调肠消瘤颗粒预防结直肠腺瘤复发的随机对照试验及药理学联合scRNA-seq分析  

Tiaochang Xiaoliu Granules in Preventing Recurrence of Colorectal Adenomas:Randomized Controlled Trial and Pharmacology Combined with scRNA-seq Analysis

作　　者：莫嘉浩 冯天香 吴少华 钟彩玲[3] 程怡 黎雄[1] 张北平[3] MO Jiahao;FENG Tianxiang;WU Shaohua;ZHONG Cailing;CHENG Yi;LI Xiong;ZHANG Beiping(The Second Clinical Medical School of Guangzhou University of Chinese Medicine,Guangzhou 510405 Guangdong,China;Shenyang Pharmaceutical University,Shenyang 110016 Liaoning,China;Guangdong Provincial Hospital of Chinese Medicine,Guangzhou 510120 Guangdong,China)

机构地区：[1]广州中医药大学第二临床医学院,广东广州510405 [2]沈阳药科大学,辽宁沈阳110016 [3]广东省中医院,广东广州510120

出　　处：《中药新药与临床药理》2025年第2期273-281,共9页Traditional Chinese Drug Research and Clinical Pharmacology

基　　金：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)。

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。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 pathwa

关 键 词：结直肠腺瘤 调肠消瘤颗粒 复发 随机对照试验 单细胞RNA测序 活性成分分析 

分 类 号：R285.6[医药卫生—中药学]