1.Discussion on Construction of a Multi-Agent "Cross-scale" Collective Decision-making Model for Superior Disease Entities in Sichuan-style Traditional Chinese Medicine
Qiuping CHEN ; Hang ZHOU ; Dan ZHENG ; Baixue LI ; Chenhao LIU ; Ju CHEN ; Jibin LIU ; Quansheng FENG ; JIANGYUMING ; Cen JIANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(14):1-13
At present, the systematic excavation of the clinical experience and academic thought of the Sichuan school of Chinese medicine vis-à-vis its dominant disease entities remains fragmentary, and replicable paradigms are scarce. Confronted with empirical fragmentation, data heterogeneity and decision-making subjectivity, the standardised distillation, inheritance and clinical translation of these distinctive experiences has become a critical bottleneck constraining the development of the Sichuan school. The integration of artificial-intelligence technologies in data processing, pattern recognition and intelligent decision-making has rendered deep mining of traditional Chinese medicine(TCM) clinical knowledge and patterns imperative. Constructing an intelligent modern TCM diagnostic-therapeutic-evaluative system is now the obligatory route for inheritance and innovation in Chinese medicine, and simultaneously provides a technological breakthrough for intelligent decision paradigms in the dominant diseases of the Sichuan school. Accordingly, this study adopts the regional academic school as its point of entry, focuses on the dominant diseases of the Sichuan school, and proposes an innovative pathway of "four-dimensional data-multi-modal fusion-multi-agent decision-making". Specifically, four data dimensions are defined and instantiated: (Ⅰ) knowledge from classical medical literature and historical case records. (Ⅱ) objective four-diagnosis phenotypic data. (Ⅲ) master physicians' prescribing regularities. (Ⅳ) characteristic mechanisms of renowned formulae. Leveraging multi-modal data fusion and generative artificial intelligence, the entire causal chain of Famous Physicians and Renowned Formulas is explicated to reconstruct the diagnostic-therapeutic cognitive logic of the regional school. Finally, a multi-agent collective-decision model is established and refined for the dominant diseases of the Sichuan school, capable of generating precise, individualised treatment regimens and thereby advancing an intelligent diagnostic-therapeutic paradigm that delivers more efficient and accurate clinical decision support.
2.Wisdom Inheritance of Distinguished Physicians' Experience Through Integration of Multimodal Data and AIGC: A Case Study on Experience in Diagnosis and Treatment of Lung Cancer with Phlegm-dampness and Blood Stasis Syndrome by Distinguished Traditional Chinese Medicine Physicians of Sichuan School
Yang YU ; Yadong MU ; Wenping LIU ; Chongcheng XI ; Li ZHANG ; Yan GAO ; Cen JIANG ; Quansheng FENG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(14):14-25
Lung cancer, with persistently high incidence and mortality rates, remains a significant global health challenge. By taking the study on the experience in diagnosis and treatment of lung cancer with phlegm-dampness and blood stasis syndrome by distinguished traditional Chinese medicine physicians of the Sichuan School as an example, the diagnosis and treatment system for lung cancer with phlegm-dampness and blood stasis syndrome, which was formed in response to the humid and foggy environment of the Sichuan Basin, possesses unique value. However, traditional inheritance modes face challenges such as fragmentation, lack of standardization, and insufficient quantification, which hinder the promotion and application of this experience. This research focused on how to leverage multimodal data and artificial intelligence-generated content (AIGC) to achieve precise analysis, intelligent inheritance, and clinical innovation of the experience in diagnosis and treatment of lung cancer with phlegm-dampness and blood stasis syndrome by distinguished traditional Chinese medicine physicians of the Sichuan School. By integrating multimodal data (encompassing four diagnostic methods of traditional Chinese medicine, modern medical imaging, clinical laboratory tests, molecular biology, and regional environmental information), a precise diagnosis and treatment system integrating macro and micro perspectives for the "disease, syndrome, and pathogenesis" was constructed. The research yielded the following results: (1) In precise syndrome differentiation, the objective quantification of the phlegm-dampness and blood stasis syndrome was achieved. By constructing a "four diagnostic methods, imaging, and molecule" correlation model, the study revealed intrinsic links between tongue and pulse parameters and the tumor microenvironment, as well as between regional climatic factors and syndrome characteristics, enabling real-time dynamic monitoring of efficacy. (2) In elucidating patterns, the study systematically explored the syndrome differentiation thoughts of Sichuan School physicians, such as the timing of purgation and tonification. A "pathogenesis, syndrome complex, and prescriptions and herb" network model was constructed, which accurately elucidated the synergistic action mechanisms of core herb pairs and quantified the dynamic compatibility patterns of reinforcing healthy Qi and eliminating pathogenic factors. (3) In intelligent empowerment, an auxiliary system integrating intelligent syndrome differentiation, treatment plan generation, and efficacy evaluation was built. This system can fuse regional characteristics with individual data, dynamically generate and optimize personalized prescriptions aligned with the experience of Sichuan School, and predict efficacy trends and potential adverse reactions. The integration of multimodal data and AIGC can effectively facilitate the structured inheritance and clinical translation of distinguished physicians' experience. The established intelligent diagnosis and treatment model integrating traditional Chinese medicine and Western medicine demonstrates clear potential in prolonging patients' progression-free survival, alleviating symptoms, and reducing adverse reactions to treatment. This study provides a referential methodological framework for the traditional Chinese medicine experience in diagnosis and treatment of lung cancer, especially the empirical inheritance and modernized development of regional academic schools. It contributes to advancing clinical diagnosis and treatment toward greater precision and personalization.
