1.Gandouling Regulates PI3K/Akt/mTOR Autophagy Signaling Pathway via LncRNA H19 for Treatment of Wilson Disease Liver Fibrosis
Xin YIN ; Han WANG ; Daiping HUA ; Lanting SUN ; Yunyun XU ; Wenming YANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(1):131-138
ObjectiveTo investigate the potential mechanisms and pathways through which Gandouling (GDL) exerts its effects in the treatment of liver fibrosis in Wilson disease. MethodsSixty male SD rats were randomly divided into six groups: the normal group, the model group, the GDL low-, medium-, and high-dose groups (0.24, 0.48, 0.96 g·kg-1), and the penicillamine group (90 mg·kg-1), with 10 rats in each group. A copper-loaded Wilson disease rat model was established by gavage administration of 300 mg·kg-1 copper sulfate pentahydrate to all groups except the normal group. Hematoxylin-eosin (HE) staining and Masson staining were used to observe the pathomorphological changes in the liver. Enzyme-linked immunosorbent assay (ELISA) was employed to measure the levels of hyaluronic acid (HA), laminin (LN), procollagen type-Ⅲ peptide (PC-Ⅲ), and collagen type-Ⅳ (C-Ⅳ). Transmission electron microscopy was used to examine the ultrastructure of liver tissues. Real-time quantitative polymerase chain reaction (Real-time PCR) was used to detect the expression levels of liver tissues and serum exosomal long noncoding RNA H19 (LncRNA H19), phosphatidylinositol 3-kinase (PI3K), protein kinase B (Akt), and mammalian target of rapamycin (mTOR). Western blot analysis was performed to assess the expression levels of PI3K, Akt, mTOR, and their phosphorylated forms, as well as autophagy-related proteins Beclin1 and microtubule-associated protein 1 light chain 3B (LC3-Ⅱ/LC3-Ⅰ) in liver tissues. Beclin1 and LC3-Ⅱ fluorescence signal intensity was observed by immunofluorescence. ResultsCompared with the normal group, the model group exhibited inflammatory cell infiltration in hepatocytes, unclear nuclear boundaries with cell cleavage and necrosis, and collagen fiber deposition around confluent areas. The levels of HA, LN, PC-Ⅲ, and C-Ⅳ were significantly elevated (P<0.01). Transmission electron microscopy revealed an increased number of autophagic vesicles, with autophagic lysosomes exhibiting a single-layer membrane structure following degradation of most envelopes. Expression levels of Beclin1 and LC3-Ⅱ/LC3-Ⅰ were significantly increased (P<0.01), and fluorescence signals of Beclin1 and LC3-Ⅱ were markedly enhanced. The protein expression levels of PI3K, Akt, mTOR, p-PI3K, p-Akt, and p-mTOR were reduced (P<0.01), while LncRNA H19 expression was increased (P<0.01), and mRNA expression levels of PI3K, Akt, and mTOR were decreased (P<0.01). After treatment with GDL, the degree of liver fibrosis was significantly improved, with decreased levels of HA, LN, PC-Ⅲ, and C-Ⅳ. The number of autophagic vesicles was significantly reduced, and expression levels of Beclin1 and LC3-Ⅱ/LC3-Ⅰ proteins were lower (P<0.01). The fluorescence signals of Beclin1 and LC3-Ⅱ weakened dose-dependently. The protein levels of PI3K, Akt, mTOR, p-PI3K, p-Akt, and p-mTOR were elevated (P<0.01), while the expression level of LncRNA H19 was reduced (P<0.01). Furthermore, the mRNA expression levels of PI3K, Akt, and mTOR increased (P<0.05, P<0.01). ConclusionGDL may alleviate liver fibrosis and reduce liver injury by regulating the PI3K/Akt/mTOR autophagy signaling pathway via LncRNA H19.
