本文關(guān)鍵詞： 戒煙成功 乙酰膽堿受體基因 基因分?jǐn)?shù) 貝葉斯網(wǎng)絡(luò) 優(yōu)勢(shì)分析　出處：《山東大學(xué)》2017年博士論文　論文類型：學(xué)位論文

【摘要】：研究背景雖然吸煙是一種可防可控的行為,世界各國(guó)也做了大量工作去控制煙草的流行,但是煙草在全球的流行趨勢(shì)并不容樂觀。2011年全球范圍內(nèi)15歲以上群體中,吸煙比例男性為36%、女性為8%。全球的統(tǒng)計(jì)結(jié)果顯示,吸煙每年給人類社會(huì)造成了大約35000億人民幣的經(jīng)濟(jì)損失;每年因吸煙導(dǎo)致疾病所引起的死亡人數(shù)約有600萬。在中國(guó),2011年15歲以上人群中的吸煙比例男性為47%、女性為2%。在中國(guó),有3億個(gè)體正處于吸煙的狀態(tài)中,處在二手煙危害中的非吸煙個(gè)體有7.4億之多。然而在中國(guó)2年以上的成功戒煙率僅為11.70%。煙草煙霧中的化學(xué)物超過4000種,很多種化學(xué)物是有毒有害的,其中有69種化學(xué)物是被確定的致癌物。吸煙幾乎可以危害到人的全部器官,導(dǎo)致一系列癌癥的發(fā)病率升高,是支氣管哮喘、腦卒中、動(dòng)脈粥樣硬化等非傳染性慢性病的誘因。吸煙已成為全球前八位死亡原因中六種疾病的主要致病因子。戒煙是文獻(xiàn)中可見到經(jīng)證明過的降低、杜絕煙草損害的唯一方法。因此,探索戒煙成功的影響因素,為針對(duì)性制定戒煙干預(yù)措施提供理論支持,成了公共衛(wèi)生工作者需要解決的一個(gè)問題。持續(xù)吸煙的主要原因是吸煙者產(chǎn)生了尼古丁依賴。尼古丁依賴是由煙草煙霧中的尼古丁造成的。煙草煙霧中的尼古丁被吸入人體經(jīng)呼吸系統(tǒng)、循環(huán)系統(tǒng)到達(dá)腦部后,首先與煙堿型乙酰膽堿受體(nicotinic acetylcholine receptors,nAChRs)結(jié)合,然后刺激中腦邊緣系統(tǒng)的多巴胺神經(jīng)元合成多巴胺,最后導(dǎo)致伏隔核區(qū)的多巴胺釋放增多,使人產(chǎn)生"愉悅感",完成物質(zhì)獎(jiǎng)賞過程。這是尼古丁依賴的生物學(xué)機(jī)制。尼古丁發(fā)揮作用的第一步是尼古丁與nAChRs的結(jié)合。煙堿型乙酰膽堿受體基因(nicotinic acetylcholine receptor gene,CHRN)起著調(diào)節(jié)煙堿型乙酰膽堿受體的作用。基因敲除模型研究表明,敲除了 CHRN的小鼠對(duì)尼古丁的某些反應(yīng)發(fā)生了改變。戒煙與尼古丁依賴是相對(duì)立的:戒煙成功、放棄吸煙的關(guān)鍵一步就是要克服尼古丁依賴。因此我們推測(cè)CHRN可能對(duì)尼古丁依賴、戒煙成功有影響。人群研究表明,CHRN的單核苷酸多態(tài)性(singlenucleotide polymorphisms,SNP)突變可以降低戒煙成功的可能性、使安慰劑組戒煙率降低、使個(gè)體的主動(dòng)戒煙次數(shù)出現(xiàn)差異。雖然現(xiàn)有的研究揭示了 CHRN與戒煙成功的某些關(guān)系,但這些研究尚存在著不足之處:第一,用單個(gè)SNP去研究基因變異與戒煙成功的關(guān)系有可能不能檢測(cè)到基因變異對(duì)戒煙成功的全部影響;第二,當(dāng)前的文獻(xiàn)中,存在結(jié)果不一致或者結(jié)果相反的情況。第三,現(xiàn)有研究缺乏用整體基因信息從基因?qū)用嫔先パ芯緾HRN與戒煙成功關(guān)系的案例。研究表明,個(gè)體因素(如年齡、職業(yè)、教育、每天吸煙量、吸煙開始年齡、吸煙年數(shù)、戒煙動(dòng)機(jī)等)與戒煙成功相關(guān)。尼古丁依賴不僅僅意味著軀體依賴也意味著心理依賴。諸多心理因素中,自我效能代表了人在一定的情景中解決問題的自信。Bandura的理論表明,具有較高自我效能的個(gè)體戒煙成功的機(jī)率相對(duì)較大。研究也顯示,曾經(jīng)吸煙者的拒煙自我效能(smoking abstinence self-efficacy,SASE)得分比現(xiàn)在吸煙者的SASE得分高。自我效能與尼古丁依賴之間存在著負(fù)向相關(guān)關(guān)聯(lián)。據(jù)此推斷SASE可能在成功戒煙中起著積極的作用�，F(xiàn)有的戒煙成功影響因素的探討大多數(shù)都是基于"單因素(基因)或多因素(基因)效應(yīng)獨(dú)立"的統(tǒng)計(jì)假設(shè),數(shù)據(jù)分析采用的是基于變量間效應(yīng)獨(dú)立的統(tǒng)計(jì)方法。這種研究設(shè)計(jì)和統(tǒng)計(jì)分析適用于單因素或效應(yīng)獨(dú)立的多因素情況。就尼古丁依賴、成功戒煙這類多因子疾病而言,通常是由多個(gè)因素(基因)組成了一個(gè)復(fù)雜的交互網(wǎng)絡(luò)系統(tǒng)�；谛�(yīng)獨(dú)立的統(tǒng)計(jì)方法,缺乏針對(duì)由多個(gè)因素(基因)所構(gòu)成的交互網(wǎng)絡(luò)的系統(tǒng)推斷,因而難以從系統(tǒng)層面闡述戒煙成功的機(jī)理。現(xiàn)有研究中,多將個(gè)體因素、心理因素作為協(xié)變量納入對(duì)遺傳因素和戒煙關(guān)系的研究中。雖然這些研究揭示了遺傳因素、個(gè)體因素、心理因素都對(duì)戒煙成功有影響,但未能揭示這三類因素對(duì)戒煙成功貢獻(xiàn)的相對(duì)大小。根據(jù)目前研究的現(xiàn)狀和不足,本研究擬進(jìn)行社區(qū)為基礎(chǔ)的病例對(duì)照研究,以成功戒煙者為病例組、以不成功戒煙者為對(duì)照組,采用綜合基因變異整體信息的基因分?jǐn)?shù)從基因?qū)用嫒パ芯緾HRN變異與戒煙成功之間的關(guān)系,并辨析遺傳因素、個(gè)體因素、心理因素在戒煙成功中的作用。研究目的1.用綜合了基因變異整體信息的基因分?jǐn)?shù)研究遺傳因素與戒煙成功的關(guān)系;2.探索遺傳因素、個(gè)體因素、心理因素在戒煙成功中的相互作用;3.比較遺傳因素、個(gè)體因素、心理因素對(duì)戒煙成功貢獻(xiàn)的相對(duì)大小。研究方法1.采用社區(qū)為基礎(chǔ)的病例對(duì)照研究,病例組由成功戒煙者組成、對(duì)照組由不成功戒煙者組成。調(diào)查對(duì)象來自于山東省3個(gè)縣的17個(gè)村莊。采用調(diào)查問卷調(diào)查吸煙者的個(gè)體因素、心理因素資料。從調(diào)查對(duì)象的血液樣品中提取DNA,并進(jìn)行基因分型,獲取吸煙者的遺傳因素資料。2.采用T檢驗(yàn)、秩和檢驗(yàn)、卡方檢驗(yàn)比較個(gè)體因素、心理因素在成功戒煙人群和不成功戒煙人群之間的分布差別。用單因素Logistic回歸分析、多因素Logistic回歸分析探索單個(gè)SNP位點(diǎn)、基因分?jǐn)?shù)與戒煙成功的關(guān)系。用卡方檢驗(yàn)探索單體型與戒煙成功的關(guān)系。3.