Objective  To collect and sort out the literature on the clinical medication experience of traditional Chinese medicine (TCM) in the treatment of hepatic precancerous lesions, and to summarize the characteristics of the disease and the treatment ideas by analyzing the rules of its formula, in order to provide instructions for the treatment of precancerous lesions of hepatocellular carcinoma with TCM in terms of medication and experience addition and subtraction.

Methods  CNKI, VIP, WanFang Data, CBM, PubMed, Web of Science, EMBASE, Cochrane databases were systematically searched, the clinical research and personal experience literature of TCM in the treatment of hepatic precancerous lesions from the establishment of the databases to December 2023 was included, and the prescription information that met the inclusion criteria was extracted. Based on “Traditional Chinese Medicine data Miner (TCM Miner)”, the medication database was established to analyze the frequency, properties and flavours of the drugs and meridian tropism. The cluster analysis were conducted by SPSS 25.0 statistical software, and the association rules were analyzed by using Apriori algorithm of SPSS Modeler 14.1, and the complex network analysis of high-frequency drugs was conducted by network module of SPSS Modeler.

Results  34 researches including 34 formulas, 110 drugs with 291 frequencies and 15 drug efficacy were included. Frequency analysis showed that the top eight types of frequently applied drugs were milkvetch root, largehead atractylodes rhizome, radix salviae miltiorrhhizae, hedyotis, carapax trionycis, zedorgy rhidoray, barbated skullcup herb, redix curcumae. The top three properties in the "four qi" were cold, warm and mild. The top three tastes of the "five flavors" were bitterness, sweetness and acridity. The top four in the frequency of meridian tropism were liver, spleen, kidney and lung. Apriori correlation analysis showed that the core drug pairs was "Hedyotis diffusa+Atractylodes". Complex network analysis showed that the core prescriptions were composed of Atractylodes, Radix Paeoniae Alba, Hedyotis diffusa, Poria cocos, Rhizoma Curcumae, Radix Curcumae Aromaticae, Trionycis Carapax, Radix Astragali, Sparganium stoloniferum, Salvia miltiorrhiza, Scutellaria barbata.

Conclusion  The TCM treatment of hepatic precancerous lesions should be based on tonifying spleen and nourishing liver, promoting blood circulation and detoxification, and combined with drugs that can promote qi-circulation, clear heat, remove blood-stasis, soften hard masses and resolve hard masses.

1.Ganesan P, Kulik LM. Hepatocellular carcinoma: new developments[J]. Clin Liver Dis, 2023, 27(1): 85-102. DOI: 10.1016/j.cld.2022.08.004.

2.Feng F, Zhao Y. Hepatocellular carcinoma: prevention, diagnosis, and treatment[J]. Med Princ Pract, 2024: 21. DOI: 10.1159/000539349.

3.黄倩, 李京涛, 张海博, 等. 李京涛诊治肝癌癌前病变经验探析[J]. 中西医结合肝病杂志, 2020, 30(3): 246-248. [Huang Q, Li JT, Zhang HB, et al. An analysis of Li Jingtao's experience in diagnosing and treating precancerous lesions of liver cancer[J]. Journal of Integrated Traditional Chinese and Western Medicine in Liver Disease, 2020, 30(3): 246-248.] DOI: 10.3969/j.issn.1005-0264.2020.03.018.

4.Stangis MM, Chen Z, Min J, et al. The hallmarks of precancer[J]. Cancer Discov, 2024, 14(4): 683-689. DOI: 10.1158/2159-8290.CD-23-1550.

5.夏锋, 李雪松. 肝细胞癌癌前病变的诊断和治疗多学科专家共识(2020版)[J]. 临床肝胆病杂志, 2020, 36(3): 514-518. [Xia F, Li XS. Expert consensus on multidisciplinary diagnosis and treatment of precancerous lesions of hepatocellular carcinoma (2020 edition)[J]. Journal of Clinical Hepatobiliary Diseases, 2020, 36(3): 514-518.] DOI: 10.3969/j.issn.1001-5256.2020.03.007.

6.Piñero F, Dirchwolf M, Pessôa MG. Biomarkers in hepatocellular carcinoma: diagnosis, prognosis and treatment response assessment[J]. Cells, 2020, 9(6): 1370. DOI: 10.3390/cells9061370.

