子女教育支出平均占家庭总支出25%-子女教育支出是什么意思

拓展创新学程第三册Unit 4What is life?基础知识盘点Ⅰ.重点单词1．wayward adj.难以控制的，任性的，倔强的2．shiver v i.& n．颤抖，哆嗦(因寒冷、恐惧、激动等)3．abyss n．深渊4．echo v i.回响，回荡n．回响，回声，回音；映现，暗示，启示，反响；共鸣，附和，重复5．torture v t.使痛苦，使苦恼，使焦急，使受煎熬；拷打，拷问n．拷打，拷问，酷刑；(精神上或肉体上的)折磨，痛苦，折磨人的事物6．clarity n．清晰，清楚，明确；清晰的思维(或理解)能力；(画面、物质或声音的)清晰，清楚，清澈7．prologue n．序言，序幕，开场白8．magnet n．磁铁，磁石，吸铁石；有吸引力的人(或地方、事物)；磁体，磁性物体9．epic adj.具有史诗性质的，史诗般的；漫长而艰难的，艰苦卓绝的；宏大的，壮丽的，给人深刻印象的n．史诗；史诗般的作品；壮举，惊人之举10．heel n．脚跟，脚后跟11．grip n．理解，了解；紧握，紧抓；(对……的)控制，影响力v t.(gripped，gripped)紧握，紧抓；使感兴趣，使激动，吸引住(某人)的注意；对……产生强有力的影响12．neglect v t.忽略，忽视，不予重视；疏于照顾，未予看管；疏忽，疏漏n．忽略，忽视，未被重视13．faculty n．官能，天赋；才能，能力；(高等院校的)系，院；(高等院校中院、系的)全体教师14．gaze n．凝视，注视v i.凝视，注视，盯着15．imprint v t.产生重大影响，铭刻，使铭记；印，压印n．印记，压印，痕迹；持久影响16．listlessness n．无精打采，没有活力17．glimpse n．一瞥，一看18．inhabitant n．(某地的)居民，栖息动物19．overtone n．弦外之音，言外之意，暗示20．hint n．暗示，提示，示意；征兆，迹象v i.& v t.暗示，透露，示意21．petty adj.小的，琐碎的，次要的；小气的，狭隘的22．overwhelmingly ad v.压倒性地，不可抵抗地23．mockery n．嘲笑，愚弄；笑柄，被嘲笑的对象24．compassionate adj.有同情心的，表示怜悯的25．vigor (BrE vigour) n．精力，力量，活力，热情26．tenderness n．和善，温柔，亲切，慈爱27．hasty adj.匆忙的，仓促而就的，草率的28．long v．渴望→longing n．(对……的)渴望，热望adj.渴望的，热望的，表示渴望的29．union n．联合，结合，合并；工会；协会，联合会，会社，俱乐部→unite v．团结；统一；(为某事)联合，联手→united adj.联合的；统一的；和谐的；一致的30．latter n．(提及的两者中)后者adj.(提及的两者中)后者的；后半期的，后面的→(反义词)former adj.前任的；以前的；前者的31．glory n．荣誉，光荣，桂冠v i.因某事而喜悦，为某事而欣喜→glorious adj.值得称道的；光荣的；荣耀的32．hazy adj.朦胧的；薄雾蒙蒙的；记不清的→hazily ad v.记不清地，模糊地33．thrill v t.使非常兴奋；使非常激动n．激动；兴奋→thrilling adj.惊险的，紧张的，扣人心弦的，令人兴奋不已的→thrilled adj.非常兴奋；极为激动34．companion n．伙伴；同伴→companionship n．友情，交谊，友谊Ⅱ.核心短语1．get to grips with sth开始理解并着手处理难题2．hold sway占统治地位；具有重大影响力3．regard...as...把……视为……4．sum up总结5．Achilles heel致命弱点6．reflect upon/on反思Ⅲ.经典句型1．“介词＋关系代词”引导的定语从句And I have tried to understand the Pythagorean power by which number holds sway above the flux. 我试图理解毕达哥拉斯学派的理论，他们认为数字控制着万物流转。

BCE中级词汇整理1. absence n.缺席, 离开2. absent adj.不在,不参与3. absenteeism n。

（经常性）旷工, 旷职4. absorb v。

吸收, 减轻（冲击、困难等）作用或影响5. abstract n。

摘要6. access n.接近（或进入)的机会,享用权v.获得使用计算机数据库的权利7. accommodation n.设施, 住宿8. account n.会计帐目9. accountancy n.会计工作10. accountant n。

会计11. accounts n.往来帐目12. account for 解释,说明13. account executive n.(广告公司）客户经理14. *accruals n。

增值, 应计15. achieve v。

获得或达到,实现,完成16. acknowledge v.承认,告知已收到(某物), 承认某人17. acquire v.获得，得到18. *acquisition n。

收购, 被收购的公司或股份19. acting adj.代理的20. activity n.业务类型21. actual adj.实在的，实际的,确实的22. adapt v。

修改, 适应23. adjust v.整理，使适应24. administration n。

实施, 经营, 行政25. administer v.管理,实施26. adopt v。

采纳, 批准,挑选某人作候选人27. advertise v.公布,做广告28. ad n.做广告, 登广告29. advertisement n.出公告，做广告30. advertising n。

广告业31. after-sales service n.售后服务32. agenda n。

议事日程33. agent n.代理人, 经纪人34. allocate v。

分配, 配给35. amalgamation n.合并, 重组36. ambition n.强烈的欲望，野心37. ＊amortise v。

精神病药物阿立哌唑的作用机理杨雯雁〔09354065〕柯玉娟〔09354097〕袁媛〔09354102〕郑小丽〔09354093〕温璐平〔09354121〕【摘要】1988年阿立哌唑的发现，是受精神分裂症的几种优势病因假说指导。

