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Article(id=1322926627864322392, tenantId=1146029695717560320, journalId=1255847919539208197, issueId=1322926492627378659, articleNumber=null, orderNo=null, doi=10.13193/j.issn.1673-7717.2025.09.040, pmid=null, cstr=null, oa=null, hot=null, price=null, onlineType=0, articleFormat=0, articleType=null, articleTypeStr=null, receivedDate=null, receivedDateStr=null, revisedDate=null, revisedDateStr=null, acceptedDate=null, acceptedDateStr=null, onlineDate=1793339886870, onlineDateStr=2026-10-30, pubDate=1757433600000, pubDateStr=2025-09-10, doiRegisterDate=null, doiRegisterDateStr=null, onlineIssueDate=1793339886870, onlineIssueDateStr=2026-10-30, onlineJustAcceptDate=null, onlineJustAcceptDateStr=null, onlineFirstDate=null, onlineFirstDateStr=null, sourceXml=null, magXml=null, createTime=1793339886870, creator=13701087609, updateTime=1793339886870, updator=13701087609, issue=Issue{id=1322926492627378659, tenantId=1146029695717560320, journalId=1255847919539208197, year='2025', volume='43', issue='9', pageStart='1', pageEnd='258', issueExtLink='null', onlineDate='null', pubDate='1757433600000', pubDateStr='2025-09-10', beforeIssueId=null, nextIssueId=null, price=null, status=1, issueComplete=1, articleOrder=1, issueType=-1, specialIssue=0, createTime=1793339854628, creator='13701087609', updateTime=1793340762858, updator='13701087609', preIssue=null, nextIssue=null, articleTotal=null, ext={EN=IssueExt(id=1322930302095590169, tenantId=1146029695717560320, journalId=1255847919539208197, issueId=1322926492627378659, language=EN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=), CN=IssueExt(id=1322930302095590170, tenantId=1146029695717560320, journalId=1255847919539208197, issueId=1322926492627378659, language=CN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=)}, issueFiles=null, downloadFileDto=null}, startPage=214, endPage=218, ext={EN=ArticleExt(id=1322926628086620505, articleId=1322926627864322392, tenantId=1146029695717560320, journalId=1255847919539208197, language=EN, title=Efficacy of Longxuejie（Resina Draconis）Combined with Fluorouracil Injection in Patients with Different TGF-β Single Nucleotide Polymorphisms, columnId=1256183365644968140, journalTitle=Chinese Archives of Traditional Chinese Medicine, columnName=Platform of Provincial Project, runingTitle=null, highlight=null, articleAbstract=
Objective

To investigate the efficacy of Longxuejie（Resina Draconis）combined with fluorouracil injection in patients with keloid scarswith different transforming growth factor-β（TGF-β）single nucleotide polymorphisms.

Methods

A total of 240 cases of keloid patients admitted to the hospital from July 2019 to January 2022 were included，which were categorized into wild group（wild-type TGF-β）and mutant group（mutant TGF-β）based on TGF-β single nucleotide polymorphisms，and themutant group was divided into rs747857 group（rs747857-type TGF-β），rs1800469 group（rs1800469 type TGF-β）and rs2241716 group（rs2241716 type TGF-β）. Five groups were treated with fluorouracil injection monotherapy or Longxuejie（Resina Draconis）combined with fluorouracil injection. The patients in the five groupswere scored by the Vancouver Scar Scale（VSS），the Patient and Observer Scar Assessment Scale（POSAS）and the Dermatologic Quality of Life Index（DLQI）scale before treatment and 12 months after the first treatment.

Results

Compared with those of the wild group，the expression levels of TGF-β mRNA in themutation group，rs747857 group，rs1800469 group and rs2241716 group increased（P<0.05）. Compared with the wild group，the patients in the mutation group，rs1800469 group and rs2241716 group under monotherapy showed a significant increase in the total VSSscore and the total POSAS score after treatment（P<0.05）；whereas，compared with monotherapy，the patients in the mutation group，rs1800469 group and rs2241716 group under the combination therapy showed a significant decrease in the total VSS score and the total POSAS scores were significantly decreased（P<0.05）. Compared with thewild group，the patients in the rs2241716 group all showed a significant increase in DLQI scale scores after treatment（P<0.05）；whereas，compared with monotherapy，the patients in the rs2241716 group under combination therapy all showed a significant decrease in DLQI scale scores after treatment（P<0.05）. Compared with the wild group，the patients in the rs1800469 and rs2241716 groups showed a significant decrease in the effective rate after treatment（P<0.05）；while compared with mono therapy，the patients in the rs1800469 and rs2241716 groups under combination therapy showed a significant increase in the effective rate after treatment（P<0.05）. Compared with the wild group，the patients in the mutation group，rs1800469 group and rs2241716 group had delayed the first apparent effect and the number of fluorouracil times to reach the first apparent effect（P<0.05）；while compared with the monotherapy，the patients in the mutation group，rs1800469 group and rs2241716 group under the combination therapy had advanced the first apparent effect and the number of fluorouracil times to reach the first apparent effect（P<0.05）. Fewer total adverse reactions were observed in the wild，mutant，rs747857，rs1800469 and rs2241716 groups under combination therapy compared with monotherapy（P<0.05）.

Conclusion

Longxuejie（Resina Draconis）combined with fluorouracil injection has better efficacy and fewer adverse effects in patients with keloids with different TGF-β single nucleotide polymorphisms.

