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医药导报
医药导报, 2017, 36(7): 804-809
doi: 10.3870/j.issn.1004-0781.2017.07.021
人血白蛋白与晶体液对成人脓毒症及脓毒症休克患者液体复苏作用Meta分析*
Albumin vs.Crystalloids in Fluid Resuscitation for Adults with Severe Spesis and Septic Shock:a Meta-analysis
孙习鹏, 陆瑶华, 李星霞, 陈燕, 郭澄
上海交通大学附属第六人民医院药剂科,上海 200233
SUN Xipeng,, LU Yaohua, LI Xingxia, CHEN Yan, GUO Cheng,
Department of Pharmcy,Sixth People’s Hospital Affiliated with Shanghai Jiaotong University,Shanghai 200233,China
通信作者 郭澄(1965-),男,浙江杭州人,主任药师,博士生导师,博士,研究方向:临床药学与临床药理。电话:021-24058098,E-mail:gboss@126.com。

作者简介 孙习鹏(1985-),男,河南新乡人,主管药师,硕士,研究方向:临床药学。电话:021-24058445,E-mail:sunxipeng@hotmail.com。
基金资助: 上海医院药学科研基金资助项目(2014-YY-03-06)
中图分类号: R977.6     文献标识码: A     文章编号: 1004-0781(2017)07-0804-06
摘要:

目的 系统评价使用人血白蛋白与晶体液对成人脓毒症及脓毒症休克患者液体复苏作用的影响。方法 采用计算机检索Cochrane Library、Pubmed、Embase、中国期刊全文数据库(CNKI)、维普中文科技期刊全文数据库(VIP)、万方数据库,检索时间从建库至2015年11月,对符合纳入标准的随机对照试验(RCT)进行质量评价,并采用RevMan5.3版软件进行Meta分析。结果 共纳入4项RCT,合计患者3 862例。人血白蛋白和晶体液对患者28 d死亡率[RR=0.95,95%CI(0.86,1.05),P=0.33]、90 d死亡率[RR=0.95,95%CI(0.86,1.05),P=0.33]、重症监护室住院时间、总住院时间、机械通气时间、肾脏替代治疗等结局指标的影响均差异无统计学意义。结论 人血白蛋白和晶体液作为复苏液体,对成人脓毒症或脓毒症休克患者的预后差异无统计学意义。
关键词: 白蛋白 ; 晶体液 ; 脓毒症 ; 液体复苏 ; Meta分析

Abstract:

Objective To systematically evaluate the effects of albumin compared with crystalloids on fluid resuscitation for adults with severe sepsis and septic shock. Methods The six databases as follows:Cochrane Library,Pubmed,Embase,CNKI,VIP and Wanfang,were retrieved by computer,from their inception to November,2015.Randomized controlled trials(RCT) in the treatment of adult patients with severe sepsis and septic shock were included for quality assessment and Meta-analysis was performed by using RevMan5.3 software. Results A total of 4 RCTs involving 3 862 participants were included.No differences were found between albumin and crystalloids resuscitation with respect to 28-day mortality[RR=0.95,95%CI(0.86,1.05),P=0.33],90-day mortality[RR=0.95,95%CI(0.86,1.05),P=0.33],duration of stay in ICU,duration of hospital stay,duration of mechanical ventilation and renal replacement therapy. Conclusion In that meta-analysis,the effects of fluid resuscitation with albumin or crystalloids were not significantly different in adults with severe sepsis and septic shock.
Key words: Albumin ; Crystalloids ; Severe sepsis ; Fluid resuscitation ; Meta-analysis

脓毒症及其引起的休克近年来随着细菌耐药性问题日益严峻,其病死率不断升高,早期有效的液体复苏是目前临床广泛使用的治疗手段之一[1-2],但选择胶体液还是晶体液作为复苏液体一直存在争议。人血白蛋白是常见的胶体溶液制剂,白蛋白作为维持血浆胶体渗透压的主要物质,是很多内源性和外源性物质的载体,具有抗炎和抗氧化作用,可以清除体内活性氧基团和氮基团,也是维持酸碱平衡的主要缓冲分子[3]。而晶体液主要包括各种浓度氯化钠溶液、林格液和平衡液等。本研究采用系统评价的方法评估人血白蛋白和晶体液作为复苏液体对成人脓毒症及脓毒症休克患者的疗效,以期为治疗方案的优化选择提供循证医学证据。

