1.Treatment of Colorectal Cancer with Traditional Chinese Medicine Based on Hippo Signaling Pathway: A Review
Shuo ZENG ; Suqin HU ; Yang HU ; Lei LUO ; Mingyan LI ; Qinsheng ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(8):297-305
Colorectal cancer, a leading malignant gastrointestinal tumor globally in terms of incidence and mortality, has seen a consistent annual rise in newly diagnosed cases. While conventional therapies like radiotherapy, chemotherapy, and surgery are available, problems such as lack of early diagnosis, poor prognosis, and drug resistance remain significant burdens for patients. Given the complex and diverse pathogenesis of colorectal cancer, there is an urgent clinical need for safe, effective, reliable, and multi-targeted therapeutic strategies. The Hippo signaling pathway, closely linked to mechanisms like tumorigenesis, cancer cell invasion, migration, and drug resistance, extensively participates in the occurrence and development of colorectal cancer, so targeting the signaling pathway for cancer prevention and treatment has become a crucial research direction in recent years. Traditional Chinese medicine (TCM) offers multi-faceted, multi-pathway, and multi-target advantages and becomes an important therapy for colorectal cancer by enhancing patients' immunity, improving the life quality, and prolonging survival. Studies show that the active components of TCM, including flavonoids, terpenoids, phenols, alkaloids, quinones, lignans, and saponins, as well as TCM compounds such as modified Sijunzi decoction, Jiedu Sangen decoction, Jianpi Jiedu compound, and Quyu Jiedu decoction, exhibit significant targeting effects on the Hippo signaling pathway. These TCMs can exert an anti-colorectal cancer effect through various mechanisms, such as inducing cancer cell autophagy and apoptosis, inhibiting epithelial-mesenchymal transition, reversing drug resistance of the tumor, and blocking the cancer cell cycle. This paper reviewed and analyzed Chinese and international research on the action mechanisms of TCM in regulating the Hippo signaling pathway for the prevention and treatment of colorectal cancer with a comprehensive overview presentation, aiming to provide new references and ideas for the clinical application of TCM and the development of new pharmacological agents in the prevention and treatment of colorectal cancer.
2.Treatment of Colorectal Cancer with Traditional Chinese Medicine Based on Hippo Signaling Pathway: A Review
Shuo ZENG ; Suqin HU ; Yang HU ; Lei LUO ; Mingyan LI ; Qinsheng ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(8):297-305
Colorectal cancer, a leading malignant gastrointestinal tumor globally in terms of incidence and mortality, has seen a consistent annual rise in newly diagnosed cases. While conventional therapies like radiotherapy, chemotherapy, and surgery are available, problems such as lack of early diagnosis, poor prognosis, and drug resistance remain significant burdens for patients. Given the complex and diverse pathogenesis of colorectal cancer, there is an urgent clinical need for safe, effective, reliable, and multi-targeted therapeutic strategies. The Hippo signaling pathway, closely linked to mechanisms like tumorigenesis, cancer cell invasion, migration, and drug resistance, extensively participates in the occurrence and development of colorectal cancer, so targeting the signaling pathway for cancer prevention and treatment has become a crucial research direction in recent years. Traditional Chinese medicine (TCM) offers multi-faceted, multi-pathway, and multi-target advantages and becomes an important therapy for colorectal cancer by enhancing patients' immunity, improving the life quality, and prolonging survival. Studies show that the active components of TCM, including flavonoids, terpenoids, phenols, alkaloids, quinones, lignans, and saponins, as well as TCM compounds such as modified Sijunzi decoction, Jiedu Sangen decoction, Jianpi Jiedu compound, and Quyu Jiedu decoction, exhibit significant targeting effects on the Hippo signaling pathway. These TCMs can exert an anti-colorectal cancer effect through various mechanisms, such as inducing cancer cell autophagy and apoptosis, inhibiting epithelial-mesenchymal transition, reversing drug resistance of the tumor, and blocking the cancer cell cycle. This paper reviewed and analyzed Chinese and international research on the action mechanisms of TCM in regulating the Hippo signaling pathway for the prevention and treatment of colorectal cancer with a comprehensive overview presentation, aiming to provide new references and ideas for the clinical application of TCM and the development of new pharmacological agents in the prevention and treatment of colorectal cancer.
