目的 探讨聚桂醇局部注射联合马来酸噻吗洛尔治疗婴幼儿血管瘤的临床疗效。方法 前瞻性选取2017年1月—2018年12月保定市儿童医院收治的血管瘤婴幼儿150例，采用信封法分为对照组（75例）和试验组（75例）。对照组给予马来酸噻吗洛尔治疗，将0.5%马来酸噻吗洛尔滴眼液用纱布湿敷在血管瘤部位及周围皮肤，早晚各1次，每次1 h。试验组给予马来酸噻吗洛尔滴眼液联合聚桂醇局部注射，马来酸噻吗洛尔滴眼液用法用量同对照组，聚桂醇局部注射方法：将聚桂醇注射液和空气按照1∶3比例混合，来回推注制成泡沫状硬化剂，制作完成后需尽快注射。也可直接注射聚桂醇原液，体积较小的血管瘤可进行单点注射；体积较大的血管瘤可进行多点注射。间隔1个月再注射1次，根据患儿情况治疗1～4个月。两组患儿均随访6个月，根据患儿恢复情况决定是否继续用药。分别于治疗前和治疗后采用视觉模拟评分（VAS）评估瘤体颜色及大小，比较两组患儿治疗前和治疗后血管瘤厚度及治疗时间，比较两组患儿治疗前和治疗后血清细胞因子［缺氧诱导因子-1α（HIF-1α）、血管内皮生长因子（VEGF）、表皮生长因子样结构域（EGFL7）、基质金属蛋白酶-9（MMP-9）］水平，记录两组不良反应发生率及临床疗效。结果 治疗前两组患儿血管瘤厚度比较，差异无统计学意义（P＞0.05）；治疗后两组患儿血管瘤厚度均较治疗前明显降低（P＜0.05），且治疗后试验组瘤体厚度明显低于对照组（P＜0.05）；试验组治疗时间明显短于对照组（P＜0.05）。治疗前两组患儿血清HIF-1α、VEGF、EGFL7、MMP-9水平比较，差异无统计学意义（P＞0.05），治疗后两组患儿血清HIF-1α、VEGF、EGFL7、MMP-9水平均较治疗前显著降低（P＜0.05），且治疗后试验组血清HIF-1α、VEGF、EGFL7、MMP-9水平显著低于对照组（P＜0.05）。治疗前两组患儿血管瘤大小及颜色VAS评分比较，差异无统计学意义（P＞0.05）；治疗后两组患儿血管瘤大小及颜色VAS评分均较治疗前显著升高（P＜0.05），且治疗后试验组血管瘤大小及颜色VAS评分显著高于对照组（P＜0.05）。试验组总不良反应发生率6.67%，与对照组总不良反应发生率（9.33%）比较，差异无统计学意义（P＞0.05）。试验组总有效率为93.33%，对照组的总有效率为74.67%，试验组总有效率显著高于对照组（P＜0.05）。结论 马来酸噻吗洛尔联合聚桂醇局部注射治疗婴幼儿血管瘤临床效果较好，不良反应少，并且能够缩短治疗时间。

Objective To investigate the clinical efficacy of lauromacrogol for local injection combined with timolol maleate in treatment of infantile hemangioma. Methods A total of 150 infants with hemangioma treated in Baoding Children's Hospital from January 2017 to December 2018 were prospectively selected and divided into control group (75 cases) and experimental group (75 cases) by envelope method. Infants in the control group were treated with timolol maleate. 0.5% Timolol Maleate Eye Drops were wet applied to the hemangioma site and surrounding skin with gauze for one hour each time, once in the morning and once in the evening. Infants in the experimental group were given lauromacrogol for local injection combined with Timolol Maleate Eye Drops. The dosage of Timolol Maleate Eye Drops was the same as that of the control group. Lauromacrogol Injection was mixed with air at 1∶3 ratio. Foam hardening agent was injected back and forth. After completion, it was necessary to be injected as soon as possible. Or Lauromacrogol Injection original solution were directly injected. The hemangioma with small volume can be injected at a single point. The larger hemangioma can be injected at multiple points. Another injection was given at an interval of one month, and the patients were treated for 1— 4 months according to the situation of the children. Both groups were followed up for six months, and whether to continue medication was decided according to the recovery of children. Visual analogue scale (VAS) was used to evaluate the color and size of tumor before and after treatment. The thickness and treatment time of hemangioma before and after treatment were compared between the two groups, and the serum cytokines [hypoxia inducible factor-1α (HIF-1 α), vascular endothelial growth factor (VEGF), epidermal growth factor like domain (EGFL7) and matrix metalloproteinase-9 (MMP-9) ] before and after treatment were compared between two groups, and the incidence of adverse reactions and clinical efficacy were recorded. Results There was no significant difference in the thickness of hemangioma between two groups before treatment (P>0.05). After treatment, the thickness of hemangioma in two groups was significantly lower than that before treatment (P<0.05), and the thickness of hemangioma in the experimental group was significantly lower than that in the control group (P<0.05). The treatment time in the experimental group was significantly shorter than that in the control group (P<0.05). Before treatment, there was no significant difference in the levels of serum HIF-1 α, VEGF, EGFL7 and MMP-9 in two groups (P>0.05). After treatment, the levels of serum HIF-1 α, VEGF, EGFL7 and MMP-9 in two groups were significantly lower than those before treatment (P<0.05). After treatment, the levels of serum HIF-1 α, VEGF, EGFL7 and MMP-9 in the experimental group were significantly lower than those in the control group (P<0.05). There was no significant difference in VAS score of hemangioma size and color between two groups before treatment (P>0.05). After treatment, the VAS scores of hemangioma size and color in two groups were significantly higher than those before treatment (P<0.05), and the VAS scores of hemangioma size and color in the experimental group were significantly higher than those in the control group (P<0.05). The total incidence of adverse reactions in the experimental group was 6.67%, and there was no significant difference between the experimental group and the control group (9.33%) (P>0.05). The total effective rate of the experimental group was 93.33%, and that of the control group was 74.67%. The total effective rate of the experimental group was significantly higher than that of the control group (P<0.05). Conclusion Lauromacrogol for local injection combined with timolol maleate in treatment of infantile hemangioma has good clinical effect, less adverse reactions, and can shorten the treatment time.

R985

河北省卫生和计划生育委员会科研基金项目(20190186)