1 资料与方法
1.1 纳入标准与排除标准

1.1.1 纳入研究 纳入的文献研究类型均为随机对照试验(randomized controlled trial,RCT),无论是否采用盲法和分配隐藏,语种限定为中文和英文。

1.1.2 纳入标准 确诊为脓毒症或脓毒症休克的成人患者,年龄>18岁,均符合脓毒症或脓毒症休克的诊断标准[4]。

1.1.3 排除标准 排除以下任意一种情况:①合并急性心肌梗死者;②有原发肝、肾衰竭需替代治疗者;③曾有心搏骤停复苏病史者;④合并急性脑梗死或脑出血者;⑤入院治疗在72 h内死亡者;⑥24 h内紧急手术者;⑦住院期间放弃积极治疗者。剔除资料不完整的文献、相似或相同的重复报道文献,只选用最新报道。

1.1.4 干预措施 试验组以人血白蛋白作为复苏液体;对照组以0.9%氯化钠溶液、平衡液、高渗盐水等作为复苏液体。

1.1.5 结局指标 包括28 d死亡率、90 d死亡率、重症监护室(ICU)住院时间、总住院时间、机械通气时间和肾脏替代治疗。

1.2 检索策略

计算机检索Cochrane Library、PubMed、Embase、中国期刊全文数据库(CNKI)、维普中文科技期刊全文数据库(VIP)、万方数据库,检索时间均从建库至2015年11月,采用“人血白蛋白”“胶体液”“白蛋白”“晶体液”“0.9%氯化钠溶液”“平衡液”“高渗盐水”“脓毒症”“脓毒症休克”“随机”“液体复苏”“colloid”“albumin”“crystalloid”“saline”“hypertonic saline solution”“sepsis”“sepsis shock”“randomized controlled tital”“fluid resuscitation”及其同名异型词等进行检索。

1.3 文献筛选、数据提取和质量评价

由2名研究人员独立进行文献筛选、数据提取和文献质量评价,并对纳入的信息进行交叉核对,遇分歧通过求助第三方讨论解决。数据提取的内容主要包括:受试人群基线特征及入组例数、干预措施及试验实施情况、文献方法学质量信息、结局指标和测量结果。方法学质量评价依据Cochrane系统评价手册进行。评价项目包括:①随机方法是否正确;②是否做到分配隐藏;③参与者是否采用盲法;④结局评估是否采用盲法;⑤有无失访或退出,如有失访或退出,是否采用意向治疗分析(ITT);⑥是否选择性报道;⑦其他偏倚来源。所有评价项目均满足者,发生偏倚的可能性最低,评为A级;如其中任何一项或多项评价标准仅部分满足或不清楚,则该研究存在相应偏倚的可能性为中等,评为B级;如其中任何一项或多项评价标准完全不满足,则该研究存在相应偏倚的高度可能性,评为C级。

1.4 统计分析

本研究采用RevMan5.3版软件进行Meta分析。采用χ2检验分析合并研究之间是否存在统计学异质性,统计学同质性较好(P>0.10,I2<50%)的研究采用固定效应模型,而有统计学异质性(P<0.10,I2>50%)的研究,通过分析人口学差异、疾病状态差异、干预措施差异等排除临床异质性后采用随机效应模型分析。二分类变量采用相对危险度(risk ratio,RR)和95%可信区间(confidence interval,CI)表示效应量的大小。连续性变量采用均数差(mean difference,MD)为效应分析统计量,连续性变量用中位数和四分位数间距表示时,根据Cochrane手册中的方法转化成平均数和标准差,中位数等于平均数,标准差等于四分位间距/1.35[5]。

2 结果
2.1 检索结果

根据既定的检索策略对相应数据库进行检索,共检索得到文献2 196篇,排除重复文献后共计1 613篇。通过阅读文献题目和摘要,排除不相关文献后共计30篇,阅读全文后根据纳入与排除标准,最终纳入4篇RCT文献(图1)。


图1 文献检索和筛选流程图

Fig.1 Flow diagram of literature retrieval and screening

2.2 纳入研究特征及其质量评价

符合纳入标准的4篇文献共3 862例患者,均诊断为脓毒症或脓毒症休克。其中,3项RCT研究方案为人血白蛋白对比0.9%氯化钠溶液,1项RCT研究方案为人血白蛋白对比晶体溶液。干预措施、结局指标、入组人数等评价纳入研究特征,见表1。当28 d死亡率或90 d死亡率均未提供时,将其他时间点死亡率如ICU死亡率或住院死亡率作为90 d死亡率。

