【摘要】：帕金森病(Parkinson disease, PD)是中老年人常見的神經(jīng)系統(tǒng)變性疾病。主要臨床表現(xiàn)包括運動遲緩,靜止性震顫,肌強(qiáng)直和姿勢步態(tài)障礙等。 隨著臨床研究的進(jìn)展,人們逐漸認(rèn)識到PD不僅僅以運動癥狀為主要臨床表現(xiàn),其非運動癥狀也很突出,包括睡眠障礙(Sleep disorders, SD)、認(rèn)知功能損害、精神障礙、自主神經(jīng)功能紊亂和感覺障礙等。近來一項對1072例PD患者進(jìn)行的調(diào)查研究顯示：幾乎所有的患者均出現(xiàn)了至少一種非運動癥狀,其中睡眠障礙、認(rèn)知功能損害和精神障礙是PD患者生活質(zhì)量下降的三大主要非運動癥狀。同運動癥狀一樣,這些非運動癥狀嚴(yán)重影響患者日常生活質(zhì)量,增加家庭和社會的經(jīng)濟(jì)負(fù)擔(dān),加速疾病的進(jìn)展,甚至是患者遠(yuǎn)期死亡的危險因素。 睡眠障礙可能在PD早期就會出現(xiàn),但多數(shù)被認(rèn)為與年老有關(guān),在臨床工作中常被患者、家屬及臨床醫(yī)師忽視。PD伴發(fā)的睡眠障礙(Parkinson disease with sleep disorders, PD-SD)主要包括：失眠、快速動眼睡眠行為障礙(Rapid eye movement sleep behavior disorder, RBD)、日間過度思睡(Excessive daytime sleepiness, EDS)、睡眠發(fā)作、睡眠呼吸暫停綜合征、不寧腿綜合征、其他異態(tài)睡眠等。據(jù)報道,60%-98%的PD患者可能出現(xiàn)RBD。有研究觀點認(rèn)為,RBD和EDS是發(fā)展成PD的臨床前期表現(xiàn),或者可能是出現(xiàn)在PD運動癥狀之前的早期非運動癥狀。 帕金森病睡眠量表(Parkinson's Disease Sleep Scale,PDSS)是一個專門用于評估PD常見睡眠問題的量表,PDSS-2是在PDSS的基礎(chǔ)上改良的新量表,能更簡單有效的評估PD患者睡眠中出現(xiàn)的問題。多導(dǎo)睡眠監(jiān)測(Polysomnography,PSG)是1957年Dement和Kleitmam創(chuàng)建的睡眠研究技術(shù),廣泛應(yīng)用于臨床。經(jīng)過不斷地發(fā)展,能同時記錄腦電圖、眼電圖、心電圖、肌電圖、口鼻氣流、血氧飽和度、鼾音、胸腹運動、腿動、體位等多項睡眠生理指標(biāo)。PSG不僅能客觀記錄反映受試者的睡眠效率、睡眠結(jié)構(gòu)以及睡眠中的異常行為等特點,還可以對一些通過病史無法準(zhǔn)確診斷的情況,如RBD、周期性腿動、呼吸暫停綜合征等進(jìn)行確診。PSG作為一種睡眠檢查手段,日益受到國內(nèi)外重視,成為睡眠障礙患者必不可少的檢查手段,配合量表可以更好的評估各種睡眠障礙。 德國Braak認(rèn)為PD的病理進(jìn)程可先后分為6期,其中2期的病理改變以下位腦干為主,影響脊核、藍(lán)斑、腦橋其他核團(tuán),繼而產(chǎn)生睡眠障礙、運動減少和情感問題等；6期的病理改變主要與累及新皮質(zhì)有關(guān),臨床表現(xiàn)為認(rèn)知功能損害、視幻覺等精神癥狀。Braak分期使人們認(rèn)識到PD早期可能出現(xiàn)一些如睡眠障礙、嗅覺障礙、情感障礙等非特異的臨床特征,并且睡眠障礙可能出現(xiàn)在認(rèn)知功能損害之前。 睡眠障礙預(yù)示著老年認(rèn)知功能損害,睡眠障礙也可以作為認(rèn)知功能損害的一個伴發(fā)癥狀表現(xiàn)出來,同時睡眠質(zhì)量下降進(jìn)一步加重認(rèn)知功能損害。大多數(shù)PD的研究中,只是孤立的研究某種臨床癥狀,很少將不同的臨床癥狀聯(lián)合起來研究,研究這些不同癥狀之間相互影響的關(guān)系,如在PD伴睡眠障礙的研究中僅注意睡眠問題而忽略了認(rèn)知功能的改變,同樣在認(rèn)知功能的研究中也可能忽略了睡眠問題。為此我們對PD患者進(jìn)行PSG監(jiān)測,分析PD伴睡眠障礙患者的-般臨床特征,主客觀睡眠特點及認(rèn)知功能特征,以期發(fā)現(xiàn)PD患者的睡眠障礙與認(rèn)知功能之間可能存在的關(guān)系。 目前引起PD伴睡眠障礙的原因尚不完全清楚,可能有多種因素參與,如患者的年齡、疾病本身、夜間癥狀波動、疾病的并發(fā)癥以及藥物治療等等。而目前關(guān)于PD伴睡眠障礙潛在病理發(fā)病機(jī)制更不清楚,且國內(nèi)外在該方面的研究也甚少。國外有研究發(fā)現(xiàn),PD伴睡眠障礙與體內(nèi)鐵代謝異常導(dǎo)致黑質(zhì)過多的鐵沉積有關(guān)。黑質(zhì)中過量的鐵沉積通過神經(jīng)炎癥機(jī)制誘導(dǎo)多巴胺能神經(jīng)元變性。大量研究已證明,神經(jīng)炎癥機(jī)制在PD的發(fā)病中起著重要作用,但其在PD伴睡眠障礙發(fā)病機(jī)制中的作用尚不清楚。 