3.Construction and Evaluation of Animal Model with "Phlegm-dampness" Syndrome
Xiaoqin LIU ; Qingzhi LIANG ; Wei JIANG ; Ling DENG ; Haoyue FENG ; Rensong YUE
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(14):26-39
According to traditional Chinese medicine (TCM) theory, impaired spleen transportation function disrupts nutrient distribution, causing metabolic accumulation of lipids that transform into pathogenic phlegm-dampness. These pathological factors disseminate through the San Jiao and obstruct meridian pathways, ultimately forming the pathogenesis described as "all disorders involve phlegm". Phlegm and dampness share common pathogenic origins but manifest distinct clinical manifestations. Dampness, as the precursor, may congeal into phlegm, while existing phlegm accumulation can further exacerbate dampness stagnation, thereby establishing a self-perpetuating pathological cycle. Modern medical research has confirmed that the essence of "phlegm-dampness" syndrome is closely associated with energy metabolism disorders, serving as a common pathological basis for metabolic syndrome, type 2 diabetes mellitus, atherosclerosis, and other major chronic diseases. As a crucial vehicle for medical experimental research, disease-syndrome combination animal models serve as an indispensable means to advance the modernization of TCM. Currently, based on classical theories such as "rich and greasy foods produce phlegm" and "physical coldness combined with cold consumption causes external pathogens to invade the skin and hair, thereby generating internal dampness", researchers primarily employ two paradigms to construct animal models of phlegm-turbidity, dampness obstruction, and phlegm-dampness syndromes: the first involves simulating TCM etiological factors (through methods like dietary irregularities, imblanace between work and rest, and combined internal-external dampness exposure), while the second combines disease with syndrome differentiation (inducing pathological changes through physical, chemical, or biological interventions). Through comprehensive evaluation incorporating macroscopic observation and microscopic index detection, model animals undergo systematic biological and pathological assessment, with further syndrome type verification achieved via the "prescription-based syndrome detection" approach. However, existing models still exhibit significant deficiencies in both the standardization of modeling methodologies and the systematization of evaluation criteria. This paper reviews the strategies for constructing "phlegm-dampness" syndrome animal models and their corresponding evaluation indices, focusing on the pathological correlations among different modeling approaches. The aim is to provide methodological guidance for research on TCM syndromes related to "phlegm-dampness" syndrome and to support the development of TCM therapies for resolving phlegm and eliminating dampness. This study not only contributes to advancing the standardization of TCM syndrome research but also provides crucial technical support for the modernization of TCM.