经历的Ⅰ、Ⅱ和Ⅲ期临床试验提示，阿立哌唑具有起效快、平安性高及耐受性好等临床特性。

多年来人们一直在探讨阿立哌唑的作用机制，其中有两种较为权威的说法。

其一，多巴胺假说。

认为脑内多巴胺能神经递质异常引起精神分裂症病症。

其二，血清素假说。

认为多巴胺的活动,受血清素能神经元调节。

我们小组旨在研究对抗最典型的精神类疾病——精神分裂症的药物作用机理的同时，增加自己的生物化学课外知识，锻炼小组合作和深入探讨和研究的能力。

【关键词】阿立哌唑；精神分裂症；多巴胺受体；作用机制一、我们选择研究精神分裂症药物的原因以及研究精神疾病的意义人类有很长一段历史对精神卫生健康的关注是一片空白。

人们片面地以为身体健康就能百分之百衡量一个人的健康程度。

然而大多数人不知道，精神健康在很大程度上影响着人们的正常生活和工作学习的进度，不健康的精神状况不仅会使自身遭受痛苦，同时也带给周围的家人朋友很大的负担。

精神疾病在古时候被认为是和宗教中的恶魔或者巫术有关，这样的误解不仅耽误了对精神病人的及时治疗，也使历史上对精神疾病这一领域的科学研究停滞不前。

1991年，尼泊尔提交了第一份关于“世界精神卫生日〞活动的报告。

由此拉开了人们关注人类精神健康的序幕。

随后的十多年里，许多国家参与进来，世界卫生组织确定将每年的10月10日作为特殊的日子“世界精神卫生日〞，提高公众对精神疾病的认识，分享科学有效的疾病知识，消除公众的偏见。

目前全世界共约有亿各类精神和脑部疾病患者，每4个人中就有1人在其一生中的某个时段产生某种精神障碍，精神卫生已经成为一个突出的社会问题。

至今，精神卫生健康已成为人类健康的一大重要领域。

我们小组旨在研究对抗最典型的精神类疾病——精神分裂症的药物作用机理的同时，增加自己的生物化学课外知识，锻炼小组合作和深入探讨和研究的能力。

doi：10.3969/j.issn.2095-3887.2021.03.001羊BMPR-IB基因非同义单核)酸多态性的生物信息学分析冯东青王慧青刘月％,敦伟涛%,刘铮铸$,巩元芳$,李晓辉4,孙洪新%(1.河北省畜牧兽医研究所，保定071000；2.河北科技师范学院，秦皇岛066000；3.河北农业大学动物医学院，保定071000；4.正定县农业农村局，正定050800)摘要:以羊BMPR-IB基因为研究对象,采用生物信息学方法，对该基因潜在的、具有生物学功能的非同义单核t酸多态性位点(nsSNPs)进行预测，通过SIFI、Po7yPhen-2、PROVEN等软件分析预测nsSNPs是否对BMPR-IB蛋白的结构及功能产生影响；通过I-Mutant3.0、BDM-PUB、GPS-SUMO、Consurf等软件分析预测有害位点nsSNPs对蛋白质稳定性、泛素化修饰位点、磷酸化修饰位点、氨基酸进化位保守水平等是否有影响。

结果表明：BMPR-IB基因存在9个nsSNPs位点，其中Q305R、R469K两个位点为主要的有害突变;9个nsSNPs位点BMPR-IB蛋白稳定性均有所降低，其中C35Y、C45S、R44H 的稳定性大大降低。

预测结果显示，Q305R、R469K为羊BMPR-IB基因的潜在功能性位点。

关键词：羊;BMPR-IB基因；非同义单核t酸多态性;生物信息学分析中图分类号:S826.2文献标识码:A文章编号:2095-3887(2021)03-0001-06Bioinformatics Analysis of N on—Synonymous Single Nucleotide Polymorphisms of Sheep BMPR—IB Gene FENG Dongqing1,2,WANG Huiqing1,3,LIU Yue1,DUN Weitao1,LIU Zhengzhu2,GONG Yuanfang2,LI Xiaohui4,SUN Hongxin1 (l.Hebei Institute of Animal Husbandry and Veterinary Medicine,Baoding071000,China;2.HePei Normal University of Science&Technology,Qinghuangdao 066000,China;3.College of Veterinary Medicine,Hebei Agricultural University,Baoding071000,China;4.Agricultural and Rural Bureau of Zhengding County,Zhengding050800,China)Abstract:Taking the sheep BMPR-IB gene as the research object,bioinformatics methods were used to predict the potential and biological non-synonymous single nucleotide polymorphisms(nsSNPs)of the gene.It was analyzed and predicted whether nsSNPs would affect the structure and function of BMPR-IB protein by using SIFI,PolyPhen-2,PROVEN and other software.It was also analyzed and predicted whether nsSNPs harmful sites would affect protein stability, ubiquitination modification sites,phosphoryla­tion modification sites,and amino acid evolutionary conservation levels by using software such as I-Mutant3.0,BDM-PUB, GPS-SUMO,and Consurf.The results showed that9nsSNPs sites were screened out, of which2sites Q305R and R469K were the main harmful mutations; the stability of BMPR-IB protein at9nsSNPs sites was reduced, of which the stability of C35Y,C45S, and R44H was greatly reduced.In conclusion,that the potential functional sites of sheep BMPR-IB gene were Q305R and R469K. Keywords:sheep;BMPR-IB;non-synonymous single nucleotide polymorphisms;bioinformatics收稿日期：2021-02-05基金项目：河北省羊产业技术体系创新团队保定综合试验推广站建设项目(HBCT2018140403);河北省羊产业技术体系创新团队遗传资源开发与利用岗项目(HBCT2018140201)作者简介:冯东青(1994-),女，硕士研究生通信作者:孙洪新(1978-),女,研究员，博士研究生，研究方向为动物遗传育种及高效养殖非同义单核l酸多态性(Non-synonymous SNPs, nsSNPs)是一种可引起氨基酸序列发生改变的单核l酸突变,这种变化很可的，蛋白质功能发生改变，或者影响蛋白折叠、结合亲和力、表达、翻及的性，进表型发生变异。

网状M eta分析GRADE证据总结表的制订、解读与应用王巍巍\杨智荣2,孙凤3’4,詹思延3’4’51. 首都医科大学附属北京安定医院，国家精神心理疾病临床医学研究中心，精神疾病诊断与治疗北京市重点实验室(北京100088)2. 英国剑桥大学临床医学院初级医疗中心（英国剑桥C B1 8RN)3. 北京大学公共卫生学院流行病与卫生统计学系（北京100191)4. 北京大学循证医学中心（北京100191)5. 北京大学第三医院，临床流行病学研究中心（北京100191)【摘要】GRADE工作组针对网状Meta分析（NMA)制订了GRADE证据总结（SoF)表，目的是规范NMA结果的证据分级过程和结果展示。