腫瘤壞死因子(TNF)是巨噬細(xì)胞產(chǎn)生的促炎性細(xì)胞因子,是目前公認(rèn)的對神經(jīng)元有損傷作用的細(xì)胞因子之一。并有研究發(fā)現(xiàn),PD黑質(zhì)紋狀體區(qū)發(fā)生明顯改變的細(xì)胞因子主要有TNF-α、白細(xì)胞介素1(IL-1)等。Mogi等經(jīng)過多次研究發(fā)現(xiàn),PD患者尾狀核、殼核處的TNF-α、轉(zhuǎn)化生長因子(TGF-a)、上皮生長因子(EGF)等濃度明顯高于患者大腦皮質(zhì)區(qū)及正常對照組的相應(yīng)部位,證實PD患者多巴胺能神經(jīng)元的變性過程的確伴有細(xì)胞因子的改變。 有研究從遺傳學(xué)角度分析PD發(fā)病過程中TNF-α及其濃度的改變,發(fā)現(xiàn)TNF-a基因多態(tài)性與散發(fā)性PD的易感性相關(guān),如rs1799964、rs1800629、rs11931074、rs3857059等位點。研究發(fā)現(xiàn),血漿TNF-a的含量與PD睡眠障礙、認(rèn)知功能損害和抑郁障礙等多項非運動癥狀有關(guān)。TNF-α在正常腦組織中呈節(jié)律性表達(dá),參與了睡眠生理調(diào)節(jié)作用,且睡眠最深時表達(dá)最高,但當(dāng)TNF-α表達(dá)過量時則抑制正常睡眠。所以,TNF-α基因不僅與PD的易感性有關(guān),也可能和PD睡眠障礙存在某些聯(lián)系。 本研究以PD伴睡眠障礙患者為主要研究對象,全面評估患者睡眠質(zhì)量,包括PDSS-2,匹茲堡睡眠質(zhì)量指數(shù)量表(PSQI)、愛波沃斯嗜睡量表(ESS), PSG監(jiān)測；認(rèn)知功能評估,包括簡易精神狀態(tài)量表(MMSE)、蒙特利爾認(rèn)知評估量表(MoCA);并應(yīng)用ELISA法檢測血漿TNF-α水平,采用連接酶檢測反應(yīng)(LDR)分型方法檢測TNF-α基因位點多態(tài)性,為PD及PD睡眠障礙的早期診斷提供生化標(biāo)記物,為臨床干預(yù)提供指導(dǎo)。 本研究包括以下主要內(nèi)容：1.帕金森病伴睡眠障礙的主客觀睡眠及認(rèn)知功能特征；2.帕金森病伴睡眠障礙與TNF-α血漿水平和基因多態(tài)性的關(guān)聯(lián)性研究。 第一章帕金森病伴睡眠障礙的主客觀睡眠及認(rèn)知功能特征 目的：探索帕金森病伴睡眠障礙的臨床特征、主客觀睡眠特點；研究帕金森病伴睡眠障礙及睡眠障礙各亞組的認(rèn)知功能特征。 方法：以66例PD患者、46例原發(fā)性睡眠障礙患者及24例正常對照作為研究對象。(1)收集所有受試者相關(guān)的臨床資料,行運動功能、焦慮抑郁、日常生活能力(ADL)的評估。(2)主觀睡眠調(diào)查：所有受試者均完成PDSS-2, PSQI, ESS的評估。(3)客觀睡眠監(jiān)測：對所有入組對象進(jìn)行連續(xù)14小時的PSG監(jiān)測。(4)認(rèn)知功能評估：對受試者行MMSE、MoCA評估。對PD伴睡眠障礙患者的一般臨床特征、主觀客觀睡眠特點及認(rèn)知功能特征進(jìn)行分析,再對PD伴睡眠障礙患者進(jìn)行亞組分型,探討各亞組的認(rèn)知功能特點。 結(jié)果： ①66例PD患者中,睡眠障礙患者48例,占72.72%,其中失眠患者27例,占40.09%,RBD患者21例,占31.81%,睡眠正常(No sleep disorders, NSD)患者18例,占27.27%。與PD-NSD組相比,PD-SD在ADL方面更差。 ②PD-SD組在PDSS-2-T, PDSS-2-1,2,3,6,15和PSQI-T, F1, F2的評分較PD-NSD組顯著增高。PD-SD組與原發(fā)性睡眠障礙組相比,在PDSS-2-T; PDSS-2-4,5,7,9,10,11,12,13,14,15, F5方面評分均增加,而在PSQI-T,F1,F3,F4方面評分則降低(P0.05)。 ③PD伴失眠與PD伴RBD的PSG監(jiān)測相比,總睡眠時間,睡眠效率,睡眠潛伏期,N1、N2、REM各期所占百分比,REM時間方面均有差異(P0.05)。 ④PD-SD組、PD-NSD組、原發(fā)性睡眠障礙組及正常對照組四組的認(rèn)知功能存在顯著差異；MMSE、MoCA及MoCA各分項中,PD-SD組及原發(fā)性睡眠障礙組較PD-NSD及正常對照組得分低,且PD-SD患者的認(rèn)知功能比原發(fā)性睡眠障礙患者的下降更明顯(P0.05)。 ⑤PD-SD的亞組分型中,PD伴RBD組的MoCA評分及MoCA分項中的注意力評分均低于PD伴失眠組(P0.05)。 結(jié)論： (1) PDSS-2較PSQI更適合PD睡眠障礙的評估,能初步了解PD伴睡眠礙的潛在影響因素； (2)PD伴睡眠障礙可能加重認(rèn)知功能障礙； (3)PD伴發(fā)不同類型的睡眠障礙對認(rèn)知功能的影響不同,PD伴RBD的認(rèn)知功能較PD伴失眠的更差。 