表1 纳入Meta分析的4项临床研究特征
Tab.1 Characteristics of the four clinical studies included in meta analysis
纳入研究与发表年 例数 中位年龄/岁 干预措施 结局指标
白蛋白组 晶体液组 白蛋白组 晶体液组 白蛋白组 晶体液组
ALBIOS 2014[3] 903 907 70 69 20%白蛋白 晶体液 ①②③④⑤⑥
CRISTAL 2013[6] 59 779 63 63 4%或5%白蛋白 等渗或高渗0.9%氯化钠溶液、缓冲液 ①②
SAFE 2011[7] 603 615 60.5*1 61.0*1 4%白蛋白 0.9%氯化钠溶液 ①③④⑤⑥
RACKOW 1983[8] 7 4 82 72 5%白蛋白 0.9%氯化钠溶液 ②

①28-day mortality;②90-day mortality;③duration of stay in ICU;④duration of hospital stay;⑤duration of mechanical ventilation;⑥renal replacement therapy;*1 mean age

①28 d死亡率;②90 d死亡率;③ICU住院时间;④总住院时间;⑤机械通气时间;⑥肾脏替代治疗;*1平均年龄

表1 纳入Meta分析的4项临床研究特征

Tab.1 Characteristics of the four clinical studies included in meta analysis

依据Cochrane系统评价手册对纳入的4项临床研究进行方法学质量评价,评价项目包括随机方法、分配隐藏、盲法、退出失访、选择性报道,见表2。其中,Y代表正确实施,偏倚风险低;U代表不清楚是否实施,偏倚风险未知; N代表未正确实施,偏倚风险高。

表2 纳入Meta分析的4项临床研究质量评价
Tab.2 Quality assessment on the four clinical studies included in meta analysis
纳入文献与发表年 随机方法 分配隐藏 参与者盲法 结局评估盲法 退出失访 选择性报道 其他偏倚 评级
ALBIOS 2014 Y Y N Y Y Y U C
CRISTAL 2013 Y Y N Y Y Y U C
SAFE 2011 Y Y Y Y Y Y Y A
RACKOW 1983 U U N U U Y U C

Y.yes;N.no;U.unclear

Y.是;N.不是;U.不清楚

表2 纳入Meta分析的4项临床研究质量评价

Tab.2 Quality assessment on the four clinical studies included in meta analysis

2.3 Meta分析

2.3.1 28 d死亡率 3项RCT均报道了28 d死亡率[3,6-7],各研究之间无统计学异质性(P=0.33,I2=11%),选择固定效应模型进行合并分析,结果显示白蛋白组28 d死亡率为31.41%,晶体液组为31.87%,两组差异无统计学意义,RR=0.95,95%CI(0.86,1.05),P=0.33,见图2。说明使用人血白蛋白和晶体液作为复苏液体对成人脓毒症及脓毒症休克患者的28 d死亡率影响相当。


图2 28 d死亡率的Meta分析森林图

Fig.2 Forest plot of 28-day mortality by meta analysis

2.3.2 90 d死亡率 3项RCT均报道了90 d死亡率[3,6,8],各研究之间无统计学异质性(P=0.92,I2=0%),选择固定效应模型进行合并分析,结果显示白蛋白组90 d死亡率为41.09%,晶体液组为40.45%,两组无统计学差异,RR=0.95,95%CI(0.86,1.05),P=0.33,见图3,说明使用人血白蛋白和晶体液作为复苏液体对成人脓毒症及脓毒症休克患者的90 d死亡率影响相当。


图3 90 d死亡率的Meta分析森林图

Fig.3 Forest plot of 90-day mortality by meta analysis

2.3.3 ICU住院天数 2项RCT均报道了ICU住院天数[3,7],各研究之间无统计学异质性(P=0.26,I2=21%),选择固定效应模型进行合并分析,结果显示两组差异无统计学意义,MD=0.40,95%CI(-0.20,1.01),P=0.19,见图4。说明使用人血白蛋白和晶体液作为复苏液体对成人脓毒症及脓毒症休克患者的ICU住院天数影响相当。


