Chinese Journal of Tissue Engineering Research ›› 2021, Vol. 25 ›› Issue (25): 4095-4100.doi: 10.12307/2021.026
Zhong Liqing, Zhong Shanshan, Han Weichao, Hu Runkai, He Shufen, Ding Shaobo
Received:
2020-08-04
Revised:
2020-08-05
Accepted:
2020-08-27
Online:
2021-09-08
Published:
2021-03-30
Contact:
Ding Shaobo, Chief pharmacist, Department of Pharmacy, Dongguan People’s Hospital, Dongguan 523000, Guangdong Province, China
About author:
Zhong Liqing, Pharmacist-in-charge, Department of Pharmacy, Dongguan People’s Hospital, Dongguan 523000, Guangdong Province, China
CLC Number:
Zhong Liqing, Zhong Shanshan, Han Weichao, Hu Runkai, He Shufen, Ding Shaobo. Systematic review of the efficacy and safety of umbilical cord-derived cell transplantation for patients with cerebral palsy[J]. Chinese Journal of Tissue Engineering Research, 2021, 25(25): 4095-4100.
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2.2 纳入研究的基本特征 文章共纳入了6项随机对照试验。脐带细胞组应用脐带来源细胞移植疗法进行治疗,对照组以正常盐水做安慰剂治疗或康复疗法治疗。有5个研究的临床试验注册号为ChiCTR1800016554,NCT01929434,NCT01147653,NCT01528436和NCT01193660。其中3个随机对照试验中使用的是人脐带间充质干细胞移植治疗,另外3个研究中使用脐血细胞移植治疗。主要通过静脉注射的方式进行细胞移植治疗。注射的细胞剂量可以分为107和108数量级。主要的结局指标是粗大运动功能测量评分、粗大运动性能测量评分和不良反应事件,其中不良反应事件包括上呼吸道感染、腹泻、便秘、发烧、恶心呕吐和荨麻疹等,见表1。"
2.3 文献质量评估结果 文章纳入了6项随机对照试验[8,12-14,16-17],其中有3项研究使用了随机数字表进行随机分 配[8,14,17],将其评价为“低风险”的选择性偏倚研究;其他3项未报告随机方法[12-13,16],但提及随机字样,文章评价为“不清楚风险”和“高风险”研究。 随机分组后,共有4项研究为双盲研 究[8,13-14,17],分别对患者组、参与医生、协调员和研究者实施了盲法,在选择偏倚、实施偏倚和测量偏倚方面,文章将其评估为“低风险”。HUANG等[12]研究是一项单盲研究,报告患者和他们的家人被设盲,但是并未提及这项研究是否对研究者和参与医生采用盲法,因此将其评估为“不清楚的风险”,存在选择偏倚、实施偏倚和测量偏倚。另一项研究未报道是否使用盲法[16],文章将其评价为“不清楚风险”或“高风险”,存在选择偏倚、实施偏倚和测量偏倚。文章认为有3项研究具有低损耗偏差的风险[12,14,16],因为在细胞移植治疗组和对照组中,缺失数据的比例很低,且分布均匀,评估为“低风险”研究;同时另外3项研究中有报告患者失去随 访[8,13,17],文章评估其为“不清楚风险”,存在随访偏倚。研究结果显示,患者生活方式和隐私的影响之间的相关性很低,可以认为出现报道偏倚的可能性很低,并将其评估为“不清楚风险”,存在报告偏倚,见图3。 "
2.4.3 各组其他结局指标结果差异 GU等[8]研究发现,与对照组相比,脐带间充质干细胞移植组在移植治疗后观察到日常生活能力量表评分(ADL),综合功能评分(CFA)评分的显著改善,差异有显著性意义。KANG等[14]研究采用正电子发射断层扫描仪(PET)扫描显示,与对照组相比,接受脐带间充质干细胞移植治疗的患者的脑室周围炎症水平显著降低。MIN等[13]研究发现接受脐带间充质干细胞移植治疗患者的BSID-Ⅱ心理量表原始得分和BSID-Ⅱ运动量表原始分数均在3和6个月内显著提高。彭亚伟等[16]研究发现脐带间充质干细胞移植组流涎频率及严重程度评分和流涎商测定在1,3,6个月均明显低于对照组,差异有显著性意义。 2.4.4 各组不良反应事件差异 为了进一步探究细胞移植治疗脑瘫患者的安全性,文章对纳入研究报道的不良反应事件进行了分析。Meta分析表明,与对照组相比,细胞移植治疗脑瘫患者的不良反应事件包括上呼吸道感染(RR=0.92,95%CI:0.68-1.23,P=0.56)、腹泻(RR=1.08,95%CI:0.60-1.96,P= 0.80)、便秘(RR=0.90,95%CI:0.39-2.07,P=0.81)、发热(RR=1.66,95%CI:0.96-2.88,P=0.07)、呕吐恶心(RR=1.71,95%CI:0.85-3.44,P=0.13)、荨麻疹(RR= 0.99,95%CI:0.34-2.85,P=0.98)、肺炎 (RR=0.99,95%CI:0.21-4.58,P= 0.99),脱发(RR=2.96,95%CI:0.32-27.47,P=0.34)和贫血(RR=3.00,95% CI: 0.32-27.87,P=0.33)差异均无显著性意义,见表2。尽管在1个研究中[16],细胞移植组患者腰椎穿刺术后出现颅内压低的情况,包括轻度头晕头痛、恶心呕吐,但躺在去掉枕头的床上,静脉滴注生理盐水,患者的症状缓解消失。"
2.5 纳入研究发表偏倚与敏感性分析结果 Meta分析发表偏倚使用漏斗图的方式进行评价,文章采用Stata 12软件对GMFM指标进行Egger发表偏倚检验,从而对本Meta分析的发表偏倚进行更准确定量的评价。定量Egger检验结果发现,截距> 0.05且可信区间包含零(95%CI:-28.76-49.79,P > 0.369),表明纳入的文献无明显发表偏倚,见图6A。 该Meta分析采用考察单项研究对总合并效应量的影响进行敏感性分析,如果敏感性分析前后合并效应量指标没有发生趋势改变,说明Meta分析结果较为可信,若敏感性分析前后结局指标发生趋势改变,提示存在与干预措施有关的潜在的重要因素,影响结果的可信度[18]。文章对异质性高的GMFM指标使用加尔布雷斯图进行敏感性分析,结果发现HUANG等[12]的研究严重偏离可信区间,见图6B,排除该研究后,发现6个月的GMFM指标由(SMD=0.91,95%CI:0.07-1.74,P=0.03)变为(SMD=0.45,95%CI:0.11-0.79,P=0.01),趋势并没有发生改变但异质性I2=86%变为I2=0%,异质性显著降低。敏感性分析结果说明合并的结局指标具有可靠性。"
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