本文对NMA-SoF表的主要内容进行详细介绍，并举例说明SoF表的使用方法和注意事项。

【关键词】G R A D E;网状Meta分析；证据总结表•方法学•D evelopm ent, elaboration and application o f grade summary o f finding table fornetwork meta-analysisWANG Weiwei1, YANG Zhirong2,SUN Feng3.4, ZHANSiyan3.451. The National Clinical Research Center f or Mental Disorders & Beijing Key Laboratory of M ental Disorders, Beijing Anding Hospital,Capital Medical University, Beijing 100088, P.R.China2. Primary Care Unit, School of C linical Medicine, University of C ambridge, Cambridge CB1 8RN, UK3. Department of E pidemiology and Biostatistics, School of P ublic Health, Peking University, Beijing 100191, P.R.China4. Center of E vidence-based Medicine and Clinical Research, Peking University, Beijing 100191, P.R.China5. Research Center of C linical Epidemiology, Peking University Third Hospital, Beijing 100191, P.R.ChinaCorrespondingauthor:SUNFeng,Email:****************.cn;ZHANSiyan,Email:*******************.cn【Abstract 】The summary of finding (SoF) table for network meta-analysis (NMA) was developed by the GRADEworking group to facilitate and consolidate understanding NMA findings and GRADE certainty of evidence. This paper introduces the development process, the structure of NMA-SoF and limitations. A NMA publication was presented as anexample to comprehensively illustrate the application of the NMA-SoF table.【Key words 】GRADE; Network meta-analysis; Summary of findings面对一个具体的临床问题，临床医生或决策者 通常需要从众多的干预措施中选择对患者最安全 有效的措施。

CHINA MEDICINE AND PHARMACY Vol.14 No.7 April 2024191[基金项目]海南省卫生计生行业科研项目（20A200278）。

基于网络药理学对破格救心汤治疗急性心力衰竭主要活性成分及潜在靶点分析张　明 李光智 林道斌广州中医药大学附属海南省中医院心血管科一病区，海南海口　570203[摘要] 目的 运用网络药理学研究方法对破格救心汤（PJD）治疗急性心力衰竭（AHF）主要活性成分及核心靶基因进行分析。

方法 采用中药系统药理学分析平台获得破格救心汤的有效活性成分及作用靶点基因，然后通过GeneCards 数据库收集AHF 疾病基因，然后对药物作用基因及疾病相关基因进行韦恩分析，确定药物作用交集靶点，然后取交集靶点进行综合分析。

结果 研究发现破格救心汤治疗AHF 的主要活性成分为槲皮素、山柰酚、谷固醇、柚皮素、人参皂苷-Rh2等，主要调控的关键基因为胱天蛋白酶3、禽肉瘤病毒17的假定转化基因、血管内皮生长因子A、白细胞介素-1β、肿瘤蛋白p53、雌激素受体α、白细胞介素-6、低氧诱导因子-1A、肿瘤坏死因子和丝氨酸/苏氨酸激酶-1。

结论 本研究结果初步探讨了破格救心汤治疗AHF 的基本药理作用及其机制，并为进一步的试验研究奠定了良好的基础。

[关键词] 网络药理学；破格救心汤；急性心力衰竭；分子对接[中图分类号] R259 [文献标识码] A [文章编号] 2095-0616（2024）07-0191-04DOI:10.20116/j.issn2095-0616.2024.07.43Network pharmacological analysis of Poge Jiuxin Decoction in thetreatment of acute heart failureZHANG　Ming LI　Guangzhi LIN　DaobinWard Ⅰ, Cardiovascular Department, Hainan Traditional Chinese Medicine Hospital Affiliated to Guangzhou University of Chinese Medicine, Hainan, Haikou 570203, China[Abstract] Objective To analyze the main active ingredients and core target genes of Poge Jiuxin Decoction (PJD) in the treatment of acute heart failure (AHF) using network pharmacology research methods. Methods The effective active ingredients and target genes of (PJD) were obtained by traditional Chinese medicine systems pharmacology database and analysis platform (TCMSP), and AHF disease genes were collected through the Gene Cards database. Then, Venn analysis was performed on the drug action genes and disease-related genes to determine the intersection action targets of drugs, and then the intersection targets were taken for comprehensive analysis. Results The study found that the main active ingredients of Poge Jiuxin Decoction in the treatment of AHF were quercetin, kaempferol, sitosterol, naringin, ginsenoside-Rh2, etc. The key regulatory genes were caspase-3, Jun proto-oncogene，AP-1 transcription factor subunit, vascular endothelial growth factor A, interleukin-1β, tumor protein p53, estrogen receptor 1, interleukin-1, hypoxia inducible factor-1A, tumor necrosis factor, and aerine/threonine kinase-1. Conclusion The results of this study preliminarily explore the basic pharmacological effects and mechanisms of Poge Jiuxin Decoction in the treatment of AHF, and lay a good foundation for further test research.[Key words] Network pharmacology; Poge Jiuxin Decoction; Acute heart failure; Molecular docking急性心力衰竭（acute heart failure，AHF）是指急性发作的左心室功能障碍，导致心室充盈程度或射血能力受损的一组复杂临床综合征[1]，是本世纪心血管病学领域的两大难题之一[2]。

·综述·Chinese Journal of Animal Infectious Diseases中国动物传染病学报我国猪瘟的流行病学及疫苗研究进展摘 要：猪瘟（CSF ）是由猪瘟病毒（CSFV ）引起的一种严重危害全球养猪业的高度接触性传染病，因其发病率和死亡率都很高，对经济造成巨大的损失，被OIE 列为必须通报的动物传染病。

我国将疫苗接种作为防控CSF 的主要手段，但由于疫苗的长期使用、温和毒力毒株的出现以及持续性感染的存在，使我国CSFV 流行株的变异呈多样性，且以远离疫苗株的变异为主。

因此，持续开展我国CSFV 流行毒株分子生物学和流行病学研究，研发能够区分疫苗野毒抗体，且提供高效免疫保护的新型基因工程疫苗，对我国CSF 的有效防控和最终净化具有重大意义。

