王 燕 姜艷蕊 孫莞綺 宋沅瑾 董叔梅 殷 勇 陳 潔 江 帆
·論著·
兒童阻塞性睡眠呼吸暫停低通氣綜合征與血壓相關性研究
王 燕1,2姜艷蕊2孫莞綺2宋沅瑾2董叔梅2殷 勇1陳 潔1江 帆1,2
目的 探討兒童阻塞性睡眠呼吸暫停低通氣綜合征(OSAHS)與血壓的相關性。方法 納入2012年7月至2013年7月以睡眠打鼾為主訴于上海兒童醫(yī)學中心睡眠障礙診治中心就診的3~18歲兒童青少年,行整夜多導睡眠圖(PSG)監(jiān)測并測量睡前收縮壓(SBP)和舒張壓(DBP)。根據(jù)PSG監(jiān)測結果分為非OSAHS組和OSAHS組,OSAHS組根據(jù)呼吸暫停低通氣指數(shù)和最低血氧飽和度分為OSAHS輕、中和重度亞組。依據(jù)2010年中國兒童青少年血壓參照標準診斷高血壓。計算收縮壓指數(shù)(SBPI)和舒張壓指數(shù)(DBPI)。分析不同程度的OSAHS與血壓的相關性。 結果 385例研究對象進入分析,平均年齡(5.5±2.3)歲,男262例,女123例。SBP (100.6 ±10.4) mmHg,DBP (63.2±8.5) mmHg,符合高血壓診斷122例(31.7%),其中嚴重高血壓42例(10.9%)。非OSAHS組261例(67.8%);OSAHS組124例,其中輕、中和重度亞組分別有54、43和27例。BMI、BMI-Z評分、頸圍、超重及肥胖患病率指標OSAHS組顯著高于非OSAHS組。①OSAHS組SBP顯著高于非OSAHS組,但調整年齡、性別和BMI-Z評分后SBP的組間差異無統(tǒng)計學意義。OSAHS輕、中和重度亞組SBP和DBP差異有統(tǒng)計學意義 (SBP:F=3.46,P=0.034;DBP:F=4.27,P=0.016),在調整了年齡、性別和BMI-Z評分后SBP和DBP的組間差異仍有統(tǒng)計學意義(P<0.05)。②非OSAHS組和OSAHS組SBPI和DBPI差異無統(tǒng)計學意義;OSAHS輕、中和重度亞組SBPI和DBPI差異有統(tǒng)計學意義(SBPI:F=2.54,P=0.046; DBPI:F=3.25,P=0.042)。③OSAHS輕、中和重度亞組高血壓檢出率差異有統(tǒng)計學意義,調整了年齡、性別以及BMI-Z評分后,OSAHS重度亞組嚴重高血壓的風險顯著高于輕度亞組,OR=5.79 (95%CI: 1.45~23.11)。 結論 鼾癥患兒高血壓檢出率顯著高于正常人群,其中重度OSAHS患兒高血壓及嚴重高血壓的發(fā)生風險最高,提示應密切監(jiān)測睡眠相關呼吸障礙患兒的血壓。
睡眠呼吸障礙; 阻塞性睡眠呼吸暫停低通氣綜合征; 高血壓; 多導睡眠監(jiān)測; 兒童
兒童阻塞性睡眠呼吸暫停低通氣綜合征(OSAHS) 為睡眠過程中頻繁發(fā)生的部分或全部上氣道阻塞,擾亂兒童正常通氣和睡眠結構而引起一系列病理生理變化的臨床綜合征[1],是嚴重影響兒童身心健康的臨床常見睡眠呼吸障礙類型之一。目前已有許多成人的前瞻性隊列研究表明,OSAHS是引起高血壓的重要獨立危險因素[2~4]。近期的1項納入1 889例為期12.2年的前瞻性隊列研究同樣證實OSAHS獨立于年齡、肥胖程度等因素,與高血壓累積患病率存在明顯的量效關系[4]。兒童OSAHS與高血壓關系的研究較少,且結論不統(tǒng)一。近期的2項美國研究均認為OSAHS是引起兒童血壓升高的獨立危險因素[5,6],與2007年的1項Meta分析結論相反[7]。國內首篇兒童OSAHS與高血壓關系的研究發(fā)表于2008年,之后有2篇文獻報道,且OSAHS診斷標準不一[8~10],兒童OSAHS與血壓的相關性值得進一步研究。
1.1 研究設計 上海交通大學醫(yī)學院附屬上海兒童醫(yī)學中心(我院)以睡眠打鼾就診的連續(xù)病例,行多導睡眠圖(PSG)監(jiān)測、體格指標和血壓測量,采用單因素和多因素分析不同程度的OSAHS與血壓的相關性。
1.2 知情同意和倫理 本研究通過我院倫理委員會審查(SCMC IRB-k2013008), 并獲得患兒家長的知情同意。
1.3 納入標準 ①以睡眠打鼾為主訴至我院兒童睡眠障礙診治中心就診的、并行PSG監(jiān)測和血壓測量者;②年齡3~18歲。
1.4 排除標準 ①排除中樞性呼吸暫?;虻屯饩C合征患兒;②經(jīng)詳細的病史了解及臨床檢查排除與其他疾病[包括唐氏綜合征、頜面異常、神經(jīng)肌肉疾病 (包括腦性癱瘓)、慢性肺病、鐮狀紅細胞病、代謝性疾病和喉軟化等]相關的OSAHS;③排除原發(fā)性高血壓,腎臟、心臟疾病及其他可能引起血壓異常疾?。虎芘懦每赡苡绊懷獕旱乃幬镎?。