用貝葉斯網(wǎng)絡(luò)模型構(gòu)建遺傳因素、個(gè)體因素、心理因素對(duì)戒煙成功產(chǎn)生作用的交互網(wǎng)絡(luò),分析遺傳因素、個(gè)體因素、心理因素對(duì)戒煙成功產(chǎn)生作用過程中的相互作用。4.采用Logistic回歸預(yù)測(cè)為基礎(chǔ)的優(yōu)勢(shì)分析比較遺傳因素、個(gè)體因素、心理因素對(duì)戒煙成功的相對(duì)作用大小。研究結(jié)果1.年齡、戒煙時(shí)年齡、吸煙年數(shù)在成功戒煙人群和不成功戒煙人群之間的分布存在統(tǒng)計(jì)學(xué)差別(P0.05):成功戒煙人群的平均年齡高于不成功戒煙人群的平均年齡,成功戒煙人群戒煙時(shí)的平均年齡低于不成功戒煙人群戒煙時(shí)的平均年齡,成功戒煙人群的平均吸煙年數(shù)少于不成功戒煙人群平均吸煙年數(shù)。吸煙開始年齡、每天吸煙量、工作、教育水平、戒煙原因在成功戒煙人群與不成功戒煙人群之間的分布無差別(P0.05)。積極情境的拒煙自我效能(smoking abstinence self-efficacy in positive/social situation,SASEP)、消極情境的拒煙自我效能(smoking abstinence self-efficacy innegative/affective situation,SASEN)、習(xí)慣情境的拒煙自我效能(smoking abstinence self-efficacy in habit/addictive situation,SASEH)、拒煙自我效能總得分(smoking abstinence self-efficacy total score,SASET)都呈現(xiàn)出成功戒煙人群的平均分?jǐn)?shù)高于不成功戒煙人群平均分?jǐn)?shù)的趨勢(shì);SASEN、SASET在成功戒煙人群與不成功戒煙人群之間的分布存在統(tǒng)計(jì)學(xué)差別(P0.05)。多因素 Logistic 回歸分析顯示,位點(diǎn) rs578776(CHRNA3)、rs660652(CHRNA3)、rs588765(CHRNA5)與戒煙成功存在顯著性關(guān)系(P0.05)。位點(diǎn)rs578776的C等位基因(OR值為0.77)、位點(diǎn)rs660652的A等位基因(OR值為0.70)、位點(diǎn)rs588765的T等位基因(OR值為0.73)是戒煙成功的危險(xiǎn)因素。單體型分析結(jié)果顯示,CHRNA3、CHRNB4分別有一個(gè)單體型與戒煙成功相關(guān)(P0.05)。CHRNA3中的單體型ACC在成功戒煙人群中出現(xiàn)的頻率低于它在不成功戒煙人群中出現(xiàn)的頻率;而CHRNB4中的單體型GGG在成功戒煙人群中出現(xiàn)的頻率高于它在不成功戒煙人群中出現(xiàn)的頻率。多因素Logistic回歸分析顯示基因分?jǐn)?shù)CHRNA3與戒煙成功存在顯著性關(guān)系(P0.05)�；蚍�?jǐn)?shù)CHRNA3為戒煙成功的危險(xiǎn)因素(OR值為0.48)。2.本研究構(gòu)建的貝葉斯網(wǎng)絡(luò)的受試者工作特征曲線下面積為0.91,能夠較好的預(yù)測(cè)結(jié)局變量。遺傳因素、個(gè)體因素、心理因素在影響戒煙成功的過程中形成了5條主要的影響通路:①年齡→戒煙原因→戒煙成功,②年齡→戒煙時(shí)年齡→吸煙年數(shù)→戒煙成功,③吸煙開始年齡→吸煙年數(shù)→戒煙成功,④每天吸煙量→SASET→戒煙成功⑤CHRNA3→ CHRNA5→ CHRNB4→戒煙成功。年齡可以通過戒煙原因、戒煙時(shí)年齡、吸煙年數(shù)等變量間接影響戒煙成功。吸煙年數(shù)是影響戒煙成功的一個(gè)關(guān)鍵節(jié)點(diǎn)。每天吸煙量可以通過影響SASET間接影響戒煙成功。CHRNA3對(duì)CHRNA5、CHRNB4在戒煙成功這一結(jié)局變量上有影響。3.優(yōu)勢(shì)分析顯示,個(gè)體因素是戒煙成功的首要影響因素(標(biāo)準(zhǔn)化權(quán)重52.22%,重要性排序?yàn)?),其后依次為遺傳因素(標(biāo)準(zhǔn)化權(quán)重28.85%,重要性排序?yàn)?)、心理因素(標(biāo)準(zhǔn)化權(quán)重18.93%,重要性排序?yàn)?)。主要結(jié)論1.個(gè)體因素是戒煙成功的影響因素,年齡、戒煙時(shí)年齡、吸煙年數(shù)在成功戒煙人群和不成功戒煙人群中的分布不同。心理因素是戒煙成功的影響因素,SASE水平越高的個(gè)體成功戒煙的機(jī)率就越大。遺傳因素是戒煙成功的影響因素,CHRNA3是戒煙成功的危險(xiǎn)因素,CHRNA3基因分?jǐn)?shù)越高越難戒煙。2.個(gè)體因素之間、個(gè)體因素與心理因素之間、遺傳因素之間在對(duì)戒煙成功的影響過程中存在依賴關(guān)系。在戒煙干預(yù)中,通過干預(yù)關(guān)鍵節(jié)點(diǎn),來提高預(yù)定目標(biāo)人群的戒煙率。3.個(gè)體因素是戒煙成功的首要影響因素,個(gè)體因素對(duì)戒煙成功的作用要大于遺傳因素的作用。戒煙干預(yù)中,應(yīng)加強(qiáng)對(duì)個(gè)體因素的關(guān)注,糾正吸煙者將戒煙不成功歸結(jié)為遺傳因素的錯(cuò)誤觀念。創(chuàng)新點(diǎn)1.本研究借助基因分?jǐn)?shù)用整體基因信息反映基因效應(yīng),從基因?qū)用嫔辖沂玖薈HRNA3是戒煙成功的影響因素,避免了單個(gè)SNP研究的某些不足,提高了檢驗(yàn)效能。2.以影響戒煙成功的乙酰膽堿受體基因?yàn)榛A(chǔ),借助貝葉斯網(wǎng)絡(luò)模型,從系統(tǒng)層面上探索遺傳因素、個(gè)體因素、心理因素對(duì)戒煙成功的影響以及各種因素之間的相互關(guān)系。3.通過優(yōu)勢(shì)分析,辨析遺傳因素、個(gè)體因素、心理因素對(duì)戒煙成功作用的相對(duì)大小,確定了個(gè)體因素是戒煙成功的首要影響因素,為戒煙干預(yù)確定優(yōu)先干預(yù)措施提供了理論基礎(chǔ)。
[Abstract]:Background although smoking is a preventable and controllable behavior, all the countries in the world have also done a lot of work to control the epidemic of tobacco, but the tobacco is popular in the global trend is not optimistic.2011 worldwide over 15 years of age groups, the smoking rate was 36% for men and women for statistical 8%. Global results show that smoking every year caused about 35000 billion yuan of economic losses to human society; every year smoking causes the number of deaths caused by the