【摘要】：現(xiàn)代醫(yī)學(xué)研究表明,復(fù)雜疾病往往是由多個(gè)基因和蛋白質(zhì)發(fā)生變異而引起的,其發(fā)病機(jī)制也可理解為多途徑、多靶點(diǎn)的生物網(wǎng)絡(luò)變化.隨著人們對(duì)疾病的治療效果的要求日益提高,特別是對(duì)復(fù)雜的疾病,僅靠單一靶點(diǎn)的藥物治療往往不能滿足疾病的治療需求.在現(xiàn)代臨床試驗(yàn)中,藥物組合在治療疾病的過(guò)程中發(fā)揮著越來(lái)越重要的作用,具有廣闊的開發(fā)和應(yīng)用前景.每種藥物單獨(dú)作用于人體時(shí),會(huì)產(chǎn)生各自的藥理效應(yīng).多種藥物組合在一起使用時(shí),則可能會(huì)使藥效增強(qiáng)并降低副作用.所以,藥物組合的研究具有重要的醫(yī)學(xué)價(jià)值.本文主要利用均勻試驗(yàn)設(shè)計(jì)來(lái)研究?jī)蓚�(gè)藥和三個(gè)藥的組合試驗(yàn).兩個(gè)藥的組合試驗(yàn),其試驗(yàn)區(qū)域?yàn)槿我獾乃倪呅?為了在任意四邊形上構(gòu)造均勻試驗(yàn)設(shè)計(jì),本文提出了一種新穎的方法,即構(gòu)造任意四邊形與單位方體[0:1]2之間的一一對(duì)應(yīng)變換,利用該變換推導(dǎo)出試驗(yàn)區(qū)域上隨機(jī)向量的分布表達(dá)式,隨后給出了在任意四邊形上均勻布點(diǎn)的算法.三個(gè)藥的組合試驗(yàn),其試驗(yàn)區(qū)域?yàn)槿我獾娜庵?同樣地,本文構(gòu)造任意三棱柱與單位三棱柱之間的一一對(duì)應(yīng)變換,并且產(chǎn)生了在任意三棱柱上均勻布點(diǎn)的算法.最后本文將所提出的方法應(yīng)用于藥物組合研究實(shí)例,可在試驗(yàn)區(qū)域上均勻布點(diǎn),同時(shí)使單藥可加模型的失擬檢驗(yàn)的功效達(dá)到最大,得到了不錯(cuò)的效果.
[Abstract]:Modern medical studies have shown that complex diseases are often caused by mutations in multiple genes and proteins, and the pathogenesis can also be understood as a variety of biological networks with multiple pathways and targets. With the increasing demand for the therapeutic effect of diseases, especially for complex diseases, the single target drug therapy is often unable to meet the needs of the treatment of diseases. In modern clinical trials, drug combinations play a more and more important role in the treatment of diseases and have a broad prospect of development and application. When each drug acts alone on the human body, it produces its own pharmacological effects. Combination of multiple drugs may enhance the efficacy and reduce side effects. Therefore, the study of drug combination has important medical value. In this paper, the uniform test design is used to study the combination test of two drugs and three drugs. The combined test of the two drugs has an arbitrary quadrilateral region. In order to construct a uniform experimental design on an arbitrary quadrilateral, a novel method is proposed in this paper, which is to construct a one-to-one corresponding transformation between an arbitrary quadrilateral and a unit square [0:1] 2. The distribution expression of random vectors in the experimental region is derived by using this transformation, and then an algorithm for uniformly distributing points on an arbitrary quadrilateral is given. The test area of the three drugs was arbitrary prism. In the same way, the one-to-one corresponding transformation between an arbitrary triangular prism and a unit triangular prism is constructed, and an algorithm for uniform distribution of points on any triangular-prism is obtained. Finally, the method proposed in this paper is applied to the case study of drug combination, which can distribute the points evenly in the experimental area, and at the same time, the efficiency of the single additive model can be maximized, and the good results are obtained.
【學(xué)位授予單位】：廣西師范大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：R96

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