, authors=Weiqiang HAN, Lisha LI, Yun CHEN, Yuntao NIE, Yuhua CHEN, authorsList=Weiqiang HAN, Lisha LI, Yun CHEN, Yuntao NIE, Yuhua CHEN, authorCompany=null, correspAuthors=Yuhua CHEN, authorNote=null, correspAuthorsNote=null, copyrightStatement=null, copyrightOwner=null, extLink=null, articleAbsUrl=null, sourceXml=null, magXml=null, pdfUrl=null, pdf=null, pdfFileSize=null, pdfExtLink=null, richHtmlUrl=null, mobilePdfUrl=null, reviewReport=null, pdfFirstPage=null, abstractGraph=null, abstractGraphContent=null, abstractVideo=null, citation=null, cebUrl=null, magXmlContent=null, mapNumber=null, fund=null), CN=ArticleExt(id=1322926628485079386, articleId=1322926627864322392, tenantId=1146029695717560320, journalId=1255847919539208197, language=CN, title=龙血竭联合氟尿嘧啶注射液对不同TGF-β单核苷酸多态性瘢痕疙瘩患者的疗效分析, columnId=1256183369033965799, journalTitle=中华中医药学刊, columnName=省级项目平台, runingTitle=null, highlight=null, articleAbstract=
目的

探讨龙血竭联合氟尿嘧啶注射液对不同转化生长因子-β（Transforming growth factor-β，TGF-β）单核苷酸多态性瘢痕疙瘩患者的疗效。

方法

纳入2019年7月—2022年1月医院收治的瘢痕疙瘩患者240例，根据TGF-β单核苷酸多态分为野生组（野生型TGF-β）、突变组（突变型TGF-β），并将突变组分为亚组：rs747857组（rs747857型TGF-β）、rs1800469组（rs1800469型TGF-β）、rs2241716组（rs2241716型TGF-β）。使用氟尿嘧啶注射液单药治疗或血竭联合氟尿嘧啶注射液治疗5组患者。5组患者治疗前和首次治疗后12个月通过温哥华瘢痕量表（Vancouver scar scale，VSS）、瘢痕评估量表（Patientand observer scar assessment scale，POSAS）和皮肤病生活质量指数（Dermatologic quality of life index，DLQI）量表进行评分。

结果

与野生组比较，突变组、rs747857组、rs1800469组、rs2241716组TGF-β mRNA的表达水平均上升（P<0.05）。与野生组相比，单药治疗下突变组、rs1800469组和rs2241716组患者在治疗后VSS总评分、POSAS总评分均显著上升（P<0.05）；而与单药治疗相比，联合治疗下突变组、rs1800469组和rs2241716组患者在治疗后VSS总评分、POSAS总评分均显著下降（P<0.05）。与野生组相比，rs2241716组患者在治疗后的DLQI量表评分均显著上升（P<0.05）；而与单药治疗相比，联合治疗下rs2241716组患者在治疗后的DLQI量表评分均显著下降（P<0.05）。与野生组相比，rs1800469组和rs2241716组患者在治疗后的有效率显著下降（P<0.05）；而与单药治疗相比，联合治疗下rs1800469组和rs2241716组患者在治疗后的有效率显著上升（P<0.05）。与野生组相比，突变组、rs1800469组和rs2241716组患者的首次显效及达到首次显效时氟尿嘧啶次数均延后（P<0.05）；而与单药治疗相比，联合治疗下突变组、rs1800469组和rs2241716组患者的首次显效及达到首次显效时氟尿嘧啶次数均提前（P<0.05）。与单药治疗相比，联合治疗下野生组、突变组、rs747857组、rs1800469组、rs2241716组的总不良反应更少（P<0.05）。

结论

龙血竭联合氟尿嘧啶注射液对不同TGF-β单核苷酸多态性瘢痕疙瘩患者有较好的疗效，和较少的不良反应。

, authors=韩伟强, 李丽莎, 陈云, 聂蕴韬, 陈誉华, authorsList=韩伟强, 李丽莎, 陈云, 聂蕴韬, 陈誉华, authorCompany=null, correspAuthors=陈誉华, authorNote=

韩伟强（1982-），男，河北邢台人，副主任医师，硕士，研究方向：瘢痕防治。

, correspAuthorsNote=
陈誉华（1965-），男，河北邢台人，主任医师，硕士，研究方向：瘢痕防治。
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韩伟强（1982-），男，河北邢台人，副主任医师，硕士，研究方向：瘢痕防治。

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韩伟强（1982-），男，河北邢台人，副主任医师，硕士，研究方向：瘢痕防治。

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组别SNP基因位置等位基因例数性别/［例（%）］年龄［岁，M（Q1，Q3）］病程时间［月，M（Q1，Q3）］TGF-β mRNA
男女
对照组--706（8.57）64（91.43）26（20，39）-0.32±0.05
野生组--623（4.84）59（95.16）26（21，36）32（29，35）0.71±0.14#
突变组--1789（5.06）169（94.94）27（22，34）32（26，39）1.03±0.22*#
rs747857组内含子G>A，C523（5.77）49（94.23）25（20，33）32（25，40）0.72±0.10
rs1800469组转录上游A>G623（4.84）59（95.16）27（23，34）31（26，39）1.43±0.30*
rs2241716组内含子C>T645（7.81）59（92.19）27（22，35）33（27，36）0.90±0.21*
), ArticleFig(id=1322926633077842306, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322926627864322392, language=CN, label=表1, caption=

6组瘢痕疙瘩患者一般资料比较

, figureFileSmall=null, figureFileBig=null, tableContent=
组别SNP基因位置等位基因例数性别/［例（%）］年龄［岁，M（Q1，Q3）］病程时间［月，M（Q1，Q3）］TGF-β mRNA
男女
对照组--706（8.57）64（91.43）26（20，39）-0.32±0.05
野生组--623（4.84）59（95.16）26（21，36）32（29，35）0.71±0.14#
突变组--1789（5.06）169（94.94）27（22，34）32（26，39）1.03±0.22*#
rs747857组内含子G>A，C523（5.77）49（94.23）25（20，33）32（25，40）0.72±0.10
rs1800469组转录上游A>G623（4.84）59（95.16）27（23，34）31（26，39）1.43±0.30*
rs2241716组内含子C>T645（7.81）59（92.19）27（22，35）33（27，36）0.90±0.21*
), ArticleFig(id=1322926633153339779, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322926627864322392, language=EN, label=null, caption=null, figureFileSmall=null, figureFileBig=null, tableContent=
组别单药治疗VSS总评分［M（Q1，Q3）］联合治疗VSS总评分［M（Q1，Q3）］
治疗前治疗后治疗前治疗后
野生组9.0（7.0，11.5）5.0（2.0，7.5）9.0（7.0，11.5）5.0（2.0，7.5）
突变组9.0（7.0，11.5）6.0（3.5，9.5）*9.0（7.0，11.5）5.0（3.0，7.0）#
rs747857组8.5（7.0，11.0）5.0（2.5，7.0）9.0（7.0，11.5）5.0（2.5，7.0）
rs1800469组9.0（7.5，11.5）6.5（4.5，9.5）*9.0（7.5，11.5）5.0（2.0，7.5）#
rs2241716组9.5（6.5，12.5）6.5（3.5，10.5）*9.5（6.5，11.5）5.5（3.0，8.5）#
), ArticleFig(id=1322926633224642948, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322926627864322392, language=CN, label=表2, caption=

