邮票的知识范例6篇

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邮票的知识

邮票的知识范文1

看着看着,我仿佛置身于这美丽的景色之中,湛蓝清澈谁愿意当我的镜子,绿树红花对我点头微笑……

地球——我们唯一的家园。看,蓝天白云漂浮在它的躯体上,绿树愿意做它的丽装……是他们,是它们支撑着地球。

有这样一句名言“当人类砍倒第一棵大树的时候,便宣告文明的开始;当人类砍倒最后一棵大树的时候,便宣告文明的结束。”从前,地球拥有大片大片的树林,水是清澈见底的,空气清新,动物和人类是很要好的朋友。每天,他们一起劳动,一起生产,生活过得幸福美满。地球非常高兴,她愿意把自己的资源奉献给生活在自己身上的儿女。可是,人类很不知足,竟滥用地球上的资源,甚至还伤害了自己的朋友——动物。人类的行为令地球母亲拉长了脸。人类还不知道自己的错误,为了满足自己,滥杀生灵,乱砍滥伐,使用东西毫无节制,终于造成了一系列的严重后果。这次,地球母亲流下了眼泪,她的眼泪是酸的,她要惩罚人类。

人类终于意识到了自己的过错,可是,要拯救地球并不是一朝一夕的事情,因此,人类发出了拯救地球的呼声。不是吗?我们使“人”变成“从”,又变成“众”;使“森”变成“林”,又变成“木”。地球上的人越来越多,树木却越来越少,资源越来越短缺。

如果我们还不重视环境的保护,如果我们还不提高警觉,也许地球上最后的生物就是我们,最后一滴水就是我们的眼泪。因此我们要十分爱惜子孙万代赖以生存的自然环境。让我们从平凡做起,从点滴做起,从自我做起,节约社会资源,爱护自然环境,让我们的家园更加美好,让我们的地球充满醉人的绿,让那充满生机的,可爱的绿色种子在全世界人民的心灵上扎下永久的根。

邮票的知识范文2

 

关键词:股票期权  激励机制  职业经理人市场  股票市场

作为企业管理层激励机制的股票期权 (ES0) ,是指企业所有者给予经营者的一种权利,经营者凭借这种权利在与企业所有者约定的期限内可以以约定的价格购买企业一定数量的股票,并在其认为合适的价位上抛出该股票以获得差价。由于股票期权的授予对象主要是经理人员,因此又常被称为“经理股票期权 (Executive Stock Option ,简称 ESO) ”。这种激励手段的精妙之处就在于它让经营者既成为企业合同收入的索取者,又是剩余收入索取者,同时经营者也承担相应的风险。这使得经营者关心所有者的利益和企业资产的增值保值,关心企业的生存和发展,同时又关心自己的收入和声誉。把给经营者的高额回报建立在企业资产升值的基础上 , 把经营者的收入最大化与企业资产增值最大化统一起来,这实际上是给经营者戴上了一个闪亮的“金手铐”。目前,全球前 500 家大工业企业中,有 89 %己向经理人实施了股票期权报酬激励制度。在欧美国家,股票期权在管理人员收入中所占比重也越来越大。

一、我国实施股票期权的特点

“春江水暖鸭先知”,股票期权的理论魅力,使我国企业界以实际行动扮演了对股票期权的先知先试角色。股票期权计划在我国至今经历了 10 余年发展时间,已形成了具有典型意义的“上海”、“北京”和“武汉”三种模式。综合现有各种模式的具体做法,我国实施股票期权制度的案例呈现出许多不同于国际规范和惯例的特点,颇具中国特色。

1. 期权不仅适用于国家控股的上市公司和非上市股份有限公司,还适用于国有独资有限责任公司。这与国外股票期权主要适用于上市公司这一点有所不同。其原因在于,国有企业希望借助于实行股票期权或期股等方式来完成改制和产权结构调整。国有企业的改制首先要解决历史遗留问题,特别是企业历史积累中各要素贡献的分割问题,以便为企业未来的公司治理构筑合理化的平台。对于市场竞争性的国有企业来说,建立一个开放的、流动的产权结构是改制所要完成的重要任务之一,意义重大。这不仅是扩大资本规模的需要,同时也有利于降低单一国有资本所承担的风险,实施更有效的激励的需要。怎样才能既保证管理人员获得能够产生较强激励效果的足够数量的股权,又能避免因分割存量资产引起的矛盾 ? 一种变通的做法就是着眼于增量企业未来的股权,即实施股票期权计划。周其仁教授认为它是绕开私有化难题的制度创新,对这一做法给予了高度评价。