1.5 PSG監(jiān)測方法 采用澳大利亞Compumedics公司生產(chǎn)的PSG監(jiān)測儀。測試前囑患兒保持1周以上的規(guī)律作息時間,1周內患有上呼吸道感染、過敏等影響鼻通氣的疾病者待疾病恢復后再安排PSG監(jiān)測。監(jiān)測當日不飲用咖啡、茶類飲料及鎮(zhèn)靜催眠劑或興奮劑。行整夜至少連續(xù)7 h的夜間睡眠監(jiān)測,記錄內容包括腦電(6導,分別為兩導額部、中央部、枕部導聯(lián))、眼動、肌電、心電、鼻氣流(使用壓力傳感器)、胸腹呼吸運動(使用壓電式胸腹帶傳感器)、腿動和經(jīng)皮血氧飽和度等指標。監(jiān)測結果電腦記錄儲存,我院睡眠中心人員經(jīng)回放人工識別,輔以電腦自動歸納整理。
1.6 血壓的測量 血壓的測量采用電子血壓計(日本TERVMO ELEMANO)。測量方法[11]:PSG監(jiān)測前,平靜休息10 min, 然后測量坐位右臂與心臟同一水平位血壓。測量2次,間隔2~3 min,取平均值;若2次測量相差>5 mmHg,測量第3次,數(shù)值相近的2次取平均值。
1.7 體格指標測定 體重和身高測量方法參照文獻[12],體重測量時著貼身衣物、赤腳,身高測量時脫鞋,直立位;頸圍測量頸部最細的部位,被測者身體直立,平視,兩臂自然下垂,口微張,皮尺水平置于頸后第7頸椎上緣及頸前喉結下方。計算BMI,并對BMI進行Z值轉換,Z=[(BMI測量值/M)L]/(L·S)。其中的L、M和S值來自中國0~18歲兒童BMI百分位數(shù)值表[13]。
1.8 診斷標準 OSAHS診斷參照中國2007年“兒童阻塞性睡眠呼吸暫停低通氣綜合征診療指南草案”[14],阻塞性睡眠呼吸暫停:睡眠中口和鼻氣流停止,但胸、腹式呼吸仍存在;低通氣:口鼻氣流信號峰值降低50%,伴有3%以上血氧飽和度下降和(或)覺醒。呼吸事件的時間長度:≥2個呼吸周期。呼吸暫停低通氣指數(shù)(AHI):每小時內呼吸暫停和低通氣次數(shù)之和。每小時呼吸暫停指數(shù)>1或AHI>5及最低動脈血氧飽和度(LSaO2)<92%診斷為OSAHS。
本研究高血壓診斷依據(jù)文獻[15]中國兒童青少年血壓參照標準:收縮壓(SBP)和(或)舒張壓(DBP)為同年齡、同性別兒童血壓95%~99%為高血壓,≥99%為嚴重高血壓。同時計算血壓指數(shù)(BPI),根據(jù)不同年齡、性別計算每例對象的SBP指數(shù)(SBPI)和DBP指數(shù)(DBPI),計算公式:BPI= (BP觀察值-P95BP值) /P95BP值×100[16]。
超重和肥胖依據(jù)中國2~18歲兒童肥胖、超重篩查BMI界值標準來界定[17],BMI>相應年齡、性別P85為超重,>P95為肥胖。
1.9 分組 依據(jù)OSAHS診斷標準,分為非OSAHS組和OSAHS組,OSAHS組根據(jù)AHI和LSaO2水平[14]分為OSAHS輕度亞組(AHI 5~10、LSaO20.85~0.91 ),中度亞組(AHI ~20、LSaO20.75~0.84),重度亞組(AHI>20、LSaO2<0.75)。
2.1 一般情況 2012年7月至2013年7月385例鼾癥患兒進入分析(圖1),平均年齡(5.5±2.3)歲,男262例(68.1%),女123例,AHI為(6.5±11.6),SBP和DBP分別為 (100.6±10.4) 和(63.2±8.5) mmHg,符合高血壓診斷122例(31.7%),嚴重高血壓42例(10.9%)。非OSAHS組261例,高血壓82例,嚴重高血壓27例;OSAHS組124例,其中輕、中和重度亞組分別為54、43和27例,高血壓40例,嚴重高血壓15例。
圖1 研究對象納入和排除流程圖
Fig 1 Flow chart of including and excluding procedure
單因素分析顯示,OSAHS組與非OSAHS組間年齡、性別構成比差異無統(tǒng)計學意義,身高、BMI、BMI-Z評分、頸圍、超重及肥胖患病率差異均有統(tǒng)計學意義(表1)。進一步調整年齡、性別和BMI-Z評分后兩組間頸圍差異有統(tǒng)計學意義(P<0.05)。調整年齡和性別后超重及肥胖患病率OSAHS組與非OSAHS組差異有統(tǒng)計學意義(P<0.05)。
Notes NC: neck circumference.1) compared between OSAHS and non-OSAHS groups