两种治疗方式下5组瘢痕疙瘩患者瘢痕疙瘩VSS评分

, figureFileSmall=null, figureFileBig=null, tableContent=
组别单药治疗VSS总评分［M（Q1，Q3）］联合治疗VSS总评分［M（Q1，Q3）］
治疗前治疗后治疗前治疗后
野生组9.0（7.0，11.5）5.0（2.0，7.5）9.0（7.0，11.5）5.0（2.0，7.5）
突变组9.0（7.0，11.5）6.0（3.5，9.5）*9.0（7.0，11.5）5.0（3.0，7.0）#
rs747857组8.5（7.0，11.0）5.0（2.5，7.0）9.0（7.0，11.5）5.0（2.5，7.0）
rs1800469组9.0（7.5，11.5）6.5（4.5，9.5）*9.0（7.5，11.5）5.0（2.0，7.5）#
rs2241716组9.5（6.5，12.5）6.5（3.5，10.5）*9.5（6.5，11.5）5.5（3.0，8.5）#
), ArticleFig(id=1322926633371443589, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322926627864322392, language=EN, label=null, caption=null, figureFileSmall=null, figureFileBig=null, tableContent=
组别单药治疗POSAS总评分［M（Q1，Q3）］联合治疗POSAS总评分［M（Q1，Q3）］
治疗前治疗后治疗前治疗后
野生组60.0（53.5，64.5）37.0（21.0，53.0）60.0（53.5，64.5）37.0（21.0，53.0）
突变组59.5（53.5，65.0）43.0（28.0，55.0）*60.0（53.5，64.5）37.0（21.0，54.0）#
rs747857组59.0（54.0，64.5）37.5（20.5，54.0）59.5（54.0，64.5）37.5（20.5，54.0）
rs1800469组59.5（52.5，65.5）44.5（28.5，55.5）*60.0（53.5，65.0）37.5（21.5，53.5）#
rs2241716组60.0（53.5，65.0）46.5（33.5，57.5）*59.5（53.0，65.5）38.5（25.5，55.5）#
), ArticleFig(id=1322926633564381574, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322926627864322392, language=CN, label=表3, caption=

两种治疗方式下5组瘢痕疙瘩患者瘢痕疙瘩POSAS评分

, figureFileSmall=null, figureFileBig=null, tableContent=
组别单药治疗POSAS总评分［M（Q1，Q3）］联合治疗POSAS总评分［M（Q1，Q3）］
治疗前治疗后治疗前治疗后
野生组60.0（53.5，64.5）37.0（21.0，53.0）60.0（53.5，64.5）37.0（21.0，53.0）
突变组59.5（53.5，65.0）43.0（28.0，55.0）*60.0（53.5，64.5）37.0（21.0，54.0）#
rs747857组59.0（54.0，64.5）37.5（20.5，54.0）59.5（54.0，64.5）37.5（20.5，54.0）
rs1800469组59.5（52.5，65.5）44.5（28.5，55.5）*60.0（53.5，65.0）37.5（21.5，53.5）#
rs2241716组60.0（53.5，65.0）46.5（33.5，57.5）*59.5（53.0，65.5）38.5（25.5，55.5）#
), ArticleFig(id=1322926635254686087, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322926627864322392, language=EN, label=null, caption=null, figureFileSmall=null, figureFileBig=null, tableContent=
组别单药治疗DLQI量表评分［M（Q1，Q3）］联合治疗DLQI量表评分［M（Q1，Q3）］
治疗前治疗后治疗前治疗后
野生组12.0（8.0，14.0）4.0（0.0，11.0）12.0（7.5，14.0）4.0（0.0，11.0）
突变组12.0（7.5，14.0）5.0（0.0，11.0）12.0（8.0，14.0）4.5（0.0，11.0）
rs747857组12.0（7.5，14.0）4.5（0.0，11.5）12.0（7.5，14.0）4.0（0.0，10.5）
rs1800469组12.5（8.0，13.5）4.5（0.0，11.5）12.0（8.0，14.0）4.5（0.0，11.5）
rs2241716组11.5（7.0，13.5）6.0（0.0，12.5）*11.5（7.0，13.5）4.5（0.0，11.5）#
), ArticleFig(id=1322926635313406344, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322926627864322392, language=CN, label=表4, caption=

两种治疗方式下5组瘢痕疙瘩患者生活质量评分

, figureFileSmall=null, figureFileBig=null, tableContent=
组别单药治疗DLQI量表评分［M（Q1，Q3）］联合治疗DLQI量表评分［M（Q1，Q3）］
治疗前治疗后治疗前治疗后
野生组12.0（8.0，14.0）4.0（0.0，11.0）12.0（7.5，14.0）4.0（0.0，11.0）
突变组12.0（7.5，14.0）5.0（0.0，11.0）12.0（8.0，14.0）4.5（0.0，11.0）
rs747857组12.0（7.5，14.0）4.5（0.0，11.5）12.0（7.5，14.0）4.0（0.0，10.5）
rs1800469组12.5（8.0，13.5）4.5（0.0，11.5）12.0（8.0，14.0）4.5（0.0，11.5）
rs2241716组11.5（7.0，13.5）6.0（0.0，12.5）*11.5（7.0，13.5）4.5（0.0，11.5）#
), ArticleFig(id=1322926635393098121, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322926627864322392, language=EN, label=null, caption=null, figureFileSmall=null, figureFileBig=null, tableContent=
组别单药治疗联合治疗
治愈显效好转无效有效率治愈显效好转无效有效率
野生组11（35.48）8（25.81）5（16.13）7（22.58）19（61.29）12（38.71）8（25.81）5（16.13）6（19.35）20（64.52）
突变组17（19.10）18（20.22）21（23.60）33（37.08）35（39.33）30（33.71）29（32.58）19（21.35）11（12.36）59（66.29）#
rs747857组8（30.77）8（30.77）5（19.23）5（19.23）16（61.54）9（34.62）9（34.62）6（23.08）2（7.69）18（69.23）
rs1800469组5（16.13）5（16.13）7（22.58）14（45.16）10（32.26）*10（32.26）10（32.26）6（19.35）5（16.13）20（64.52）#
rs2241716组4（12.50）5（15.63）9（28.13）14（43.75）9（28.13）*11（34.38）10（31.25）7（21.88）4（12.50）21（65.63）#
), ArticleFig(id=1322926635648950666, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322926627864322392, language=CN, label=表5, caption=