本文重点对我国CSFV 的分子生物学特征及CSF 疫苗研究进展进行了综述，为CSF 防控提供参考。

关键词：猪瘟；猪瘟病毒；分子流行病学；疫苗；防控中图分类号： S858.28文献标志码：A文章编号：1674-6422（2022）06-0211-08Epidemiology and Vaccine Research Progress of Classical Swine Fever in ChinaMA Shuai 1, ZHENG Shilei 2, ZHAO Ming 1, WANG Yuan 1, ZHANG Yanqi 1, BING Qizheng 1,DUAN Xiaoxiao 1, CAO Zhi 3(1. Qingdao Animal Disease Prevention and Control Center, Qingdao 266100, China; 2. YEBIO Bioengineering Co., Ltd. of Qingdao,Qingdao 266114, China; 3. Qingdao Agricultural University, Qingdao 266109, China)收稿日期：2020-07-09作者简介：马帅，男，兽医师，硕士，主要从事动物疫病的流行病学及防制对策研究通信作者：曹志，E-mail：*****************.cn Abstract: Classical swine fever (CSF) remains one of the most economically important viral diseases of domestic pigs and wild boar worldwide. Classical swine fever virus (CSFV) is highly contagious with high morbidity and mortality. As such, it is an OIE-listed disease. In China, vaccination is used as the main means for the prevention and control of CSF. Because of the long-term use of the vaccine, the emergence of mild virulent strains and presence of persistent infection, the diverse variations of CSFV epidemic strains are present in China, which vary far away from the vaccine strains. Therefore, it is very important to carry out the research on molecular biology and epidemiology of CSFV epidemic strains and develop new genetic engineering vaccines that can be differentiated from wild infection for the effective control and eradication of CSF in China. This paper focuses on the research progress of molecular biology of CSFV and vaccines, providing a reference for CSF prevention and control.Key words: Classical swine fever; classical swine fever virus; molecular epidemiology; vaccine; prevention and control2022,30(6):211-218马 帅1，郑世磊2，赵 明1，王 媛1，张严琦1，邴啟政1，段笑笑1，曹 志3（1.青岛市动物疫病预防控制中心，青岛266100；2.青岛易邦生物工程有限公司，青岛266114；3.青岛农业大学，青岛266109）· 212 ·中国动物传染病学报2022年12月猪瘟（Classical swine fever, CSF）也称猪霍乱，是由猪瘟病毒（Classical swine fever virus, CSFV）引起的猪和野猪的一种高度接触性、高致死性传染病，一年四季均可发生[1]。

大豆异黄酮对幼年小鼠生殖发育的影响Δ许文达＊，董思林，张晗，宋迎琳，迟镜仪，赵振军，石慧 #（烟台大学生命科学学院，山东 烟台　264005）中图分类号 R 965；Q 418 文献标志码 A 文章编号 1001-0408（2024）06-0678-05DOI 10.6039/j.issn.1001-0408.2024.06.07摘要 目的 探讨大豆异黄酮（SI ）对幼鼠生殖发育的影响。

方法 将C 57BL/6幼鼠随机分为对照组和SI 小、大剂量组（10、100mg/kg ），每组10只，雌雄各半。

各药物组幼鼠灌胃相应药液，每天1次，持续2周。

末次灌胃后，计算幼鼠的体重增长百分比，检测血清雌二醇、睾酮水平以及生殖器官组织中丙二醛（MDA ）含量、总抗氧化能力（T-AOC ）和超氧化物歧化酶（SOD ）、谷胱甘肽过氧化物酶（GSH-Px ）活性，观察其生殖器官组织的病理改变，并检测其细胞凋亡情况。

结果 与对照组比较，SI 大剂量组雌性幼鼠的体重增长百分比显著升高，而雄性幼鼠的体重增长百分比显著降低（P ＜0.05或P ＜0.01）。

SI 各剂量组幼鼠卵巢组织均可见囊性卵泡，睾丸组织可见精母细胞排列松散，附睾组织可见部分上皮细胞脱落。

SI 各剂量组雌性幼鼠血清睾酮水平和雄性幼鼠血清睾酮、雌二醇水平，SI 小剂量组雌性幼鼠卵巢组织中GSH-Px 活性和SI 各剂量组雌性幼鼠卵巢组织中T-AOC ，以及SI 各剂量组雄性幼鼠睾丸及附睾组织细胞凋亡率均显著升高（P ＜0.05或P ＜0.01）；SI 各剂量组雌性幼鼠血清雌二醇水平，SI 大剂量组雌性幼鼠卵巢组织中SOD 活性和SI 各剂量组雌性幼鼠卵巢组织中MDA 含量，以及SI 各剂量组雌性小鼠卵巢组织细胞凋亡率均显著降低（P ＜0.05或P ＜0.01）。

结论 SI 可提高雌性幼鼠卵巢组织的抗氧化应激能力，减少其氧化应激损伤，但对雄性幼鼠的生殖器官具有一定的蓄积毒性。

交叉滞后路径分析在变量因果时序关系研究中的应用周广帅V 范冰冰* 1'2王春霞3 4游顶云"刘言训薛付忠陈伟5张涛*基金项目：国家自然科学基金(81973147,81673271)1. 山东大学齐鲁医学院公共卫生学院(250012)2. 山东大学健康医疗大数据研究院3. 济宁医学院附属医院健康管理中心4. 昆明医科大学公共卫生学院5. 美国杜兰大学公共卫生与热带医学院流行病学系 △通信作者：张涛，E-mail : taozhang@ sdu. edu. cn【提 要】目的 介绍交叉滞后路径分析原理及其在变量间因果时序关系研究中的应用。

方法 交叉滞后路径分 析模型基于交叉滞后面板设计,估计的路径系数具有明确的时间顺序关系，满足因果推断中“因在前果在后”的时序性要求。

利用健康随访数据构建体重指数(BMI )与血尿酸(UA )的交叉滞后路径分析模型，探索BMI 和UA 的因果时序关系。

结果 调整混杂因素后，基线BMI 到随访时UA 的路径系数(p 2 =0. 060,P <0.001)明显大于基线UA 到随访时BMI 的 路径系数(P 1 = -0.009,P =0.056)，且两系数间的差异具有统计学意义(P 2 > P 1,P <0.001)。

