覃蓮香,楊乃寧,于春洋,王藝萍,肖躍飛
·論著·
不同劑量左旋肉毒堿對難治性繼發(fā)性甲狀旁腺功能亢進(jìn)患者心功能的影響
覃蓮香,楊乃寧,于春洋,王藝萍*,肖躍飛
目的觀察不同劑量左旋肉毒堿對難治性繼發(fā)性甲狀旁腺功能亢進(jìn)(R-SHPT)患者心功能的影響。方法選取2013—2016年在航天中心醫(yī)院就診擬行甲狀旁腺切除術(shù)(PTX)治療的R-SHPT患者43例,采用隨機(jī)數(shù)字表法將患者分為左旋肉毒堿大劑量治療組(高劑量組,n=22),左旋肉毒堿常規(guī)劑量治療組(常規(guī)劑量組,n=21)。高劑量組給予左旋肉毒堿2 g加入0.9%氯化鈉溶液20 ml靜脈注射,1次/d,連續(xù)應(yīng)用2周,使用總量為28 g。常規(guī)劑量組在透析結(jié)束時(shí)予以左旋肉毒堿1 g加入0.9%氯化鈉溶液20 ml靜脈注射,連續(xù)應(yīng)用2周,使用總量為6 g。檢測治療前后腦鈉肽(BNP)、肌鈣蛋白I(cTnI)水平,并于治療前后測量左心室舒張末期內(nèi)徑(LVEDD)、室間隔舒張末厚度(IVSdT)、左心室后壁舒張末厚度(LVPWdT)、左心室射血分?jǐn)?shù)(LVEF)、舒張?jiān)缙诤褪鎻埻砥谧蠓渴野昕谧畲笱魉俣戎?E/A) 等指標(biāo)。結(jié)果兩組治療前BNP、cTnI、LVEDD、IVSdT、LVPWdT、LVEF、E/A比較,差異均無統(tǒng)計(jì)學(xué)意義(P>0.05);兩組治療后LVEF、E/A比較,差異無統(tǒng)計(jì)學(xué)意義(P>0.05);常規(guī)劑量組治療后BNP、cTnI、LVEDD、IVSdT、LVPWdT高于高劑量組(P<0.05)。常規(guī)劑量組治療前、后LVEF、E/A比較,差異均無統(tǒng)計(jì)學(xué)意義(P>0.05);常規(guī)劑量組治療后BNP、cTnI、LVEDD、IVSdT、LVPWdT低于治療前(P<0.05)。高劑量組治療后BNP、cTnI、LVEDD、IVSdT、LVPWdT低于治療前,LVEF、E/A高于治療前(P<0.05)。治療后高劑量組手術(shù)回歸率為63.6%(14/22),高于常規(guī)劑量組的28.6%(6/21)(χ2=5.31,P=0.021)。結(jié)論高劑量左旋肉毒堿治療R-SHPT患者促進(jìn)心臟功能恢復(fù)、改善左心室重構(gòu)效果更佳,能為患者行PTX治療創(chuàng)造更好時(shí)機(jī)。
甲狀旁腺功能亢進(jìn)癥,繼發(fā)性;腎透析;左旋肉毒堿;心肌損傷;心臟結(jié)構(gòu)和功能
本研究背景:
目前左旋肉毒堿應(yīng)用于維持性血液透析患者劑量為常規(guī)劑量,且尚未見左旋肉毒堿改善維持性血液透析合并心功能不全相關(guān)報(bào)道,更無應(yīng)用于難治性繼發(fā)性甲狀旁腺功能亢進(jìn)的研究及報(bào)道。但已有大劑量左旋肉毒堿應(yīng)用于治療急性心肌梗死的報(bào)道,且取得良好效果。故本文應(yīng)用較大劑量左旋肉毒堿治療難治性繼發(fā)性甲狀旁腺功能亢進(jìn)合并心功能異常,需要行甲狀旁腺切除術(shù)(PTX)的患者,改善了患者心功能,為手術(shù)創(chuàng)造時(shí)機(jī),改善預(yù)后,也為臨床用藥提供指導(dǎo)和參考。
難治性繼發(fā)性甲狀旁腺功能亢進(jìn)(refractory secondary hyperparathyroidism,R-SHPT)是指經(jīng)過規(guī)范的控制高磷飲食、充分透析以及磷結(jié)合劑和活性維生素D藥物治療仍不能控制的持續(xù)高血磷、高甲狀旁腺激素(parathyroid hormone,PTH),快速進(jìn)展的高轉(zhuǎn)運(yùn)骨病,并發(fā)心肌損傷、心血管鈣化、心肌肥厚等并發(fā)癥,需甲狀旁腺切除術(shù)(parathyroidectomy,PTX)治療[1]。但臨床上,部分R-SHPT患者進(jìn)行術(shù)前風(fēng)險(xiǎn)評估,卻因心功能異常,手術(shù)風(fēng)險(xiǎn)高,而暫不能行手術(shù)治療。左旋肉毒堿是一種低分子量的氨基酸衍生物小分子,其生理學(xué)作用是將長鏈脂肪酸由細(xì)胞液轉(zhuǎn)運(yùn)至線粒體基質(zhì),從而進(jìn)行脂肪酸的β氧化,是心臟和骨骼肌使用的主要能量來源[2-4]。