两种治疗方式下5组瘢痕疙瘩患者治疗后的疗效评价

, figureFileSmall=null, figureFileBig=null, tableContent=
组别单药治疗联合治疗
治愈显效好转无效有效率治愈显效好转无效有效率
野生组11（35.48）8（25.81）5（16.13）7（22.58）19（61.29）12（38.71）8（25.81）5（16.13）6（19.35）20（64.52）
突变组17（19.10）18（20.22）21（23.60）33（37.08）35（39.33）30（33.71）29（32.58）19（21.35）11（12.36）59（66.29）#
rs747857组8（30.77）8（30.77）5（19.23）5（19.23）16（61.54）9（34.62）9（34.62）6（23.08）2（7.69）18（69.23）
rs1800469组5（16.13）5（16.13）7（22.58）14（45.16）10（32.26）*10（32.26）10（32.26）6（19.35）5（16.13）20（64.52）#
rs2241716组4（12.50）5（15.63）9（28.13）14（43.75）9（28.13）*11（34.38）10（31.25）7（21.88）4（12.50）21（65.63）#
), ArticleFig(id=1322926635741225355, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322926627864322392, language=EN, label=null, caption=null, figureFileSmall=null, figureFileBig=null, tableContent=
组别单药治疗联合治疗
时间（月）次数（次）时间（月）次数（次）
野生组6.0（2.2，10.4）4.1（3.0，6.0）6.0（2.2，10.4）4.1（3.0，6.0）
突变组6.3（3.1，11.0）5.2（3.5，7.0）*6.1（2.4，10.8）4.2（3.0，6.5）#
rs747857组5.8（2.3，10.4）4.2（3.0，6.5）5.9（2.0，10.4）4.1（3.0，6.5）
rs1800469组6.8（3.3，11.8）*6.3（3.5，7.5）*6.0（2.3，11.0）#4.2（3.5，6.0）#
rs2241716组6.6（3.5，11.4）*5.8（3.5，8.0）*6.3（2.7，11.5）#4.4（3.5，6.5）#
), ArticleFig(id=1322926636026438028, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322926627864322392, language=CN, label=表6, caption=

两种治疗方式下5组瘢痕疙瘩患者首次显效及达到首次显效时氟尿嘧啶次数

, figureFileSmall=null, figureFileBig=null, tableContent=
组别单药治疗联合治疗
时间（月）次数（次）时间（月）次数（次）
野生组6.0（2.2，10.4）4.1（3.0，6.0）6.0（2.2，10.4）4.1（3.0，6.0）
突变组6.3（3.1，11.0）5.2（3.5，7.0）*6.1（2.4，10.8）4.2（3.0，6.5）#
rs747857组5.8（2.3，10.4）4.2（3.0，6.5）5.9（2.0，10.4）4.1（3.0，6.5）
rs1800469组6.8（3.3，11.8）*6.3（3.5，7.5）*6.0（2.3，11.0）#4.2（3.5，6.0）#
rs2241716组6.6（3.5，11.4）*5.8（3.5，8.0）*6.3（2.7，11.5）#4.4（3.5，6.5）#
), ArticleFig(id=1322926636097741197, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322926627864322392, language=EN, label=null, caption=null, figureFileSmall=null, figureFileBig=null, tableContent=
组别单药治疗联合治疗
毛细血管扩张色素沉着局部凹陷药物沉渣色素脱失总不良反应毛细血管扩张色素沉着局部凹陷药物沉渣色素脱失总不良反应
野生组7（22.58）5（16.13）2（6.45）2（6.45）3（9.68）19（61.29）3（9.68）3（9.68）2（6.45）2（6.45）2（6.45）12（38.71）#
突变组35（39.33）17（19.10）8（8.99）6（6.74）4（4.49）70（78.65）6（6.74）6（6.74）7（7.87）7（7.87）4（4.49）30（33.71）#
rs747857组6（23.08）5（19.23）3（11.54）3（11.54）1（3.85）18（69.23）0（0.00）2（7.69）4（15.38）3（11.54）1（3.85）10（38.46）#
rs1800469组12（38.71）8（25.81）3（9.68）2（6.45）2（6.45）27（87.10）*2（6.45）3（9.68）2（6.45）0（0.00）0（0.00）7（22.58）#
rs2241716组17（53.13）*4（12.50）2（6.25）1（3.13）1（3.13）25（78.13）4（12.50）1（3.13）1（3.13）4（12.50）3（9.38）13（40.63）#
), ArticleFig(id=1322926636169044366, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322926627864322392, language=CN, label=表7, caption=