第二章帕金森病伴睡眠障礙與TNF-a血漿水平和基因多態(tài)性關(guān)聯(lián)性的研究 目的：對PD伴睡眠障礙患者的血漿TNF-a水平進(jìn)行檢測,探討血漿TNF-α水平與PD伴睡眠障礙的關(guān)系；對中國漢族PD患者進(jìn)行TNF-a基因的多態(tài)性分析,探討TNF-α基因多態(tài)性與PD伴睡眠障礙的相關(guān)性。 方法：以96例PD患者和96例正常對照為研究對象,再將PD組分為PD-SD組和PD-NSD組；采用ELISA法檢測血漿TNF-α水平,比較PD-SD組、PD-NSD組和對照組血漿TNF-a濃度；再以237例PD患者和259例正常對照為研究對象,對PD組進(jìn)行睡眠評估,按照PSQI評估將PD患者分為PD-SD組與PD-NSD組,應(yīng)用連接酶檢測反應(yīng)(LDR)分型方法測序,對PD與對照人群及PD-SD與PD-NSD的TNF-a基因的2個SNP位點(rsl799964、rs1800629)進(jìn)行基因型分析。比較各組基因型和等位基因的總體分布頻率。率的比較用X2檢驗,P0.05差異有統(tǒng)計學(xué)意義。 結(jié)果： ①PD-SD組、PD-NSD組與對照組三組間血漿TNF-α濃度存在顯著差異,且PD-SD組較PD-NSD組血漿TNF-α水平明顯增加(P0.05)。 ②經(jīng)檢驗,PD組和對照組各位點基因型分布符合Hardy-Weinberg平衡。兩組rs1799964位點基因型(C/C、C/T、T/T)和rs1800629位點基因型(A/A、A/G、G/G)的總體分布頻率及等位基因(T、C)(A、G)總體分布頻率差異無統(tǒng)計學(xué)意義(P0.05)。 ③將PD組分為PD-SD組和PD-NSD組,對兩組行上述位點的基因型和等位基因總體分布頻率的比較,結(jié)果顯示兩組間rs1799964和rs1800629位點基因型總體分布頻率及等位基因頻率分布差異無統(tǒng)計學(xué)意義(P0.05)。 結(jié)論： (1)血漿TNF-α水平在PD伴睡眠障礙中的含量增高,可能參與PD伴睡眠障礙的發(fā)病過程。 (2)TNF-a基因rs1799964, rs1800629位點的多態(tài)性與中國漢族人群PD伴睡眠障礙的發(fā)病可能無關(guān)。
[Abstract]:Parkinson's disease (Parkinson disease, PD) is a common neurodegenerative disease of middle and old people. The main clinical manifestations include dystagmus, static tremor, myotonic and postural gait disorders.
With the progress of clinical research, people gradually realize that PD is not only the main clinical manifestation of motor symptoms, but also its non motor symptoms are also prominent, including sleep disorder (Sleep disorders, SD), cognitive impairment, mental disorder, autonomic nervous dysfunction and sensory obstacle. A recent study of 1072 patients with PD has been investigated and studied. Almost all patients had at least one non motor symptom, in which sleep disorders, cognitive impairment, and mental disorders were the three major non motor symptoms of the decline in the quality of life of PD patients. As with exercise symptoms, these non motor symptoms seriously affected the daily living quality of the patients and increased the economic burden of family and society. Rapid disease progression is even a risk factor for long-term mortality.