左旋肉毒堿主要合成器官為肝臟和腎臟[2-3],亦可通過食物供應(yīng),主要來自牛肉[3]。有研究顯示,大劑量左旋肉毒堿在治療急性心肌梗死中取得良好效果,無不良反應(yīng)[5]。另外,左旋肉毒堿為低分子物質(zhì),可由血液凈化清除[6]。而R-SHPT常并發(fā)心臟病變,加上由于透析清除、內(nèi)源性合成減少、攝入減少等原因,左旋肉毒堿缺乏更嚴(yán)重。針對維持性血液透析患者,目前多數(shù)研究僅給予血液透析丟失部分的左旋肉毒堿常規(guī)劑量的補(bǔ)充,補(bǔ)充后患者各項(xiàng)指標(biāo)確有明顯改善[7-8],但其劑量是否能夠滿足R-SHPT患者需要尚不能明確,且其針對R-SHPT并發(fā)心臟功能異常研究也尚未見報(bào)道。本研究通過對R-SHPT患者補(bǔ)充不同劑量左旋肉毒堿,包括血液透析丟失基本劑量的補(bǔ)充及較大劑量補(bǔ)充進(jìn)行對比分析,為R-SHPT患者改善心臟病變治療提供臨床指導(dǎo),并進(jìn)一步為手術(shù)治療創(chuàng)造時(shí)機(jī)。
1.1 納入與排除標(biāo)準(zhǔn) 納入標(biāo)準(zhǔn):(1)慢性腎臟病(CKD)5期維持性血液透析患者;(2)符合R-SHPT診斷標(biāo)準(zhǔn)[9],并有PTX手術(shù)指征[10]患者;(3)術(shù)前按照2007年美國心臟病學(xué)會(huì)/美國心臟協(xié)會(huì)(ACC/AHA)制訂的圍術(shù)期心血管危險(xiǎn)性評估[11]對患者進(jìn)行評估,并與麻醉科、心內(nèi)科共同協(xié)商判定因其心血管風(fēng)險(xiǎn)高,而暫不能行PTX手術(shù)治療患者。排除標(biāo)準(zhǔn):(1)入選前1個(gè)月內(nèi)發(fā)生急性感染、心腦血管事件或創(chuàng)傷;(2)結(jié)締組織病活動(dòng)期;(3)腫瘤;(4)活動(dòng)性肝病。
1.2 一般資料 選取2013—2016年在航天中心醫(yī)院就診擬行PTX治療的R-SHPT患者43例,其中男27例,女16例;年齡32~65歲,平均年齡(49.0±10.3)歲;原發(fā)?。郝阅I小球腎炎20例,高血壓腎損害12例,糖尿病腎病5例,慢性腎盂腎炎2例,梗阻性腎病1例,多囊腎1例,原因不明2例。采用隨機(jī)數(shù)字表法將患者分為左旋肉毒堿大劑量治療組(高劑量組),左旋肉毒堿常規(guī)劑量治療組(常規(guī)劑量組)。
1.3 治療方法 患者均使用德國費(fèi)森尤斯公司4008B和4008S透析機(jī),使用一次性聚砜膜透析器(德國費(fèi)森尤斯公司,F(xiàn)7),動(dòng)靜脈內(nèi)瘺作為血管通路,血流速度為200~250 ml/min,透析液流速為500 ml/min,透析液鈣離子濃度為1.50 mmol/L(河北紫薇山制藥有限責(zé)任公司),透析3次/周,4 h/次,采用普通肝素和/或低分子肝素抗凝。
高劑量組給予左旋肉毒堿(意大利Sigma-Tau藥廠生產(chǎn),商品名為可益能,進(jìn)口注冊證號H20080513)2 g加入0.9%氯化鈉溶液20 ml靜脈注射,1次/d,連續(xù)應(yīng)用2周,使用總量為28 g。常規(guī)劑量組在透析結(jié)束時(shí)予以左旋肉毒堿1 g加入0.9%氯化鈉溶液20 ml靜脈注射,補(bǔ)充血液凈化丟失的左旋肉毒堿,連續(xù)應(yīng)用2周,使用總量為6 g。
1.4 療效觀察 治療前抽取患者空腹靜脈血8 ml,2 ml加入含K2-EDTA的干燥抗凝瓶中送檢血常規(guī),采用美國Beckman公司生產(chǎn)的Coulter JTR型全自動(dòng)18項(xiàng)參數(shù)血細(xì)胞分析儀檢測血紅蛋白(Hb);3 ml加入無抗凝劑瓶送檢,并于1 h內(nèi)以3 000 r/min離心5 min,分離血清,然后采用全自動(dòng)生化分析儀(日本OLYMPUS公司AU600型)測定血尿素氮(BUN)、血肌酐(Scr)、血鈣(Ca)、血磷(P)、肌酸激酶(CK)、肌酸激酶同工酶(CK-MB);另外3 ml于1 h內(nèi)以3 000 r/min離心5 min,分離血漿,應(yīng)用化學(xué)發(fā)光法(采用美國Beckman公司Access2特種蛋白儀)測定全段PTH水平;治療前、治療后分別抽取空腹靜脈血3 ml加入無抗凝劑瓶,于1 h內(nèi)以3 000 r/min離心5 min,分離血清,然后應(yīng)用化學(xué)發(fā)光法(采用美國Beckman公司Access2特種蛋白儀)檢測腦鈉肽(BNP)、肌鈣蛋白I(cTnI),其中cTnI試劑盒購自瑞士羅氏公司。并在治療前及治療后由本院心臟彩超室專人采用PHILIPS Sonos 5500彩色多普勒超聲儀,探頭頻率為2.5~4.0 MHz測量左心室舒張末期內(nèi)徑(LVEDD)、室間隔舒張末厚度(IVSdT)、左心室后壁舒張末厚度(LVPWdT)、左心室射血分?jǐn)?shù)(LVEF)、舒張?jiān)缙诤褪鎻埻砥谧蠓渴野昕谧畲笱魉俣戎?E/A)等指標(biāo),比較組內(nèi)及組間治療前后參數(shù)間的差別。