2. 股票期权已不再是一种选择权,经营者必须购买。西方成熟的股票期权是一种选择权,而不是一种义务。受益人可以在未来某个时期因股票市价高于期权的执行价格而行权,也可以因股价低于执行价而放弃行权。但是在国有企业现行的股票期权激励中,期权不仅是一种权利,同时也是带有一定强制性的义务,企业的主要经营者必须实际购买本企业股票。比如武汉国资公司的延期支付计划,对公司法定代表人而言,根本不是一种拥有选择权的股票期权,而是将其所有的已经分配的风险收入的指定部分拿去购买本公司的股票。对北京的期股试行办法来说,经营者必须在三年任期内按既定价格分期缴纳股款,购买本企业一定数量的股份;在经营者缴足股款之前,这部分股份属于“期股”,经营者对这一部分股份只有表决权和收益权,而没有所有权,待全部股款缴足后,期股的所有权才属于经营者;经营者任期届满两年后,经审计合格,该股份可以变现。可见,在我国实施的股票期权,名为股票期权计划,实为“股票购买计划”,经营者获得的股票期权是一种残缺不全的所有权,从法律上来看,这种所谓的股票期权已有经营担保的性质。

3. 非国有中小股东利益在制度设计中未受到重视。从股票期权在我国的实践来看,不论是上海还是北京、武汉,其实施方案都是由政府国资、财政等部门发文规定,程序上一般都是让国有控股股东代表提出一项议案,由股东会作出决议。由于资本多数决定原则,国有控股股东的提议都能够获得通过,从而使其意志处于支配地位,产生对中小股东的约束力。由于国有股东提出的股票期权议案是以国有资产的保值增值作为考核指标的,这实际上排斥了中小股东在股票期权决策上应有的权利,造成了国有股东与中小股东之间事实上的不平等。这样,获赠股票期权的经营者只须对国有控股股东负责就行了,而无需考虑其他中小股东的利益。而且,国有股东的代表人或者主管部门的工作人员并不直接从公司收益增加或股票价值上涨中受益,他们作为有限理性人有其自身独特的效用。这决定了他们与公司经营者签订的股票期权协议中的各项考核指标的订立和监管,并不一定能够与“以业绩为中心”、着眼于长期激励的股票期权制度的精髓相一致。

4. 我国股票期权具有惩罚机制。在激励与约束上,我国股票期权更多地偏向了约束一方。北京市规定,如经营者任期未满而主动离职,或任期内未达到协议规定的考核指标,取消其所拥有期股权及其收益,个人现金出资部分也作相应扣除。武汉规定,完成净利未达到 50 %的,扣罚以前年度股票期权 40 %,而期股却是用经营者的部分薪酬购买的。上海市规定,中途离职利未达经营指标的,不予兑现股权收益,并扣除一定数额的个人资产抵押金。这样,股票期权就成了一种担保之债,具有惩罚性。

二、股票期权的适用条件

作为一种公司企业的薪酬改革,股票期权制度产生于美国,美国不仅市场经济非常成熟,而且有关公司、证券的法律制度也非常完善。当我们欲将一个植根于成熟市场经济国家的制度成功地移植到我们这样尚在“转轨”的国家时,就必须仔细考察、理解它的生存土壤,否则就可能出现“南桔北枳”的危险。就股票期权在国外的发展情况来看,它的良好运作离不开以下几个方面的适用条件:

邮票的知识范文3

外国长篇小说《鲁滨孙漂流记》在作家笛福的笔下构造出了一位机智勇敢的主人公——“鲁滨孙”。在这部小说里,鲁滨孙在一个荒岛上生活了二十八年,经历了孤独的拷打、安全的威胁、饥饿的侵蚀······许多番风雨后,靠自己的本事活了下来。

鲁滨孙不畏艰险、机智勇敢、聪明能干、乐观理智的精神让我不由得惊叹,这是一个有着多么顽强意志力的“平凡人”。在绝望之际,他竟可以用超乎于凡人的冷静与理智将希望罗列出来,用自己独有的力量努力维持着他的整个精神世界,创造着别样的奇迹。

在我的生涯中,鲁滨孙令我最为钦佩的“知足常安”这个最伟大的精神特点,我却没学到一丝一毫。我承认我是个负能量满身的人:抱怨自己家境没有别人好、抱怨自己的天赋没比别人高、埋怨天气的多变、埋怨那些不顺心的事物、自卑着自己没有比别人大方、自卑着自己没比他人受欢迎、自卑着试卷上那一个又一个鲜艳的红叉······一切没有达到自己的理想的百分百完美的所有事物如同“过检产品”那样都被我打上了“不合格”的印记,使我终日笼罩在积着雨滴的黑压压的乌云下。可是鲁滨孙的“知足常乐”与我对比起来,他所遭受的苦难与我的小事相比,似一天一地,完全没得比,使我异常羞愧。

“知足常乐”这个在我心目中最为伟大的精神支柱,将在我人生夜空的帷幕下熠熠生辉。

邮票的知识范文4

关键词 技能大赛 传票翻打 训练法

中图分类号:G712 文献标识码:A DOI:10.16400/ki.kjdkz.2016.04.018

Abstract The healthy operation of the skills competition promotes the healthy development of Vocational and technical education. Is introduced in this paper the author of financial skills competition "summons turned to fight" the research contents of training program was effective, and expounds the correct target training, good training attitude and scientific training methods, healthy psychological quality is participate in the skills competition has been essential to the success, the author in the "summons turned to fight" cultivation of player skill training of some methods and experience.