2.2 BP和BPI比較 圖2顯示,非OSAHS組平均SBP為(99.9±10.1) mmHg,DBP為(62.9±8.8) mmHg;OSAHS組平均SBP為(102.2±10.6) mmHg,DBP為(63.7±8.0) mmHg。單因素分析兩組間僅SBP差異有統(tǒng)計學意義,線性回歸調整年齡、性別和BMI-Z評分后SBP的組間差異無統(tǒng)計學意義。非OSAHS組平均SBPI為(-8.1±8.6), DBPI為(-12.1±12.1);OSAHS組SBPI為(-6.9±9.6),DBPI為(-11.9±10.9);兩組間SBPI和DBPI差異均無統(tǒng)計學意義。
圖2顯示,非OSAHS組與OSAHS組3個亞組間的比較顯示,SBP和DBP差異有統(tǒng)計學意義(SBP:F=3.68,P=0.012;DBP:F=2.69,P=0.046),組間兩兩比較顯示OSAHS重度亞組SBP和DBP顯著高于非OSAHS組和OSAHS輕度亞組(圖2),但調整了年齡、性別和BMI-Z評分后4個亞組間的血壓值差異無統(tǒng)計學意義。
圖2顯示,OSAHS亞組間的SBP和DBP差異均有統(tǒng)計學意義(SBP:F=3.46,P=0.034;DBP:F=4.27,P=0.016),在調整了年齡、性別和BMI-Z評分后差異仍有統(tǒng)計學意義(P<0.05),亞組間兩兩比較顯示OSAHS重度亞組的SBP、DBP顯著高于輕度亞組,而OSAHS中度和輕度亞組SBP、DBP差異無統(tǒng)計學意義。
圖2顯示,SBPI和DBPI在OSAHS輕、中和重度亞組間差異有統(tǒng)計學意義(SBPI:F=2.54,P=0.046;DBP:F=3.25,P=0.042),亞組間兩兩比較顯示OSAHS重度亞組的SBPI及DBPI顯著高于輕度亞組,OSAHS亞組和輕度亞組間SBPI和DBPI差異無統(tǒng)計學意義。
圖2 組間血壓和血壓指數(shù)比較
Fig 2 Comparsion of blood pressure and blood pressure index among different groups
Notes SBP: systolic blood pressure; SBPI: systolic blood pressure index;DBP: diastolic blood pressure; DBPI: diastolic blood pressure index; 1)vssevere OSAHS subgroup,P<0.05; 2)vsnon OSAHS group,P<0.05
2.3 不同程度OSAHS與高血壓檢出率的相關性 OSAHS組與非OSAHS組高血壓檢出率分別為32.2%(40/124)和31.3%(82/262),差異無統(tǒng)計學意義(χ2=0.09,P=0.760)。OSAHS輕、中和重度亞組高血壓檢出率分別為22.2%(12/54)、37.2%(16/43)和44.4%(12/27),在調整了年齡、性別及BMI-Z評分后,3個亞組間高血壓檢出率差異有統(tǒng)計學意義(P=0.045), 高血壓檢出率OSAHS重度亞組高于輕度亞組(OR=2.87,95%CI: 1.03~7.99),OSAHS中度與輕度亞組差異無統(tǒng)計學意義(OR=2.29,95%CI: 0.91~5.76)。
OSAHS輕、中和重度亞組嚴重高血壓檢出率分別為7.4%(4/54)、7.0%(3/43)和29.6%(8/27);在調整了年齡、性別及BMI-Z評分后,3個亞組間嚴重高血壓檢出率差異有統(tǒng)計學意義(P=0.012),嚴重高血壓檢出率OSAHS重度亞組高于輕度亞組(OR=5.79,95%CI: 1.45~23.11),OSAHS中度與輕度亞組差異無統(tǒng)計學意義(OR=1.01,95%CI: 0.21~4.95)。
國內外報道兒童OSAHS患病率為1.2%~5.7%[18~20],近年來有研究報道認為OSAHS得不到有效控制會對兒童的身心發(fā)育產(chǎn)生重要不良影響[21]。本研究通過對我院兒童睡眠障礙診治中心為期1年的病例收集分析發(fā)現(xiàn),在以鼾癥為主訴就診的患兒中,無論其是否最終確診為OSAHS,其高血壓檢出率(非OSAHS組31.3%,OSAHS組32.2%)均遠高于以同樣標準在中國普通兒童人群中所調查的高血壓患病率(3%~20%)[22~24〗[25]。同時,本研究進一步對確診OSAHS兒童及其不同嚴重程度對血壓的影響進行分析,發(fā)現(xiàn)重度OSAHS患兒SBP和DBP均高于輕度OSAHS患兒,而且重度OSAHS患兒高血壓和嚴重高血壓檢出率均明顯高于輕度OSAHS患兒。