2.Anti-tumor Mechanism of Traditional Chinese Medicine with Effect of Softening Hardness and Dissipating Mass: A Review
Yue HU ; Linfeng WANG ; Yue LI ; Rui LIU ; Baojin HUA
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(1):276-286
The global burden of malignant tumors keeps increasing, and the increased morbidity and mortality make malignant tumors one of the major challenges to global health. Currently, malignant tumors are mainly managed by surgical resection, radiotherapy, chemotherapy, targeted therapy, and immunotherapy, which, however, usually cause serious adverse reactions, such as tissue damage, immune function inhibition, and multidrug resistance, affecting the prognosis and quality of life of the patients. Traditional Chinese medicine with low toxic and side effects and multi-target, multi-system, and multi-pathway therapeutic effects has shown positive therapeutic potential in cancer treatment. In particular, the traditional Chinese medicine with the effects of softening hardness and dissipating mass, which contains a variety of active ingredients, have shown strong inhibitory effects on tumor cells. Such medicine can not only directly attack tumor cells and inhibit their proliferation and invasion but also exert therapeutic effects by inducing apoptosis, blocking tumor-related signaling pathways, and inhibiting tumor angiogenesis. In addition, traditional Chinese medicine can improve the overall efficacy of cancer treatment by regulating the immune status of the body and reversing the drug resistance of tumor cells. Traditional Chinese medicine can exert the anti-tumor effect by regulating intracellular signaling pathways, which is one of the research hotspots in this field. Signaling pathways such as signal transducer and activator of transcription 3 (STAT3), phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR), and mitogen-activated protein kinase (MAPK) play a key role in the formation and development of tumors. Traditional Chinese medicine can regulate the growth, apoptosis, and metabolic process of tumor cells by affecting the activity of these signaling pathways, thus exerting the therapeutic effects on tumors. Based on these mechanisms, a large number of experimental studies and clinical trials have proved that traditional Chinese medicine has broad prospects in anti-tumor treatment. To further verify these research results and provide a basis for the clinical application of traditional Chinese medicine and the development of new drugs, a systematic review and integrated analysis of the research reports on the anti-tumor effect of traditional Chinese medicine was carried out to summarize the anti-tumor mechanisms of traditional Chinese medicine. This review is expected to promote the wide application of traditional Chinese medicine in anti-tumor treatment worldwide and bring more hope and possibility to cancer patients.
3.Application of machine learning in the diagnosis and treatment of chronic hepatitis C
Hua HAN ; Zhongping DUAN ; Yang WANG
Journal of Clinical Hepatology 2025;41(1):141-144
With the development of artificial intelligence, machine learning has shown great potential in the field of medical health. Machine learning conducts a comprehensive analysis of patient data including clinical features, blood tests, and imaging examinations and establishes corresponding mathematical models to achieve the diagnosis and treatment of diseases and the prediction of disease conditions, thereby guiding disease management. With reference to the latest research findings, this article reviews the application of machine learning in chronic hepatitis C and related research advances.
4.Modified Ditan Tang Regulates Biorhythm-related Genes in Rat Model of Non-alcoholic Fatty Liver Disease
Zhiwen PANG ; Yu LIU ; Nan SONG ; Jie WANG ; Jingxuan ZHU ; Zhen HUA ; Yupeng PEI ; Qun WANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(6):115-124