4.Application of HTS2 Technology in Traditional Chinese Medicine and Formulas: A Review
Xiaohong YI ; Yumei WANG ; Yuhui CHEN ; Dong WANG ; Lijun HUANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(14):40-49
High-throughput sequencing-based high-throughput screening (HTS2) technology, as a new advancement in the field of high-throughput biotechnology, is the world's first technology to integrate high-throughput sequencing into large-scale drug screening and target discovery. The artificially designed DNA probes were bound to the undetermined mRNAs of thousands of genes in cell lysates, and then the probes were ligated with ligases. The large-scale simultaneous detection of gene expression changes in thousands of drug-treated cell samples was performed using barcoding, automated operating platforms, and high-throughput sequencers. This technology enables high-throughput identification of drugs that significantly perturb the gene expression profiles characteristic of diseases. It can also take gene expression signature as the readout and exert great high-throughput advantages in the screening of multi-drug, multi-component, and multi-target drugs, as well as the research on complex mechanisms. Therefore, it is particularly suitable for elucidating the multi-target mechanisms of traditional Chinese medicine and identifying its multi-effective components. Its main technical advantages include high throughput, automation, and low cost. In recent years, HTS2 technology has yielded important achievements in the elucidation of the mechanism of action of traditional Chinese medicine formulas, the scientific connotation analysis of the regional characteristics of traditional Chinese medicine, the targeted isolation of active compounds of traditional Chinese medicine, and the discovery of novel pharmacological functions of monomeric compounds of traditional Chinese medicine. In the era of artificial intelligence, HTS2 technology will serve as a powerful tool for generating high-quality, original big data of traditional Chinese medicine, providing core data support and promoting AI-driven traditional Chinese medicine research. Ultimately, HTS2 technology offers new strategies and critical data support for deeply analyzing the scientific connotation of traditional Chinese medicine and discovering novel traditional Chinese medicine-based drugs, thereby accelerating the modernization and internationalization of traditional Chinese medicine in China.
5.Technologies and Research Applications of Large Language Models in Traditional Chinese Medicine
Yuxiu ZENG ; Qiong ZHAO ; Chongcheng XI ; Quansheng FENG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(14):50-59
The integration of large language model (LLM) and traditional Chinese medicine (TCM) promotes the informatization of TCM,and also provides a new direction for the inheritance and innovation of TCM in the new era. Based on the research background of LLM,the development process of LLM based on the Transformer architecture is summarized,and the research progress of LLM in TCM is reviewed. The main process of constructing TCM LLMs and the key techniques used by researchers during model development are summarized. Based on the related literature, the main application scenarios of TCM LLMs and the research explorations conducted by TCM researchers using LLMs are outlined. Meanwhile,the current challenges faced in the development of TCM LLMs are analyzed. Further improvements are urgently needed in the construction of high-quality data,the evaluation methodology of TCM LLMs,the interpretability of the model, multimodal fusion of TCM LLMs, and the development of TCM prescription recommendation models. Looking forward to the future development of LLM in TCM,it is expected to provide a reference for the deeper integration of LLMs and TCM,and facilitate the modernization of TCM.
6.Mechanisms on Chronicity of Infectious Diseases from Warm Disease Theory of Pathogen Invading Nutrient and Blood Aspects: Integrating Classical Wisdom with Innovative Perspectives
Baixue LI ; Hang ZHOU ; Jibin LIU ; Xia LI ; Xiyang LIU ; Haihui LIU ; Peijie WU ; Dong WANG ; Cen JIANG ; Wenjun WU ; Quansheng FENG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(14):60-69
The chronicity of infectious diseases is an important field in the collaborative research of traditional Chinese and Western medicine. The warm disease theory of pathogen invading nutrient and blood aspects in traditional Chinese medicine (TCM) takes the struggle between healthy Qi and pathogenic Qi and cementation of Yin as the core pathogenesis, providing a unique theoretical framework for explaining the common pathology of infectious chronic diseases. This theory originated from Yin-Yang interaction in the Internal Classic and was enriched with WU Youke's theory of intruding pathogen interacting and lingering in blood vessels and YE Tianshi's theory of long-term illness entering collaterals. Combining the theory with modern medical knowledge, our team has condensed the dynamic pathogenesis model of deficiency (nutrient and blood aspects) and excess (pathogen) interacting in the blood collaterals of Yin aspect, the core feature of which is the four-dimensional interactions of cause (pathogen characteristics), location (three Yin locations of diseases), nature (deficiency and excess), and potential (transmission trend). The common pathology of infectious chronic diseases is reflected in interactions. That is, the interactions between nutrient and blood deficiency (immune exhaustion and metabolic disorder) and pathogen excess (pathogen persistence and fibrous hyperplasia) in the liver collaterals (Jueyin), kidney collaterals (Shaoyin), lung collaterals (Taiyin) and other blood collaterals of Yin aspect form the pathological damage characterized by immune inflammatory response-continuous tissue damage with excessive repair. Taking the inheritance and innovative development of classics as the main line, this paper systematically discusses the scientific connotation of the theory of pathogen invading nutrient and blood aspects and the paths of inheritance and innovation and clarifies the original significance of this theory in the chronic development of infectious diseases. Furthermore, taking clinical diseases as an example, this paper reflects the guiding value of this classical theory in the modern diagnosis and treatment of infectious diseases with integrated traditional Chinese and Western medicine and the application potential of this theory in solving complex medical problems through the construction of the innovative paradigm of precise diagnosis and treatment with integrated traditional Chinese and Western medicine.
