芨芨草纤维形态的研究

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石河子大学学报（自然科学版） 2004年第2期22卷 154-156页

作者：周玲玲刘升学石河子大学生物工程学院新疆石河子832000

对新疆石河子盐碱荒地上栽培的芨芨草茎秆的纤维进行了详细研究,通过扫描电镜制片观察,发现芨芨草茎秆表皮下有20～30层厚壁细胞连接成的纤维组织带,我们用显微镜测量法对其纤维进行了测量,结果如下:纤维的平均长度为1.11mm,平均宽度为... 详细信息

对新疆石河子盐碱荒地上栽培的芨芨草茎秆的纤维进行了详细研究,通过扫描电镜制片观察,发现芨芨草茎秆表皮下有20～30层厚壁细胞连接成的纤维组织带,我们用显微镜测量法对其纤维进行了测量,结果如下:纤维的平均长度为1.11mm,平均宽度为9.4μm,长宽比为118,细胞壁平均厚度为2.73μm,纤维平均腔径为3.87μm,壁腔比为1.42,纤维长度多集中在0.81～1.20mm范围内。可见芨芨草纤维细而长,长宽比大,壁腔比小,若能加以开发利用,是一种优质的造纸原料。

关键词：芨芨草纤维形态造纸

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Computing infrastructure for big data processing

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Frontiers of Computer Science 2013年第2期7卷 165-170页

作者： ling liu Distributed Data Intensive Systems Lab School of Computer Science Georgia Institute of TechnologyUSA Atlanta 30332

With computing systems undergone a fundamen- tal transformation from single-processor devices at the turn of the century to the ubiquitous and networked devices and the warehouse-scale computing via the cloud, the parallelism has become ubiquitous at many levels. At micro level, par- allelisms are being explored from the underlying circuits, to pipelining and instruction level parallelism on multi-cores or many cores on a chip as well as in a machine. From macro level, parallelisms are being promoted from multiple ma- chines on a rack, many racks in a data center, to the glob- ally shared infrastructure of the Internet. With the push of big data, we are entering a new era of parallel computing driven by novel and ground breaking research innovation on elas- tic parallelism and scalability. In this paper, we will give an overview of computing infrastructure for big data processing, focusing on architectural, storage and networking challenges of supporting big data paper. We will briefly discuss emerging computing infrastructure and technologies that are promising for improving data parallelism, task parallelism and encour- aging vertical and horizontal computation parallelism.

关键词： big data cloud computing data analytics elas-tic scalability heterogeneous computing GPU PCM bigdata processing

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天然和饱水红砂岩三轴压缩蠕变变形试验研究

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三峡大学学报（自然科学版） 2025年第1期47卷 9-15页

作者：刘桃根胡凯李玲王伟湖南工学院土木与建筑工程学院湖南衡阳421002 河海大学岩土工程科学研究所南京210098 江西职业技术大学建筑工程学院江西九江332007

蠕变特性和长期强度是红砂岩地区岩体工程安全评价的关键要素,饱水软化效应对红砂岩蠕变特性和长期强度具有重要影响.采用全自动岩石三轴压缩伺服流变仪,开展天然与饱水红砂岩的三轴压缩试验和三轴压缩蠕变试验.试验结果表明:峰值强度... 详细信息

蠕变特性和长期强度是红砂岩地区岩体工程安全评价的关键要素,饱水软化效应对红砂岩蠕变特性和长期强度具有重要影响.采用全自动岩石三轴压缩伺服流变仪,开展天然与饱水红砂岩的三轴压缩试验和三轴压缩蠕变试验.试验结果表明:峰值强度、弹性模量和蠕变破坏应力因饱水软化效应而降低,围压对其降幅有削弱作用,蠕变破坏应力与峰值强度的比值在0.75~0.98之间;饱水软化效应能增强蠕变瞬时变形,减弱蠕变变形及蠕变应变速率;环向应变比轴向应变更早进入稳态蠕变阶段和加速蠕变阶段;稳态蠕变速率与偏压的变化关系符合指数函数关系;长期强度因饱水软化作用而降低,却因围压增加而增大,长期强度与峰值强度的比值在0.62~0.92之间;裂纹损伤应力与长期强度相差较大,裂纹损伤应力视为长期强度有待进一步考究.