3.Traditional Chinese Medicine Treatment of Colorectal Cancer Based on AMPK Signaling Pathway: A Review
Yang HU ; Suqin HU ; Shuo ZENG ; Lei LUO ; Mingyan LI ; Qinsheng ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(9):266-275
Colorectal cancer is a common malignant tumor of the digestive system. In recent years, its incidence rate and mortality are increasing year by year. Due to the complex pathogenesis and poor prognosis of patients, colorectal cancer poses a serious threat to human physical and mental health. Currently, although Western medicine treatment methods can to some extent inhibit tumor growth and alleviate patient symptoms, postoperative recurrence, metastasis, multiple adverse reactions, and susceptibility to drug resistance are prominent issues, resulting in unsatisfactory overall treatment outcomes. Therefore, exploring more efficient and safe treatment methods has become an urgent task. The adenosine monophosphate-activated protein kinase (AMPK) signaling pathway plays a regulatory role in the growth, differentiation, apoptosis, and autophagy of colorectal cancer cells, and is widely involved in the occurrence and development of colorectal cancer. It is considered an important target for colorectal cancer treatment. Traditional Chinese medicine has unique advantages in the treatment of colorectal cancer, as it can exert its effects through multiple mechanisms and pathways. It can prevent postoperative recurrence and metastasis, reduce adverse reactions to radiotherapy and chemotherapy, and improve patients' quality of life. It has become a key means of treating colorectal cancer. Research has shown that active ingredients in traditional Chinese medicine such as flavonoids, polyphenols, terpenes, and esters, as well as traditional Chinese medicine compounds such as Qingjie Fuzheng Granules and some traditional Chinese medicine extracts, have significant regulatory effects on AMPK and its interaction signaling pathways. They exert their anti-colorectal cancer effects by inducing autophagy and apoptosis in colorectal cancer cells, promoting ferroptosis, inhibiting epithelial-mesenchymal transition, reversing drug resistance, and arresting the cell cycle. This article reviewed and summarized the relevant research on traditional Chinese medicine in the treatment of colorectal cancer in recent years, with a focus on the mechanism of traditional Chinese medicine in regulating the AMPK signaling pathway for the treatment of colorectal cancer. It is expected to provide ideas and references for the development of new drugs for clinical anti-colorectal cancer treatment.
4.Pre-operative risk assessment of hepatocellular carcinoma recurrence in liver transplant recipients by non-invasive detection of pre-existing genetic lesions
Suqin YANG ; Sunbin LING ; Jianhua LI ; Yan WANG ; Jiapei WANG ; Qiwei HUANG ; Fanming LIU ; Yiqi ZHUANG ; Yingyu ZHENG ; Rui WANG ; Zhe YANG ; Xiaoping ZHENG ; Kai WANG ; Zhikun LIU ; Jun CHEN ; Jianguo WANG ; Haiyang XIE ; Lin ZHOU ; Leiming CHEN ; Guoqiang CAO ; Dandan CHEN ; Junfang JI ; Bin ZHAO ; Chao JIANG ; Di LU ; Xuyong WEI ; Hangjin JIANG ; Qiaonan SHAN ; Hengbo SHI ; Yong-Zhen XU ; Shusen ZHENG ; Zhengxin WANG ; Shengda LIN ; Xiao XU
Clinical and Molecular Hepatology 2026;32(2):884-903
Background/Aims:
Liver transplantation (LT) following total hepatectomy is a life-saving treatment for hepatocellular carcinoma (HCC). The HCC recurrence after LT hinders the effectiveness of the procedure. The objective of this study is to develop a pre-operative risk stratification model based on a liquid biopsy.