图4 ICU住院天数的Meta分析森林图

Fig.4 Forest plot of duration of stay in ICU by meta analysis

2.3.4 总住院时间 2项RCT均报道了总住院时间[3,7],各研究之间无统计学异质性(P=0.65,I2=0%),选择固定效应模型进行合并分析,结果显示两组差异无统计学意义,MD=0.37,95%CI(-0.58,1.32), P=0.44,见图5。说明使用人血白蛋白和晶体液作为复苏液体对成人脓毒症及脓毒症休克患者的总住院时间影响相当。


图5 总住院时间的Meta分析森林图

Fig.5 Forest plot of total duration of hospital stay by meta analysis

2.3.5 机械通气时间 2项RCT报道了机械通气时间[3,7],各研究之间无统计学异质性(P=0.28,I2=14%),选择固定效应模型进行合并分析,结果显示两组差异无统计学意义,MD=0.31,95%CI(-0.23,0.86),P=0.26,见图6。说明使用人血白蛋白和晶体液作为复苏液体对成人脓毒症及脓毒症休克患者的机械通气时间影响相当。


图6 机械通气天数的Meta分析森林图

Fig.6 Forest plot of duration of mechanical ventilation by meta analysis

2.3.6 肾脏替代治疗 ALBIOS研究报道了成人脓毒症及脓毒症休克患者使用两种复苏液体后肾脏替代治疗使用率,白蛋白组为24.6%(222/903),晶体液组为21.4%(194/907),两组差异无统计学意义,P=0.11[3]。SAFE研究报道了两组患者肾脏替代治疗使用天数,白蛋白组为(1.2±3.6) d,晶体液组为(1.0±3.1) d,两组差异无统计学意义,P=0.14[7]。

2.3.7 发表偏倚 为全面反映纳入研究的发表偏倚情况,采用28 d死亡率对纳入文献进行倒漏斗图分析,见图7。结果显示,代表3项RCT的散点基本呈倒漏斗状,对称分布于有效线两侧,都落在95%线性范围内,发表偏倚较小。


图7 入选RCT发表偏倚倒漏斗图

Fig.7 Inverted funnel plot of publication bias in the included RCT

3 讨论

早期足够的液体复苏以维持有效的血管容量和组织灌注可明显提高脓毒症及脓毒症休克患者的预后。晶体溶液由于其有效性和廉价易得等优点,经常用于危重患者的液体复苏。晶体溶液由小分子如钠离子、氯离子等组成,大量补充晶体液可能引起高钠血症、高氯血症、酸中毒等不良反应,这对凝血功能、肾功能、胃肠功能和呼吸功能等都有影响[9]。此外,由于其相对分子质量小,晶体溶液可以轻易通过受损的毛细血管半透膜,导致血管内液体扩容持续性降低[10]。而白蛋白的相对分子质量较大,可以更有效保持血管内液体,扩容持续时间久。因此,与晶体溶液相比,白蛋白可以更好地增加胶体渗透压和中心静脉压,降低心率[11]。

本研究评估人血白蛋白和晶体液作为复苏液体对成人脓毒症及脓毒症休克患者的疗效。研究结果表明,人血白蛋白组和晶体液组对患者28 d死亡率、90 d死亡率、ICU住院时间、总住院时间、机械通气时间及肾脏替代治疗等研究指标的影响均差异无统计学意义。表明人血白蛋白和晶体液作为复苏液体,对成人脓毒症及脓毒症休克患者的预后无差异,使用人血白蛋白并无临床获益。此外,采用倒漏斗图方法进行了发表偏倚分析,对称性良好,各研究都落在95%线性范围内,提示文献偏倚较小,可信度较高。

本研究也存在一些局限性,如:①纳入文献数量较少,检索出2 196篇文献,符合条件的仅入选4项研究且均为国外研究,缺少中国人的临床研究数据,建议国内研究单位开展高质量、多中心、大样本的RCT研究;②结局指标方面,有的文献使用均数±标准差描述连续型变量,有的文献使用中位数和四分位数描述,需要经过数据转化才能进行合并分析,因此可能造成偏差。

综上所述,人血白蛋白和晶体液作为复苏液体,对成人脓毒症及脓毒症休克患者的预后无差异。而在关注人血白蛋白和晶体液复苏效果的同时,也应该充分考虑到使用人血白蛋白带来的医疗费用增加和输注血液制品的风险。