2.1 兩組一般資料比較 兩組性別、年齡、透析齡、Hb、BUN、Scr、Ca、P、CK、CK-MB、PTH水平比較,差異均無統(tǒng)計(jì)學(xué)意義(P>0.05,見表1)。
2.2 兩組治療前后BNP、cTnI及二維超聲心動(dòng)圖檢測指標(biāo)比較 兩組治療前BNP、cTnI、LVEDD、IVSdT、LVPWdT、LVEF、E/A比較,差異均無統(tǒng)計(jì)學(xué)意義(P>0.05);兩組治療后LVEF、E/A比較,差異無統(tǒng)計(jì)學(xué)意義(P>0.05);常規(guī)劑量組治療后BNP、cTnI、LVEDD、IVSdT、LVPWdT高于高劑量組,差異均有統(tǒng)計(jì)學(xué)意義(P<0.05)。常規(guī)劑量組治療前、后LVEF、E/A比較,差異均無統(tǒng)計(jì)學(xué)意義(P>0.05);常規(guī)劑量組治療后BNP、cTnI、LVEDD、IVSdT、LVPWdT低于治療前,差異均有統(tǒng)計(jì)學(xué)意義(P<0.05)。高劑量組治療后BNP、cTnI、LVEDD、IVSdT、LVPWdT低于治療前,LVEF、E/A高于治療前,差異均有統(tǒng)計(jì)學(xué)意義(P<0.05,見表2)。
2.3 兩組治療后圍術(shù)期心臟風(fēng)險(xiǎn)評估 治療后兩組患者重新評估圍術(shù)期心臟風(fēng)險(xiǎn),高劑量組回歸手術(shù)14例(63.6%),常規(guī)劑量組回歸手術(shù)6例(28.6%),高劑量組手術(shù)回歸率高于常規(guī)劑量組,差異有統(tǒng)計(jì)學(xué)意義(χ2=5.31,P=0.021)。
表1 兩組一般資料比較Table 1 Comparison of baseline characteristics of the two groups
注:Hb=血紅蛋白,BUN=尿素氮,Scr=血肌酐,Ca=血鈣,P=血磷,CK=肌酸激酶,CK-MB=肌酸激酶同工酶,PTH=甲狀旁腺激素;a為χ2值,b為Z值,余檢驗(yàn)統(tǒng)計(jì)量值為t值
表2 兩組治療前后BNP、cTnI及二維超聲心動(dòng)圖檢測指標(biāo)比較Table 2 Comparison of values of BNP,cTnI and two-dimensional echocardiographic parameters in the two groups before and after treatment
注:BNP=腦鈉肽,cTnI=肌鈣蛋白I,LVEDD=左心室舒張末期內(nèi)徑,IVSdT=室間隔舒張末厚度,LVPWdT=左心室后壁舒張末厚度,LVEF=左心室射血分?jǐn)?shù),E/A=舒張?jiān)缙诤褪鎻埻砥谧蠓渴野昕谧畲笱魉俣戎?;a為Z值
繼發(fā)性甲狀旁腺功能亢進(jìn)癥(secondary hyperparathyroidism,SHPT)是指CKD出現(xiàn)腎功能減退時(shí),由于1,25-(OH)2-D3減少、高血磷、低血鈣等因素刺激甲狀旁腺使之增生肥大并分泌過多的PTH,所引起的鈣、磷和骨代謝紊亂及心血管、神經(jīng)肌肉、皮膚等多系統(tǒng)損傷的一組臨床綜合征[9,12]。透析患者中SHPT發(fā)生率為55.7%[13]。通過低磷飲食,配合使用磷結(jié)合劑、活性維生素D,以及充分透析可使多數(shù)患者的代謝指標(biāo)和臨床癥狀控制在理想范圍[14]。但仍有部分患者因藥物治療效果不佳而發(fā)展為R-SHPT。R-SHPT以不能控制的持續(xù)高PTH、高血磷以及快速進(jìn)展的高轉(zhuǎn)運(yùn)骨病和心肌肥厚、心肌損傷、心血管鈣化為特點(diǎn),嚴(yán)重影響患者的生活質(zhì)量和預(yù)后,此類患者可行PTX,且效果優(yōu)于內(nèi)科治療[1]。