國內外研究普遍認為成人OSAHS與高血壓之間存在重要相關性[2~4],而這種相關性在兒童青少年中也得到了部分研究的證實。2008年,美國有研究[5]在幼兒園和小學隨機抽取700名5~12歲兒童,通過整夜PSG監(jiān)測和睡前血壓測量,發(fā)現(xiàn)AHI與SBP間有顯著相關性。另1項美國調查[11]隨機抽取239名6~11歲小學生,通過睡前血壓測量和家用便攜式PSG數(shù)據(jù)采集,發(fā)現(xiàn)阻塞性睡眠呼吸障礙與高血壓患病率密切相關。中國香港的一項調查隨機抽取306名6~13歲學齡兒童[9],行整夜PSG和24 h動態(tài)血壓(ABP)監(jiān)測,發(fā)現(xiàn)AHI>5的兒童清醒期、睡眠期SBP和DBP均顯著高于AHI≤5的患兒,組間的睡眠期高血壓檢出率差異亦有統(tǒng)計學意義。日本1項研究[26]對23名3~12歲初診疑似睡眠呼吸障礙的兒童行整夜PSG及ABP監(jiān)測,結果顯示AHI>10的患兒清醒期和快速眼動睡眠(REM)期血壓值明顯高于AHI≤10的患兒。國內有研究對145例5~14歲鼾癥患兒的研究顯示,OSAHS患兒的夜間血壓值高于單純鼾癥患兒,而且夜間血壓下降值減低,但清醒期血壓和高血壓檢出率差異無統(tǒng)計學意義[8]。但也有部分研究認為睡眠呼吸障礙與兒童的血壓水平無相關性。美國1項研究對60例5~17歲疑似睡眠呼吸障礙患兒行整夜PSG及ABP監(jiān)測[15],顯示AHI>5的患兒清醒期DBP明顯低于AHI<1和AHI 1~5的患兒,而SBP及睡眠期血壓與AHI無相關性。有Meta分析顯示[7],兒童OSAHS與血壓之間無顯著相關性,但納入文獻的調查方法及診斷標準不統(tǒng)一。
本研究未發(fā)現(xiàn)OSAHS組與非OSAHS組間的高血壓檢出率存在統(tǒng)計學差異,與文獻[5,9]報道結果的不一致,考慮與上述文獻的高血壓檢出率來源于OSAHS患兒與正常人群之間的比較有關。但本研究在不同嚴重程度OSAHS亞組之間,發(fā)現(xiàn)其高血壓以及嚴重高血壓的檢出率顯著不同,與多數(shù)文獻結果得出一致的趨勢[11,26,27],其中文獻[27]與本研究受試對象均為鼾癥患兒。已有相關研究發(fā)現(xiàn)不符合OSAHS診斷的單純鼾癥患兒其心血管功能可能已經(jīng)受到影響[28],因此即使沒有診斷為OSAHS,其血壓水平也可能在一定程度上受到影響,應引起臨床醫(yī)生高度重視。
本研究在血壓的測量上采用了電子血壓計,就電子血壓計在高血壓的判定標準方面,目前已有研究對中國香港[15]和上海[29]的兒童進行了不同性別、年齡血壓水平的百分位曲線構建。香港兒童年齡跨度為6~18歲,上海為2~6歲;其中香港地區(qū)研究的樣本量較大,且同時考慮了兒童的身高和體重狀況對血壓的影響。但此兩項研究均無法涵蓋本研究樣本年齡跨度(3~18歲)。以水銀血壓計的血壓值評判標準來評估電子血壓計的測量結果,需要明確兩種測量方法之間的相關性。有成人研究[30]認為水銀血壓計與電子血壓計在血壓測量結果上一致性較好,差異無統(tǒng)計學意義,在兒童中的探索研究或是在兒童中建立完備的電子血壓計評定標準,是今后在完善兒童血壓評定中的重要課題。
另外,本研究顯示OSAHS組BMI-Z評分及超重肥胖患病率顯著高于非OSAHS組, OSAHS的發(fā)病原因是多方面的,而肥胖是其中一項重要高危因素,已在廣泛的成人研究中得以證實,兒童肥胖度增加,患有高血壓的危險同時也增加[31]。提示,兒童的肥胖程度、OSAHS、高血壓之間存在密切的相關性。本研究在調整了BMI-Z評分后,OSAHS嚴重程度與高血壓依然存在顯著相關性,提示兩者間的關聯(lián)獨立于肥胖因素而存在。同時本研究還發(fā)現(xiàn)OSAHS組和非OSAHS組的頸圍差異有統(tǒng)計學意義,AHI與頸圍存在顯著的正相關。既往已有成人研究表明頸圍與AHI有顯著相關性,對OSAHS嚴重程度有預測作用[32,33];本研究結果提示在兒童青少年時期也可觀察到這種相關性。一般認為成人OSAHS患者主要是由于咽部和氣道周圍脂肪導致了上氣道的狹窄和形態(tài)改變,同時脂肪沉積增加上氣道的順應性而使氣道容易塌陷,但在兒童中是否也存在這一情況,值得進一步研究。
本研究的不足之處,①采用ABP較普通的血壓測量更全面,可有效的避免“白大衣高血壓”,對高血壓的診斷意義可能更大;但此項技術在大樣本的人群調查中存在一定難度。②PSG監(jiān)測的兒童可能存在首夜效應,受睡眠環(huán)境改變和檢查儀器的影響,睡眠結構與日常情況可能會有所不同,在一定程度上影響監(jiān)測結果。
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(本文編輯:張崇凡)
