仙方活命饮治疗囊性中性粒细胞性肉芽肿性乳腺炎热毒证的临床疗效及机制探讨

Clinical efficacy and mechanism of Xianfang Huoming Yin in treating cystic neutrophilic granulomatous mastitis with heat-toxin syndrome

目的观察仙方活命饮对囊性中性粒细胞性肉芽肿性乳腺炎(CNGM)热毒证患者的临床疗效及潜在作用机制。方法将72例CNGM热毒证患者随机分为对照组与试验组,每组各36例;试验组予仙方活命饮口服治疗,对照组予左氧氟沙星口服治疗,两组疗程均为14 d。观察比较疾病活动指数、疾病活动度、肿块大小、疼痛数字分级评分法(NRS)评分、炎症指标的变化。免疫荧光法检测乳腺组织内中性粒细胞胞外诱捕网(NETs)标志物瓜氨酸化组蛋白H3(CitH3)、髄过氧化物酶(MPO)含量的变化。结果①试验过程中,对照组脱落2例,试验组剔除1例、脱落2例,最终完成试验者67例,其中对照组34例、试验组33例。完成14d药物治疗后进一步接受手术治疗者共40例,其中对照组22例、试验组18例,每组随机选取5例纳入NETs形成相关指标机制分析。②局部症状活动指数,治疗前后组内比较,对照组疼痛活动指数降低(P<0.05),脓肿活动指数升高(P<0.05);试验组肿块、疼痛、红热活动指数均降低(P<0.05)。组间治疗后比较,试验组肿块、疼痛、红热活动指数低于对照组(P<0.05)。③全身症状活动指数,治疗前后组内比较,对照组发热活动指数降低(P<0.05),试验组发热、其他相关炎症症状活动指数降低(P<0.05)。组间治疗后比较,两组各项全身症状活动指数比较,差异无统计学意义(P>0.05)。④疾病活动指数,治疗前后组内比较,对照组全身症状活动指数、疾病活动指数下降(P<0.05),试验组局部、全身症状活动指数及疾病活动指数均下降(P<0.05)。组间治疗后比较,试验组局部症状活动指数、疾病活动指数低于对照组(P<0.05)。⑤治疗后,两组高活动度例数减少、低活动度及中活动度例数增多,其中试验组高活动度比例从78.8%下降到36.4%;两组疾病活动度分布情况比较,试验组优于对照组(P<0.05)。⑥治疗后,试验组肿块变小(P<0.05),对照组肿块大小无明显变化(P>0.05);两组疼痛NRS评分均降低(P<0.05),且试验组低于对照组(P<0.05)。⑦治疗前后组内比较,试验组红细胞沉降率水平降低(P<0.05),对照组白细胞、中性粒细胞水平降低(P<0.05);组间治疗后比较,两组各项炎症指标比较,差异无统计学意义(P>0.05)。⑧治疗后,两组CitH3的光密度(IOD)、面密度(AD)值均下降(P<0.05),且试验组低于对照组(P<0.05);试验组MPO的IOD、AD值下降(P<0.05),且试验组低于对照组(P<0.05)。结论仙方活命饮能改善CNGM热毒证患者乳房局部炎症症状,降低疾病活动度,在局部症状改善方面疗效优于左氧氟沙星,在全身症状改善方面疗效与左氧氟沙星相当;其可能通过清除乳腺炎症组织中过量产生的NETs发挥疗效。

Objective To explore the clinical efficacy and potential mechanism of Xianfang Huoming Yin in treating patients with cystic neutrophilic granulomatous mastitis(CNGM)with heat-toxin syndrome.Methods Seventy-two patients with CNGM with heat-toxin syndrome were randomly divided into a control group(n=36)and a treatment group(n=36).The treatment group received oral Xianfang Huoming Yin,and the control group received oral levofloxacin treatment,both for a duration of 14 days.Clinical efficacy was observed,and changes in disease activity index,disease activity,lump size,pain NRS score,and inflammatory indicators were compared.Immunofluorescence was used to detect changes in the content of neutrophil extracellular traps(NETs)markers in breast tissue,such as citrullinated histone H3(CitH3)and myeloperoxidase(MPO).Results①During the trial,2 patients dropped out in the control group,1 patient was removed and 2 patients dropped out in the treatment group,leaving 67 patients who completed the study,with 34 in the control group and 33 in the treatment group.A total of 40 patients underwent further surgical treatment after completing 14 days of medication,with 22 patients from the control group and 18 from the treatment group.Five cases from each group were randomly selected for NETs formation mechanism analysis.②Intra-group comparisons before and after treatment showed that the control group had a decrease in the pain activity index(P<0.05)and an increase in the abscess activity index(P<0.05)in terms of local symptom activity index;In the treatment group,there was a significant decrease in the activity indexes for lump size,pain,and redness(P<0.05).Post-treatment comparisons between groups showed that the treatment group had lower activity indexes for lump size,pain,and redness than the control group(P<0.05).③In terms of the global symptom activity index,intra-group comparisons before and after treatment showed a decrease in fever activity index in the control group(P<0.05),and reductions in fever and other related inflammatory symptom activity indexes in the treatment group(P<0.05).Post-treatment comparisons between the groups showed no statistically significant differences in the overall global symptom activity indexes(P>0.05).④In terms of disease activity index,intra-group comparisons before and after treatment showed a decrease in global symptom activity index and disease activity index(P<0.05)in the control group and a decrease in local,global symptom activity index,and disease activity index(P<0.05)in the treatment group.After treatment,the treatment group showed lower local symptom activity index and disease activity index(P<0.05)than the control group.⑤After treatment,cases with high activity decreased,and cases with low and moderate activity increased in both groups,with the proportion of cases with high activity in the treatment group dropping from 78.8%to 36.4%.There was a significant difference in the distribution of disease activity between two groups,with the treatment group performing better than the control group(P<0.05).⑥After treatment,lump size reduced in the treatment group(P<0.05),with no significant change in the control group(P>0.05);both groups showed lowered pain NRS scores(P<0.05),with the treatment group scoring even lower(P<0.05).⑦Intra-group comparisons before and after treatment showed that erythrocyte sedimentation rate decreased in the treatment group(P<0.05),and white blood cell count and neutrophil count decreased in the control group(P<0.05).Post-treatment comparisons showed that there was no significant difference in inflammatory indicators between two groups(P>0.05).⑧After treatment,both groups showed a reduction in CitH3 IOD and AD values(P<0.05),with the treatment group lower than the control group(P<0.05);the treatment group also showed a decrease in MPO IOD and AD values(P<0.05),lower than the control group(P<0.05).Conclusions Xianfang Huoming Yin could improve local inflammatory symptoms,and reduce disease activity in patients with CNGM with heat-toxin syndrome.Its efficacy in improving local symptoms is superior to levofloxacin,and comparable in improving global symptoms.The underlying mechanism of its therapeutic effect may be related to the clearance of excess NETs in inflamed breast tissue.