本研究選擇的43例R-SHPT患者均來自于外院,患者在進(jìn)入透析的前幾年因?yàn)榻?jīng)濟(jì)等因素通常透析次數(shù)<3次/周,很少達(dá)到尿素清除指數(shù)(Kt/v)>1.4,且未能定期抽血檢測血生化、PTH并及時(shí)藥物干預(yù),上述因素均可能是R-SHPT及其心臟并發(fā)癥的發(fā)展因素,與文獻(xiàn)報(bào)道結(jié)果一致[1,15]。且這些患者也因?yàn)榻?jīng)濟(jì)原因極少補(bǔ)充左旋肉毒堿,SHPT的心臟并發(fā)癥進(jìn)一步加重,進(jìn)而導(dǎo)致PTX前評估心血管風(fēng)險(xiǎn)高,而無法手術(shù)治療。
R-SHPT患者引起心臟不斷惡化的機(jī)制:PTH作為尿毒癥毒素,能引起CKD患者的心血管系統(tǒng)結(jié)構(gòu)和功能異常,是CKD患者心血管疾病的獨(dú)立危險(xiǎn)因素[15-16];另外,尿毒癥透析患者由于透析清除、內(nèi)源性合成減少、攝入減少等原因,導(dǎo)致左旋肉毒堿嚴(yán)重缺乏。左旋肉毒堿缺乏可導(dǎo)致心肌能量代謝異常,心肌能量代謝障礙是各種原因引起的心肌損傷包括心肌挫傷發(fā)生的重要機(jī)制,也是心肌受損后繼發(fā)心功能障礙的重要因素,而心功能障礙導(dǎo)致cTnI進(jìn)一步升高[17]。cTnI和心肌重構(gòu)關(guān)系密切,cTnI所反映的微小心肌損傷可引起心肌重構(gòu)[18],心肌重構(gòu)又可引起心肌細(xì)胞的降解和結(jié)構(gòu)蛋白的丟失,繼而導(dǎo)致cTnI升高[19-20];而PTH作為獨(dú)立心臟病變危險(xiǎn)因素,可引起心臟結(jié)構(gòu)和功能異常,出現(xiàn)cTnI升高及心肌重構(gòu),由此可見,PTH、心肌損傷和心肌重構(gòu)三者關(guān)系密切并互相影響,形成惡性循環(huán)[21]。本研究從改善R-SHPT心肌能量代謝為突破口,短期提升心臟功能,為PTX創(chuàng)造機(jī)會(huì)。結(jié)果顯示無論是評估心功能不全程度指標(biāo)BNP、心肌損傷指標(biāo)cTnI,還是評估心臟重構(gòu)的超聲指標(biāo),高劑量組左旋肉毒堿治療后較治療前指標(biāo)均明顯好轉(zhuǎn);常規(guī)劑量組治療后較治療前BNP、cTnI、LVEDD、IVSdT、LVPWdT也明顯下降。常規(guī)劑量組治療后BNP、cTnI、LVEDD、IVSdT、LVPWdT高于高劑量組。另外,治療后對兩組患者重新進(jìn)行圍術(shù)期心臟風(fēng)險(xiǎn)評估,均有部分患者能回歸手術(shù)治療,其中高劑量組手術(shù)回歸率高于常規(guī)劑量組。由此可見,左旋肉毒堿通過改善R-SHPT患者心功能,為PTX創(chuàng)造時(shí)機(jī),而PTX對高PTH的根治性治療作用,打破了PTH、心肌損傷和心肌重構(gòu)三者之間的惡性循環(huán),進(jìn)一步改善了心功能。綜上所述,左旋肉毒堿治療能改善R-SHPT患者心功能,其中高劑量左旋肉毒堿的療效更明顯,而常規(guī)劑量左旋肉毒堿不能滿足R-SHPT合并心功能異?;颊咴趪g(shù)期治療需求。
左旋肉毒堿改善R-SHPT患者心功能的可能機(jī)制是:左旋肉毒堿協(xié)助長鏈脂肪酸進(jìn)入線粒體,促進(jìn)脂肪酸氧化分解,產(chǎn)生三磷腺苷(ATP),同時(shí)也減少細(xì)胞外堆積的長鏈脂肪酸對細(xì)胞膜毒性作用和損傷[22-23];心肌細(xì)胞實(shí)現(xiàn)功能及代謝的直接能量為ATP,其60%~80%來源于脂肪代謝;而R-SHPT患者存在心肌肥厚,心肌細(xì)胞缺血、低氧,并且心肌細(xì)胞左旋肉毒堿缺乏,阻礙脂肪酸氧化,導(dǎo)致ATP生成減少,細(xì)胞外長鏈脂肪酸大量堆積,加速心肌細(xì)胞的變性、壞死。因此,及時(shí)補(bǔ)充左旋肉毒堿,可能糾正心肌細(xì)胞內(nèi)線粒體能量代謝,從而起到保護(hù)心肌的作用,改善心功能及心肌重構(gòu)[24-25]。