Sleep disorders may appear early in the PD, but most are thought to be associated with age. In clinical work, patients, families and clinicians neglect the.PD associated sleep disorders (Parkinson disease with sleep disorders, PD-SD), including insomnia, and rapid eye movement sleep behavior disorder (Rapid eye movement sleep) R, RBD), excessive daytime sleep (Excessive daytime sleepiness, EDS), sleep seizures, sleep apnea syndrome, restless leg syndrome, and other heteromorphic sleep. It is reported that 60%-98% PD patients may appear RBD. in the view that RBD and EDS are the pre clinical manifestations of PD, or may be before the symptoms of movement symptoms. Early non motor symptoms.
The Parkinson Disease Sleep Scale (PDSS) is a scale specially designed to assess the common sleep problems of PD. PDSS-2 is a modified new scale on the basis of PDSS, which can be used to assess the problems in the sleep of PD patients more easily and effectively. Polysomnography (Polysomnography, PSG) was created in 1957. Sleep research technology, widely used in clinical. After continuous development, the ability to record electroencephalogram, electrocardiogram, electrocardiogram, electromyography, EMG, nose and mouth airflow, oxygen saturation, snoring, thoracic and abdominal movement, leg movement, body position, etc.,.PSG can not only objectively record the sleep efficiency, sleep structure, and sleep differences of the subjects. The diagnosis of.PSG, such as RBD, cyclical leg movement, and apnea syndrome, can be used as a means of sleep examination, which is becoming a necessary measure for patients with sleep disorders. Hindering.
German Braak believes that the pathological process of PD can be divided into 6 stages, of which 2 stages of pathology change the following brain stem mainly, affecting the spinal nucleus, blue spots, and the other nuclei of the pontine, resulting in sleep disorders, movement reduction and emotional problems, and the 6 stage of pathological changes are mainly related to the involvement of the neocortex, the clinical manifestation is cognitive impairment, visual hallucination and other semen The.Braak staging of the symptoms of God has made people realize that early PD may have some nonspecific clinical features such as sleep disorders, olfactory disorders, and emotional disorders, and sleep disorders may occur before cognitive impairment.