ObjectiveTo investigate the effects of modified Ditan tang on genes related to the transcription-translation feedback loop (TTFL) of biorhythm in the rat model of non-alcoholic fatty liver disease (NAFLD) and its mechanism for prevention and treatment of NAFLD. MethodsSixty-five healthy SPF male SD rats were randomly assigned into blank (n=20), model (n=15), and low-, medium-, and high-dose (2.68, 5.36, and 10.72 g·kg-1·d-1, respectively) modified Ditan tang (n=10) groups. Other groups except the blank group were fed a high-fat diet for 12 weeks. The modified Ditan tang groups were treated with the decoction at corresponding doses by gavage, and the blank and model groups were treated with an equal volume of normal saline from the 9th week for 4 weeks. The levels of triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) in the serum were measured by an automatic biochemical analyzer. TG and non-esterified fatty acid (NEFA) assay kits were used to measure the levels of TG and NEFA in the liver. The pathological changes in the hypothalamus and liver were observed by hematoxylin-eosin staining, and the lipid deposition in the liver was observed by oil red O staining. The levels of brain-muscle ARNT-like protein 1 (BMAL1/ARNTL) in the hypothalamus and liver were determined by immunohistochemical staining. The mRNA and protein levels of BMAL1, circadian locomotor output cycles kaput (CLOCK), period circadian clock 2 (PER2), and cryptochrome1 (Cry1) in the hypothalamus and liver were determined by Real-time PCR and Western blot, respectively. ResultsCompared with the blank group, the model group showed elevated levels of TG, TC, LDL-C, AST, and ALT (P<0.01) and a lowered level of HDL-C (P<0.05) in the serum, elevated levels of TG and NEFA in the liver (P<0.01), pyknosis and deep staining of hypothalamic neuron cells, and a large number of vacuoles in the brain area. In addition, the model group showed lipid deposition in the liver, up-regulated mRNA and protein levels of CLOCK and BMAL1 (P<0.01), and down-regulated mRNA and protein levels of Cry1 and PER2 (P<0.01) in the hypothalamus and liver. Compared with the model group, all the three modified Ditan tang groups showed lowered levels of TG, TC, LDL-C, ALT, and AST (P<0.05, P<0.01) and an elevated level of HDL-C (P<0.05) in the serum, and lowered levels of TG and NEFA (P<0.05, P<0.01) in the liver. Furthermore, the three groups showed alleviated pyknosis and deep staining of hypothalamic neuron cells, reduced lipid deposition in the liver, down-regulated mRNA and protein levels of CLOCK and BMAL1 (P<0.05, P<0.01), and up-regulated mRNA and protein levels of Cry1 and PER2 (P<0.05, P<0.01) in the hypothalamus and liver. ConclusionModified Ditan tang can reduce lipid deposition in the liver and regulate the expression of CLOCK, BMAL1, Cry1, and PER2 in the TTFL of NAFLD rats.
5.Study on the effect of berberine combined with fluconazole on fluconazole-tolerant Candida albcians strains
Zecheng SONG ; Shanshan MA ; Qiaoling HU ; Hua ZHONG ; Yan WANG
Journal of Pharmaceutical Practice and Service 2025;43(2):87-91
Objective To investigate the combined effect of berberine (BBR) and fluconazole (FLC) on FLC-tolerant Candida albicans in vitro. Methods The sensitivity of 8 strains of Candida albicans to FLC was assessed by determining their minimal inhibitory concentration (MIC) using broth microdilution method. FLC-tolerant strains were screened from FLC-sensitive strains by disk diffusion assay. The effect of BBR combined with FLC on FLC-tolerant Candida albicans was investigated by disk diffusion assay. Results All eight strains of Candida albicans exhibited sensitivity to FLC, with minimal inhibitory concentration (MIC50) values below 0.5 μg/ml. Strains Y0109, 9821, 7879, 7654, and 9296 displayed colony growth in the inhibition zone after 48 h of constant temperature incubation, indicating FLC tolerance. When strains Y0109 and 9821 were subjected to a combination of BBR and FLC, the number of colonies within the inhibition zone decreased progressively with the increase of BBR concentration following a 48 h constant temperature culture. The inhibition zone became clear with the increasing of BBR concentration and increased with the increase of FLC loading, which showed a dose-dependent relationship. Conclusion The BBR combined with FLC demonstrated efficacy against FLC-tolerant strains.