Methods:
We conducted a comprehensive multi-omics study of 260 HCC patients from three centers, including clinical data, low-coverage whole-genome sequencing of cell-free DNA (cfDNA) from plasma, as well as whole-exome, single-nucleus RNA, and spatial transcriptomics from matched tumor and non-tumor tissues.
Results:
We identified cfDNA-derived copy number alteration (CNA) signatures associated with post-transplant recurrence. By integrating cfDNA-derived CNA profiles with single-cell transcriptomic data, we traced recurrence-associated cfDNA to a distinct subpopulation of malignant cells within the primary tumor. These cells were embedded in a pro-metastatic microenvironment of specialized endothelial subtypes and cancer-associated fibroblasts. Notably, most recurrence-associated lesions were detectable in cfDNA prior to liver transplantation (LT). Building on these insights, we developed the ZJU Criteria based on CNA fragments and tumor markers, a pre-LT risk prediction tool that integrates conventional clinical factors with cfDNA-derived CNA signatures, and validated it using internal and independent external cohorts.
Conclusion
Our findings suggest that post-transplant recurrence commonly originates from advanced subclones that emerge late during tumor evolution. The ZJU Criteria provides an accurate, non-invasive strategy that significantly improves pre-LT risk stratification and clinical decision-making for patients with HCC.
5.Anti-liver Cancer Effect of Traditional Chinese Medicine Monomers Based on AMPK/mTOR Signaling Pathway: A Review
Yang HU ; Suqin HU ; Shuo ZENG ; Lei LUO ; Mingyan LI ; Qinsheng ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(18):260-268
Liver cancer, as a malignant tumor with high incidence and mortality worldwide, has shown a year-by-year increase in both incidence and mortality in China. Currently, Western medicine has achieved certain efficacy in the clinical management of liver cancer in terms of inhibiting tumor growth, alleviating patient symptoms, and delaying disease progression. However, its limitations cannot be ignored. Significant side effects, increasingly severe drug resistance, and limited improvement in patient survival collectively make the overall therapeutic outcomes fall short of ideal expectations. Therefore, exploring more effective and safer treatment strategies has become a critical issue that urgently needs to be addressed in the field of oncology. The adenosine monophosphate-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) signaling pathway plays a central regulatory role in the physiological processes of liver cancer cells, including proliferation, differentiation, apoptosis, and autophagy, and is considered a key molecular target for anti-liver cancer therapy. Traditional Chinese medicine (TCM), characterized by its multi-pathway and multi-mechanism synergistic effects, has become an important component of the current comprehensive treatment system for liver cancer. Among these, TCM monomeric compounds, owing to their well-defined chemical structures and precisely analyzable pharmacological mechanisms, represent an important breakthrough in anti-liver cancer drug development. Studies have shown that various TCM monomeric compounds, including flavonoids, alkaloids, polyphenols, saponins, terpenoids, and quinones, can regulate the AMPK/mTOR signaling pathway and its upstream and downstream protein expression. Through these mechanisms, they induce autophagy and apoptosis in liver cancer cells, inhibit aerobic glycolysis, reverse drug resistance, promote ferroptosis, block epithelial-mesenchymal transition, and inhibit angiogenesis, thereby effectively suppressing the growth and metastasis of liver cancer cells. Based on this, this article systematically reviews recent studies on TCM monomeric compounds in the treatment of liver cancer, and further analyzes in depth their mechanisms in regulating the AMPK/mTOR signaling pathway, so as to provide ideas and references for the development of new anti-liver cancer drugs.