7.Nevola R, Ruocco R, Criscuolo L, et al. Predictors of early and late hepatocellular carcinoma recurrence[J]. World J Gastroenterol, 2023, 29(8): 1243-1260. DOI: 10.3748/wjg.v29.i8.1243.

8.朱迎, 钦伦秀. 肝癌免疫生物治疗的现状及评价[J].中国实用外科杂志, 2016, 36(6): 636-640. [Zhu Y, Qin LX. Recent progress of biological immunotherapy for hepatocellular carcinoma[J]. Chinese Journal of Practical Surgery, 2016, 36(6): 636-640.] DOI: 10.7504/CJPS.ISSN1005-2208.2016.06.13.

9.Xie M, Lin Z, Ji X, et al. FGF19/FGFR4-mediated elevation of ETV4 facilitates hepatocellular carcinoma metastasis by upregulating PD-L1 and CCL2[J]. J Hepatol, 2023, 79(1): 109-125. DOI: 10.1016/j.jhep.2023.02.036.

10.宁麟, 孙建光. 原发性肝癌癌前病变中西医研究进展 [J]. 世界科学技术-中医药现代化, 2021, 23(10): 3590-3598. [Ning L, Sun JG. Progress in traditional Chinese and western medicine research on precancerous lesions of primary liver cancer[J]. World Science and Technology-Modernization of Traditional Chinese Medicine, 2021, 23(10): 3590-3598.] DOI: 10.11842/wst.20210506008.

11.陈天阳, 成扬, 陈建杰. 中医药防治肝癌前病变的研究进展[J]. 广西医学, 2019, 41(24): 3189-3192. [Chen  TY, Cheng Y, Chen JJ. Research progress on traditional Chinese medicine in the prevention and treatment of precancerous lesions of liver cancer[J]. Guangxi Medical Journal, 2019, 41(24): 3189-3192.] DOI: 10.11675/j.issn.0253-4304. 2019.24.22.

12.Wang Y, Chu F, Lin J, et al. Erianin, the main active ingredient of Dendrobium chrysotoxum Lindl, inhibits precancerous lesions of gastric cancer (PLGC) through suppression of the HRAS-PI3K-AKT signaling pathway as revealed by network pharmacology and in vitro experimental verification[J]. J Ethnopharmacol, 2021, 279: 114399. DOI: 10.1016/j.jep.2021.114399.

13.李淑娣, 王振, 刘江凯, 等. 基于细胞信号通路探讨黄芪活性成分抗肝纤维化的研究进展[J]. 中国药理学通报, 2023, 39(1): 18-23. [Li SD, Wang Z, Liu JK, et al. Research progress on the anti liver fibrosis effect of active ingredients in Astragalus membranaceus based on cell signaling pathways[J]. Chinese Pharmacological Bulletin, 2023, 39(1): 18-23.] DOI: 10.13457/j.cnki.jncm.2017.10.016.

14.Zhu B, Zhang QL, Hua JW, et al. The traditional uses, phytochemistry, and pharmacology of Atractylodes macrocephala Koidz.: a review[J]. J Ethnopharmacol, 2018, 226: 143-167. DOI: 10.1016/j.jep.2018.08.023.

15.Zhang Z, Wang X, Zhang L, et al. Wnt/β-catenin signaling pathway in trophoblasts and abnormal activation in preeclampsia (review)[J]. Mol Med Rep, 2017, 16(2): 1007-1013. DOI: 10.3892/mmr.2017.6718.

16.朱云, 李成, 林鑫盛, 等. 白术多糖对肝癌细胞增殖及侵袭的抑制作用及其机制[J]. 南方医科大学学报, 2019, 39(10): 1180-1185. [Zhu Y, Li C, Lin X, et al. Effect of atractylodes macrocephala polysaccharide on proliferation and invasion of hepatocellular carcinoma cells in vitro[J]. Journal of Southern Medical University, 2019, 39(10): 1180-1185.] DOI: 10.12122/j.issn.1673-4254.2019.10.08.

17.李圣豪, 郝立园, 国英琳, 等. 丹参水溶性组分SABP对小鼠肝癌免疫微环境的影响[J].肿瘤防治研究, 2021, 48(7): 694-698. [Li SH, Hao LY, Guo  YL, et al. Effect of SABP, a water-soluble component of salvia miltiorrhiza, on immune microenvironment of mice with liver cancer[J]. Cancer Research on Prevention and Treatment, 2021, 48(7): 694-698.] DOI: 10.3971/j.issn.1000-8578.2021.20.1405.