復旦大學附屬兒科醫(yī)院如新中華兒童心臟病基金專科培訓項目招生通知
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有意參加培訓者請與復旦大學附屬兒科醫(yī)院社會發(fā)展部(上海市閔行區(qū)萬源路399號,郵編201102)聯(lián)系。聯(lián)系人:羅偉奮,劉玉媚;電子郵箱ekyy2012@163.com,聯(lián)系電話:021-64931850,傳真:021-64931932。
Relationship between obstructive sleep apnea hypopnea syndrome and blood pressure in children
WANG Yan1,2, JIANG Yan-rui2, SUN Wan-qi2, SONG Yan-jin2, DONG Shu-mei2, YIN Yong1, CHEN Jie1, JIANG Fan1,2
(1 Pediatric Sleep Center, Shanghai Children's Medical Center affiliated to Shanghai Jiaotong University School of Medicine; 2 Department of Developmental and Behavioral Pediatrics, Shanghai Children's Medical Center affiliated to Shanghai Jiaotong University School of Medicine, Ministry of Education Shanghai Key Laboratory of Children's Environmental Health, Shanghai 200127, China )
JIANG Fan,E-mail:fanjiang@shsmu.edu.cn
ObjectiveTo explore the relationship between obstructive sleep apnea hypopnea syndrome (OSAHS) and blood pressure in children.MethodsOvernight polysomnography(PSG) was conducted in the Pediatric Sleep Center of Shanghai Jiaotong University School of Medicine affiliated to Shanghai Children's Medical Center for children aged 3-18 years, who were recruited in outpatient clinic from July 2012 to July 2013 with complaint of sleep snoring. Systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measured for everyone before sleep in the evening. All children were divided into non-OSAHS group and OSAHS group according to PSG result, and then OSAHS group was divided into mild, moderate and severe subgroups according to apnea hypopnea index (AHI) and lowest oxygen saturation (LSaO2). The diagnosis of hypertension was made according to blood pressure reference standards for Chinese children and adolescents 2010. Systolic blood pressure index (SBPI) and diastolic blood pressure index (DBPI) were calculated. Then further analysis was was performed to evaluate the relationship between severities of OSHAS and blood pressure levels. ResultsA total of 385 children were enrolled in our study, with average age (5.5±2.3) years, 262 boys, SBP (100.6±10.4) mmHg and DBP (63.2±8.5) mmHg. 122 (31.7%) children met the criteria of hypertension and 42(10.9%) were severe hypertension. 