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中医药治疗胃癌的模块化特征及机制:基于数据挖掘和药理学的鉴定

Modular characteristics and the mechanism of Chinese medicine's treatment of gastric cancer: a data mining and pharmacology-based identification.

作者信息

Xu Xintian, Chen Yaling, Zhang Xingxing, Zhang Ruijuan, Chen Xu, Liu Shenlin, Sun Qingmin

机构信息

Oncology Department, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China.

No. 1 Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing, China.

出版信息

Ann Transl Med. 2021 Dec;9(24):1777. doi: 10.21037/atm-21-6301.

Abstract

BACKGROUND

Traditional Chinese medicine (TCM) is increasingly extensively being applied as a complementary and alternative therapy for gastric cancer (GC); however, there is a lack of large-scale evidence-based deep learning for the guidance of its clinical prescription.

METHODS

The combinational search terms of "Gastric cancer and/or gastric malignancy" and "Traditional Chinese Medicine" were used to retrieve clinical study-based herbal prescriptions from public database over the past 3 decades [1990-2020]. Association rules mining (ARM) was used to analyze the prescription patterns of the herbs extracted from the eligible studies. Deep machine learning and computational prediction were conducted to explore candidate prescriptions with general applicability for GC. The action mechanism of the preferred prescription was investigated through network pharmacology, and further validated via and experiments.

RESULTS

A total of 194 clinical study-based herbal prescriptions with good efficacy for GC were collected. TCM with focus on invigorating the Spleen and tonifying the vital- is a promising adjuvant therapy for GC. The preferred prescription is composed of , , , , , and so on. We screened 74 bioactive compounds and 2,128 predictive targets of the preferred prescription from public databases. Eventually, 135 GC-related genes were identified as the targets of the preferred prescription. The compound-target network revealed that the crucial substances in the preferred prescription are quercetin, kaempferol, baicalein, and nobiletin. Experimentally, the preferred prescription was validated to modulate GC cell survival and inhibit tumor progression mainly via the hTERT/MDM2-p53 signaling pathway and .

CONCLUSIONS

TCM aimed at invigorating the Spleen and tonifying the vital- is a promising adjuvant therapy for GC, which offers a guidance for worldwide use of TCM in the treatment of GC.

摘要

背景

中医药(TCM)越来越广泛地被用作胃癌(GC)的补充和替代疗法;然而,缺乏基于大规模证据的深度学习来指导其临床处方。

方法

使用“胃癌和/或胃恶性肿瘤”和“中医药”的组合检索词,从过去30年(1990 - 2020年)的公共数据库中检索基于临床研究的草药处方。使用关联规则挖掘(ARM)分析从符合条件的研究中提取的草药处方模式。进行深度机器学习和计算预测,以探索对GC具有普遍适用性的候选处方。通过网络药理学研究首选处方的作用机制,并通过实验进一步验证。

结果

共收集到194个对GC疗效良好的基于临床研究的草药处方。以健脾补气为主的中医药是GC有前景的辅助治疗方法。首选处方由等组成。我们从公共数据库中筛选出首选处方的74种生物活性化合物和2128个预测靶点。最终,确定了135个与GC相关的基因作为首选处方的靶点。化合物 - 靶点网络显示,首选处方中的关键物质是槲皮素、山奈酚、黄芩素和川陈皮素。实验上,首选处方被验证主要通过hTERT/MDM2 - p53信号通路调节GC细胞存活并抑制肿瘤进展。

结论

以健脾补气为主的中医药是GC有前景的辅助治疗方法,为全球中医药治疗GC提供了指导。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5acc/8756228/4cba2b10e052/atm-09-24-1777-f1.jpg

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