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.Mechanism of Jinshui Huanxian Component Formula Ⅱ Combined with Matrix Softening in Ameliorating Pulmonary Fibrosis Through Inhibition of Epithelial-mesenchymal Transition
Xiaojie WU ; Mingyan LI ; Shiyu KUANG ; Xiling PENG ; Xiaorong HOU ; Han LIU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(18):108-121
ObjectiveTo determine whether Jinshui Huanxian component formula Ⅱ (ECC-JHF Ⅱ) and matrix hardness interfere with the process of epithelial-mesenchymal transition (EMT) during pulmonary fibrosis by regulating integrin β1 (ITG β1), and to elucidate the underlying mechanism. MethodsA pulmonary fibrosis mouse model was established by a single intratracheal instillation of bleomycin (BLM). To observe the disease progression at various time points, the mice were sacrificed before modeling and on days 7, 14, 21, 28 and 42 after modeling for assessment of relevant indicators. To evaluate the therapeutic effect of drug intervention, the mice were given ECC-JHF Ⅱ and pirfenidone (PFD) by gavage starting on day 29 after modeling for 14 days of treatment, after which the mice were sacrificed. Pulmonary function, pathological changes, collagen deposition, lung tissue hardness and EMT markers were detected. Polyethylene glycol (PEG) composite hydrogels with different hardness were prepared in vitro using biomaterials such as eight-arm polyethylene glycol thiol (PEG-SH) and eight-arm polyethylene glycol maleimide (PEG-MAL). Human type Ⅱ alveolar epithelial cells cultured in hard matrix culture dishes were treated with low, medium, and high doses of ECC-JHF Ⅱ (15.31, 30.63, 61.25 mg·L-1) to observe the intervention effect of ECC-JHF Ⅱ on EMT induced by transforming growth factor beta 1 (TGF-β1). Human type Ⅱ alveolar epithelial cells cultured on soft (3.8 kPa) and hard (culture dishes, ~ GPa) matrices were treated with ECC-JHF Ⅱ, respectively. The mRNA and fluorescence expression levels of the epithelial marker E-cadherin (CDH1), the mesenchymal marker N-cadherin (CDH2) and vimentin (VIM), as well as ITG β1, were detected by real-time quantitative polymerase chain reaction (Real-time PCR) and immunofluorescence. Western blot was used to detect the protein expression of CDH1, CDH2 and ITG β1, and the biomechanical mechanism of ECC-JHF Ⅱ on EMT and pulmonary fibrosis was further verified by knocking down and specific activation of ITG β1. ResultsECC-JHF Ⅱ treatment improved BLM-induced pulmonary fibrosis in mice, as evidenced by significantly increased minute ventilation (MV) and 50% expiratory flow at tidal volume (EF50) (P<0.05), and significantly increased tidal volume (TV) after treatment (P<0.01) compared with the model group. Immunohistopathological analysis revealed attenuated inflammation and alveolar injury, reduced deposition of type Ⅰ collagen (Col-Ⅰ), and significantly decreased lung tissue stiffness (P<0.01), thereby alleviating disease progression. The real-time PCR results showed that, compared with the model group, the ECC-JHF Ⅱ group showed increased CDH1 expression and decreased CDH2 and VIM expression in mouse lung tissues (P<0.05, P<0.01), indicating that ECC-JHF Ⅱ inhibited the EMT process to ameliorate pulmonary fibrosis. In vitro experimental results showed that both ECC-JHF Ⅱ and matrix softening reversed the EMT phenotype switch. Specifically, compared with the hard matrix group, the cells cultured on the soft matrix exhibited significantly upregulated expression of the epithelial marker CDH1 (P<0.01) and significantly downregulated expression of the mesenchymal markers CDH2 and VIM (P<0.05). Furthermore, ECC-JHF Ⅱ inhibited the expression of ITG β1 both in vitro and in vivo. Knockdown and specific activation of ITG β1 further confirmed that ITG β1 is involved in the regulatory process by which ECC-JHF Ⅱ inhibits EMT and ameliorates pulmonary fibrosis
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 progress on the mechanism of atherosclerosis caused by triglyceride-rich lipoprotein and its residues
Meiyi LIU ; Mingyan SHAO ; Yuanyuan GUAN ; Fangli LI ; Lingru LI
Chinese Journal of Arteriosclerosis 2025;33(4):355-362
Triglyceride(TG)is transported in the blood as specific triglyceride-rich lipoprotein(TRL).When TRL is overproduced or the catabolism is not timely,cholesterol ester-rich residues is formed.Both TRL and its residues contribute to the development of atherosclerosis(As)through various direct and indirect mechanisms.Currently,the combination of lifestyle interventions and Western medicines is considered the preferred treatment strategy for As.Howev-er,lipid-lowering therapy alone cannot fully eliminate the residual risk of As.In contrast,traditional Chinese medicine emphasizes the holistic regulation of bodily functions to prevent and treat As.This paper will begin by examining the met-abolic mechanisms of TRL,elucidate the role of TRL and its residues in the risk of As occurrence,and summarize current strategies targeting the TRL metabolic pathway to reduce the incidence of As.