7.Modern Pharmacological Mechanisms and Clinical Applications of Xuan-dredging Wind Medicinals: A Review
Yu HU ; Zhen YE ; Qiaobo YE ; Kaihua QIN ; Mingjie WANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(14):70-83
Since Li Dongyuan formally proposed the concept of "wind medicinals" (Feng Yao),their clinical application has been highly valued by physicians throughout history. However,influenced by the evolution of the term and connotation of "wind medicinals" in modern times,its conceptual understanding,leading to a decline in clinical utilization. Since the new century,Professor Wang Mingjie has integrated LIU Wanxu's sweat pore (Xuanfu) theory into the reinterpretation of wind medicinals,proposing the "Xuanfu-dredging wind medicinal theory", which has gained widespread recognition in academic circles,revitalizing their clinical application. This study traces the origin of the Xuan-dredging wind medicinals theory and reviews their current functions and clinical applications,finding that the theoretical framework is preliminarily established. Characterized by their pungent and dispersing properties,wind medicines act by opening the Xuanfu throughout the body,exerting therapeutic effects such as dispelling pathogens,resolving stagnation,and enhancing treatments like blood-activation,spleen-fortification,and heat-clearing. They are widely used,showing advantages in treating systemic diseases including ophthalmic and cardiovascular/cerebrovascular disorders. Modern pharmacological research indicates preliminary consensus on hypotheses of cerebral,intestinal,hepatic,and renal Xuanfu. studies on formulas (e.g.,Qufeng Tongqiao Fang),single herbs (e.g.,Mahuang and Gegen),and active constituents (e.g.,tetramethylpyrazine) provide evidence that wind medicines improve key mechanisms like blood-brain barrier function and cerebral microcirculation (material basis of cerebral Xuanfu),supporting their use in brain disorders (e.g.,cerebral ischemia,depression). Despite clinical and pharmacological support,the clinical application system for wind medicines remains incomplete. Future efforts should focus on high-quality clinical research and mechanistic studies to establish personalized application systems,enhance Xuanfu opening practices,and ensure the effectiveness and safety of wind medicines.
8.Qijia Rougan Decoction Ameliorates Liver Fibrosis Through miRNA-mRNA Network
Yumei WANG ; Peijie WU ; Shaoxiu JI ; Han YU ; Xiaohong ZUO ; Xiaofeng CHEN
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(14):84-90
ObjectiveTo explore the mechanism by which Qijia Rougan decoction ameliorates liver fibrosis through amino acid/fatty acid metabolic reprogramming and phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) pathway, based on the miRNA-mRNA regulatory network and the interaction between metabolism and signaling pathways. MethodsSprague-Dawley (SD) rats were randomized into four groups (n=8): control, model, and low-dose and high-dose (7.0, 28.0 g·kg-1·d-1, respectively) Qijia Rougan decoction. Liver fibrosis was induced by subcutaneous injection of carbon tetrachloride (CCl4). From week 9, drug intervention was implemented for 7 weeks. After the final administration, the pathological changes in the liver were evaluated through hematoxylin-eosin (HE) and picrosirius red (PSR) staining. An automated biochemical analyzer was used to measure the serum levels of biochemical indicators, including alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), total bile acid (TBA), albumin (ALB), and cholesterol (TC). High-throughput miRNA sequencing was performed to identify differentially expressed miRNAs (DemiRs) during liver fibrosis. A miRNA-mRNA interaction network was constructed to identify key targets, which were then subjected to GO and KEGG enrichment analyses. The expression levels of selected DemiRs were validated by Real-time PCR. ResultsCompared with the control group, the model group showed marked hepatic lobular necrosis, increased collagen deposition, significant fibrosis, elevated serum levels of ALT, AST, ALP, and TBA (P<0.01), and declined levels of ALB and TC (P<0.01). Compared with the model group, Qijia Rougan decoction treatment reduced hepatic necrosis, collagen accumulation, and fibrosis, lowered the serum levels of ALT, AST, ALP, and TBA (P<0.01), and raised the levels of ALB and TC (P<0.01). Integrated miRNA-seq and RNA-seq analysis identified 31 DemiRs (6 upregulated and 25 downregulated) and 498 targets. The expression trends of four selected DemiRs, including rno-miRNA-376b-3p, were consistent with sequencing results (R2=0.93). Functional annotation revealed that top 20 upregulated targets were enriched in amino acid and fatty acid metabolism, while top 20 downregulated targets were significantly associated with the PI3K/Akt signaling pathway and cancer progression. ConclusionQijia Rougan decoction alleviates liver fibrosis by reconstructing the miRNA-mRNA regulatory network, promoting metabolic reprogramming, and inhibiting the PI3K/Akt signaling pathway. These findings provide mechanism evidence supporting the multi-targeted antifibrotic effects of traditional Chinese medicine compound formulas.