disease is about 6 million. In China, people over 15 years in 2011 the smoking rate of the male was 47%, female was 2%. in China, there are 300 million individuals are smoking status, smoking in the individual second-hand smoke in 740 million. However, in 2 years China success rate was only 11.70%. chemical compounds in tobacco smoke more than 4000 kinds, many kinds of chemicals are toxic, of which there are 69 kinds of Chemicals are identified carcinogens. Almost all smoking harm to human organs, leading to a series of cancer incidence is increased, bronchial asthma, stroke, atherosclerosis and other causes of non infectious chronic disease. Smoking has become the main pathogenic factor of six kinds of diseases in the world's top eight causes of death in quitting smoking is. In the literature can be seen by reducing proven, the only way to prevent tobacco damage. Therefore, to explore the influence factors of successful smoking cessation, to develop targeted smoking cessation interventions and provide theoretical support for the public health workers need to solve a problem. The main reason is the continued smoking smokers had nicotine dependence and nicotine dependence. Is caused by nicotine in tobacco smoke. The nicotine in tobacco smoke is inhaled through the respiratory system, circulatory system reaches the brain, first with nicotinic acetylcholine Receptor (nicotinic acetylcholine receptors, nAChRs) combined, then stimulate the synthesis of dopamine mesolimbic dopamine neurons, resulting in nucleus accumbens dopamine release increased, make people have a "sense of pleasure", complete the material reward process. This is the biological mechanism of nicotine dependence. The first step is to play the role of nicotine and nicotine combined with nAChRs the nicotinic acetylcholine receptor gene (nicotinic acetylcholine receptor gene, CHRN) plays a regulatory role of nicotinic acetylcholine receptors. Gene knockout model study showed that addition changed some reaction of CHRN mice to nicotine. Smoking cessation and nicotine dependence is the opposite: quit smoking, quit smoking is the key step to to overcome nicotine dependence. So we speculate that CHRN may have effect on nicotine dependence, smoking cessation success. Study group showed that CHR The polymorphism of N (singlenucleotide polymorphisms SNP) mutation can reduce the likelihood of successful smoking cessation, the placebo group smoking rate decreased, the active smoking individual differences occur frequently. Although the existing research reveals some relationship between CHRN and smoking cessation success, but these studies still exist shortcomings: first, using a single SNP to the relationship between gene variation and smoking cessation research success all influence is unable to detect the gene mutation on smoking cessation success possible; second, the current literature, there are inconsistent results or results to the contrary. Third, the lack of existing research to study CHRN and quit smoking from the relationship between the gene level with whole genome information case. The results show that individual factors (such as age, occupation, education, smoking, smoking age, years of smoking, smoking and smoking related work