在时间顺序上BMI 增加先于 UA 升高发生。

结论BMI 增加可能是高尿酸血症的原因，交叉滞后路径分析模型可以有效的识别变量间的因果时序关系。

【关键词】交叉滞后路径分析因果时序关系体重指数尿酸【中图分类号】R195.1【文献标识码】A DOI 10. 3969/j.issn. 1002 -3674. 2020.06.004Application of Cross-lagged Path Analysis in Studying Temporal Relationship between Intercorrelated VariablesZhou Guangshuai , Fan Bingbing, Wang Chunxia , et al( Department of Biostatistics , School of Public Health , Cheeloo College of Medicine ,Shandong University (250012) , Jinan )[Abstract ] Objective To introduce the principle of cross-lagged path analysis model and its application in the temporal sequences between intercorrelated variables. Methods The cross-lagged path analysis model is based on the cross-lagged panel design , its path coefficient indicates a clear temporal sequence , which satisfies the temporality that cause precedes outcome in causal inference. We built a cross-lagged path analysis model to examine the temporal relationship between body mass index (BMI) and uric acid ( UA ) by using the longitudinal data. Results After adjusting for covariates , the path coefficient from baseline BMI to follow-up UA( p 2 =0. 060,P <0. 001) was significantly greater than the path coefficient from baseline UA to follow-up BMI(p 1 = -0. 009,P =0. 056) , with P <0. 001 for difference between p 〔 and p ?. Increased BMI levels precede higher UA levels. Conclusion Elevated BMI levels might lead to the development of hyperuricemia in later life. The cross-lagged path analysis model is an effective method for examining the temporal relationship between intercorrelated variables.[Key words ] Cross-lagged path analysis ；Temporal sequence ；Body mass index ；Uric acid实际研究中，通常利用因果图(casual diagram )的 方式直观地标识危险因素之间的相关或因果关系，从而清晰地表达混杂效应、中介效应等多种因果推断的关键概念［l ］o 如图1所示的因果图模型,X 为解释变 量,Y 为反应变量,Z 为另一个解释变量。