18.赵珍, 李明花. 丹参酮ⅡA对人肝癌细胞Huh7增殖与凋亡的影响[J]. 中医肿瘤学杂志, 2020, 2(2): 33-38. [Zhao Z, Li MH. Effects of tanshinone IIA on proliferation and apoptosis of human hepatocellular carcinoma Huh7 cells[J]. Journal of Oncology in Chinese Medicine, 2020, 2(2): 33-38.] DOI: 10.19811/j.cnki.ISSN2096-6628.2020.02.013.

19.丘佩容, 邓鑫, 陈泽山, 等. 丹参抗肝癌潜在机制的研究进展[J]. 中华中医药学刊, 2023, 41(1): 103-106. [Qiu P, Deng X, Chen ZS, et al. Research progress on the potential mechanism of Salvia officinalis against hepatocellular carcinoma[J]. Chinese Archives of Traditional Chinese Medicine, 2023, 41(1): 103-106.] DOI: 10.13193/j.issn.1673-7717.2023.01.024.

20.许晶, 石凤芹, 杜可心, 等. 基于网络药理学探讨“半枝莲-白花蛇舌草”抗乳腺癌的作用机制[J]. 中国中药杂志, 2020, 45(18): 4448-4454. [Xu J, Shi FQ, Du KX, et al. Mechanism of "Scutellaria barbata-Hedyotis diffusa" against breast cancer based on network pharmacology[J]. China Journal of Chinese Materia Medica, 2020, 45(18): 4448-4454.] DOI: 10.19540/j.cnki.cjcmm.20200302.502.

21.王倩, 陈亭亭, 王守梅, 等. 半枝莲乙醇提取物对高低转移性肝细胞癌细胞生长和侵袭的影响[J]. 中医学报, 2023, 38(3): 584-594. [Wang Q, Chen TT, Wang SM, et al. Effects of Banzhilian (Scutellaria barbata) extract on growth and invasion of high and low metastatic hepatocellular carcinoma cells[J]. China Journal of Chinese Medicine, 2023, 38(3): 584-594.] DOI: 10.16368/j.issn.1674-8999. 2023.03.097.

22.Yang PW, Chen TT, Zhao WX, et al. Scutellaria barbata D.Don and Oldenlandia diffusa (Willd.) Roxb crude extracts inhibit hepatitis-B-virus-associated hepatocellular carcinoma growth through regulating circRNA expression[J]. J Ethnopharmacol, 2021, 275: 114110. DOI: 10.1016/j.jep.2021.114110.

23.杨培伟, 朱金霞, 陈欣菊, 等. 半枝莲-白花蛇舌草调控Wnt/β-catenin轴对肝癌迁移和侵袭的作用机制研究[J/OL]. 中药药理与临床, 2024-04-26. [Yang PW, Zhu JX, Chen XJ, et al. Mechanism of SCUTELLARIAE BARBATAE HERBA and Hedyotis diffusa Willd. Regulating Wnt/β-catenin Axis on Migration and Invasion of Hepatocellular Carcinoma[J/OL]. Pharmacology and Clinics of Chinese Materia Medica, 2024-04-26.] DOI: 10.13412/j.cnki.zyyl.20240424.001.

24.伍梦思, 刘华, 谭年花, 等. 鳖甲煎丸调控EGFR/MAPK/ERK通路对MHCC-97H肝癌细胞的影响[J]. 北京中医药大学学报, 2024, 47(3): 394-406. [Wu MS, Liu H, Tan NH, et al. The effect of Biejiajian Pills on regulating the EGFR/MAPK/ERK pathway in MHCC-97H liver cancer cells[J]. Journal of Beijing University of Traditional Chinese Medicine, 2024, 47(3): 394-406.] DOI: 10.3969/j.issn.1006-2157.2024.03.014.

25.孙杏倩, 蔡俊飞, 高家菊, 等. 基于网络药理学和文献探讨异喹啉类生物碱抗肝癌研究进展[J]. 粮油食品科技, 2021, 29(1): 122-130. [Sun XQ, Cai JF, Gao JJ, et al. Research progress of isoquinoline alkaloids against liver cancer based on network pharmacology and literature[J]. Science and Technology of Cereals, Oils and Foods, 2021, 29(1): 122-130.] DOI: 10.16210/j.cnki.1007-7561. 2021.01.017.