motivation). Nicotine dependence Not only means that the physical dependence also means psychological dependence. Many psychological factors, self-efficacy that represents people solve problems in certain Situational Confidence in.Bandura's theory, has a higher probability of successful smoking cessation self-efficacy individuals is relatively large. The research also showed that former smokers to smoke self-efficacy (smoking abstinence self-efficacy. SASE) scores than current smokers. The higher the SASE score between self-efficacy and nicotine dependence are negative related. Inferred that SASE may play a positive role in smoking cessation. Existing smoking cessation success factors influencing the majority are based on single factor (gene) or multi factor (gene) statistical hypothesis the effect of independent ", data were analyzed by statistical methods are based on independent variables effect. This research design and statistical analysis for single factor or effect Many independent factors. This kind of smoking cessation nicotine dependence, multi factor disease, which is usually caused by multiple factors (genes) formed a complex interaction network system. Statistical method based on independent effect, lack of response by a number of factors (genes) that constitute the system interactive network, thus it is difficult to explain the mechanism from the system level of successful smoking cessation. In the current study, the individual factors, psychological factors as a covariate in the research on genetic factors and smoking cessation relationships. Although these studies have revealed the genetic factors, individual factors, psychological factors have influence on quitting smoking, but failed to reveal the relative sizes of the three kinds of contribution the factors of successful smoking cessation. According to the present situation of the research and the lack of control of quasi community based on the case, to successfully quit smoking as the case group, to successfully quit smoking as control The comprehensive score group, gene mutation of the whole information to study the relationship between CHRN mutation and smoking cessation success from the gene level, and analysis of the genetic factors, individual factors, the role of psychological factors in smoking cessation success. Objective: 1. comprehensive relationship between gene fraction genetic factor gene mutation and overall information of successful smoking cessation; 2. to explore the genetic factors, individual factors, interaction of psychological factors in smoking cessation success; 3. compared with genetic factors, individual factors, the relative contribution of psychological factors on smoking cessation success. Methods 1. community-based case-control study cases by smokers, the control group is composed of former smokers. Survey from 3 counties in Shandong Province in 17 villages. Individual factors by questionnaire survey of smokers, psychological factors. The blood samples from the data surveyed in the DNA extraction and genotyping data, genetic factors.2. for smokers with T test, rank sum test, chi square test to compare individual factors, psychological factors in distribution between people and successfully quit smoking successfully