DEPARTMENT OF HEALTH & HUMAN SERVICES Public Health ServiceFood and Drug AdministrationSilver Spring, MD 20993 Maria Anne RochaSenior Manager, Regulatory AffairsSunovion Pharmaceuticals Inc.84 Waterford Dr.Marlborough, MA 01752-7010RE: NDA # 021912BROVANA® (arformoterol tartrate) Inhalation SolutionMA # 382Dear Ms. Rocha:The Office of Prescription Drug Promotion (OPDP) of the U.S. Food and Drug Administration (FDA) has reviewed patient brochures titled Neb SABA Patient Type [BROV138-12], DPI Patient Type [BROV136-12], MDI Patient Type [BROV137-12], and Add-On Patient Type [BROV139-12], for BROVANA® (arformoterol tartrate) Inhalation Solution (Brovana) submitted by Sunovion Pharmaceuticals Inc. (Sunovion) under cover of Form FDA 2253. The patient brochures are misleading because they overstate the efficacy of Brovana, make unsubstantiated claims, including unsubstantiated superiority claims, and minimize the risks associated with the drug. Thus, the patient brochures misbrand the drug in violation of the Federal Food, Drug, and Cosmetic Act (FD&C Act), 21 U.S.C. 352(a). Cf. 21 CFR 202.1 (e)(6)(i), (ii); (e)(7)(viii).BackgroundBelow are the indication and summary of the most serious and most common risks associated with the use of Brovana.1 According to its FDA-approved product labeling (PI) (emphasis in original):BROVANA (arformoterol tartrate) Inhalation Solution is indicated for the long-term, twice daily (morning and evening) maintenance treatment ofbronchoconstriction in patients with chronic obstructive pulmonary disease(COPD), including chronic bronchitis and emphysema. BROVANA InhalationSolution is for use by nebulization only.Important Limitations of UseBROVANA Inhalation Solution is not indicated to treat acute deteriorations of chronic obstructive pulmonary disease[.]1 This information is for background purposes only and does not necessarily represent the risk information that should be included in the promotional pieces cited in this letter.BROVANA Inhalation Solution is not indicated to treat asthma. The safety and effectiveness of BROVANA Inhalation Solution in asthma have not beenestablished.Brovana is associated with a number of serious risks. The PI contains a Boxed Warning regarding asthma-related death as well as Contraindications in patients with a history of hypersensitivity to arformoterol, racemic formoterol, or to any other components of Brovana and in patients with asthma without the use of a long-term asthma control medication. The PI also contains Warnings and Precautions including deterioration of disease and acute episodes, excessive use of Brovana and use with other Long-Acting Beta2-Agonists (LABA), paradoxical bronchospasm, cardiovascular effects, coexisting conditions, hypokalemia and hyperglycemia, and immediate hypersensitivity reactions.The most common adverse reactions associated with Brovana during clinical trials were pain, chest pain, back pain, diarrhea, sinusitis, leg cramps, dyspnea, rash, flu syndrome, peripheral edema, and lung disorder.Overstatement of EfficacyPromotional materials are misleading if they contain representations or suggestions that a drug is better or more effective than has been demonstrated by substantial evidence or substantial clinical experience.Pages 1, 3, and 4 of each of the patient brochures contain the tagline (bolded emphasis in original), “Get back into daily living,” in conjunction with the Brovana trade dress. These claims, along with the headline claim (bolded emphasis in original), “With the right COPD medicine, you may get back to daily living[,]” on page 3 of each of the patient brochures, misleadingly overstate the efficacy of Brovana by suggesting that an outcome of treatment with Brovana is the ability for patients to resume their baseline activities of daily living. According to the CLINICAL STUDIES section of the PI, treatment with Brovana demonstrated an approximately 11% change in mean forced expiratory volume in one second (FEV1) from study baseline FEV1 at the end of the dosing interval over 12 weeks of treatment compared to placebo. Although Brovana may improve patients’ mean FEV1, we are not aware of substantial evidence or substantial clinical experience demonstrating that the magnitude of the effect the drug has on FEV1 taken together with any drug-related side effects (e.g., paradoxical bronchospasm, cardiovascular effects, pain, chest pain, back pain, diarrhea, sinusitis, leg cramps, dyspnea, rash, flu syndrome, peripheral edema, and lung disorder), results in an overall positive impact on patients’ ability to resume their baseline activities of daily living. If you have data to support these claims, please submit them to FDA for review. Unsubstantiated Superiority Claims/Unsubstantiated ClaimsPromotional materials are misleading if they contain a drug comparison that represents or suggests that a drug is safer or more effective than another drug, when this has not been demonstrated by substantial evidence or substantial clinical experience.Page 1 of the patient brochures includes the following headline claims, respectively (bolded emphasis in original):∙ “If you have COPD, Are you using your nebulizer sometimes 4 or more times a day?” (NEB SABA [nebulizer Short-Acting Beta2-Agonists] Patient Type brochure)∙ “If you have COPD, Do you feel you’re just not able to breathe in all your medicine?” (DPI [dry-powder inhaler] Patient Type brochure)∙ “If you have COPD, Is it hard for you to depress your inhaler and time your breaths to get your medicine out?” (MDI [metered dose inhaler] Patient Typebrochure)∙ “If you have COPD, Do you take your medicine correctly, but still feel like you may need something more?” (Add-On Type brochure)Furthermore, page 2 of each of the patient brochures includes the following presentation (bolded emphasis in original):“Do any of the statements below capture how you feel? Check the onesthat do.∙ I use my nebulizer sometimes 4 or more times a day__so it's often easier for me just to stay at home. Sometimes I even need it in the middle ofthe night∙When I use my inhaler, it just doesn’t feel like I’m able to breathe in all of my medicine, or that all the medicine is coming out∙My hands don’t move as well anymore, so it’s hard for me to use my inhaler. I have trouble timing my hands with my breathing∙I’m taking my medicine, but it feels like I may need something moreBring this with you into the exam room, and ask your doctor if BROVANA®(arformoterol tartrate) Inhalation Solution is right for you.”The totality of these claims and presentations as set forth in each of these brochures, along with the headline claim on page 3 of each of the brochures referenced above (“With the right COPD medicine, you may get back to daily living”), suggests that Brovana (the “right” COPD medicine) is clinically superior to other available COPD therapies. Specifically, these claims and presentations suggest that Brovana will be effective for patients who have not had success with other COPD therapies based on Brovana’s ability to overcome the potential challenges associated with these therapies, such as their respective dosing regimens (e.g., therapies dosed four or more times a day) or delivery systems (e.g., DPIs or MDIs). We are not aware of any adequate and well-controlled head-to-head studies supporting the implication that Brovana is clinically superior to other COPD therapies. We acknowledge that according to the CLINICAL STUDIES section of the PI, the trials associated with the approval of Brovana did include an active comparator, salmeterol. However, these studies were not designed to measure clinical superiority, and thus do not constitute substantial evidence tosupport these claims. If you have data to support these claims, please submit them to FDA for review.In addition, the claims above regarding the potential difficulty patients may encounter depressing an inhaler to administer therapy (e.g. “My hands don’t move as well anymore, so it’s hard for me to use my inhaler.”) are misleading because they imply that patients with compromised manual dexterity will more easily be able to administer Brovana as compared to other COPD inhaler therapies. We are not aware of any evidence to support these claims. Proper use of Brovana, as described in the Medication Guide, includes lengthy directions for use, which include opening a foil pouch and removing a ready-to-use vial, opening the ready-to-use vial, squeezing the medication out of the ready-to-use vial into the reservoir of a jet nebulizer, connecting the reservoir to either a mouthpiece or face mask, connecting the nebulizer tubing to the compressor, and cleaning the nebulizer after use. Therefore, in the absence of adequate evidence to demonstrate that patients with compromised manual dexterity are more easily able to administer Brovana as compared to other inhaled COPD therapies, the above claims are misleading.Minimization of Risk InformationPromotional materials are misleading if they fail to present information about risks associated with a drug with a prominence and readability reasonably comparable with the presentation of information related to the effectiveness of the drug. Factors impacting prominence and readability include typography, layout, contrast, headlines, paragraphing, white space, and other techniques apt to achieve emphasis. The patient brochures prominently present efficacy claims in large, bolded font size and colorful text and graphics surrounded by a significant amount of white space. In contrast, risk information is presented in small font, surrounded by little white space, and in single-spaced format. The overall effect of this presentation undermines the communication of important risk information, minimizing the risks associated with Brovana, and misleadingly suggests that Brovana is safer than has been demonstrated by substantial evidence or substantial clinical experience.Conclusion and Requested ActionFor the reasons described above, the patient brochures misbrand Brovana in violation of the FD&C Act, 21 U.S.C. 352(a). Cf. 21 CFR 202.1 (e)(6)(i), (ii); (e)(7)(viii).OPDP requests that Sunovion immediately cease the dissemination of violative promotional materials for Brovana such as those described above. Please submit a written response to this letter on or before November 7, 2013, stating whether you intend to comply with this request, listing all promotional materials (with the 2253 submission date) for Brovana that contain violations such as those described above, and explaining your plan for discontinuing use of such violative materials.Please direct your response to the undersigned at the Food and Drug Administration, Center for Drug Evaluation and Research, Office of Prescription Drug Promotion, 5901-B Ammendale Road, Beltsville, Maryland 20705-1266 or by facsimile at (301) 847­8444. To ensure timely delivery of your submissions, please use the full address above and include a prominent directional notation (e.g. a sticker) to indicate that the submission isintended for OPDP. Please refer to MA # 382 in addition to the NDA number in all future correspondence relating to this particular matter. OPDP reminds you that only written communications are considered official.The violations discussed in this letter do not necessarily constitute an exhaustive list. It is your responsibility to ensure that your promotional materials for Brovana comply with each applicable requirement of the FD&C Act and FDA implementing regulations.Sincerely,{See appended electronic signature page}Matthew J. Falter, Pharm.D.Regulatory Review OfficerOffice of Prescription Drug Promotion{See appended electronic signature page}Kathleen Klemm, Pharm.D.Team LeaderOffice of Prescription Drug Promotion----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------This is a representation of an electronic record that was signed electronically and this page is the manifestation of the electronic signature./s/MATTHEW J FALTER10/24/2013KATHLEEN KLEMM10/24/2013。