Sleep disorders indicate impairment of cognitive function in the elderly, and sleep disorders can also be seen as a symptom of cognitive impairment, while sleep quality decreases further exacerbating cognitive impairment. Most of the PD studies are only isolated to study some clinical symptoms, and rarely combine different clinical symptoms to study, The relationship between these different symptoms, such as the neglect of cognitive function changes in the study of PD with sleep disorders, may also overlook the sleep problems in the study of cognitive function. For this reason, we do PSG monitoring for the patients with PD and analyze the clinical features of the patients with PD with sleep disorders, the subject and the guest. Objective To observe the characteristics of sleep and cognitive function in order to find out the possible relationship between sleep disorders and cognitive function in PD patients.
The causes of PD with sleep disorders are not yet fully understood. There may be a variety of factors involved, such as the age of the patient, the disease itself, the fluctuation of nocturnal symptoms, the complications of the disease, and the drug treatment. The current mechanism of the underlying pathological pathogenesis of PD with sleep disorders is less clear, and there are few studies at home and abroad. A number of studies have shown that the mechanism of neuroinflammation plays an important role in the pathogenesis of PD, but it is in the pathogenesis of PD with sleep disorders. The effect is not yet clear.
Tumor necrosis factor (TNF) is a proinflammatory cytokine produced by macrophages. It is recognized as one of the cytokines that have damage to neurons. Some studies have found that the major changes in the striatum of the PD substantia nigra are TNF- alpha, interleukin 1 (IL-1) and other.Mogi, and the caudate nucleus of PD patients The concentrations of TNF- alpha, transforming growth factor (TGF-a) and epithelial growth factor (EGF) at the putamen were significantly higher than those of the cerebral cortex and the normal control group. It was confirmed that the degeneration process of dopaminergic neurons in PD patients was indeed associated with the change of cytokines.
A genetic analysis of the changes in TNF- alpha and its concentration in the pathogenesis of PD was studied. It was found that the polymorphism of the TNF-a gene was associated with the susceptibility to sporadic PD, such as rs1799964, rs1800629, rs11931074, rs3857059 and other loci. The study found that the content of TNF-a in plasma was associated with many non motor symptoms such as PD sleep disorder, cognitive impairment and depressive disorder. .TNF- alpha is rhythmical in normal brain tissue, participates in the physiological regulation of sleep, and expresses the highest sleep at the deepest level. But when the expression of TNF- alpha is excessive, it inhibits normal sleep. Therefore, the TNF- alpha gene is not only related to the susceptibility of PD, but also may be associated with PD sleep disorder.
The purpose of this study was to assess the quality of sleep in patients with PD with sleep disorders, including PDSS-2, the Pittsburgh sleep quality index (PSQI), the EPO sleepy sleepiness scale (ESS), PSG monitoring, and the cognitive function assessment, including the simple mental state scale (MMSE), and the Montreal cognitive Assessment Scale (MoCA); and the ELISA method test. The plasma TNF- alpha level was measured and the ligase detection reaction (LDR) typing was used to detect the polymorphism of TNF- alpha gene loci, which provided biochemical markers for the early diagnosis of PD and PD sleep disorders, providing guidance for clinical intervention.
This study includes the following main contents: 1. the subjective and objective sleep and cognitive functions of Parkinson's disease with sleep disorders; 2. the association of sleep disorders with sleep disorders and TNF- alpha plasma level and gene polymorphism in Parkinson's disease.
Chapter 1 subjective and objective sleep and cognitive function in Parkinson's disease with sleep disorders
Objective: To explore the clinical features of Parkinson's disease with sleep disorders, the characteristics of subjective and objective sleep, and to study the cognitive functions of the subgroups of Parkinson's disease with sleep disorders and sleep disorders.
Methods: 66 patients with PD, 46 patients with primary sleep disorders and 24 normal controls were used as subjects. (1) all subjects were collected and related clinical data were collected, exercise function, anxiety and depression, and daily living ability (ADL) assessment. (2) subjective sleep survey: all subjects completed the evaluation of PDSS-2, PSQI, ESS. (3) objective sleep supervision. Test: PSG monitoring of all the subjects for 14 hours. (4) evaluation of cognitive function: MMSE, MoCA assessment of subjects. The general clinical features, subjective objective sleep characteristics and cognitive function of patients with PD with sleep disorders were analyzed, and then the subtypes of PD with sleep disorders were subdivided, and the cognitive functions of each subgroup were discussed. Characteristic.