6.Traditional Chinese Medicine Treatment of Liver Cancer Based on Hippo Signaling Pathway: A Review
Yang HU ; Suqin HU ; Shuo ZENG ; Lei LUO ; Mingyan LI ; Qinsheng ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(19):315-325
Liver cancer, as a malignant digestive tract tumor with high incidence and mortality rates globally, has witnessed continuous increases in both incidence and mortality in recent years. Although modern medical treatment methods have achieved certain results in disease control, the treatment of liver cancer remains challenging due to the low early diagnosis rate, obvious toxic and side effects, and widespread drug resistance. Against this backdrop, exploring more efficient and safer treatment strategies is of utmost urgency. The Hippo cascade signaling pathway plays a crucial regulatory role in processes such as the proliferation, differentiation, apoptosis, and invasion of liver cancer cells. It is extensively involved in the occurrence and development of liver cancer, serving as an important target for anti-liver cancer treatment research. Traditional Chinese medicine (TCM) can exert anti-liver cancer effects through multiple approaches, mechanisms, and pathways. It has shown remarkable efficacy in preventing postoperative recurrence and metastasis of liver cancer, reducing adverse reactions of radiotherapy and chemotherapy, and improving the quality of life, thus becoming a key component of comprehensive liver cancer treatment. Studies have confirmed that the TCM active components including flavonoids, alkaloids, terpenoids, polyphenols, saponins, and quinones, as well as the TCM compound prescriptions such as compound Banmao capsules, Erzhu Jiedu decoction, Pianzaihuang, and Zhenggan prescription, can effectively regulate the Hippo signaling pathway. They exert significant anti-liver cancer effects through multiple mechanisms, such as inducing autophagy and apoptosis of liver cancer cells, improving macrophage polarization, blocking epithelial-mesenchymal transition, inhibiting glycolytic metabolism, promoting immune cell activation, reversing tumor drug resistance, and arresting the cell cycle. This study used "liver cancer" "Hippo" "signaling pathway" and "traditional Chinese medicine" as the main keywords to search multiple literature databases, including PubMed, CNKI, and VIP. By discussing and analyzing the mechanisms of TCM in regulating the Hippo signaling pathway for the treatment of liver cancer in the past five years, this paper aims to provide ideas and references for the research and development of new anti-liver cancer drugs in clinical practice.
7.Research on the influence of CYP2A6 gene polymorphism on liver function injury in the treatment of hyperthyroidism with methimazole
Zuzhi ZHAO ; Haixia ZHAO ; Pengfei XU ; Yinghao FAN ; Peng SUN ; Suqin ZHANG ; Xinguang QIU ; Jianhua LI
Chinese Journal of Endocrine Surgery 2025;19(4):527-532
Objective:To investigate the influence of cytochrome P450 2A6 (CYP2A6) gene polymorphisms on liver function injury in patients with hyperthyroidism treated with methimazole.Methods:The study selected 90 patients with hyperthyroidism who were treated with methimazole in the Department of Thyroid Surgery at the First Affiliated Hospital of Zhengzhou University from Sept. 2023 to Aug. 2024 as the research subjects. Based on the occurrence of liver injury, they were divided into a liver injury group ( n=36) and a non-liver injury group (n=54). Peripheral blood DNA was extracted from the patients, and the CYP2A6 gene genotypes (rs8192725, rs8192720, and rs28399433) were detected using the polymerase chain reaction (PCR) amplification method. The association between CYP2A6 gene polymorphisms and liver injury induced by methimazole treatment in hyperthyroidism was analyzed. Results:The comparison of genotype distribution frequencies at the rs8192725 locus between the liver injury group and the non-liver injury group showed a statistically significant difference ( P<0.05). The AG and GG genotypes at the rs8192725 locus were protective factors against liver injury in patients with hyperthyroidism (AG vs. AA, OR: 0.21; 95% CI: 0.08-0.57; P<0.05; GG vs. AA, OR: 0.24; 95% CI: 0.06-0.89; P<0.05; AG+GG vs. AA, OR: 0.22; 95% CI: 0.09-0.54; P<0.05). The frequency of the G allele of rs8192725 in the liver injury group was significantly lower than that in the non-liver injury group (G vs. A, OR: 0.36; 95% CI: 0.19-0.70; P<0.05), indicating that it is a protective factor for liver injury in hyperthyroid patients receiving methimazole treatment. Conclusions:The CYP2A6 gene polymorphism at the rs8192725 locus is associated with the occurrence of liver injury in patients with hyperthyroidism treated with methimazole. The G allele may be a protective factor against liver injury in patients with hyperthyroidism, suggesting that individualized treatment plans can be developed based on the patient's genotype.