9.Guizhi Fulingwan Alleviate Hepatic Fibrosis by Modulating mtDNA/NLRP3/Caspase-1/GSDMD Signaling Pathway
Yu TANG ; Xuli YANG ; Qiang YANG ; Xiaojie WANG ; Yongxiang GAO ; Xueping LI
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(14):91-99
ObjectiveTo investigate the mechanism of Guizhi Fulingwan (GFW) against hepatic fibrosis, focusing on elucidating the regulatory effect of GFW on the mitochondrial DNA (mtDNA)/NOD-like receptor protein 3 (NLRP3)/cysteinyl aspartate-specific proteinase-1 (Caspase-1)/gasdermin D (GSDMD) signaling pathway. MethodsForty-two male Sprague-Dawley (SD) rats were randomly allocated into six groups (n=7): control, model, low/medium/high-dose (0.14, 0.28, 0.56 g·kg-1·d-1) GFW (GFW-L, GFW-M, GFW-H), and Dahuang Zhechong pills (DZW, 1.8 g·kg-1·d-1). The rat model of hepatic fibrosis was induced by intraperitoneal injection of carbon tetrachloride. General conditions of the rats were observed. Serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were measured. Liver histopathology and collagen deposition were observed through hematoxylin and eosin (HE) staining and Masson's trichrome staining. Transmission electron microscopy (TEM) was employed to observe structural alterations and damage of cellular ultrastructures including mitochondria. Mitochondrial membrane potential (MMP, ΔΨm) was detected by flow cytometry. Serum levels of interleukin-1β (IL-1β) and interleukin-18 (IL-18) were measured by enzyme-linked immunosorbent assay (ELISA). The mRNA levels of mtDNA and NLRP3 in the liver tissue were quantified by Real-time polymerase chain reaction (Real-time PCR). The protein levels of key molecules in the NLRP3/Caspase-1/GSDMD signaling pathway in the liver tissue were determined by Western blot. ResultsCompared with the control group, the model group exhibited a decrease in body weight (P<0.01), an increase in liver index (P<0.01), elevations in serum ALT and AST levels (P<0.01), and typical fibrotic features such as disorganized hepatocytes, inflammatory infiltration, and increased collagen deposition in the liver tissue. TEM revealed significant karyotheca degeneration, mitochondrial swelling, endoplasmic reticulum expansion, and organelle efflux in the model group. In addition, the model group showed decreased ΔΨm (P<0.01), up-regulated mRNA levels of mtDNA and NLRP3 (P<0.01) and protein levels of NLRP3, Caspase-1, and GSDMD (P<0.01) in the liver tissue, and increased serum levels of IL-1β and IL-18 (P<0.01). Compared with that in the model group, the body weight increased in GFW-L, GFW-M, and DZW groups (P<0.05) and markedly increased in the GFW-H group (P<0.01). The liver index decreased in the GFW groups and DZW group (P<0.01). The serum ALT level declined in the GFW-L group (P<0.05), and the serum ALT and AST levels decreased in the GFW-M, GFW-H, and DZW groups (P<0.01). Histopathological damage and fibrosis were alleviated to varying degrees, and TEM revealed mitigated ultrastructural injuries including mitophagy, mitochondrial swelling, and endoplasmic reticulum expansion in the drug intervention groups. The ΔΨm increased in GFW groups without statistical significance. The mRNA level of mtDNA in the liver tissue was down-regulated in the GFW-M (P<0.05), GFW-H (P<0.01), and DZW (P<0.01) groups. The mRNA level of NLRP3 was down-regulated in GFW-M, GFW-H, and DZW groups (P<0.01). Western blot analysis showed significantly down-regulated protein level of NLRP3 in all the GFW groups and the DZW group (P<0.01). The protein level of GSDMD-N was down-regulated in GFW-H and DZW groups (P<0.01). The protein level of cleaved Caspase-1 was down-regulated in GFW-M (P<0.05), GFW-H (P<0.01), and DZW (P<0.01) groups. In addition, the serum levels of IL-1β and IL-18 declined in GFW-H and DZW groups (P<0.01). ConclusionGFW can suppress pyroptosis to ameliorate CCl4-induced hepatic fibrosis, potentially through mitigating mitochondrial damage, inhibiting inflammasome assembly and activation, and blocking pro-inflammatory cytokine release.