Result:
(1) of 66 patients with PD, 48 cases of sleep disorders, accounting for 72.72%, 27 cases of insomnia, 40.09%, 21 of RBD patients, 31.81%, and 18 cases of normal sleep (No sleep disorders, NSD), accounting for 27.27%. worse in ADL than in PD-NSD group.
In group PD-SD, the scores of PDSS-2-T, PDSS-2-1,2,3,6,15 and PSQI-T, F1, F2 were significantly higher than those in the PD-NSD group. Compared with the primary sleep disorder group, the score of.PD-SD group was increased in PDSS-2-T, PDSS-2-4,5,7,9,10,11,12,13,14,15, F5.
(3) the percentage of total sleep time, sleep efficiency, sleep latency, N1, N2, REM and REM time were different (P0.05) compared with the PSG monitoring of PD and PD with RBD.
(4) there were significant differences in cognitive function between group PD-SD, group PD-NSD, primary sleep disorder group and normal control group. Among the sub items of MMSE, MoCA and MoCA, group PD-SD and primary sleep disorder group had lower scores than those in PD-NSD and normal control group, and the cognitive function of PD-SD patients was more obvious than those of primary sleep disorder (P0.05).
Among the subtypes of PD-SD, the MoCA scores and the attention scores in MoCA scores of PD and RBD groups were lower than those of PD with insomnia group (P0.05).
Conclusion:
(1) PDSS-2 is more suitable for evaluation of PD sleep disorders than PSQI, and can preliminarily understand the potential influence factors of PD with sleep disturbance.
(2) PD with sleep disorders may aggravate cognitive dysfunction.
(3) PD with different types of sleep disorders had different effects on cognitive function. The cognitive function of PD with RBD was worse than that of PD with insomnia.
The second chapter is about the association between Parkinson's disease and sleep disturbance and TNF-a plasma level and gene polymorphism.
Objective: to detect the plasma TNF-a level in patients with PD with sleep disorder, to explore the relationship between the level of plasma TNF- alpha and PD with sleep disorders, and to analyze the polymorphism of TNF-a gene in Chinese Han people with PD, and to explore the correlation between the polymorphism of TNF- a gene and PD with sleep disorder.
Methods: 96 PD patients and 96 normal controls were studied. The PD group was divided into PD-SD group and PD-NSD group. The level of plasma TNF- alpha was detected by ELISA, and the concentration of TNF-a in PD-SD group, PD-NSD group and control group was compared. 237 cases of PD patients and 259 normal controls were studied, and the PD group was sleep evaluated, and the PSQI assessment would be evaluated. PD patients were divided into group PD-SD and group PD-NSD, and sequenced by ligase detection reaction (LDR) typing method, the 2 SNP loci (rsl799964, rs1800629) of TNF-a gene of PD and PD-SD and PD-NSD were analyzed by genotyping. The overall frequency of genotype and allele of each group was compared. Learning meaning.
Result:
(1) There were significant differences in plasma TNF-a levels between PD-SD group, PD-NSD group and control group, and plasma TNF-a levels in PD-SD group were significantly higher than those in PD-NSD group (P 0.05).
(2) the distribution of genotypes in group PD and control group was consistent with Hardy-Weinberg balance. The overall distribution frequency of two groups of rs1799964 loci genotypes (C/C, C/T, T/T) and rs1800629 loci genotypes (A/A, A/G, G/G) and the overall frequency difference of alleles (T, C) were not statistically significant.
(3) the PD group was divided into PD-SD group and PD-NSD group. The comparison of the genotype and allele distribution frequency of the two groups showed that there was no significant difference in the general distribution frequency and allele frequency distribution of the rs1799964 and rs1800629 loci between the two groups (P0.05).
Conclusion:
(1) increased plasma TNF- alpha levels in PD with sleep disorders may be involved in the pathogenesis of PD accompanied by sleep disorders.
(2) the polymorphism of the rs1799964 and rs1800629 loci of TNF-a gene may not be related to the incidence of PD sleep disorders in Chinese Han population.
【學(xué)位授予單位】：南方醫(yī)科大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2014
【分類號】：R742.5

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相關(guān)期刊論文 前1條

1 劉賢臣;唐茂芹;胡蕾;王愛禎;吳宏新;趙貴芳;高春霓;李萬順;;匹茲堡睡眠質(zhì)量指數(shù)的信度和效度研究[J];中華精神科雜志;1996年02期

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