6.Advances in the application of digital technology in orthodontic monitoring
WANG Qi ; LUO Ting ; LU Wei ; ZHAO Tingting ; HE Hong ; HUA Fang
Journal of Prevention and Treatment for Stomatological Diseases 2025;33(1):75-81
During orthodontic treatment, clinical monitoring of patients is a crucial factor in determining treatment success. It aids in timely problem detection and resolution, ensuring adherence to the intended treatment plan. In recent years, digital technology has increasingly permeated orthodontic clinical diagnosis and treatment, facilitating clinical decision-making, treatment planning, and follow-up monitoring. This review summarizes recent advancements in digital technology for monitoring orthodontic tooth movement, related complications, and appliance-wearing compliance. It aims to provide insights for researchers and clinicians to enhance the application of digital technology in orthodontics, improve treatment outcomes, and optimize patient experience. The digitization of diagnostic data and the visualization of dental models make chair-side follow-up monitoring more convenient, accurate, and efficient. At the same time, the emergence of remote monitoring technology allows orthodontists to promptly identify oral health issues in patients and take corresponding measures. Furthermore, the multimodal data fusion method offers valuable insights into the monitoring of the root-alveolar relationship. Artificial intelligence technology has made initial strides in automating the identification of orthodontic tooth movement, associated complications, and patient compliance evaluation. Sensors are effective tools for monitoring patient adherence and providing data-driven support for clinical decision-making. The application of digital technology in orthodontic monitoring holds great promise. However, challenges like technical bottlenecks, ethical considerations, and patient acceptance remain.
7.Regulation of Tumor Immune Homeostasis by Programmed Cell Death and Intervention Effect of Traditional Chinese Medicine Under Theory of Regulating Qi and Resolving Toxins
Bingwei YANG ; Xue CHEN ; Chenglei WANG ; Haoyu ZHAI ; Weidong LI ; Baojin HUA
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(7):212-220
Tumor immune homeostasis is a dynamic equilibrium state in which the body removes abnormal mutated cells in time to prevent tumor development without damaging other normal cells under the surveillance of the immune system. It is an important concept to understand the process of tumor development. Programmed cell death (PCD) is a kind of regulable cell death including various forms such as apoptosis, autophagy, pyroptosis, necrosis, and ferroptosis. It is regarded as an important way for the body to remove abnormal or mutated cells. In recent years, modern research has found that PCD has a bi-directional regulatory effect on carcinogenesis and tumor development. In the early stage of tumor formation, PCD can control tumor development in time by playing a specific immune clearance role, while in the later tumorigenic stage, PCD can promote the growth and development of tumor cells by forming a tumor-specific microenvironment, resulting in carcinogenic effects. Therefore, PCD is regarded as an important way to maintain tumor immune homeostasis. Based on the idea of ''supporting the vital Qi and cultivating the root'' by professors Yu Guiqing and Piao Bingkui, the team proposed the theory of ''regulating Qi and resolving toxins'' and applied it to clinical tumor prevention and treatment. Based on the theory of ''regulating Qi and resolving toxins'', the research summarized the current progress of modern medical research on mechanisms related to PCD to explore the role of PCD in the regulation of tumor immune homeostasis. The article believed that the harmonious state of Qi movement was the basic condition for normal PCD to maintain tumor immune homeostasis, while the disorder of Qi movement and the evolution of tumor toxicity were the core processes of abnormal PCD and disorder of tumor immunity homeostasis, which led to the escape and development of tumor cells. Therefore, under the guidance of ''regulating Qi and removing toxins'', the idea of full-cycle prevention and treatment of tumors was proposed summarily. In the early stage of tumor formation, the method of ''regulating Qi movement and strengthening vital Qi'' was applied to reestablish tumor immune homeostasis and to promote the elimination of abnormal cells. In the late tumorigenic stage, the method of ''resolving toxins and dispelling evils'' was applied to reverse the specific microenvironment of tumors and inhibit the development of tumor cells, with a view to providing new theoretical support for the prevention and treatment of tumors through traditional Chinese medicine.