10.Action of Immune Microenvironment and Metabolic Reprogramming in Hepatocellular Carcinoma Based on "Deficiency of Healthy Qi and Stasis Toxins"
Xia LI ; Jiexiong YANG ; Xiyang LIU ; Wenjun WU ; Cen JIANG ; Quansheng FENG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(14):100-109
Hepatocellular carcinoma (HCC), a malignancy with high mortality, exhibits poor survival rates and prognosis. The profound suppression of the tumor immune microenvironment (TIME) and the abnormal hyperactivity of metabolic reprogramming (MR) are the two primary factors driving HCC progression. Traditional Chinese medicine has demonstrated significant efficacy in HCC treatment. The team proposed that "deficiency of healthy Qi and stasis toxins" was the core pathogenesis of HCC, closely associated with TIME suppression and MR hyperactivity. This paper proposed that a suppressed state of the TIME was the biological manifestation of "deficiency of healthy Qi", where the functional exhaustion of effector T lymphocytes and natural killer cells reflected the decline of "healthy Qi" in eliminating pathogens. Conversely, the expansion and activation of immunosuppressive cells, such as regulatory T cells (Tregs), M2-like tumor-associated macrophages (TAM-M2), and myeloid-derived suppressor cells (MDSCs) , represent the dysfunction of "healthy Qi" in maintaining homeostasis. MR serves as the material basis of "stasis toxins". Stasis toxins exhibit heat stagnation, manifested by abnormal hyperactivity of glycolysis and lipid synthesis. They demonstrate migratory propensity, as toxic metabolites like lactic acid and prostaglandin E2 promote tumor invasion and metastasis. They display a consumptive nature, reflected in the functional suppression of immune cells. The vicious cycle between TIME and MR is the biopathological reflection of "deficiency of healthy Qi intertwined with stasis toxins". Immunosuppression exacerbates MR, while toxic metabolites further impair immune function, establishing a pathogenic chain of "deficiency leading to stasis, and stasis toxins damaging healthy Qi". The primary therapeutic approach is reinforcing healthy Qi, resolving stasis, and removing toxins, which can reinforce and tonify healthy Qi to regulate pathways, such as phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt), C-X-C chemokine receptor type 4/ C-X-C chemokine ligand 12 (CXCR4/CXCL12), and toll-like receptor 4/ nuclear factor-kappa B/ signal transducer and activator of transcription 3 (TLR4/NF-κB/STAT3), adjust T lymphocyte ratios, inhibit Tregs/TAM-M2 function, and downregulate immune checkpoints, including programmed death ligand 1/programmed death 1(PD-L1/PD-1), and reshape TIME. It is also involved in resolving stasis and removing toxins to modulate phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) and hypoxia-inducible factor-1α (HIF-1α) signaling pathways, suppress key enzymes in glycolysis and lipid synthesis, and block toxic metabolite production. Thus, this therapy synergistically regulates the immune and metabolic network, breaks the vicious cycle of "deficiency in healthy Qi and stasis toxins", and offers a novel strategy for integrating traditional Chinese medicine and Western medicine in HCC treatment.

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