8.A clinical research of endoscopic submucosal dissection for ileocecal valve lipoma
Shaobin LUO ; Li WANG ; Keyang FAN ; Zuqiang LIU ; Hao HU ; Wenzheng QIN ; Zhen ZHANG ; Mingyan CAI ; Jianwei HU ; Lili MA ; Yiqun ZHANG ; Yunshi ZHONG ; Quanlin LI ; Pinghong ZHOU
Chinese Journal of Digestive Endoscopy 2025;42(6):469-473
Objective:To evaluate the efficacy and safety of endoscopic submucosal dissection (ESD) for the treatment of ileocecal valve lipoma.Methods:A retrospective cohort study was performed on data of ileocecal lipoma patients who underwent ESD at the Endoscopy Center of Zhongshan Hospital, Fudan University from December 2013 to June 2023. According to the lesion location, the patients were divided into ileocecal valve group and cecum group. The operation time, operation speed, en bloc resection rate, complications, and follow-up outcomes between the two groups were compared.Results:A total of 59 patients with ileocecal lipoma were enrolled, including 31 patients in the ileocecal valve group and 28 patients in the cecum group.There were no significant differences in gender, age, specimen size, or lesion size between the two groups ( P>0.05). Lipomas in both the ileocecal valve group and the cecum group were successfully resected by ESD. The en bloc resection rates were 100.0% (31/31) and 92.9% (26/28) respectively, and the difference was not statistically significant ( χ2=0.033, P=0.133). Median operative duration significantly differed between the two groups ( ileocecal valve group 26 min VS cecum group 20 min, Z=-0.136, P=0.027), as did resection speed (ileocecal valve group 0.14 cm2/min VS cecum group 0.24 cm2/min, Z=-0.223, P=0.022). Adverse events included one postoperative fever in the ileocecal valve group and one delayed bleeding in the cecum group. During the median follow-up of 38 months (7-106 months), there was no case of residual tumor or recurrence. Conclusion:Despite technical challenges in ESD of ileocecal valve lipoma, it is still a safe, feasible and effective treatment method.
9.Effect of Qingfei-Jiedu-Huatan Formula on severe pneumonia in rats via mTOR-regulated alveolar macrophage autophagy
Mingyan JIA ; Yingjin LIANG ; Kang ZHANG ; Ya LI ; Wenshuai JI ; Chen DU ; Xinxin KONG ; Kai XIE ; Pengzhen JING ; Haifeng WANG
Chinese Journal of Pathophysiology 2025;41(7):1383-1391
AIM:This study aims to investigate the mechanism by which Qingfei-Jiedu-Huatan Formula(QJHF)regulates autophagy in alveolar macrophages through mTOR in the treatment of severe pneumonia(SP)in rats.METHODS:Sixty SPF-grade male rats were randomly assigned to six groups:control,model,QJHF,moxifloxacin(MOX),rapamycin(RAPA),and QJHF+RAPA,with ten rats in each group.An SP rat model was established using Klebsiella pneumoniae.After seven days of treatment,changes in IL-33 and IFN-γ levels in bronchoalveolar lavage fluid(BALF)were measured using ELISA.Histopathological alterations in lung tissue were assessed via HE staining,and the autophagy of alveolar macrophages was detected using immunofluorescence co-localization methods.The expression levels of mTOR,beclin-1,and LC3 mRNA in lung tissue were analyzed using qPCR,while Western blot was employed to assess the protein levels of p-mTOR/mTOR,beclin-1,and LC3-II/LC3-I.RESULTS:Compared to the control group,the model group exhibited a deteriorated condition,characterized by alveolar wall rupture and thickening,significant inflammatory cell infiltration in the alveolar cavity,and extensive lung tissue damage(P<0.01).Elevated levels of IL-33 and IFN-γ in BALF were also observed(P<0.01),along with increased colocalization of CD68 and LC3 in immunofluorescence analy-sis.The mTOR mRNA expression in lung tissue decreased(P<0.01),while LC3 and beclin-1 mRNA expressions in-creased(P<0.01).Additionally,the protein expression ratio of p-mTOR/mTOR decreased(P<0.01),whereas LC3-II/LC3-I and beclin-1 protein levels increased(P<0.01).In comparison to the model group,significant improvements were noted after treatment with QJHF and MOX(P<0.01),while RAPA treatment led to a worsening of these indicators(P<0.05).A slight improvement was observed with the QJHF combined with RAPA intervention,though this was not statisti-cally significant.No significant differences were found between the MOX and QJHF groups.However,the QJHF+RAPA group displayed notable improvements in various indicators compared to the RAPA group(P<0.05).CONCLUSION:The QJHF can mitigate the inflammatory response associated with severe pneumonia,potentially by activating mTOR phos-phorylation activity,which in turn inhibits excessive autophagy in alveolar macrophages.
