目的 探討聚桂醇局部注射聯(lián)合馬來酸噻嗎洛爾治療嬰幼兒血管瘤的臨床療效。方法 前瞻性選取2017年1月—2018年12月保定市兒童醫(yī)院收治的血管瘤嬰幼兒150例，采用信封法分為對照組（75例）和試驗組（75例）。對照組給予馬來酸噻嗎洛爾治療，將0.5%馬來酸噻嗎洛爾滴眼液用紗布濕敷在血管瘤部位及周圍皮膚，早晚各1次，每次1 h。試驗組給予馬來酸噻嗎洛爾滴眼液聯(lián)合聚桂醇局部注射，馬來酸噻嗎洛爾滴眼液用法用量同對照組，聚桂醇局部注射方法：將聚桂醇注射液和空氣按照1∶3比例混合，來回推注制成泡沫狀硬化劑，制作完成后需盡快注射。也可直接注射聚桂醇原液，體積較小的血管瘤可進(jìn)行單點注射；體積較大的血管瘤可進(jìn)行多點注射。間隔1個月再注射1次，根據(jù)患兒情況治療1～4個月。兩組患兒均隨訪6個月，根據(jù)患兒恢復(fù)情況決定是否繼續(xù)用藥。分別于治療前和治療后采用視覺模擬評分（VAS）評估瘤體顏色及大小，比較兩組患兒治療前和治療后血管瘤厚度及治療時間，比較兩組患兒治療前和治療后血清細(xì)胞因子［缺氧誘導(dǎo)因子-1α（HIF-1α）、血管內(nèi)皮生長因子（VEGF）、表皮生長因子樣結(jié)構(gòu)域（EGFL7）、基質(zhì)金屬蛋白酶-9（MMP-9）］水平，記錄兩組不良反應(yīng)發(fā)生率及臨床療效。結(jié)果 治療前兩組患兒血管瘤厚度比較，差異無統(tǒng)計學(xué)意義（P＞0.05）；治療后兩組患兒血管瘤厚度均較治療前明顯降低（P＜0.05），且治療后試驗組瘤體厚度明顯低于對照組（P＜0.05）；試驗組治療時間明顯短于對照組（P＜0.05）。治療前兩組患兒血清HIF-1α、VEGF、EGFL7、MMP-9水平比較，差異無統(tǒng)計學(xué)意義（P＞0.05），治療后兩組患兒血清HIF-1α、VEGF、EGFL7、MMP-9水平均較治療前顯著降低（P＜0.05），且治療后試驗組血清HIF-1α、VEGF、EGFL7、MMP-9水平顯著低于對照組（P＜0.05）。治療前兩組患兒血管瘤大小及顏色VAS評分比較，差異無統(tǒng)計學(xué)意義（P＞0.05）；治療后兩組患兒血管瘤大小及顏色VAS評分均較治療前顯著升高（P＜0.05），且治療后試驗組血管瘤大小及顏色VAS評分顯著高于對照組（P＜0.05）。試驗組總不良反應(yīng)發(fā)生率6.67%，與對照組總不良反應(yīng)發(fā)生率（9.33%）比較，差異無統(tǒng)計學(xué)意義（P＞0.05）。試驗組總有效率為93.33%，對照組的總有效率為74.67%，試驗組總有效率顯著高于對照組（P＜0.05）。結(jié)論 馬來酸噻嗎洛爾聯(lián)合聚桂醇局部注射治療嬰幼兒血管瘤臨床效果較好，不良反應(yīng)少，并且能夠縮短治療時間。

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

河北省衛(wèi)生和計劃生育委員會科研基金項目(20190186)