[关键词]
[摘要]
目的 评价调肠消瘤颗粒预防结直肠腺瘤(CRA)复发的疗效并进行药理学分析。方法 首先采取单中心 双盲随机对照试验,将结直肠腺瘤切除术后患者随机分为两组:一组接受调肠消瘤颗粒治疗,另一组接受调肠 消瘤模拟颗粒治疗,疗程6个月。对1年后结肠镜检查结果进行审查。主要评估结果是1年随访时结直肠腺瘤 检出率。然后使用UHPLC-QE Orbitrap HRMS对调肠消瘤颗粒的活性成分进行分析和筛选,并使用R软件完成 核心靶点筛选和功能富集。最后,使用单细胞测序数据进行细胞注释、细胞通讯和其他分析,以筛选出细胞通 讯的核心效应通路和特定信号通路。结果 随机对照试验结果表明,调肠消瘤颗粒组术后 1 年腺瘤复发率 (12.0%)明显低于模拟组(37.1%),两组之间的差异具有统计学意义。药理学研究和分析结果表明,调肠消瘤 颗粒预防结直肠腺瘤复发的核心基因包括 AKT1、TP53、TNF、IL6、CASP3、VEGFA、INSR、IL1B、MAPK3 和 EGFR。通过分析结直肠腺瘤患者的单细胞测序数据集,预防结直肠腺瘤复发的关键途径可能是 VISFATIN 途径,主要的细胞通讯途径是NAMPT - INSR。通信过程是从胚胎干细胞传输信号,并由胚胎干细胞、上皮细 胞和内皮细胞接收。调节过程可能涉及内皮间充质转化调节和脂质代谢。结论 调肠消瘤颗粒能有效降低结直 肠腺瘤术后 1年复发率。其可能通过调节 VISFATIN通路来干扰内皮间充质转化调节和脂质代谢,以防止结直 肠腺瘤的复发和恶化。这些发现可能有助于调肠消瘤颗粒的临床应用。
[Key word]
[Abstract]
Objective To evaluate the efficacy of Tiaochang Xiaoliu Granules in preventing the recurrence of colorectal adenoma (CRA) and to conduct a further pharmacological analysis. Methods A single-center, double-blind, randomized controlled trial was conducted in this study. Patients who underwent resection for CRA were randomly divided into two groups: one group received the treatment with Tiaochang Xiaoliu Granules, while the other group received the treatment with placebo Granules for a duration of six months. One year later, colonoscopy results were reviewed,with the primary outcome being the CRA detection rate at follow-up. Additionally,ultra-high-performance liquid chromatography coupled with quadrupole-exactive orbitrap mass spectrometry was employed to identify the active ingredients in Tiaochang Xiaoliu Granules. Core target screening and functional enrichment were performed using R software, and single-cell RNA sequencing(scRNA-seq)data were analyzed for cell annotation and communication pathways to identify key effector and signaling pathways. Results The randomized controlled trial revealed a one-year adenoma recurrence rate of 12.0% in the Tiaochang Xiaoliu Granules group significantly lower than that observed in the placebo group(37.1%), with statistically significant difference between the two groups. Pharmacological analyses identified core genes associated with CRA recurrence prevention, including AKT1, TP53, TNF, IL6, CASP3, VEGFA, INSR, IL1B, MAPK3, and EGFR. Further analysis of single-cell sequencing data suggested that the VISFATIN pathway plays a crucial role in preventing CRA recurrence, with the primary cellular communication occurring through the NAMPT-INSR pathway,involved in transmitting signals from embryonic stem cells to epithelial cells and endothelial cells. This process may be regulated by endothelial-mesenchymal transition(EndMT)and lipid metabolism. Conclusion Tiaochang Xiaoliu Granules significantly reduce the one-year recurrence rate following CRA surgery. The mechanism may involve regulation of the VISFATIN pathway,influencing EndMT and lipid metabolism to mitigate CRA recurrence and progression. These findings support the clinical application of Tiaochang Xiaoliu Granules in preventing CRA.
[中图分类号]
R285.6
[基金项目]
广东省教育厅高校科研项目(2021ZDZX2059);广州中医药大学“双一流”与高水平大学学科协同创新团队项目(2021xk58);广东省 中医院临床研究专项资助研究(YN10101914);广州市科技厅 2025年度市校(院)企联合资助专题项目(SL2024A03J00115);广东省科技创新战略 专项(pdjh2021b0123)