Key words skill competition; summons turned to fight; training methods

近年来,随着我国市场经济的高速发展,懂技术的实操型人才缺乏,国家高度重视职业中学的技能教育,职业技术教育正面临着一个前所未有的发展机遇。为了促进职业技术教育的健康蓬勃发展,每年全国、省、市各级教育部门都组织了各种项目的技能大赛,这些比赛是各职业技术学校的竞技展示平台。 各个学校都很重视这些比赛,都希望在比赛中取得好成绩,以树立学校在社会上的良好声誉。

本文研究的“传票翻打”是财经商贸类技能大赛中的一个单独项目,同时它也是电算化会计综合的一个组成项目。“传票翻打”主要是指采用爱丁数码公司翰林提专用设备进行小键盘传票算。笔者自2010年开始至今一直担任学校传票翻打技能训练队的训练工作,从开始的懵懂状态到逐渐走上训练的正轨,笔者积累了一定的经验,本文总结了在“传票翻打”技能训练中培养选手的一些方法和心得体会,其目的是想与同仁交流探讨, 以更好地提高这个项目的训练水平。

1 让学生树立正确的训练目标,端正训练态度

(1)良好的动机能给行动以强大的推动力。人只有在达到一定的动机水平时,其工作能量才能最大限度地发挥出来,传票翻打也是如此。技能训练都是枯燥、乏味的,为了激发学生训练的兴趣,教师在训练的最初要先让学生们知道参加技能竞赛的重要意义。竞赛中获奖既是让自己的综合技能得到提高,又能为学校争得荣誉,也为自己将来就业获得一项有力的证明。竞赛中即使失利未获得奖项,个人也可以通过参赛获得很多宝贵的经验。学生们明确了竞赛的意义,自然清楚自己的训练目标就是刻苦训练,提高水平,争取获奖。

(2)学生明确了自己的训练目标后,教师就要注重培养学生的刻苦钻研和吃苦耐劳精神。一个人要想成功,就一定要在困难中保持恒心和毅力。职中学生的坚持精神不一定很足,需要教师经常用激励的语言去督促和鞭策,更需要运用科学的方法加以引导, 在整个训练过程中教师也要加强学生自觉性的培养,要求学生能主动刻苦地训练, 培养学生的自制力和定力。

2 用科学的方法指导技能训练

2.1 重视基本功的训练

“传票翻打”是由基本指法训练、数字综合录入、传票录、传票算四个部分组成,它们是互相联系、互相制约、 循序渐进的统一体,缺一不可。“传票翻打”训练应该是一个循序渐进的过程。

首先,培养学生通过基本指法训练练出正确的输入手势,正确的指法是提高技能水平的关键。笔者有一个综合项目的选手一开始练习时是只用三个手指来操作全部的小键盘,手法很笨拙。笔者规定她一定要按照指法的规则,每只手指各司其职,先将基本指法训练练习五小时,再练习数字综合录入五小时,经过两段基础的强化训练,她克服了问题,五指手指可以发挥各自的作用了,这时才要求她进行传票录和传票算的训练。

其次,控制好击键的速度和力度也很重要。在训练的一开始,教师就应叫学生学会控制击键的力度,击键手法太软,可能会打不出数字;击键太用力,易出现将数字打重复的问题,而且长时间练习时容易疲劳,学生耐力会不够;击键的速度也应该前后保持基本一致,十分钟内速度变化大会影响自己的心理状态,就更容易出现数字输入错误。为了让学生在比赛现场适应软硬程度不同的键盘,教师还应该在比赛前一个月找一些软硬程度不同的键盘供学生练习适应。

再次,要加强盲打训练。要提高录入速度,只有正确的操作姿势和指法,没有很好的盲打基本功是不行的。训练伊始,个别学生盲打不过关,为了让学生练成盲打,可用数字综合录入练习,方法是在数字综合录入功能里动手设置十个阿拉伯数字和“+”、 “.”,在键盘和眼睛中间加一块薄纸,学生录入时只能抬头看屏幕,不能看键盘,这样既可遮住学生看键盘的视线, 又不影响学生击键时手指的灵活动作, 迫使学生只能看屏幕,在熟记键盘的基础上练成准确的盲打。

2.2 制定科学的训练计划

笔者的学校,一般会提前半年就由训练老师制定一个详细的训练计划。根据计划安排,教师在每一个训练阶段制定相应的要求,学生在训练过程中会经过一个“突飞猛进”的时期和一个“原地踏步”期。在“突飞猛进”期要提高训练强度,要求学生每天最少打18组题目,还要学生自己制定每个星期一定要达到的训练目标,如果达不到目标成绩就按照训练队学生们自己的约定接受小“惩罚”。学生们每个星期要填写成长记录表,写下自己的总结与反思。在“原地踏步”期教师要对学生加强思想教育,教育学生坚持训练。训练的过程中要求学生先全力提高速度,比如翻打水平达到可以在10分钟打完18组或者17组题目以后,再注意提高准确度, 将速度和准确度相结合。