The authors have declared that no competing interests exist.
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感染性休克是急诊临床工作中多见和治疗较困难的一类休克。近年来，抗感染治疗和器官功能支持技术取得了长足的进步，但严重感染的死亡率仍高达30％～70％。随着感染性休克的研究越来越深入，其临床治疗原则与方法有较大的变化与发展。本文试就当前感染性休克临床治疗的研究新进展做一综述，希望为临床工作提供参考。
DOI:10.3969/j.issn.1002-1949.2015.04.001      URL    
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[2] 刘伟,王燕荣,王永兴.脓毒症液体治疗进展与争议[J].临床急诊杂志,2015,16(7):567-570.
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[6] ANNANE D,SIAMI S,JABER S,et al.Effects of fluid resuscitation with colloids vs crystalloids on mortality in critically ill patients presenting with hypovolemic shock:the CRISTAL randomized trial[J].JAMA,2013,310(17):1809-1817.
Evidence supporting the choice of intravenous colloid vs crystalloid solutions for management of hypovolemic shock remains unclear.To test whether use of colloids compared with crystalloids for fluid resuscitation alters mortality in patients admitted to the intensive care unit (ICU) with hypovolemic shock.A multicenter, randomized clinical trial stratified by case mix (sepsis, trauma, or hypovolemic shock without sepsis or trauma). Therapy in the Colloids Versus Crystalloids for the Resuscitation of the Critically Ill (CRISTAL) trial was open label but outcome assessment was blinded to treatment assignment. Recruitment began in February 2003 and ended in August 2012 of 2857 sequential ICU patients treated at 57 ICUs in France, Belgium, North Africa, and Canada; follow-up ended in November 2012.Colloids (n65=651414; gelatins, dextrans, hydroxyethyl starches, or 4% or 20% of albumin) or crystalloids (n65=651443; isotonic or hypertonic saline or Ringer lactate solution) for all fluid interventions other than fluid maintenance throughout the ICU stay.The primary outcome was death within 28 days. Secondary outcomes included 90-day mortality; and days alive and not receiving renal replacement therapy, mechanical ventilation, or vasopressor therapy.Within 28 days, there were 359 deaths (25.4%) in colloids group vs 390 deaths (27.0%) in crystalloids group (relative risk [RR], 0.96 [95% CI, 0.88 to 1.04]; P65=65.26). Within 90 days, there were 434 deaths (30.7%) in colloids group vs 493 deaths (34.2%) in crystalloids group (RR, 0.92 [95% CI, 0.86 to 0.99]; P65=65.03). Renal replacement therapy was used in 156 (11.0%) in colloids group vs 181 (12.5%) in crystalloids group (RR, 0.93 [95% CI, 0.83 to 1.03]; P65=65.19). There were more days alive without mechanical ventilation in the colloids group vs the crystalloids group by 7 days (mean: 2.1 vs 1.8 days, respectively; mean difference, 0.30 [95% CI, 0.09 to 0.48] days; P65=65.01) and by 28 days (mean: 14.6 vs 13.5 days; mean difference, 1.10 [95% CI, 0.14 to 2.06] days; P65=65.01) and alive without vasopressor therapy by 7 days (mean: 5.0 vs 4.7 days; mean difference, 0.30 [95% CI, -0.03 to 0.50] days; P65=65.04) and by 28 days (mean: 16.2 vs 15.2 days; mean difference, 1.04 [95% CI, -0.04 to 2.10] days; P65=65.03).Among ICU patients with hypovolemia, the use of colloids vs crystalloids did not result in a significant difference in 28-day mortality. Although 90-day mortality was lower among patients receiving colloids, this finding should be considered exploratory and requires further study before reaching conclusions about efficacy.clinicaltrials.gov Identifier: NCT00318942.
DOI:10.1001/jama.2013.280502      PMID:24108515      URL    
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[7] SAFE STUDY INVESTIGATORS,FINFER S,MCEVOY S,et al.Impact of albumin compared to saline on organ function and mortality of patients with severe sepsis[J].Intensive Care Med,2011,37(1):86-96.
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[8] RACKOW E C,FALK J L,FEIN I A,et al.Fluid resuscitation in circulatory shock:a comparison of the cardiorespiratory effects of albumin,hetastarch,and saline solutions in patients with hypovolemic and septic shock[J].Crit Care Med,1983,11(11):839-850.
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[9] VINCENT J L,GOTTIN L.Type of fluid in severe sepsis and septic shock[J].Minerva Anestesiol,2011,77(12):1190-1196.