两种治疗方式下5组瘢痕疙瘩患者不良反应

, figureFileSmall=null, figureFileBig=null, tableContent=
组别单药治疗联合治疗
毛细血管扩张色素沉着局部凹陷药物沉渣色素脱失总不良反应毛细血管扩张色素沉着局部凹陷药物沉渣色素脱失总不良反应
野生组7（22.58）5（16.13）2（6.45）2（6.45）3（9.68）19（61.29）3（9.68）3（9.68）2（6.45）2（6.45）2（6.45）12（38.71）#
突变组35（39.33）17（19.10）8（8.99）6（6.74）4（4.49）70（78.65）6（6.74）6（6.74）7（7.87）7（7.87）4（4.49）30（33.71）#
rs747857组6（23.08）5（19.23）3（11.54）3（11.54）1（3.85）18（69.23）0（0.00）2（7.69）4（15.38）3（11.54）1（3.85）10（38.46）#
rs1800469组12（38.71）8（25.81）3（9.68）2（6.45）2（6.45）27（87.10）*2（6.45）3（9.68）2（6.45）0（0.00）0（0.00）7（22.58）#
rs2241716组17（53.13）*4（12.50）2（6.25）1（3.13）1（3.13）25（78.13）4（12.50）1（3.13）1（3.13）4（12.50）3（9.38）13（40.63）#
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龙血竭联合氟尿嘧啶注射液对不同TGF-β单核苷酸多态性瘢痕疙瘩患者的疗效分析
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韩伟强 , 李丽莎 , 陈云 , 聂蕴韬 , 陈誉华
中华中医药学刊 | 省级项目平台 2025,43(9): 214-218
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中华中医药学刊 |省级项目平台 2025 , 43 (9) : 214 -218
龙血竭联合氟尿嘧啶注射液对不同TGF-β单核苷酸多态性瘢痕疙瘩患者的疗效分析
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韩伟强, 李丽莎, 陈云, 聂蕴韬, 陈誉华
作者信息
  • 邢台市人民医院，河北 邢台 054000
通讯作者:
陈誉华（1965-），男，河北邢台人，主任医师，硕士，研究方向：瘢痕防治。
作者简介:

韩伟强（1982-），男，河北邢台人，副主任医师，硕士，研究方向：瘢痕防治。

Efficacy of Longxuejie（Resina Draconis）Combined with Fluorouracil Injection in Patients with Different TGF-β Single Nucleotide Polymorphisms
Weiqiang HAN, Lisha LI, Yun CHEN, Yuntao NIE, Yuhua CHEN
Affiliations
  • Medical Cosmetology Department，Xingtai People＇s Hospital，Xingtai 054000，Hebei，China
出版时间: 2025-09-10 doi: 10.13193/j.issn.1673-7717.2025.09.040
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摘要
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目的

探讨龙血竭联合氟尿嘧啶注射液对不同转化生长因子-β（Transforming growth factor-β，TGF-β）单核苷酸多态性瘢痕疙瘩患者的疗效。

方法

纳入2019年7月—2022年1月医院收治的瘢痕疙瘩患者240例，根据TGF-β单核苷酸多态分为野生组（野生型TGF-β）、突变组（突变型TGF-β），并将突变组分为亚组：rs747857组（rs747857型TGF-β）、rs1800469组（rs1800469型TGF-β）、rs2241716组（rs2241716型TGF-β）。使用氟尿嘧啶注射液单药治疗或血竭联合氟尿嘧啶注射液治疗5组患者。5组患者治疗前和首次治疗后12个月通过温哥华瘢痕量表（Vancouver scar scale，VSS）、瘢痕评估量表（Patientand observer scar assessment scale，POSAS）和皮肤病生活质量指数（Dermatologic quality of life index，DLQI）量表进行评分。

结果

与野生组比较，突变组、rs747857组、rs1800469组、rs2241716组TGF-β mRNA的表达水平均上升（P<0.05）。与野生组相比，单药治疗下突变组、rs1800469组和rs2241716组患者在治疗后VSS总评分、POSAS总评分均显著上升（P<0.05）；而与单药治疗相比，联合治疗下突变组、rs1800469组和rs2241716组患者在治疗后VSS总评分、POSAS总评分均显著下降（P<0.05）。与野生组相比，rs2241716组患者在治疗后的DLQI量表评分均显著上升（P<0.05）；而与单药治疗相比，联合治疗下rs2241716组患者在治疗后的DLQI量表评分均显著下降（P<0.05）。与野生组相比，rs1800469组和rs2241716组患者在治疗后的有效率显著下降（P<0.05）；而与单药治疗相比，联合治疗下rs1800469组和rs2241716组患者在治疗后的有效率显著上升（P<0.05）。与野生组相比，突变组、rs1800469组和rs2241716组患者的首次显效及达到首次显效时氟尿嘧啶次数均延后（P<0.05）；而与单药治疗相比，联合治疗下突变组、rs1800469组和rs2241716组患者的首次显效及达到首次显效时氟尿嘧啶次数均提前（P<0.05）。与单药治疗相比，联合治疗下野生组、突变组、rs747857组、rs1800469组、rs2241716组的总不良反应更少（P<0.05）。

结论

龙血竭联合氟尿嘧啶注射液对不同TGF-β单核苷酸多态性瘢痕疙瘩患者有较好的疗效，和较少的不良反应。

龙血竭  /  氟尿嘧啶  /  TGF-β  /  单核苷酸多态性  /  瘢痕疙瘩
Objective

To investigate the efficacy of Longxuejie（Resina Draconis）combined with fluorouracil injection in patients with keloid scarswith different transforming growth factor-β（TGF-β）single nucleotide polymorphisms.

Methods

A total of 240 cases of keloid patients admitted to the hospital from July 2019 to January 2022 were included，which were categorized into wild group（wild-type TGF-β）and mutant group（mutant TGF-β）based on TGF-β single nucleotide polymorphisms，and themutant group was divided into rs747857 group（rs747857-type TGF-β），rs1800469 group（rs1800469 type TGF-β）and rs2241716 group（rs2241716 type TGF-β）. Five groups were treated with fluorouracil injection monotherapy or Longxuejie（Resina Draconis）combined with fluorouracil injection. The patients in the five groupswere scored by the Vancouver Scar Scale（VSS），the Patient and Observer Scar Assessment Scale（POSAS）and the Dermatologic Quality of Life Index（DLQI）scale before treatment and 12 months after the first treatment.