261(67.8%) children were in non-OSAHS group, 124(32.2%) were in OSAHS group. In the OSAHS group, 54, 43 and 27 children were classified into mild, moderate and severe subgroups respectively. Compared with non-OSAHS group, the OSAHS group had higher BMI,BMI-Zscores, neck circumference, prevalence of overweight and obesity. ①SBP of OSAHS group was higher than non-OSAHS group, but it lost significance after adjustment of age, sex and BMI-Z. Both of the SBP and DBP statistically varied among different OSAHS severity groups (SBP:F=3.46,P=0.034; DBP:F=4.27,P=0.016), even adjusted by age, sex and BMI-Zscores. ② SBPI and DBPI did not significantly differ between OSAHS and non-OSAHS groups. In the OSAHS group, SBPI and DBPI significantly varied among different severity subgroups (SBPI:F=2.54,P=0.046; DBP:F=3.25,P=0.042). ③The hypertension prevalence was significantly different among 3 OSAHS subgroups. Severe OSAHS children had higher risk of hypertension compared with mild OSAHS children, OR=2.87(95%CI: 1.03~7.99), for severe hypertension, the OR increased to 5.79, (95%CI: 1.45-23.11). ConclusionThe prevalence of hypertension is higher in children with sleep snoring than the general population, especially in the children with severe OSAHS. More attention should be paid to monitoring blood pressure for the children with sleep disordered breathing.
Sleep related breathing disorders; Obstructive sleep apnea hypopnea syndrome; Hypertension; Polysomnography; Children
國家自然科學基金:81172685;科技部973培育項目:2010CB535000;上海市啟明星計劃:13QH1401800;上海市教委曙光計劃:11SG19
1 上海交通大學醫(yī)學院附屬上海兒童醫(yī)學中心睡眠障礙診治中心 上海,200127;2 上海交通大學醫(yī)學院附屬上海兒童醫(yī)學中心發(fā)育行為兒科,教育部和上海市環(huán)境與兒童健康重點實驗室 上海,201127
江帆,E-mail:fanjiang@shsmu.edu.cn
10.3969/j.issn.1673-5501.2014.03.001
2014-04-12
2014-05-21)