本研究的不足之處:本試驗(yàn)未能進(jìn)行血清或尿液及組織中左旋肉毒堿水平的檢測。既往研究已證實(shí)左旋肉毒堿的消耗相當(dāng)迅速,不存在蓄積可能[26]。另外,目前文獻(xiàn)關(guān)于透析患者左旋肉毒堿的最大使用劑量為“每次透析后2 g”[27-28],故本研究選擇此劑量探討左旋肉毒堿對R-SHPT患者,尤其是擬行PTX合并心臟病變的R-SHPT患者心臟的改善作用,為臨床R-SHPT患者治療提供一定指導(dǎo)。但仍需進(jìn)一步擴(kuò)大樣本量并聯(lián)合測定左旋肉毒堿水平以確定R-SHPT患者的最適左旋肉毒堿治療劑量。
總之,高劑量左旋肉毒堿治療R-SHPT合并心臟病變的患者在促進(jìn)心臟功能恢復(fù)、改善左心室重構(gòu)的效果更明顯,能為患者行PTX治療創(chuàng)造更多時(shí)機(jī),最終改善患者預(yù)后。
作者貢獻(xiàn):覃蓮香、王藝萍進(jìn)行文章的構(gòu)思與設(shè)計(jì)、研究的實(shí)施與可行性分析、論文的修訂、負(fù)責(zé)文章的質(zhì)量控制及審校;覃蓮香、楊乃寧、于春洋進(jìn)行數(shù)據(jù)收集;覃蓮香進(jìn)行數(shù)據(jù)整理、統(tǒng)計(jì)學(xué)處理、結(jié)果的分析與解釋、撰寫論文;王藝萍、肖躍飛對文章整理負(fù)責(zé),監(jiān)督管理。
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2016-12-14;
2017-10-20)
(本文編輯:賈萌萌)
EffectofDifferentDosesofL-carnitineontheCardiacFunctioninPatientswithRefractorySecondaryHyperparathyroidism
QINLian-xiang,YANGNai-ning,YUChun-yang,WANGYi-ping*,XIAOYue-fei
DepartmentofNephrology,AerospaceCenterHospital(AerospaceClinicalMedicineCollegeofPekingUniversity),Beijing100049,China
ObjectiveTo investigate the effect of different doses of L-carnitine on the cardiac function in patients with refractory secondary hyperparathyroidism (R-SHPT).MethodsWe enrolled 43 cases of R-SHPT who needed to undergo the selective parathyroidectomy (PTX) in Aerospace Center Hospital between 2013 and 2016 and divided them into high-dose group (n=22) and conventional-dose group (n=21) by the random number table.The high-dose group
2-week intravenous injection of 2 g L-carnitine diluted in 20 ml 0.9% sodium chloride solution,once daily,the total amount of L-carnitine used was 28 g.The conventional-dose group received intravenous injection of 1 g L-carnitine diluted in 20 ml 0.9% sodium chloride solution at the end of every hemodialysis (three times a week) for two weeks,and the total amount of L-carnitine used was 6 g.The brain natriuretic peptide (BNP),cardiac troponin I (cTnI) and left ventricular end-diastolic dimension (LVEDD),interventricular septal thickness at end-diastole(IVSdT),left ventricular posterior wall thickness at end- diastole (LVPWdT),left ventricular ejection fraction(LVEF),and