8.Meta-Analysis of Animal Experiments on Astragali Radix or Its Ingredients for Acute Pancreatitis
Xingxin CAO ; Aiyi LI ; Jinghan HOU ; Mingxue LI ; Yanyan LI ; Weihua JIN ; Fengmei YANG ; Suqin DUAN ; Zhanlong HE
Laboratory Animal and Comparative Medicine 2025;45(5):561-573
Objective Based on the Preferred Reporting Items for Systematic reviews and Meta-Analyses(PRISMA)guidelines,to obtain precise and reliable comprehensive effect conclusions by quantitatively combining pharmacodynamic results from animal experiments investigating Astragali Radix(single-entity Astragali Radix preparation)or its ingredients for treatment of acute pancreatitis(AP)in literature reports through meta-analysis.Methods Databases including China National Knowledge Infrastructure(CNKI),VIP Database for Chinese Technical Periodicals(VIP),Wanfang Data Knowledge Service Platform,China Biomedical Literature Database(CBMdisc),PubMed,and Web of Science(WOS)were searched from inception to March 2025 for animal studies related to Astragali Radix(single-entity Astragali Radix preparation)or its ingredients for AP treatment.Risk of bias for included studies was assessed with SYRCLE tool.Heterogeneity among studies was evaluated according to Cochrane Handbook using Cochrane's Qtest and/2statistic.Sensitivity analysis was performed using the leave-one-out method,and publication bias risk was detected using Egger's test.Results A total of 297 articles were retrieved,and after screening and evaluation,19 animal studies were finally included for meta-analysis.These 19 publications cover SD rats,as well as three breeds of mice:C57BL/6 mice,BALB/c mice,and Kunming mice.SYRCLE scores ranged from 3 to 4.The results of the sensitivity analysis showed that no study significantly affected the heterogeneity index.The results of Egger's test showed a significant publication bias with P<0.05.Cochrane's Qtest and I2statistic indicated substantial heterogeneity among studies.Meta-analysis results of 19 animal studies showed that single-entity Astragali Radix preparation(Astragali Radix injection)could reduce serum amylase(AMY)levels,an AP-specific indicator.The Astragali Radix ingredients could decrease both AMY and lipase(LPS)levels.Astragali Radix injection or its ingredients could reduce serum levels of tumor necrosis factor-α(TNF-α),interleukin(IL)-6,and IL-1 β,while increasing IL-10 levels;could increase serum levels of superoxide dismutase(SOD)and glutathione peroxidase(GSH-Px),and decrease malondialdehyde(MDA)levels.High-dose groups of Astragali Radix injection or Astragali Radix ingredients were more effective than low-dose groups in reducing AMY,TNF-α,and IL-6 levels and increasing SOD levels,but dosage effect on MDA levels was not demonstrated.Conclusion Evidence-based analysis of animal experiment results shows that in various animal models including SD rats,C57BL/6 mice,BALB/c mice,and Kunming mice,Astragali Radix injection or its ingredients can effectively reduce expression or secretion levels of AP-specific indicators(AMY and LPS).The mechanisms may be related to some inflammatory mediators,including reducing TNF-α,IL-6,and IL-1 β levels and increasing IL-10 levels;They may also intervene in oxidative/antioxidative equilibrium,such as increasing SOD and GSH-Px levels and reducing MDA levels.Except for MDA,dose-response relationships are shown for reducing AMY,TNF-α,and IL-6 levels and increasing SOD levels with Astragali Radix injection or its ingredients.However,due to high heterogeneity,potential publication bias risk,and species differences between animal models and human diseases in existing studies,further high-quality clinical trials or animal experiments are still needed in the future.