2.3 训练过程忌拔苗助长,设计有针对性的训练

“传票翻打”训练内容要科学,训练过程要循序渐进,由易到难逐渐增加难度。在指法训练中,以分指录入为主,逐渐过渡到综合录入;传票练习中先练习传票录,再练习传票算。训练过程忌拔苗助长,特别是对于一年级的新手,必须先练好基本功,再进行数字综合录入、传票算,稳步前进,才能达到较好的训练效果。训练过程中也应因人而异,对学生个人情况单独观察分析,找出问题后要有针对性地进行弥补训练。教学中笔者发现,有的学生不会使用大拇指,只能用四个手指击键;有的学生小指不灵活,击键不够力,或者紧张时小指不到位。针对这些特殊的情况,要对他们进行有针对性的反复训练,如在数字综合录入里专门设置“0,1,2,3”这四个数,让学生练习拇指和食指的分指协调动作,克服用食指击“0”键的问题。

2.4 对学生加强自我意识和自我评价的培养

引导学生正确认识和评价自己很重要,自我批评、评价是一个人前进的动力,有意识地引导学生经常分析和检查自己,学生在训练中才能进步得更快。结合自我评价和自我激励的需要,笔者为学生设计了“每周传票翻打成长记录表”,要求每位学生在每天训练时记录自己当天的几次训练成绩,每周用150字左右写下自己的总结和反思,然后为下周定一个要达到的目标。“每周传票翻打成长记录表”部分表格如表1所示:

教师可根据“每周传票翻打成长记录表” 的成绩情况进行每周的训练总结,从而制定对策或调整下周的训练计划。

3 加强学生心理素质的培养

心理素质是决定一个人成才和成功的必要条件。传票翻打比赛时间短、竞争激烈,选手们充分发挥技能水平并取得优异成绩是优良的翻打技巧和稳定心理的有机结合。 为了让学生发挥正常,笔者也研究了一些心理素质培养的方法,在训练的间隙和比赛前对学生们加强了必要的心理辅导。具体方法如下:

3.1 培养学生的自信心

自信心是一种能够战胜各种困难而实现自己理想的情绪状态。教师应该在平时的训练中暗示学生自己学校的水平和其他兄弟学校的水平差不多,只要再拼搏努力,就有希望进入前列。这样一来,学生才觉得有可能实现自己想达到的目标,也才会有拼搏的动力。比赛前的一星期,更要对学生加强自信心的培养,教师可用语言提醒学生,“你们是很棒的,我对你们绝对有信心” 、“放心吧,你们的水平在全市都是领先的”。

3.2 用模拟训练法加强学生心理素质的培养

学生们在一个陌生的环境中比赛时经常会感到不安和紧张,模拟训练就是人为的制造或模拟比赛环境,让学生们逐步适应紧张环境,并产生抗干扰能力,以便在正式的比赛时保持比较稳定的心态。模拟训练法包括, 通过在自己学校组织的专业学生的技能大赛,模拟实际比赛的场景;加强与其他几所兄弟学校的交流,通过与其他兄弟学校合办校际联谊赛的方式进行模拟比赛,做到“知己知彼,百战不殆”。 这些措施对稳定学生的情绪状态和发挥出高水平是有好处的。

3.3 放下“包袱”,轻装上阵

许多优秀学生比赛失利的主要原因就是过分看重比赛成绩,对自己期望过高,背上了思想“包袱”,加重了思想负担 。教师在赛前的一天和即将比赛前的一刻都要认真观察学生,发现问题要及时采取措施帮助学生。比赛前的一天,教师要提醒学生练习呼吸调节法,有意识地进行舒缓的腹式呼吸,使内心得到慰藉。到达比赛现场,学生有紧张情绪时,教师要用自己镇定的情绪感染学生,使不良情绪得到有效的控制。 教师可运用语言暗示,如 “今年参赛的选手很多是新人,水平都不是很高”,让学生心理得到放松以稳定情绪。

综上所述,正确的训练目标、良好的训练态度、科学的训练方法、健康的心理素质是参加技能大赛取得成功的必备条件。

参考文献

[1] 姚家新.竞赛心理咨询与心理训练[M].北京:人民体育出版社,1995.

邮票的知识范文5

【关键词】 幽门螺旋杆菌; 胃滞留剂; 漂浮剂型; 草药; 黑柯子; 黄连素

Helicobacter pylori are very common pathogenic bacteria colonizing about half of all populations and associated with the development of serious gastroduodenal diseases like gastric lymphoma, peptic ulcers and acute chronic gastritis. Current drug regimes are not wholly effective. Other problems related with the current drug regimes are lack of patient compliance, side effects and bacterial resistance. Thus, drug delivery to the site of residence in the gastric mucosa may help in solving the problems associated with the current drug therapy. Gastric retentive delivery systems potentially allow increased penetration and thus increased drug concentration at the site of action. Floating drug delivery systems, expandable or swellable drug delivery systems and bioadhesive systems are the major areas of interest to formulate gastroretentive drug delivery system against H. pylori. Generally, problems with these formulations are lack of specificity and the dependence on mucus turnover, so they fail to persist in the stomach. Gastric mucoadhesive systems are hailed as a promising technology to address this issue, penetrating the mucus layer and prolonging activity at the mucusepithelial interface. Gastroretentive delivery strategies, specifically with regard to their application as a delivery system to target Helicobacter, are a very attractive field which can cure these troublesome infections.