Results

Compared with those of the wild group，the expression levels of TGF-β mRNA in themutation group，rs747857 group，rs1800469 group and rs2241716 group increased（P<0.05）. Compared with the wild group，the patients in the mutation group，rs1800469 group and rs2241716 group under monotherapy showed a significant increase in the total VSSscore and the total POSAS score after treatment（P<0.05）；whereas，compared with monotherapy，the patients in the mutation group，rs1800469 group and rs2241716 group under the combination therapy showed a significant decrease in the total VSS score and the total POSAS scores were significantly decreased（P<0.05）. Compared with thewild group，the patients in the rs2241716 group all showed a significant increase in DLQI scale scores after treatment（P<0.05）；whereas，compared with monotherapy，the patients in the rs2241716 group under combination therapy all showed a significant decrease in DLQI scale scores after treatment（P<0.05）. Compared with the wild group，the patients in the rs1800469 and rs2241716 groups showed a significant decrease in the effective rate after treatment（P<0.05）；while compared with mono therapy，the patients in the rs1800469 and rs2241716 groups under combination therapy showed a significant increase in the effective rate after treatment（P<0.05）. Compared with the wild group，the patients in the mutation group，rs1800469 group and rs2241716 group had delayed the first apparent effect and the number of fluorouracil times to reach the first apparent effect（P<0.05）；while compared with the monotherapy，the patients in the mutation group，rs1800469 group and rs2241716 group under the combination therapy had advanced the first apparent effect and the number of fluorouracil times to reach the first apparent effect（P<0.05）. Fewer total adverse reactions were observed in the wild，mutant，rs747857，rs1800469 and rs2241716 groups under combination therapy compared with monotherapy（P<0.05）.

Conclusion

Longxuejie（Resina Draconis）combined with fluorouracil injection has better efficacy and fewer adverse effects in patients with keloids with different TGF-β single nucleotide polymorphisms.