10.Endoscopic submucosal dissection of gastrointestinal polyps with a novel plasma radio frequency generator and a disposable mucosal incision knife: A prospective, multicenter, non-inferiority, randomized, controlled clinical trial
Baohui SONG ; Guijun SHI ; Xiaoyue XU ; Jiaxin XU ; Li FENG ; Jianguang XU ; Pinghong ZHOU ; Mingyan CAI
Chinese Journal of Gastrointestinal Surgery 2025;28(4):384-391
Objective:To evaluate the efficacy and safety of a new plasma radiofrequency generator and a disposable mucosal incision knife for endoscopic submucosal dissection (ESD) of gastrointestinal lesions.Methods:This study is a prospective, randomized, non-inferiority multicenter study (Chinese Clinical Trial Registry No.: ChiCTR2000041394). The inclusion criteria for cases are as follows: (1) being able to understand and voluntarily participate in this clinical trial, and voluntarily signing the informed consent form; (2) being 18-70 years old, regardless of gender; (3) having a gastrointestinal lesion and meeting the endoscopic treatment conditions for the indications of endoscopic submucosal dissection (ESD). The exclusion criteria are: (1) meeting the contraindications for ESD; (2) having a surgical contraindication due to coagulation dysfunction or still taking anticoagulants 1 week before surgery; (3) having coagulation dysfunction, that is, the prothrombin time is prolonged by more than 3 seconds (more than 5 seconds in patients with liver disease), or the activated partial thromboplastin time is prolonged by more than 10 seconds, and the platelet count is < 70×10?/L; (4) having severe cardiopulmonary insufficiency and being unable to tolerate the surgery; (5) being a reproductive-aged woman with a positive blood or urine pregnancy test or a lactating woman; (6) the investigator deems that there are other factors that are not suitable for inclusion or affect the subject's participation. Patients who underwent ESD treatment for gastrointestinal lesions from March 2019 to April 2023 at the Endoscopy Center of Zhongshan Hospital Affiliated to Fudan University, the Department of Gastroenterology of Minhang District Central Hospital in Shanghai, and the Department of Gastroenterology of Quzhou People's Hospital were prospectively included. The experimental group used a new plasma radiofrequency therapy instrument and a disposable mucosal incision knife, while the control group used a high-frequency electrosurgical system and a disposable mucosal incision knife. The primary efficacy indicator was the en bloc resection success rate, the secondary efficacy indicators included the coagulation success rate, and the operation stability of the plasma radiofrequency therapy instrument and the disposable mucosal incision knife; the safety indicators included the incidence of intraoperative bleeding, intraoperative perforation, and postoperative complications. Results:The study cohort comprised 194 patients, 95 in the experimental group and 99 in the control group. Analysis of the full set showed rates of en bloc resection of 97.89% (93/95) and 96.97% (96/99) in the experimental and control groups, respectively; the difference being 0.53% (-5.58%, 6.64%). Analysis of the compliance set showed rates of en bloc resection of 97.83% (90/92) and 96.88% (93/96) in the experimental and control groups, respectively; the difference being 0.58% (-5.79%, 6.94%). These data indicate that the rate of en bloc resection in the experimental group using plasma radiofrequency therapy and disposable mucosal incision was not inferior to that of the control group. The rates of achieving intraoperative coagulation in the experimental and control groups were 7.14% (5/70) and 5.97% (4/67), respectively; this difference is not statistically significant ( P=1.000). The control group had a significantly better rate of using the same instruments throughout the procedure than did the experimental group ( P<0.001). In the safety analysis set, the incidences of intraoperative and postoperative adverse events did not differ significantly between the two groups (both P>0.05). Conclusion:Plasma radiofrequency therapy equipment and a disposable mucosal incision knife are safe and effective instruments for performing ESD of gastrointestinal lesions.

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