H. pylori is a Gramnegative, microaerophilic, spiral and flagellated bacterium, with unipolarsheathed flagella that provides motility. Its spiral shape and high motility allows it to penetrate mucus, resist gastric emptying and remain in the host gastrointestinal (GI) tract. It is now firmly established that infection with this bacterium is the cause of chronic active gastritis. Its isolation radically changed the conceptualisation of several chronic gastrointestinal illnesses including gastritis and peptic ulcers, and elimination of the causative organism became the goal of therapies [1]. Estimates from the WHO in 1994 claimed that about half of the world’s population was infected with H. pylori and although most infections are silent, a portion of the infected population will subsequently present with associated disease including chronic gastritis, peptic and duodenal ulcers. About 550 000 new cases a year of gastric cancerabout 55% of the worldwide totalwere attributed to H. pylori, and it was predicted that by 2020 to enter the top ten of leading causes of death worldwide[2, 3]. H. pylori is a very perse specy and cancer risks may be increased with strains having virulenceassociated genes (cytotoxinassociated gene, CagA), host genetics and environmental factors. The incidence of infection is higher in developing countries with up to 80%90% of adults being infected whereas in developed countries prevalence ranges from 10%50%[4].

1 Mechanism of H. pylori infections

Infection with H. pylori occurs predominately in childhood mainly between the ages 1 to 5, via oral ingestion of the bacterium, and lasts until the end of life with intrafamilial transmission being the major route in developed countries. The possible routes of transmission are food and water. The major feature of H. pylori infection is progressive injury to the gastric mucosa and its function[5, 6]. The bacterium adheres to the gastric epithelial cells, producing a direct injurious effect that is then amplified by production and release of a vacuolating cytotoxin (VacA)[7, 8]. H. pylori produces a variety of enzymes and is characterised by a high urease activity. Urea is broken down into bicarbonate and ammonia that protects the bacterium in the acid environment of the stomach. The ammonium ions produced can be toxic to the gastric superficial epithelial cells. Urease stimulates inflammatory cytokine production and activates mononuclear phagocytes. Although, after colonisation, the host immune defences are stimulated, and there is increased secretory IgA (sIgA) detected in the gastric mucosa and raised specific IgG, while the infected host is not able to eliminate the organism. Colonisation results in persistent gastric inflammation but the clinical course of infection can be very variable[9].

2 Current treatment of H. pylori infections

The treatment for eradication of H. pylori is complicated, requiring a minimum of two antibiotics in combination with gastric acid inhibitors. Although H. pylori is sensitive to many antibiotics in vitro, no single agent is effective alone in vivo. Firstly, the bacterium resides below the gastric mucus adherent to the gastric epithelium and thus access of drugs to this site is limited. Secondly, the strain may have acquired resistance to the commonly used antimicrobial drugs[10]. These infections are currently treated with a firstline triple therapy treatment, consisting of one proton pump inhibitor (PPI) and two antibiotics. None of the antibiotics used achieves sufficient eradication when used alone and also require adjuvant therapy[11]. This consists of agents increasing pH within the stomach to allow local action of antibiotics not active at low pH, and PPIs are used at a dose equivalent to 20 mg omeprazole twice daily. It was suggested that ranitidine bismuth citrate (RBC) regimens may be less influenced by antibiotic resistance than PPIbased therapies[12].

The most effective therapies combine two antibiotics including clarithromycin and amoxicillin with a gastric acid inhibitor. However, increasing resistance to current antibiotics is driving research to produce alternatives to the commonly used therapies. In addition to increasing levels of antibiotic resistance, the hostile environment of the stomach, reducing antibiotic bioavailability at the site of action, contributes to failures in treatment[13]. Current recommended regimes are not wholly effective, for example, triple therapy with bismuth, metronidazole and amoxicillin or tetracycline has an eradication efficiency of 60%80%, and patient compliance, sideeffects and bacterial resistance can be problematic with this regime[14]. Alternatives proposed include quadruple therapies, based on, for example, colloidal bismuth subcitrate, tetracycline, metronidazole and omeprazole[15]. Patient compliance with such a complicated dosage regime could be improved by combining the therapies in a single dosage form, and a capsule containing bismuth biskalcitrate, metronidazole and tetracycline (Helicide) has been developed in an effort to improve patient compliance and has currently received approval[16]. There is concern regarding acquired resistance to two of the commonly prescribed antibiotics: clarithromycin and metronidazole. Although not as widespread, resistance to metronidazole can also be problematic but it can be overcome in some cases by lengthening the duration of treatment[17].