Fluid resuscitation is an essential aspect of the management of patients with severe sepsis and septic shock, especially in the early stages of disease. Which fluid should be used for this purpose has been a topic of ongoing and sometimes heated debate for many years, yet this is still little evidence to support one fluid over another. Each fluid type has specific adverse effects, and all fluids when given in excess can be detrimental. In this article, we will review the advantages and limitations of the key fluid types currently used for the resuscitation of critically ill patients with sepsis, including the crystalloids (saline solutions and Ringer's lactate), and the colloids (albumin, gelatins, dextrans, and hydroxyethyl starches). We will then briefly summarize the limited evidence to support use of one fluid type over another, and provide general suggestions for fluid use in these patients.
DOI:10.1056/NEJMra1208623      PMID:21750487      Magsci     URL    
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[10] ZAMPIERI F G,PARK M,AZEVEDO L C.Colloids in sepsis:evenly distributed molecules surrounded by uneven questions[J].Shock,2013,39(Suppl 1):42-49.
Abstract Colloids are frequently used for fluid expansion in the intensive care unit, although its use on several clinical scenarios remains unproven of any relevant clinical benefit. The purpose of this article was to carry out a narrative review regarding the safety and efficacy of colloids in patients with sepsis and septic shock, with emphasis on the most commonly used colloids, albumin and starches. Colloids are effective fluid expanders and are able to restore the hemodynamic profile with less total volume than crystalloids. These properties appear to be preserved even in patients with sepsis with increased capillary permeability. However, some colloids are associated with renal impairment and coagulation abnormalities. Starch use was associated with increased mortality in two large clinical trials. Also, starches probably have significant renal adverse effects and may be related to more need for renal replacement therapy in severe sepsis. Albumin is the only colloid that has been shown safe in patients with sepsis and that may be associated with improved outcomes on specific subpopulations. No trial so far found any robust clinical end point favoring colloid use in patients with sepsis. Because there is no proven benefit of the use of most colloids in patients with sepsis, its use should not be encouraged outside clinical trials. Albumin is the only colloid solution that has proven to be safe, and its use may be considered on hypoalbuminemic patients with sepsis. Nevertheless, there are no robust data to recommend routine albumin administration in sepsis. Starch use should be avoided in patients with sepsis because of the recent findings of a multicenter randomized study until further evidence is available.
DOI:10.1097/SHK.0b013e31828faf82      PMID:23481502      URL    
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[11] FINFER S.Reappraising the role of albumin for resuscitation[J].Curr Opin Crit Care,2013,19(4):315-320.
Fluid resuscitation is a common intervention in acute medical practice. The optimum fluid for resuscitation remains hotly debated and it is likely to vary from one clinical situation to another. Human albumin solutions have been available since the 1940s, but their use varies greatly around the world. This review examines the current evidence for and against the use of albumin as a resuscitation fluid.Fluid resuscitation with albumin has been compared to resuscitation with saline in large high-quality trials in adult ICU patients and in African children. Within overall equivalent effects, albumin may offer a slight mortality benefit in adult ICU patients with severe sepsis whilst increasing mortality in patients with traumatic brain injury. There are no recent high-quality trials comparing albumin to synthetic colloid solutions. In African children with febrile illness and compensated shock, the effects of bolus resuscitation with albumin and saline are similar, but both increase mortality compared to treatment that avoids fluid boluses.Fluid resuscitation with albumin is well tolerated and produces similar results to resuscitation with saline. Albumin should be avoided in patients with traumatic brain injury; possible benefits in adults with severe sepsis remain to be confirmed.
DOI:10.1097/MCC.0b013e3283632e42      PMID:23778074      Magsci     URL    
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关键词（key words）
白蛋白
晶体液
脓毒症
液体复苏
Meta分析
Albumin
Crystalloids
Severe sepsis
Fluid resuscitation
Meta-analysis
作者
孙习鹏
陆瑶华
李星霞
陈燕
郭澄
SUN Xipeng
LU Yaohua
LI Xingxia
CHEN Yan
GUO Cheng