2 Professor Pei Zhengxue’s Understanding of the Etiology and Pathogenesis of Primary Liver Cancer

2 Professor Pei Zhengxue’s Understanding of the Etiology and Pathogenesis of Primary Liver Cancer

Although ancient Chinese texts do not record the term “liver cancer,” based on its clinical manifestations—such as hard, stone-like masses in the upper abdomen, flank pain, emaciation, poor appetite, abdominal distension, jaundice, ascites, etc.—it can be categorized under conditions like “zhengjia,” “jiju,” “xiaotong,” “huangdan,” and “guchang.” Therefore, it can be said that TCM has long had treatments for liver cancer. Professor Pei Zhengxue believes that the onset of primary liver cancer can be summarized as internal and external factors. External factors refer to pathogenic evils such as the Six Evils accumulating in the zang-fu organs (the liver). Internal factors involve inherent deficiency of righteous qi, imbalance of yin and yang, abnormal circulation of qi and blood, and dysfunction of the zang-fu organs. The combination of internal and external factors leads to qi stagnation and blood stasis, phlegm-dampness and toxic pathogenic factors accumulating, ultimately resulting in tumor formation.

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Research on Pei Zhengxue’s Series of Formulas and Medications

As stated in “Plain Questions·Great Discussion on Yin-Yang Correspondence”: “In treating disease, one must seek the root.” Professor Pei Zhengxue believes that the internal cause of tumor formation is deficiency of righteous qi, which is the root of the disease; while external factors are the accumulation of pathogenic evils, which are the manifestation of the disease. Professor Pei Zhengxue summarizes this as: primary liver cancer is a condition of deficiency at the root and excess at the manifestation, meaning that although the tumor appears locally, it is actually a local manifestation of a systemic disease—a condition of overall deficiency with localized excess. Therefore, in treatment, he proposes: strengthen righteous qi to eliminate accumulation, and eliminate accumulation to reinforce the root. As Zhang Yuanzhi said: “Nourish the righteous qi and the accumulation will naturally dissipate, just as if everyone in the hall were a gentleman, even if there were a few bad people, they would eventually have no place to hide. Now, if true qi is strong…accumulation will naturally disappear.”

3 Experimental Indicators

IFN-γ is primarily secreted by activated T cells and natural killer cells (NK cells); in mice, it is produced by the Th1 subset. IFN-γ participates in immune responses in multiple ways: it effectively increases the expression of major histocompatibility complex (MHC) class I molecules, facilitating antigen presentation and enhancing immune responses; it inhibits tumor cell proliferation; promotes antibody production by B cells; induces cytotoxic effects in NK cells and cytolytic T cells (CTLs)[8]; and it can also enhance TNF-α-induced apoptosis[9–11].

The mechanisms by which IFN-γ inhibits tumor cell proliferation mainly include: ① inhibition of angiogenesis within tumors[12]; ② direct cytotoxic effects on malignant tumor cells[8]; ③ interferon affects the mitotic cycle of tumor cells, inducing apoptosis[9–11]; ④ exerting anti-tumor activity by influencing the extracellular matrix[1].

TNF-α is one of the most potent anti-tumor factors in the tumor necrosis factor family, produced by activated macrophages/monocytes, NK cells, and fibroblasts. It is currently the cytokine with the strongest anti-tumor effect and has systemic actions. Its main roles include participating in inflammatory responses, regulating immune responses, activating T cells; promoting IL-2 production and triggering inflammatory responses; enhancing the expression of IL-2 receptors, epidermal growth factor receptors (EGFR), and major histocompatibility complex class II antigens; and exerting anti-tumor effects (inducing tumor cell apoptosis).

IFN-γ and TNF-α, as specific indicators reflecting the body’s immune function, participate in the entire process of tumor development and regression. Professor Pei Zhengxue’s prescription for treating liver cancer—Pei’s Soft Liver and Anti-Ascites Pill (which has the functions of strengthening righteous qi and reinforcing the root, promoting qi flow and activating blood circulation to remove blood stasis, softening the liver and dispersing nodules, and clearing heat and detoxifying)—happens to regulate the body’s immune function and exert anti-tumor effects. Therefore, this experiment selects IFN-γ and TNF-α as experimental indicators, appropriately reflecting Professor Pei Zhengxue’s theoretical system for treating tumors, and also aligning with his view that “primary liver cancer is a condition of deficiency at the root and excess at the manifestation; although the tumor appears locally, it is actually a local manifestation of a systemic disease—a condition of overall deficiency with localized excess. Therefore, in treatment, he proposes: strengthen righteous qi to eliminate accumulation, and eliminate accumulation to reinforce the root.”

This experiment establishes an H22 tumor-bearing mouse model to observe the effects of Pei’s Soft Liver and Anti-Ascites Pill on serum TNF-α and IFN-γ levels in mice, exploring the pill’s anti-tumor effects and the anti-tumor and immune-regulating mechanisms of traditional Chinese herbal medicines from the perspective of cytokines, providing sufficient scientific theoretical basis for its widespread clinical application and laying the foundation for developing this formulation into a new type of highly effective anti-tumor Chinese medicine.

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Research on Pei Zhengxue’s Series of Formulas and Medications

Experimental Study