3 Drug delivery systems for gastric retention

Major problems in the eradication of H. pylori are the presence of antibioticresistant bacteria requiring multiple drugs with complicated dosing schedules and bacterial residence in an environment where high drug concentrations are difficult to achieve. In order to ensure that the therapy is adequately delivered to the unique niche of the gastric mucosa, development of oral dosage forms with prolonged gastric residence is desirable. Gastric retentive delivery systems have been studied for a number of years, and generally requirements of such strategies are that the vehicle maintains a controlled release of drug and exhibits prolonged residence time in the stomach. Overcoming the physiological barriers of the human GI tract is a major challenge facing successful development of gastric retentive systems and leads to problems with reproducibility. In addition to the thick protective mucus layer, gastrointestinal motility patterns are another obstacle facing drug delivery to the stomach. In the fasted state, the interdigestive myoelectric motor complex (IMMC) is a 2hour cycle of peristaltic activity that regulates motility patterns[18]. Phase Ⅲ of the IMMC is also called the housekeeper wave and consists of strong, intense contractions designed to remove debris such as undigested food from the stomach[19, 20]. Gastric residence time will depend on which phase of IMMC is active. In the fed state, the stomach churns food to sizes less than 1 mm, which is then emptied to the duodenum. Type of the food determines its residence time in the stomach with liquids emptying rapidly and solids much more slowly. Gastric residence time is generally longer in the fed rather than fasted state. The gastric residence time of dosage forms is also influenced by posture, age, gender, disease status and concomitant medication. A number of different techniques have been explored to increase gastric retention including high density and magnetic systems, but the three main systems are floating systems, bio/mucoadhesive systems and swelling systems.

4 Floating drug delivery systems

Various approaches had been made since the late 1970s to utilise floating behaviour in order to prolong residence. Designs include hydrodynamically balanced systems (HBS), microspheres, gasgenerating systems and raftforming systems. Originally, such systems were proposed to reduce fluctuations in drug levels and provide sustained release as the duration of most oral sustained release preparations is 812 hours, due to a relatively short GI transit time[21, 22]. HBS has a bulk density lower than gastric fluids and contain one or more colloids formulated into a single unit with the drug and other additives, which swell on contact with water and facilitate floating[23, 24]. A density of less than 1.0 g/mL is required. A triplelayer floating tablet system was proposed containing a swellable gasgenerating layer, a swellable drugcontaining layer (with tetracycline and metronidazole) and a rapidly dissolving layer containing bismuth salts. The system was capable of providing sustained release of the antibiotics in vitro at pH 1.8 and demonstrated buoyancy in vitro, however no in vivo results are reported. Tablets containing a 1︰2 ratio of hydroxypropylcellulose to amoxicillin, with a gasgenerating system, failed to improve efficacy. These large singlelayer tablets remained buoyant in vitro but bioavailability was reduced to 80.5% as compared with conventional capsules in fasted humans[25]. Intersubject variability in gastric transit times with floating tablets and HBS results in unreliable and irreproducible residence times in the stomach and remains a significant problem with such systems. This can be addressed by using multipleunit pided systems such as microspheres. As these can spread evenly through the stomach contents, they can avoid the problems of variable and early gastric emptying or bursting associated with the singleunit systems. Polymers used in formulation of floating multipleunits include caesingelatin acrylic polymers such as Eudragits and alginates[26]. Alginic acid is a polysaccharide consisting of Dmannuronic acid and Lguluronic acid. It forms a bioadhesive and stable gel with palent cations such as calcium and the sodium salt been used in a variety of oral and topical formulations. Floating alginate systems such as Gaviscon form a buoyant gel which floats on the gastric contents alleviating symptoms of heartburn. Its stability in acidic media has made it a popular choice for gastric retentive delivery systems. For example, floating multiple units consisting of a calcium alginate core, separated from a calcium alginate/polyvinyl alcohol (PVA) membrane by an air compartment displayed prolonged gastric retention after a meal. Alginate beads are commonly prepared by extruding alginate, dropwise, into a solution containing Ca2+. The resultant beads are porous and can be used to encapsulate a variety of drugs with a wide range of physicochemical properties[27]. Adequate control of drug release from such formulations often requires some modification to the matrix. For example, foambased floating microspheres can be prepared by adding polypropylene foam powder to an organic solution containing dissolving polymer (Eudragit RS or polymethyl methacrylate, PMMA) and drug. Upon solvent evaporation, freeflowing microspheres are formed with extended release profiles[28]. Two types of alginate floating beads containing metronidazole were compared; one formulation contained chitosan and the other contained vegetable oils. In vitro release was complete from all formulations within two hours. Following administration to guinea pigs, it was concluded that after three hours chitosancontaining particles resulted in increased drug levels in the gastric mucosa as compared with metronidazole solution[29]. A multipleunit floating dosage form formulated using calcium alginate was prepared by dropping sodium alginate solution into calcium chloride and the resultant particles were freezedried. Amoxicillin was incorporated into these beads by addition of drug to the calcium chloride solution. Once the sodium alginate was extruded into the solution, the resultant gel beads were left for thirty minutes before extraction and freezedrying. Amylose was also added to the formulation in an attempt to reduce the release rate. Amoxicillin release showed an initial burst effect and the release was described by Higuchi kinetics, implying that it is controlled by diffusion of the drug through a porous matrix. Gammascintigraphic studies showed evidence of gastric retention of the floating beads in all seven subjects even following normal food intake.