广东省八校2024-2025学年高三上学期9月联合检测英语试题一、阅读理解China’s Best New Outdoor AttractionsWhen it comes to tourist attractions, here are a few of our favorites.The Grand Canal, the world’s longest human-made riverStretching 1, 782 kilometers, China’s Grand Canal is the world’s longest human-made river. Inscribed as a UNESCO World Heritage Site in 2014, the Grand Canal-also known as Jing-Hang Canal-runs from Beijing to Hangzhou and connects s to multiple waterways, including the Yellow River and the Yangtze River.Jiangsu Garden Expo ParkNanjing’s Garden Expo Park Scenic Spot showcases the region’s famous Jiangsu-style gardens. It is home to beautiful, classic Jiangsu-style gardens and other attractions, including a water botanical garden, a theater and a pedestrian shopping street. Among the highlights is Suzhou Garden, which was inspired by the Canglang Pavilion—a UNESCO World Heritage Site in nearby Suzhou.Universal Beijing ResortOpened in September 2021, the 169-hectare Universal Beijing Resort is the world’s fifth and largest Universal Studios theme park. There are seven themed lands offering dozens of shows and rides, many of them outdoors: The Wizarding g World of Harry Potter；Transformers Metrobase; Hollywood; WaterWorld; Minion Land；Jurassic World Isla Nublar; and Kung Fu Panda Land of Awesomeness.Glamping (豪华露营) and stargazing at Ningxia’s Desert Star Hotel Ningxia Hui Autonomous Region experiences little rainfall and enjoys around 300 days of clear skies yearly,making it one of the best places to enjoy China’s desert landscapes and engage in some serious stargazing. One of the top ways to experience Ningxia is by checking into the Desert Star Hotel in Ningxia’s Zhongwei City. The complex offers indoor and outdoor dining options, a swimming pool, an astronomy-themed theater and family-friendly sand activities. 1．Which attraction is listed as a UNESCO World Heritage Site?A．Jing-Hang Canal.B．Jiangsu Garden Expo Park.C．Universal Beijing Resort.D．Ningxia’s Desert Star Hotel.2．What does Universal Beijing Resort offer?A．Several dozen themed lands.B．Astronomy-themed movies.C．Outdoor shows and rides.D．A pedestrian shopping street.3．What can visitors do in Ningxia’s Desert Star Hotel?A．Attend a concert.B．Play with sand.C．Swim in the ocean.D．Enjoy classic gardens.Rowan Atkinson was born in a middle-class family. He had a speaking disability right from his childhood. This gave him a tough time in his childhood and at the start of his career. He was constantly bullied and laughed at because of his look and his speaking disability. This made him very shy and quiet. He didn’t have a lot of friends and the several rejections left him feel lonely. Rowan was very much interested in science. And he decided to pursue a career in this field.After he completed his Master’s degree, he realized acting was something he really wanted to pursue. He auditioned for several TV shows but faced back-to-back rejections, because he didn’t have a good face and grand body in addition to his stammering (口吃的) problem as well. Rowan kept his passion alive and worked hard towards reaching his dreams. He aimed at making people laugh and with persistent efforts over the years he has successfully established this.After the several rejections he started creating original comedy sketches. Interestingly he realized that whenever he played some characters, he spoke fluently. He used it as an inspiration for his acting. This is exactly where Rowan’s life changed.Rowan continued pursuing his dreams, despite all the hardships and rejections he had faced because of his looks and disorder. He had a major breakthrough when he started his own show Mr. Bean. Mr. Bean was “strange, surreal and non-speaking character”. He proved that even without a Hollywood face or a heroic body, you can become one of the most loved and respected actors in the world.Life always rewards those who are willing to keep moving forward. He teaches us that for success all you really need is hard work. Never let your fears and disabilities stop your life. Walk past these and make yourself better. Your hard work and efforts are sure to pay off one day. 4．What can we know about Rowan when he was young?A．He liked bullying his classmates.B．He had a few friends and felt lonely.C．He showed little interest in science.D．He recovered from his speaking disability.5．Why did Rowan want to act?A．He wanted to become popular.B．He enjoyed staying in the stage.C．He intended to make people happy.D．He was eager to overcome his drawback. 6．What made Rowan’s life change?A．That he was respected by the audience.B．That he could speak fluently in some characters.C．That he got a Hollywood face and a herbic body.D．That he received a. Master’s degree in science.7．What contributed to Rowan’s success according to the text?A．His wisdom B．His independence.C．His honesty.D．His willpower.Human beings are not alone in having invented vaccination, while honeybees got there first and they can run what look like vaccination programmes, which has been confirmed by Gyan Harwood of the University of Illinois, Urbana-Champaign.Queen bees vaccinate their eggs before they are laid. But the question is how the queen receives her antigen supply, for she lives purely on royal jelly, a substance secreted by nurse bees when they are in the life stage of feeding the young. Dr Harwood wondered if the nurses combined the royal jelly they produced with pieces from pathogens they had consumed while eating something brought in from outside.To test this idea, they collected about 150 nurse bees and divided them among six queenless mini hives equipped with the young to look after. They fed the nurses on sugar-water, and for three of the hives they added Paenibacillus larvae, a bacterium causing a disease, to sugar-water.Dr Harwood and Dr Salmela labeled the bacteria with a certain dye, to make them easy to track. And, sure enough, microscope confirmed that Paenibacillus larvae were getting into royal jelly secreted by those bees which had been fed with the sugar-water. Moreover, examination of this royal jelly revealed higher levels of defensive substance, compared with royal jelly from bees that had not been mixed with Paenibacillus larvae. This substance is thought to help bee immune systems fight against bacterial infections.All told, these findings suggest that nurse bees are indeed, via their royal jelly, passing antigens on to the queen, then into eggs. They also mean, because the young receive royal jelly forthe first few days after they hatch, the nurses are giving the young the second antigens. Each young bee is therefore being vaccinated twice.8．What puzzled Dr Harwood from paragraph 2?A．What the royal jelly consists of.B．Where nurse bees receive pathogens.C．How the antigen come into the queen bees' bodies.D．Whether honeybees run vaccination earlier than man.9．How did Dr Harwood develop his experiment?A．By dividing bees into different roles.B．By keeping track of the special bacterium.C．By changing the components of royal jelly.D．