9.Coinfection with coxsackievirus A6 and B1 in a Syrian hamster animal model
Jinghan HOU ; Suqin DUAN ; Hongjie XU ; Wenting SUN ; Mingxue LI ; Yanyan LI ; Weihua JIN ; Lixiong CHEN ; Quan LIU ; Yuan ZHAO ; Fengmei YANG ; Zhanlong HE
Chinese Journal of Comparative Medicine 2025;35(1):30-40
Objective To establish an animal model of hand,foot,and mouth disease(HFMD)in Syrian hamsters coinfected with coxsackievirus A6(CVA6)and coxsackievirus B1(CVB1).Methods 42 Syrian hamsters were divided into a CVA6 infection group,CVB1 infection group,CVA6 and CVB1 coinfection group and control group.A HFMD model was established by nasal instillation of virus solution and phosphate-buffered saline.Clinical and physiological indicators and detoxification status were monitored and recorded for 15 d,and animals were selected on day 7(D7)after infection for histopathology and viral antigen and nucleic acid testing.Results Hamsters in the single-infection and coinfection groups showed clinical symptoms similar to human HFMD.White blood cell,neutrophil,and lymphocyte result were characteristic of viral infection.Both viral nucleic acids were detected in throat swabs,feces,blood,and tissues and both viruses were isolated from fecal samples.Pathological damage and positive co-localization of CVA6 and CVB1 viral antigen proteins and nucleic acids were found in brain and other tissues.Conclusions Nasal instillation of a CVA6 and CVB1 mixture can successfully coinfect Syrian hamsters,replicate herpes infection similar to human HFMD,and cause pathological viral myocarditis and encephalitis damage.The result showed that the coinfection group was more seriously affected than the single-infection group,with worse clinical symptoms,increased viral replication,and obvious tissue pathological damage.This study provides a reference for further basic and clinical research into human enterovirus coinfection.
10.Network pharmacology analysis of efficacy and mechanism of Astragalus in the treatment of viral pancreatitis
Xingxin CAO ; Suqin DUAN ; Jinghan HOU ; Junchi MA ; Aiyi LI ; Zhanlong HE
Chinese Journal of Comparative Medicine 2025;35(5):1-11
Objective To explore the efficacy and underlying mechanism of Astragalus in the treatment of viral pancreatitis using network pharmacology,with confirmation of its efficacy and mechanism in cell experiments.Methods Astragalus and viral pancreatitis targets obtained from the Traditional Chinese Medicine Systems Pharmacology(TCMSP)and GeneCards databases were combined to obtain intersection targets.GO functional enrichment and KEGG signaling pathway enrichment analyses of therapeutic targets were conducted using the Database for Annotation,Visualization,and Integrated Discovery(DAVID)database.The interactions between therapeutic targets were analyzed using the STRING database and Cytoscape 3.10.2,and the core therapeutic targets were screened.Molecular docking between the most effective therapeutic components and the core targets was performed using PyMOL 3.0 and AutoDock Tools 1.5.7.CVB3 was used to construct a viral pancreatitis cell model for verification of the core targets.Results Seventy-eight therapeutic targets were identified.Enrichment analyses revealed the possible involvement of pathways related to cancer,lipids and atherosclerosis,and PI3K-AKT signaling.AKT1,TP53,HIF1A,CASP3,IL-6,and MMP9 were identified as possible core targets.The result of cell experiments showed that the expression level of AMY was significantly increased in the model group(P<0.05).The Astragalus injection group exhibited significantly decreased expression levels of AMY,AKT1,TP53,HIF1A,CASP3,IL-6,and MMP9 compared with the model group(P<0.05).Conclusions Astragalus injection effectively treated viral pancreatitis,and its therapeutic mechanism may involve reduced expression levels of AKT1,TP53,HIF1A,CASP3,IL-6,and MMP9.

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