A major limitation with such systems is the requirement for sufficient volumes of gastric acid within the stomach to enable the devices to float. It may be that using a single approach to localise delivery in the stomach may not be sufficient to resist the forces of gastric emptying. It was therefore envisaged that a floating dosage form with mucoadhesive polymers could extend the period of gastric retention, exploiting the retentive properties of the floating system and the ability of bioadhesive formulations to adhere to inflamed tissue. Floating, bioadhesive microsphere systems containing acetohydroxamic acid (AHA), a cytoplasmic urease inhibitor, were prepared. A solution of AHA and the acrylic polymer (Eudragit E) in ethanol/dichloromethane was added to an aqueous PVA solution to form an oilinwater emulsion. The drug and polymer precipitated due to preferential diffusion of ethanol into the aqueous phase. After evaporation of the dichloromethane, the particles were dried and an air cavity was produced inside the spheres giving the particles the ability to float[30]. These particles were spraycoated with the mucoadhesive polymer, polycarbophil. Floating ability was demonstrated in vitro and demonstrated greater percentage growth inhibition of H. pylori in vitro than free drug. Release rates were extended due to the polycarbophil coating[31]. Similar preparations using polybisphenolA carbonate as the coating polymer also showed buoyancy, extended drug release and inhibition of growth of H. pylori in vitro. Clearance of an inoculated strain of H. pylori from the stomach of gerbils following oral delivery of the encapsulated drug was shown to be better than free drug, presumably due to better retention. Although AHA has been shown to be effective at reducing gastritis in a Mongolian gerbil model, further studies are needed to prove that established antibiotics could also be successfully encapsulated into, and released from, such formulations and their efficacy demonstrated in human models[30].

5 Herbal and integrative drugs against H. pylori infections

5.1 Black myrobalan The aqueous extract of black myrobalan (Terminalia chebula Retz) has been shown to have uniform antibacterial activity against ten clinical strains of H. pylori[32, 33]. This activity was bactericidal after 3 h and was stable after autoclaving. Although Sato and coworkers[34] reported gallic acid and ethyl gallate in T. chebula Retz and have shown antibacterial activity of ethanol extracts of this plant against both methicillin resistant and sensitive Staphylococcus aureus and other bacteria, the components of T. chebula Retz aqueous extracts responsible for the observed bacteriocidal activity remain unknown[35]. The antibacterial activity of aqueous extracts of black myrobalan against H. pylori was significantly higher than that of ether and alcoholic extracts. The aqueous extract preserved its antibacterial activity after autoclaving for 30 min at 121 ℃ and was inhibitory at 125150 mg/L. When the plant powder was tested directly against H. pylori, without grinding and (or) extraction and using Colombia Agar plates, the mean inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) values were 150 and 175 mg/L, respectively.

5.2 Ginger Ginger root (Zingiber officinale Rosc.) has been used traditionally for the treatment of gastrointestinal ailments such as motion sickness, dyspepsia and hyperemesis gravidarum, and is also reported to have chemopreventative activity in animal models[36]. The gingerols are a group of structurally related polyphenolic compounds isolated from ginger and known to be the active constituents. Since H. pylori is the primary etiological agent associated with dyspepsia, peptic ulcer disease and the development of gastric and colon cancer, the antiH. pylori effects of ginger and its constituents were tested in vitro[37]. A methanol extract of the dried powdered ginger rhizome, fractions of the extract and the isolated constituents, 6, 8 and 10gingerol and 6shogoal, were tested against 19 strains of H. pylori, including 5 CagApositive strains. The methanol extract of ginger rhizome inhibited the growth of all 19 strains in vitro with a MIC range of 6.25 to 50 μg/mL. One fraction of the crude extract, containing the gingerols, was active and inhibited the growth of all H. pylori strains with an MIC range of 0.78 to 12.5 μg/mL and with significant activity against the CagApositive strains. These data demonstrate that ginger root extracts containing the gingerols inhibit the growth of H. pylori CagApositive strains in vitro and this activity may contribute to its chemopreventative effects[38].

5.3 Turmeric Curcumin, a polyphenolic chemical constituent derived from turmeric (Curcuma longa L.), has been shown to prevent gastric and colon cancers in rodents[39]. Many mechanisms had been proposed for the chemopreventative effects, although the effect of curcumin on the growth of H. pylori has not been reported. H. pylori is a group 1 carcinogen and is associated with the development of gastric and colon cancer. A methanol extract of the dried powdered turmeric rhizome and curcumin were tested against 19 strains of H. pylori, including 5 CagApositive strains. Both the methanol extract and curcumin inhibited the growth of all strains of H. pylori in vitro with a minimum inhibitory concentration range of 6.2550 μg/mL. These data demonstrate that curcumin inhibits the growth of H. pylori CagApositive strains in vitro, and this may be one of the mechanisms by which curcumin exerts its chemopreventative effects[40, 41].