quit smoking population difference. Using single factor Logistic regression analysis, Logistic regression analysis to explore the individual SNP sites. The relationship between gene fraction and successful smoking cessation. To explore the relationship between haplotype and.3. quit successfully used Bayesian network model to construct the genetic factors, individual factors by chi square test, interactive network psychological factors have an effect on smoking cessation, analysis of genetic factors, individual factors, psychological factors on quitting smoking interaction effect in the process of using.4. Logistic regression prediction based comparative advantage analysis of genetic factors, individual factors, psychological factors on the relative contributions of successful smoking cessation. Results 1. age, When you stop smoking age, there was statistical difference in distribution between the years of smoking and quit smoking cessation among populations (P0.05): the average age of the population is higher than the average age of smoking cessation did not quit the crowd, mean age of smoking cessation quit when populations are less successful quitting smoking cessation of smoking, average smoking cessation in the number of years not less than the average number of years of smoking people quit smoking. Age, level of daily smoking, work, education, distribution in the crowd and the reasons for quitting smoking cessation among people not quit no difference (P0.05). The positive situation of anti smoking self-efficacy (smoking abstinence self-efficacy in positive/social situation, SASEP), negative situation of anti smoking self-efficacy (smoking abstinence self-efficacy innegative/affective situation, SASEN), the anti smoking habits situation since I (smoking abstinence self-efficacy in habit/addictive performance situation, SASEH), anti smoking self-efficacy score (smoking abstinence self-efficacy total score, SASET) are showing the average score was higher than that of people successfully quit smoking successfully quit smoking population average trend; SASEN, there was statistical difference between the distribution of SASET in the crowd and not quit smoking cessation success the crowd (P0.05). Logistic regression analysis showed that rs578776 locus (CHRNA3), rs660652 (CHRNA3), rs588765 (CHRNA5) and quit smoking significantly (P0.05). The relationship between the loci of rs578776 C allele (OR = 0.77), the site of rs660652 A allele (OR 0.70), the site of rs588765 T allele (OR = 0.73) were risk factors of successful smoking cessation. Haplotype analysis showed that CHRNA3 and CHRNB4 have a haplotype and smoking cessation success (P0.05) The.CHRNA3 haplotype of ACC in the quit crowd appear less frequently than it appears in the quit in the crowd and haplotype frequency; GGG in CHRNB4 successfully quit smoking crowd appear frequency is higher than it is in the crowd not successfully quit smoking frequency. Logistic regression analysis showed that there was a significant relationship between the success of the gene score CHRNA3 and smoking cessation (P0.05). The gene fraction CHRNA3 as a risk factor of successful smoking cessation (OR = 0.48) Bayesian network.2. constructed in the study of the subject