By observing nurse bees' different behaviors.10．What can we infer according to the results of the experiment?A．Nurse bees are the key to vaccination for bee group.B．The nurse bees pass the antigen only to the queen.C．Bacteria-used royal jelly has fewer defense substances.D．Two vaccinations are given to young bees by caregivers directly.11．Where is the text probably taken from?A．A pet guide.B．A social website.C．An official document.D．A medical magazine.The British has obeyed the “keep to the left” rule for long. Have you ever wondered why? There is a historical reason for this: it’s all to do with keeping your sword hand free! In the Middle Ages you never knew who you were going to meet when travelling on horseback. Most people are right-handed, so if a stranger passed by on the right of you, your right hand would be free to use your sword if required.Indeed the “keep to the left” rule goes back even further in time; archaeologists have discovered evidence suggesting that the Romans drove carts and wagons on the left, and it is known that Roman soldiers always marched on the left. This “rule of the road” was officially sanctioned in 1300 AD when Pope (教皇) Boniface Ⅷ declared that all pilgrims (朝圣者)travelling to Rome should keep to the left.This continued until the late 1700s when large wagons became popular for transporting goods. These wagons were drawn by several pairs of horses and had no driver’s seat. Instead, in order to control the horses, the driver sat on the horse at the back left, thus keeping his whip hand free. Sitting on the left however made it difficult to judge the traffic coming the other way, as anyone who has driven a left-hand drive car along the winding lanes of Britain will agree!In Britain there wasn’t much call tor these massive wagons and the smaller British vehicles had seats for the driver to sit on behind the horses. As most people are right-handed, the driver would sit to the right of the seat so his whip hand was free. Traffic congestion in 18th century London led to a law being passed to make all traffic on London Bridge keep to the left in order to reduce collisions. This rule was incorporated (并入) into the Highway Act of 1835 and was adopted throughout the British Empire.12．What probably happened in the Middle Ages?A．Passers-by walked on the right.B．Strangers fought every time they met.C．People would be attacked by strangers.D．Tourists travelled everywhere without limit. 13．What does the underlined word “sanctioned” in Paragraph 2 mean?A．Recognized.B．Designed.C．Explained.D．Postponed. 14．What was the attitude of drivers in the late 18th century to driving on the left?A．Unclear.B．Indifferent.C．Negative.D．Doubtful. 15．Which of the following can be the best title for the text?A．What Is the “Keep to the Left” Rule?B．Why Do the British Drive on the Left?C．Where Was “Drive on the Left” Carried Out?D．When Is the “Keep to the Left” Rule Popular?There are so many definitions of wisdom. Simply put, wisdom is a mix of insight, common sense, experience, and results to sound judgement. It is not merely a desirable quality but an absolute necessity in a world filled with chaos, controversy, and conflicts. 16 It shines our way through darkness.Growing up with, fairly takes and fantasy movies, I always associated wisdom with Gandalf, Yoda, and Albus Dumbledore. Although these characters have given every one of us tonsof inspiration, wisdom actually lies within ourselves. 17 And how?18 You will never grow from being in your comfort zone, which is why you need to get out of it. Do change your routine and experience as much as what life takes you to! In fact, there are always several sides to a life story. To identify the truth, you need to be receptive to different views. Never base your perspective on the most popular opinions. It is not emotion-based either. Instead, train your mind to be a judgment-free space for ideas. Open-mindedness opens new pathways to profound insights.What if you are desperate for personal growth and improvement? 19 The more time you spend with them, the more transfer of knowledge there will be. Your tutors can be whoever is wiser than you. Yet prior to that, engage in dialogue with them to find out why.Rome was not built in a day. 20 It is important to acknowledge that it takes a span of your life and continuous effort to mature in wisdom as you navigate (找到正确的方法) life’s challenges.A．Individuals need to bring it out.B．It isn’t something you are born with.C．Knowledge speaks, but wisdom listens.D．Remember developing wisdom is beyond a destination.E．A shortcut to do that is to have wise people as your tutors.F．In order to navigate in it, wisdom becomes our guiding light.G．Starting up new experiences is an avenue for acquiring wisdom.二、完形填空V olunteering at Greenpeace is more than a simple individual action. It is a collective force 21 a vision of a greener and fairer world.When I took my first step as a volunteer with Greenpeace Brazil, I had no idea how this experience would 22 my life and my commitment to our planet. Through Greenpeace. I 23 other people, understood how the community functioned, and exchanged 24 with fellow members. Today, looking back, I see how 25 impactful this journey has been, not only for me but also for the communities in the local groups that, we embraced(拥抱) with26 .What makes this experience even more 27 is how our campaigns come to life through the 28 of everyone and the passion each of us nurtures for the environment. Whether in the fight against climate change, the defense of forests, or the protection of oceans, each of us plays a 29 role in our own way.Over time, I have seen our local community 30 awareness and taking action on local environmental issues, especially regarding the mining 31 we face in our state. I witnessed the building of strong connections with other organizations, 32 our movement for a sustainable planet.My initial motivation for volunteering at Greenpeace was to do my part in 33 the environment. Today, I know that I am doing much more. I am part of a global movement that is changing the world. In this 34 , I have found not only an incredible community of people but also a purpose that 35 me every day.21．A．improving B．increasing C．discovering D．shaping 22．A．introduce B．transform C．control D．create 23．A．connected with B．competed against C．went through D．got across 24．A．impression B．money C．experience D．work 25．A．incredibly B．strangely C．unfairly D．fortunately 26．A．creativity B．friendship C．success D．passion 27．A．expensive B．welcoming C．meaningful D．inviting 28．A．kindness B．support C．agreement D．consideration 29．A．general B．familiar C．normal D．decisive 30．A．raising B．encouraging C．developing D．building 31．A．benefits B．businesses C．challenges D．operations 32．A．starting B．strengthening C．designing D．reducing 33．A．decorating B．constructing C．changing D．protecting 34．A．journey B．career C．environment D．campaign 35．A．orders B．surprises C．inspires D．calls三、语法填空阅读下面短文，在空白处填入1个适当的单词或括号内单词的正确形式。