mitral ratio of peak early to late diastolic filling velocity (E/A) were measured in all the patients before and after treatment.ResultsBefore treatment,the values of BNP,cTnI,LVEDD,IVSdT,LVPWdT,LVEF and E/A did not differ significantly between the two groups(P>0.05).After treatment,the values of LVEF and E/A in the two groups were similar (P>0.05),but the values of BNP,cTnI,LVEDD,IVSdT and LVPWdT in the conventional-dose group were much higher than those in the high-dose group(P<0.05);the values of LVEF and E/A in the conventional-dose group did not change significantly as compared with those measured before treatment (P>0.05),while those of BNP,cTnI,LVEDD,IVSdT and LVPWdT were obviously lower compared with those measured before treatment (P<0.05);the values of BNP,cTnI,LVEDD,IVSdT and LVPWdT were much lower and those of LVEF and E/A were much higher in the high-dose group compared with those measured before treatment (P<0.05);the high-dose group had higher proportion of patients meeting the requirements of PTX than the conventional-dose group〔63.6%(14/22)vs. 28.6%(6/21),χ2=5.31,P=0.021〕.ConclusionHigh dose of L-carnitine treatment for patients with R-SHPT is better in the aspects of promoting heart function recovery and improving left ventricular remodeling,which could create better opportunity for the patient who would receive PTX.
Hyperparathyroidism,secondary;Renal dialysis;L-carnitine;Myocardial injury;Cardiac structure and function
100049北京市,航天中心醫(yī)院(北京大學(xué)航天臨床醫(yī)學(xué)院)腎內(nèi)科
*通信作者:王藝萍,主任醫(yī)師;E-mail:wypdoc@sohu.com
R 582.1
A
10.3969/j.issn.1007-9572.2017.06.y34
覃蓮香,楊乃寧,于春洋,等.不同劑量左旋肉毒堿對難治性繼發(fā)性甲狀旁腺功能亢進(jìn)患者心功能的影響[J].中國全科醫(yī)學(xué),2017,20(32):4002-4007.[www.chinagp.net]
QIN L X,YANG N N,YU C Y,et al.Effect of different doses of L-carnitine on the cardiac function in patients with refractory secondary hyperparathyroidism[J].Chinese General Practice,2017,20(32):4002-4007.
*Correspondingauthor:WANGYi-ping,Chiefphysician;E-mail:wypdoc@sohu.com