8.Regulation of Tumor Immune Homeostasis by Programmed Cell Death and Intervention Effect of Traditional Chinese Medicine Under Theory of Regulating Qi and Resolving Toxins
Bingwei YANG ; Xue CHEN ; Chenglei WANG ; Haoyu ZHAI ; Weidong LI ; Baojin HUA
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(7):212-220
Tumor immune homeostasis is a dynamic equilibrium state in which the body removes abnormal mutated cells in time to prevent tumor development without damaging other normal cells under the surveillance of the immune system. It is an important concept to understand the process of tumor development. Programmed cell death (PCD) is a kind of regulable cell death including various forms such as apoptosis, autophagy, pyroptosis, necrosis, and ferroptosis. It is regarded as an important way for the body to remove abnormal or mutated cells. In recent years, modern research has found that PCD has a bi-directional regulatory effect on carcinogenesis and tumor development. In the early stage of tumor formation, PCD can control tumor development in time by playing a specific immune clearance role, while in the later tumorigenic stage, PCD can promote the growth and development of tumor cells by forming a tumor-specific microenvironment, resulting in carcinogenic effects. Therefore, PCD is regarded as an important way to maintain tumor immune homeostasis. Based on the idea of ''supporting the vital Qi and cultivating the root'' by professors Yu Guiqing and Piao Bingkui, the team proposed the theory of ''regulating Qi and resolving toxins'' and applied it to clinical tumor prevention and treatment. Based on the theory of ''regulating Qi and resolving toxins'', the research summarized the current progress of modern medical research on mechanisms related to PCD to explore the role of PCD in the regulation of tumor immune homeostasis. The article believed that the harmonious state of Qi movement was the basic condition for normal PCD to maintain tumor immune homeostasis, while the disorder of Qi movement and the evolution of tumor toxicity were the core processes of abnormal PCD and disorder of tumor immunity homeostasis, which led to the escape and development of tumor cells. Therefore, under the guidance of ''regulating Qi and removing toxins'', the idea of full-cycle prevention and treatment of tumors was proposed summarily. In the early stage of tumor formation, the method of ''regulating Qi movement and strengthening vital Qi'' was applied to reestablish tumor immune homeostasis and to promote the elimination of abnormal cells. In the late tumorigenic stage, the method of ''resolving toxins and dispelling evils'' was applied to reverse the specific microenvironment of tumors and inhibit the development of tumor cells, with a view to providing new theoretical support for the prevention and treatment of tumors through traditional Chinese medicine.
9.Research advances in traditional Chinese medicine for the treatment of hepatocellular carcinoma by regulating immune cells
Lijuan LONG ; Zongyu WANG ; Yali ZHAO ; Chuanfu QIN ; Hua QIU
Journal of Clinical Hepatology 2025;41(2):349-358
Hepatocellular carcinoma (HCC) is a common malignant tumor with a high mortality rate, an insidious onset, and complex pathological mechanisms. In the tumor microenvironment, tumor-promoting immune cells protect tumor cells from immune attacks, while dysfunction of anti-tumor immune cells causes the inhibition of immune response, thereby leading to the continuous deterioration of cancer. In recent years, traditional Chinese medicine has shown good efficacy in the treatment of HCC, and it can inhibit the proliferation and metastasis of cancer cells by regulating immune cells. By analyzing related articles in China and globally, this article summarizes how immune cells affect the progression of HCC through the immunosuppressive pathway and how traditional Chinese medicine exerts an anti-HCC effect by regulating immune cells, in order to provide theoretical basis and reference for optimizing the treatment of HCC.
10.Pathogenesis and Treatment Strategies of Tumor Angiogenesis Based on the Theory "Latent Wind in Collaterals"
Zhenqing PU ; Guibin WANG ; Chenyang ZHANG ; Yi LI ; Bo PANG ; Baojin HUA
Journal of Traditional Chinese Medicine 2025;66(2):139-144
This article combined the pathogenic characteristics of "latent wind" with the theory of collateral diseases to clarify the pathological features of tumor blood vessels, including their active proliferation, high permeabi-lity, and promotion of metastasis. The theory framework of "latent wind in collaterals" as the tumor mechanism was proposed, which suggests that at the site of tumor lesions, the collaterals inherit the nature of latent wind to grow excessively, adopt an open and discharge nature to leak essence, and tumor toxins, characterized by their rapid movement and frequent changes, spread and metastasize, driving the progression of malignant tumors. Focusing on the fundamental pathogenesis of "latent wind in collaterals", specific clinical treatment principles and methods centered on treating wind are proposed, including regulating qi and dispelling wind, clearing heat and extinguishing wind, unblocking collaterals and expelling wind, and reinforcing healthy qi to calm wind, so as to provide references for enhancing the precision of traditional Chinese medicine in treating malignant tumors.


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