area under the curve is 0.91, can better predict the outcome variable. Genetic factors, individual factors, psychological factors formed 5 main the effects of impact pathway in the process of successful smoking cessation: age, smoking causes to quit smoking and age, smoking age, years of smoking, quit smoking, smoking, smoking and age years The number to quit smoking and the daily smoking amount to SASET and CHRNA3 to CHRNA5 and quit smoking, smoking cessation success. CHRNB4 age can quit smoking, age, years of smoking and other variables indirectly to quit smoking. Smoking is a key point of successful smoking cessation. Smoking can affect every day.CHRNA3 CHRNA5 to successfully quit smoking by affecting SASET, CHRNB4 in the smoking cessation success outcome variables on Impact Analysis of.3. advantage display, individual factors are primary factors of successful smoking cessation (standard weight of 52.22%, ranking 1), followed by genetic factors (standard weight of 28.85%, ranking 2), psychological factors (standard weight of 18.93%, the importance of the order of 3). The main conclusions 1. individual factors, effects of smoking cessation success age, smoking age, years of smoking in the crowd and not quit successfully The distribution of smoking in the crowd. Different psychological factors are the factors affecting the probability of successful smoking cessation, the higher the SASE level of the individual to successfully quit smoking more. Genetic factors are smoking cessation success, CHRNA3 is a risk factor for smoking cessation success, CHRNA3 gene, higher scores are difficult to quit.2. individual factors, individual factors and psychological factors, genetic factors in process of successful smoking cessation in dependence. In the smoking cessation intervention, through the intervention of the key nodes, to improve the target population.3. quit rate of individual factors is the first smoking cessation success factors, individual factors of successful smoking cessation effect is greater than the role of genetic factors in smoking cessation intervention. That should strengthen the individual factors of concern, correct smokers will quit smoking is not successful due to genetic factors misconceptions. This study uses 1. innovation points in the whole body based gene Because the gene effect information reflected from the gene level revealed that CHRNA3 is the influence factors of successful smoking cessation, to avoid some shortcomings of single SNP research, improve the effectiveness of.2. based on acetylcholine receptor gene effects of smoking cessation success, using Bayesian network model to explore the genetic factors, from the system level between the individual factors, psychological impact the factors of successful smoking cessation and various factors of the relationship between.3. through the analysis of the advantages of genetic factors, individual factors, the relative size of psychological factors on quitting smoking effect, determine the individual factor is the primary influence factor of successful smoking cessation, quit smoking

【學(xué)位授予單位】：山東大學(xué)
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2017
【分類號(hào)】：R163

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