关键词：红砂岩蠕变特性长期强度饱水软化效应裂纹损伤应力

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水饺蒸煮皮防塌陷调控技术研究

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食品研究与开发 2017年第8期38卷 56-60页

作者：庞玲玲刘霞李喜宏李丽梅张新韩聪聪席冉贠娟天津科技大学食品工程与生物技术学院天津300457

为解决鲜水饺冻藏后饺子皮易塌陷失水的问题,在制皮过程中辅以适量赋形剂和持水剂,通过单因素试验分别探究了这两类改良剂对饺皮塌陷度和吸水率的影响。并对改良饺皮制得的水饺成品进行色度检测和感官评价,经四因素三水平正交试验优化... 详细信息

为解决鲜水饺冻藏后饺子皮易塌陷失水的问题,在制皮过程中辅以适量赋形剂和持水剂,通过单因素试验分别探究了这两类改良剂对饺皮塌陷度和吸水率的影响。并对改良饺皮制得的水饺成品进行色度检测和感官评价,经四因素三水平正交试验优化改良剂复配参数。确定复合改良剂最佳配方为:木薯醋酸酯淀粉1%、谷朊粉2.0%,海藻酸钠0.2%,复合磷酸盐0.5%,硬脂酰乳酸钠0.4%。按此配方进行重复性验证试验得到饺皮塌陷度0.4 mm、59.9%,水饺成品色度值93.30、感官评分96。结果表明该复合改良剂能有抑制饺皮塌陷失水,制得的水饺成品具有良好的消费品质。

关键词：鲜水饺塌陷失水复合改良剂正交试验

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Durability and microstructure analysis of the road base material prepared from red mud and flue gas desulfurization fly ash

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International Journal of Minerals,Metallurgy and Materials 2020年第4期27卷 555-568页

作者： Emile Mukiza ling-ling Zhang Xiao-ming liu School of Metallurgical and Ecological Engineering University of Science and Technology BeijingBeijing 100083China School of Energy and Environmental Engineering University of Science and Technology BeijingBeijing 100083China

The present study aimed to investigate the durability and microstructure evolution of road base materials(RBM)prepared from red mud and flue gas desulfurization fly *** durability testing showed that the strength of RBM with the blast furnace slag addition of 1wt%,3wt%and 5wt%reached 3.81,4.87,and 5.84 MPa after 5 freezing–thawing(F–T)cycles and reached 5.21,5.75,and 6.98 MPa after 20 weting–drying(W–D)cycles,*** results also indicated that hydration products were continuously formed even during W–D and F–T exposures,resulting in an increase of the strength and durability of *** observed increase of macropores(>1μm)after F–T and W–D exposures suggested that the mechanism of RBM deterioration is pore enlargement due to cracks that develop inside their ***,the F–T exposure showed a greater negative effect on the durability of RBM compared to the W–D *** leaching tests showed that sodium and heavy metals were solidified below the minimum requirement,which indicates that these wastes are suitable for use as a natural material replacement in road base construction.

关键词： red mud road base material durability microstructure damage mechanism

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DFT Study on Two C_4N_(12)O_4 Isomers with Pagodane- and Isopagodane-like Structures

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Chinese Journal of Structural Chemistry 2005年第11期24卷 1264-1270页

作者： liu Feng-ling WANG Jin-Shan PENG ling Department of Chemistry Shandong Normal University Jinan 250014 China

Geometries, energies, and vibrational frequencies for two C4N12O4 isomers with pagodane- and isopagodane-like structures have been calculated at the B3LYP/6-31G＊ *** 1 and 2 are of D2h and D2d symmetry, respectively. Heats of formation for the two C4N12O4 isomers have been estimated in this paper, indicating they would be reasonable candidates for high energy density materials.

关键词： two C4N12O4 isomers with pagodane-like structures high energy density material,B3LYP/6-31G* vibrational frequency heat of formation

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