Longxuejie（Resina Draconis）  /  fluorouracil  /  TGF-β  /  single nucleotide polymorphism  /  keloid
韩伟强, 李丽莎, 陈云, 聂蕴韬, 陈誉华. 龙血竭联合氟尿嘧啶注射液对不同TGF-β单核苷酸多态性瘢痕疙瘩患者的疗效分析. 中华中医药学刊, 2025 , 43 (9) : 214 -218 . DOI: 10.13193/j.issn.1673-7717.2025.09.040
Weiqiang HAN, Lisha LI, Yun CHEN, Yuntao NIE, Yuhua CHEN. Efficacy of Longxuejie（Resina Draconis）Combined with Fluorouracil Injection in Patients with Different TGF-β Single Nucleotide Polymorphisms[J]. Chinese Archives of Traditional Chinese Medicine, 2025 , 43 (9) : 214 -218 . DOI: 10.13193/j.issn.1673-7717.2025.09.040
正文
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瘢痕疙瘩是一种人类特有的皮肤损伤的病理愈合，表现出种族和家庭倾向。主要临床表现为创面边缘外持续性肿瘤样增生及浸润邻近组织[1]。在中国，瘢痕疙瘩的发病率高达4.6%～16%。瘢痕疙瘩形成的机制是复杂的，并基于几个影响因素，包括转化生长因子-β（Transforming growth factor-β，TGF-β）[2]。TGF-β由损伤组织分泌释放，在病理性纤维化中起决定性作用[3]。另有证据表明，瘢痕疙瘩成纤维细胞表达TGF-β的能力显著增强[4]。此外，TGF-β的表达水平对治疗瘢痕疙瘩至关重要，目前针对TGF-β信号通路设计了多种治疗策略（药物、siRNA、shRNA、miRNA）以干扰成纤维细胞介导的瘢痕疙瘩进展[5]。由于TGF-β的表达水平主要受遗传控制，疾病的病程可能与TGF-β基因座的不同等位基因变化有关[6]。单核苷酸多态性（Single nucleotide polymorphisms，SNPs）常影响相应基因的表达水平，并与多种疾病相关。研究发现[7]，由于基因和调控区域的SNP导致TGF-β表达增加的个体对同一种治疗方案呈现出不同疗效。然而，作为瘢痕疙瘩形成的关键分子TGF-β，其SNP在瘢痕疙瘩患者中的主要存在形式是什么尚不清晰，并且，这些TGF-β的SNP是否影响治疗的效果也尚不明确。氟尿嘧啶注射液是一种能够有效减轻组织对损害性刺激产生的病理反应的药物，常被用于治疗瘢痕疙瘩[8]。然而，随着研究的深入，越来越多的证据表明，中药在防治瘢痕疙瘩方面展现出了广阔的前景[9]。中医认为，瘢痕疙瘩的形成多是由于水火炙热、外物损伤皮肤组织、余素内蕴、气滞血瘀以及外邪入侵经络等因素所导致[10]。在伤口愈合的过程中，瘢痕过度增生，长期积累便形成了瘢痕疙瘩。现代药理研究也证实，龙血竭具有抗炎抑菌、抗肿瘤以及治疗瘢痕疙瘩等多种作用，为中药治疗瘢痕疙瘩提供了有力的科学依据[11]。基于此，本研究通过一代测序鉴定了瘢痕疙瘩患者中TGF-β的主要SNPs为rs747857、rs1800469、rs2241716，旨在探讨龙血竭联合氟尿嘧啶注射液对不同TGF-β单核苷酸多态性瘢痕疙瘩患者的疗效。
1　资料与方法
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1.1　研究对象及分组
根据《现代瘢痕学》[12]中瘢痕疙瘩的诊断标准，纳入2019年7月—2022年1月邢台市人民医院收治的瘢痕疙瘩患者240例，共计356处瘢痕疙瘩。空腹12 h后，用乙二胺四乙酸（EDTA）作为抗凝剂获得患者静脉血样本。按照制造商的建议，使用树脂柱从外周血细胞的缓冲层中提取基因组DNA（PureLink，K182104A），并储存在-20℃直到使用。使用NanoDrop 2000cTM分光光度计在260 nm处测量DNA浓度。TGFβ单核苷酸多态位点rs747857、rs1800469、rs2241716通过聚合酶链反应（Polymerase chain reaction，PCR）在位于19号染色体上的TGFB1基因调控区进行扩增，并交由北京擎科进行一代测序分析。依据测序结果判定TGFB1基因多态性，野生型TGF-β为野生组（62例），突变型为突变组（178例），同时突变组分为3个亚组：rs747857型TGF-β为rs747857组（52例），rs1800469型TGF-β为rs1800469组（62例），rs2241716型TGF-β为rs2241716（64例），这3种突变型基因型的地区分布上差异无统计学意义（P>0.05）。每个组别受试人员中一半接受单药治疗，另一半接受联合治疗。纳入标准：①指定TGF-β多态性的瘢痕疙瘩患者；②无瘢痕疙瘩治疗史；③临床资料完整者。排除标准：①肝、肾功能不全者；②患有癌症者；③患有自身性免疫病者；④患有精神疾病者；⑤瘢痕疙瘩大小在4～5 mm内。选取同一时间70例健康志愿者作为对照组，其中男4例，女66例。所有患者均签署知情同意书，并且本研究获得我院的伦理委员会批准，批准号：〔2019〕033。
1.2　方法
1.2.1　药物治疗
对于单药治疗，将5-氟尿嘧啶注射液（天津金耀药业有限公司，国药准字号：H12020959，规格：0.025 g/mL）。剂量为1 mL/cm2，消毒后瘢痕内水平注射至皮损微泛白，治疗每月1次，共完成12次治疗。治疗结束后随访12个月。对于联合治疗，除了用上述5-氟尿嘧啶注射液外，将0.3～0.9 g的血竭粉与2～5 mL的75%乙醇混合均匀后，直接涂抹在创面上，无需额外覆盖。根据创面的大小和深度，每天涂抹2～3次，持续用药12个月。
1.2.2　VSS和POSAS评分
治疗前和首次治疗后12个月通过温哥华瘢痕量表（Vancouver scar scale，VSS）和瘢痕评估量表（Patient and observer scar assessment scale，POSAS）进行评分。VSS包含厚度、柔软度、色泽、血管分布条目，总分为0～15分。POSAS包含疼痛程度、瘙痒程度、颜色、硬度、厚度及自我感受条目，总分为12～120分。VSS和POSAS的评分越高说明患者瘢痕疙瘩病情越严重。
1.2.3　疗效评价
治疗6和12个月后，依据VSS和POSAS评分进行瘢痕疙瘩疗效评价并计算有效率，患者总评分＝VSS评分×10+POSAS评分。总评分220～270分为无效，120～220分为好转，20～120分为显效，12～20分为治愈。有效率＝（显效患者+治愈患者）/当组患者人数×100%。
1.2.4　生活质量评分
通过皮肤病生活质量指数（Dermatologic quality of life index，DLQI）量表评估治疗前和首次治疗后12个月瘢痕疙瘩的患者生活质量。DLQI量表共有10个问题，包括症状对身体的影响、症状对心理的影响、症状对日常活动的影响、症状对休闲娱乐的影响、症状对工作学习的影响、症状对人际关系的影响、症状对体育运动的影响、症状对性生活的影响、症状对治疗的影响、症状对家庭的影响，总分为0～30分。总分越低越好。
1.2.5　安全性评价
观察记录4组患者治疗期间及治疗后12个月内不良反应发生情况，包括色素脱落、局部凹陷、色素沉着、药物沉渣、毛细血管扩张等不良反应发生情况。
1.2.6　TGF-β mRNA水平的检测
收取患者治疗前的静脉血5 mL。使用RNA提取试剂盒抽取总RNA，逆转录试剂盒进行反转录后进行实时荧光定量PCR检测TGF-β的表达水平。以甘油醛-3-磷酸脱氢酶（Glyceraldehyde-3-phosphate dehydrogenase，GAPDH）为内参，使用2ΔCT法进行相对定量。
1.3　统计学处理
使用SPSS进行统计学分析。计量资料均不符合正态分布，以中位数（四分位数间距）［M（P25，P75）］表示。使用Mann-Whitney U检验两组计量资料的差异。使用Fisher＇s exact test检验两组计数资料的差异。Pearson相关系数分析TGF-β mRNA的表达水平与VSS总评分、POSASS总评分、DLQI量表评分的相关性。P<0.05认为差异有统计学意义。
2　结果
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2.1　患者一般资料比较
与对照组比较，单药治疗组和联合治疗组的野生组和突变组患者TGF-β mRNA的表达水平均上升（P<0.05）；与野生组比较，突变组、rs1800469组、rs2241716组患者TGF-β mRNA的表达水平均上升（P<0.05）。在性别、年龄和病程时间等一般资料方面，野生组、突变组以及rs747857、rs1800469、rs2241716三个亚组的单药治疗组与联合治疗组之间的差异均无统计学意义（P>0.05），见表1。