26.倪雯婷, 潘燕红, 王爱云, 等. 破血消癥中药抗肿瘤转移研究进展[J]. 中草药, 2016, 47(24): 4472-4477. [Ni WT, Pan YH, Wang AY, et al. Research progress in inhibition of Chinese materia medica with breaking blood stasis and resolving mass on tumor metastasis[J]. Chinese Traditional and Herbal Drugs, 2016, 4472-4477.] DOI: 10.7501/j.issn.0253-2670.2016.24.028.

27.张金良. 膈下逐瘀汤联合西药治疗乙型肝炎肝硬化代偿期临床观察[J]. 新中医, 2017, 49(10): 52-54. [Zhang  JL. Clinical observation of gexia zhuyu tang combined with western medicine for hepatitis B compensatory phase cirrhosis[J] Journal of New Chinese Medicine, 2017, 49(10): 52-54.] DOI: 10.13457/j.cnki.jncm.2017.10.016.

28.孟博博, 芮冉, 董夏, 等. 中医药防治肝癌癌前病变恶性转化研究进展[J]. 河北中医, 2018, 40(11): 1752-1756. [Meng BB, Rui R, Dong X, et al Research progress on the prevention and treatment of malignant transformation of precancerous lesions in liver cancer with traditional Chinese medicine[J]. Hebei Traditional Chinese Medicine, 2018, 40(11): 1752-1756.] DOI: 10.3969/j.issn.1002-2619. 2018.11.035.

29.孙童, 胡世平, 杨大国, 等. 正肝方对二乙基亚硝胺诱导的肝癌前病变模型大鼠肝组织PTEN/PI3K/AKT信号通路的影响[J]. 世界中西医结合杂志, 2023, 18(7): 1278-1284, 1314. [Sun T, Hu SP, Yang DG, et al. Zhenggan prescription regulates the PTEN/PI3K/AKT signaling pathway in the rat model of diethylnitrosamine-induced precancerous lesion of liver[J]. World Journal of Integrated Traditional and Western Medicine, 2023, 18(7): 1278-1284, 1314.] DOI: 10.13935/j.cnki.sjzx.230702.

30.薛丹, 刘永刚, 曾立伟, 等. 从肝玄府微癥结辨治肝癌癌前病变[J]. 现代中西医结合杂志, 2024, 33(3): 379-383. [Xue D, Liu YG, Zeng LW, et al Distinguishing and treating precancerous lesions of liver cancer from the micro crux of liver Xuanfu[J]. Modern Journal of Integrated Traditional Chinese and Western Medicine, 2024, 33(3): 379-383.] DOI: 10.3969/j.issn.1008 -8849.2024.03.016.

31.李冀, 李想, 高彦宇, 等. 清热解毒药对肿瘤治疗及其信号通路调节作用的研究进展[J].中国实验方剂学杂志, 2019, 25(24): 188-195. [Li J, Li X, Gao Y, et al. Effect of Qingre Jiedu medicine in treating tumor and regulating signaling pathway[J]. Chinese Journal of Experimental Traditional Medical Formulae, 2019, 188-195.] DOI: 10.13422/j.cnki.syfjx.20191727.

32.王惠茹, 梁爽, 张骞, 等. 原发性肝癌中活血化瘀类常用中药的成分及作用分析[J]. 中国医药科学, 2024, 14(8): 45-48. [Wang HR, Liang S, Zhang Q, et al. Analysis of the components and effects of commonly used Chinese herbal medicines for activating blood and resolving stasis in primary liver cancer[J]. China Medicine and Pharmacy, 2024, 14(8): 45-48.] DOI: 10.20116/j.issn2095-0616.2024.08.11.

33.蔡雪, 于莉华, 刘晓利, 等. 基于免疫微环境探讨养阴扶正解毒法治疗原发性肝癌[J]. 中西医结合肝病杂志, 2024, 34(4): 351-354. [Cai X, YLH, Liu XL, et al. Exploring the treatment of primary liver cancer with nourishing yin, strengthening the body, and detoxifying methods based on immune microenvironment[J]. Chinese Journal of Integrated Traditional and Western Medicine on Liver Diseases, 2024, 34(4): 351-354.] DOI: 10.3969/j.issn.1005-0264.2024.004.015.