5.4 Thyme A popular herbal remedy in ancient Egypt, Greece and Rome, thyme was mainly used for headaches, digestive problems, respiratory illness, and as a moodenhancer. Researcher who investigated the antimicrobial properties of 21 essential oils against five important foodborne pathogens, including Escherichia coli (E. coli) noted that thyme was very effective at inhibiting the bacteria. Thyme extract was compared with several antibacterials; it had a significant inhibitory effect on H. pylori[42].

5.5 Licorice In a recent study at the Institute of Medical Microbiology and Virology, Germany, researchers found that licorice extract produced a potent effect against strains of H. pylori that are resistant against clarithromycin, one of the antibiotics typically used in the three antibiotic treatment regimens[43]. The authors concluded that this study provides hope that licorice extract can form the basis for an alternative treatment for H. pylori infections[44].

5.6 Berberine Berberine is a plant alkaloid isolated from the roots and bark of several plants including golden seal, barberry, Coptis chinensis Franch. and Yerba mansa. Berberinecontaining plants have been used medicinally in ayurvedic and Chinese medicine, and are known to have antimicrobial activity against a variety of organisms including bacteria, viruses, fungi, protozoans, helminths, and chlamydia. More recently, berberine had been demonstrated to be effective against H. pylori[45].

5.7 Goshuyn (Evodia rutaecarpaa Chinese herb) After testing no less than 113 Chinese herbs for antiH. pylori activity in vitro, Japanese researchers identified goshuyn (Evodia rutaecarpa) as the most effective medical plant. Subsequently, they conducted a randomised clinical trial of two synthetic antibiotics versus the same combination plus goshuyn. The eradication rates were 60% and 80%, respectively[46].

5.8 Other Chinese herbals In an animal study or bacteriostatic test of 53 Chinese herbs, Zhang et al[47] found Coptis chinensis, Rheum palmatum, Panax notogenseng and Magnolia officinalis were effective against H. pylori. Prunus mume and Corydalis yanhusuo were moderate effective.

6 Conclusion

The gastric retention approaches as well as herbal drugs described here have applications for treatment of H. pylori infection although further development is required for each to be fully effective, especially in human studies. Overcoming the high mucus turnover rate and resulting limited retention times is a challenge for bioadhesive systems, and swelling systems must guarantee clearance from the stomach after a certain time to prevent any obstruction. The lack of availability of biocompatible chemical cross linking agents is a major stumbling block in the development of covalently crosslinked hydrogels. Floating systems are available commercially, and combination approaches, using floating behaviour and mucoadhesion, have also shown promise. Exploiting dual mechanisms of retention may provide the strength and reproducibility required to permit successful advancement in this field. So in future, a combination of herbal drugs with the novel drug delivery systems mentioned above, may lead to an important breakthrough in the herbal/integrative treatment of H. pylori infections.

7 Acknowledgement

I would like to acknowledge Dr. K. Pundarikakshudu for giving constant help to compile the information and in preparation of this article. I am also very much thankful to Prof. B.M. Peerzada and Prof. Manish Shah for constant encouragement.

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邮票的知识范文6

为了加强证券(股票)交易印花税的管理,明确税收政策,支持国有企业改革,现就有关国有股权无偿转让征收证券交易印花税的问题,明确如下:

一、对经国务院和省级人民政府决定或批准进行政企脱钩、对企业(集团)进行改组和改变管理体制、变更企业隶属关系,以及国有企业改制、盘活国有企业资产,而发生的国有股权无偿划转行为,暂不征收证券交易印花税。

二、对不属于第一条所述情况的国有股权无偿转让行为,仍应征收证券交易印花税。计税依据为转让股份的面值,税率为4‰。

三、凡属于第一条范围内的国有股权无偿划转行为,由企业(单位)和主管税务机关按所附《上市公司国有股权无偿转让暂不征收证券(股票)交易印花税审批规程》的要求,报国家税务总局审批。

本通知自文到之日起执行。

附件:上市公司国有股权无偿转让暂不征收证券(股票)交易印花税审批规程

    一、企业或单位报送审批的条件和必备文件

对上市公司国有股权无偿转让符合本通知第一条规定范围,需要给予暂不征收证券(股票)交易印花税的,须由企业(单位)按下列要求提出申请报告:

(一)转让方企业(单位)名称、隶属关系、经济性质、企业或单位所在地址;

(二)受让方企业(单位)名称、隶属关系、经济性质、企业或单位所在地址;

(三)转让股权的股数和金额、转让形式、批准部门,以及申请豁免证券交易印花税的理由;

(四)申请报告应附证明文件和材料如下:

1.国务院及其授权部门或者省级人民政府的国有股权无偿转让审批文件;

2.国有股权无偿转让的可行性研究报告;

3.国有股权无偿转让的受让企业(单位)章程;

4.国有股权无偿转让的受让企业(单位)《企业法人营业执照》副本复印件;

5.向社会公布的国有股权无偿转让事宜的预案公告复印件。

二、税务机关审批程序

(一)由国有股权无偿转让或者受让的企业(单位)通过上海、深圳证券交易所向证券交易所所在地市一级国家税务局提交税收暂不征收的申请;

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