2.2　各组患者瘢痕疙瘩评分
与治疗前相比，两种治疗方式下野生组、突变组、rs747857组、rs1800469组、rs2241716组患者在治疗后VSS总评分、POSAS总评分均显著下降，差异有统计学意义（P<0.05）。与野生组相比，单药治疗下突变组、rs1800469组和rs2241716组患者在治疗后VSS总评分、POSAS总评分均显著上升，差异有统计学意义（P<0.05）。与单药治疗相比，联合治疗下突变组、rs1800469组和rs2241716组患者在治疗后VSS总评分、POSAS总评分均显著下降，差异有统计学意义（P<0.05），见表2、表3。同时，TGF-β mRNA的表达水平与VSS总评分（r＝0.421）、POSASS总评分（r＝0.399）均呈正相关（P<0.05）。
2.3　5组患者生活质量评分
与治疗前相比，两种治疗方式下野生组、突变组、rs747857组、rs1800469组、rs2241716组患者在治疗后的生活质量评分均显著下降，差异有统计学意义（P<0.05）。与野生组相比，单药治疗下rs2241716组患者在治疗后的生活质量评分均显著上升，差异有统计学意义（P<0.05）。与单药治疗相比，联合治疗下rs2241716组患者在治疗后的生活质量评分均显著下降，差异有统计学意义（P<0.05），见表4。同时，TGF-β mRNA的表达水平与DLQI量表评分（r＝0.409）呈正相关（P<0.05）。
2.4　5组患者疗效评价
达到治愈的患者，治疗后瘢痕疙瘩均消失；达到显效和好转的患者，治疗后瘢痕疙瘩明显减小。与野生组相比，单药治疗下rs1800469组和rs2241716组患者在治疗后的有效率显著下降（P<0.05），差异有统计学意义。与单药治疗相比，联合治疗下突变组、rs1800469组和rs2241716组患者在治疗后的有效率显著上升（P<0.05），差异有统计学意义，见表5。
2.5　5组患者首次显效及达到首次显效时氟尿嘧啶次数
与野生组相比，单药治疗下突变组、rs1800469组和rs2241716组患者的首次显效及达到首次显效时氟尿嘧啶次数均延后（P<0.05），差异有统计学意义。与单药治疗相比，联合治疗下突变组、rs1800469组和rs2241716组患者的首次显效及达到首次显效时氟尿嘧啶次数均提前（P<0.05），差异有统计学意义，见表6。
2.6　5组患者不良反应
与野生组相比，单药治疗下rs1800469组的总不良反应更多，差异有统计学意义（P<0.05）。与单药治疗相比，野生组、突变组、rs747857组、rs1800469组、rs2241716组患者在治疗后的不良反应更少（P<0.05），差异有统计学意义，见表7。
3　讨论
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TGF-β/Smad信号通路的持续激活导致成纤维细胞和肌成纤维细胞长期过度激活，这是异常瘢痕中胶原过度形成的必要条件[13-14]。由于TGF-β水平的表达被认为主要受遗传控制，不同的单核苷酸多态可能在易感性中发挥重要作用，并可能影响瘢痕疙瘩的病情和治疗过程。本研究分析了野生型TGF-β、rs747857型TGF-β、rs1800469型TGF-β、rs2241716型TGF-β对瘢痕疙瘩治疗的影响，发现不同的TGF-β单核苷酸多态会影响氟尿嘧啶注射液对瘢痕疙瘩的疗效，但是并不影响龙血竭联合氟尿嘧啶注射液的疗效。
与野生组相比，突变组、rs1800469组和rs2241716组患者的首次显效及达到首次显效时氟尿嘧啶次数均延后；而与单药治疗相比，联合治疗下突变组、rs1800469组和rs2241716组患者的首次显效及达到首次显效时氟尿嘧啶次数均提前。与野生组相比，rs1800469组单药治疗的总不良反应更多。作为瘢痕疙瘩形成的关键分子TGF-β，其表达水平在疾病进展中发挥重要功能。单核苷酸多态rs1800469位于TGF-β的转录上游。单核苷酸多态rs2241716存在于TGF-β的内含子区域。在许多真核生物中，包括哺乳动物、植物、酵母和昆虫，存在“内含子介导的增强”的现象，即内含子可以在不作为转录因子结合位点的情况下增加基因表达[15]。因此，rs1800469和rs2241716可能影响TGF-β的转录水平。接下来本研究组探讨了不同TGF-βSNP的瘢痕疙瘩患者的TGF-β的表达水平，并分析其与氟尿嘧啶治疗的疗效以及不良反应的相关性，发现突变组、rs1800469组、rs2241716组野生组和突变组患者TGF-β mRNA的表达水平均上升。并且，TGF-β mRNA的表达水平与VSS总评分、POSASS总评分、DLQI量表评分均呈正相关。因此，TGF-βSNP引起的表达水平变化可能是影响瘢痕疙瘩的疗效的原因。研究发现，rs1800469与多种疾病进展相关，包括结直肠癌和肺癌[16-17]。同时，结直肠癌和肺癌中TGF-β存在表达异常情况[18]。此外，rs2241716具有增加慢性阻塞性肺疾病的风险[19]。研究发现[20]，TGF-β/Smad通路参与了慢性阻塞性肺疾病的进展。因此，rs1800469和rs2241716可能是多种与TGF-β相关疾病的风险因子。与单药治疗相比，联合治疗下野生组、突变组、rs747857组、rs1800469组、rs2241716组的总不良反应更少。研究表明[21]，龙血竭主要包含黄酮类、苯丙素类、皂苷类、甾醇类、木脂素类和二苯乙烯类等多种成分。深入的药理研究进一步揭示了龙血竭的广泛药理作用，其中包括抗炎、保护心血管、防辐射、抗纤维化、抑菌、促进创面愈合以及保护中枢神经等[22-23]。这些药理作用使得龙血竭在医学领域具有潜在的应用价值，尤其在治疗瘢痕疙瘩等皮肤疾病方面展现出独特的效果。
在本研究中，与野生组相比，rs1800469组和rs2241716组患者在治疗后的有效率显著下降。在20世纪90年代，氟尿嘧啶被引入用于治疗瘢痕疙瘩。氟尿嘧啶可以阻断嘧啶胸苷的合成，而嘧啶胸苷是DNA复制所必需的核苷[24]。荟萃分析发现氟尿嘧啶大约对70%的瘢痕疙瘩患者有效[25]。对氟尿嘧啶的治疗无效可能是瘢痕疙瘩患者个体的异质性导致的。TGF-β rs1800469和rs2241716这两种异质性可能是导致部分瘢痕疙瘩患者对5-氟尿嘧啶不敏感的原因之一。与单药治疗相比，联合治疗下rs1800469组和rs2241716组患者在治疗后的有效率显著上升。因此，针对rs1800469型或rs2241716型TGF-β的瘢痕疙瘩患者可以尝试龙血竭联合氟尿嘧啶注射液的治疗策略。
综上所述，龙血竭联合氟尿嘧啶注射液对不同TGF-β单核苷酸多态性瘢痕疙瘩患者有较好的疗效，和较少的不良反应。
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  • 河北省卫生健康委员会项目(20201572)
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2025年第43卷第9期
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doi: 10.13193/j.issn.1673-7717.2025.09.040
  • 首发时间：2026-10-30
  • 出版时间：2025-09-10
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河北省卫生健康委员会项目(20201572)
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    邢台市人民医院，河北 邢台 054000

通讯作者:

陈誉华（1965-），男，河北邢台人，主任医师，硕士，研究方向：瘢痕防治。
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Family		 属数
Number of
genus		 种数
Number of
species		 占总种数比例
Percentage of
total species (%)		 属
Genus		 种数
Number of
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鹅膏菌科Amanitaceae 2 11 5.26 鹅膏菌属 Amanita 10 4.78
小菇科 Mycenaceae 2 12 5.74 丝盖伞属 Inocybe 5 2.39
多孔菌科 Polyporaceae 8 14 6.70 蜡蘑属 Laccaria 5 2.39
红菇科 Russulaceae 3 23 11.00 小皮伞属 Marasmius 6 2.87
小菇属 Mycena 11 5.26
光柄菇属 Pluteus 5 2.39
红菇属 Russula 17 8.13
栓菌属 Trametes 5 2.39
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