II. Research on the Spleen

The spleen is the foundation of postnatal life, governing middle qi and overseeing transportation and transformation; it is the source of qi and blood production and, like the kidney, plays a crucial role in human growth, development, health, and aging. The theories and doctrines concerning the spleen are an important component of the fundamental theories of Traditional Chinese Medicine. In recent years, researchers have employed experimental methods to study the essence of the spleen and have achieved promising preliminary results. The "spleen" in TCM encompasses the following three aspects:

1. The Spleen Governs Transportation and Transformation

The meaning of the spleen's governance of transportation and transformation in TCM is broadly related to modern medicine's digestive, absorptive, gastrointestinal motility, and metabolic systems.

(1) The Spleen and Digestion

When the spleen fails to properly transport and transform, indigestion and loss of appetite occur. Some studies have used salivary amylase activity as an indicator and found that in patients with spleen deficiency, salivary amylase activity significantly decreases under effective load (acid stimulation), whereas in healthy individuals it increases. Others have observed that in patients with gastric pain due to spleen deficiency, both basal acid output (BAO) and peak acid output (PAO) are markedly lower than in normal individuals. Additionally, measurements of pepsinogen activity in 24-hour urine samples from chronic gastritis patients with spleen deficiency symptoms show no significant difference compared to healthy individuals. The Beijing Institute of Traditional Chinese Medicine has measured amylase activity in the urine of patients with spleen deficiency and found it significantly lower than in healthy people, preliminarily indicating reduced pancreatic amylase secretion in these patients. Furthermore, pancreatic function tests conducted on patients with spleen deficiency reveal decreased chymotrypsin secretion.

From the above research, it can be seen that whenever spleen qi is deficient and its transportation and transformation functions are impaired, salivary amylase secretion, basal and peak gastric acid output, urinary amylase activity, pancreatic amylase secretion, and chymotrypsin function all decrease below normal levels. This demonstrates that one of the key manifestations of the TCM concept of "spleen dysfunction" is the reduction in various digestive secretory functions.

(2) The Spleen and Absorption

In addition to the reduced secretion of various digestive enzymes, spleen dysfunction also involves changes in gastrointestinal absorption. For example, some domestic institutions use xylose excretion rate as an indicator to study the small intestinal absorption status of patients with spleen deficiency. The Beijing Institute of Traditional Chinese Medicine found that children with rickets and those prone to respiratory diseases who exhibit spleen deficiency symptoms have lower xylose excretion rates than normal. After strengthening the spleen through treatment, as the spleen deficiency symptoms improve, the xylose excretion rate also returns to normal. Similar results were obtained when the same experiment was repeated on adults with spleen deficiency symptoms. Pathological observations of gastric tissue from patients with extensive gastrectomy due to spleen deficiency revealed enhanced regeneration of gastric mucosal epithelial cells but impaired differentiation into mature cells. Additionally, pathological examinations of duodenal biopsy specimens from patients with chronic gastritis and peptic ulcers exhibiting spleen deficiency symptoms showed flattened mucosal villi, increased damage, and sparse or shed microvilli.

(3) The Spleen and Gastrointestinal Motility

Spleen dysfunction also manifests as altered gastrointestinal motility. Patients with spleen deficiency typically experience belching, acid regurgitation, abdominal distension, and loose stools. According to TCM, this is evidence of disharmony between the ascending and descending functions of the spleen and stomach—what is referred to as "disharmony of ascent and descent," which essentially means spleen dysfunction. X-ray barium meal examinations have shown that most patients with spleen deficiency exhibit reduced gastrointestinal peristalsis and prolonged gastric emptying time. Using surface gastric electrical wave measurements as an indicator, it has been found that patients with spleen deficiency have lower amplitude of surface gastric electrical waves, a phenomenon that is particularly evident both on an empty stomach and after eating. After employing spleen-strengthening and qi-tonifying methods, these conditions quickly improve. Furthermore, using 13I isotope tracing to observe gastrointestinal emptying function, it has been discovered that tumor patients with spleen deficiency exhibit significantly faster gastrointestinal emptying compared to non-spleen-deficient tumor patients and healthy individuals, with improvements observed after taking spleen-strengthening and qi-tonifying medications.

(4) The Spleen and Metabolism

Spleen dysfunction also entails disturbances in the metabolic processes of nutrients. It has been found that patients with atrophic gastritis and superficial gastritis who exhibit spleen deficiency symptoms have lower serum isocitrate dehydrogenase activity than normal individuals (P<0.01). After treatment with Xiangsha Liujunzi Tang, this activity increases, though the difference before and after treatment remains significant, the post-treatment level still does not reach normal. These patients also exhibit lower serum lactate dehydrogenase activity than normal, which significantly increases after treatment with Xiangsha Liujunzi Tang. Additionally, observations of gastric mucosa from patients with gastric pain due to spleen deficiency reveal a marked reduction in the average number of subcellular mitochondria per unit area, along with mitochondrial swelling, membrane defects, and cristae rupture. Mitochondria are organelles responsible for cellular biooxidation of nutrients and contain the enzymes necessary for oxidation. Therefore, studying the morphology and function of mitochondria in patients with spleen deficiency is highly meaningful for exploring the essence of the spleen.

2. The Spleen Governs Middle Qi

Middle qi is the foundation of postnatal life and an important component of the body's vital energy. As TCM states: "Where evil gathers, qi must be deficient," and "If vital energy resides within, evil cannot invade." Thus, vital energy and middle qi to some extent encompass immune function, and TCM also holds the view that a strong spleen resists pathogenic factors. Some researchers divide internal medicine inpatients into two groups: those with spleen deficiency and those without. Using peripheral blood lymphocyte counts, PHA skin tests, total E-rosette formation cell ratios, and active E-rosette formation ratios as indicators, they found that patients with spleen deficiency exhibit a clear tendency toward weakened cellular immunity, with the degree of decline positively correlated with the severity of anemia and hypoproteinemia in these patients. Similar findings have been observed in patients with chronic bronchitis, peptic ulcers, chronic nonspecific colitis, and chronic hepatitis who also exhibit spleen deficiency symptoms. Some researchers have used square capillary electrophoresis to examine lymphocytes in patients with spleen deficiency and found a significant decrease in lymphocyte electrophoretic mobility. This decline in lymphocyte electrophoretic ability indicates a corresponding decline in lymphocyte electrophoretic vitality, which may be one of the reasons for the weakened immunity in patients with spleen deficiency. Other studies have examined the content of Siga in the saliva of patients with peptic ulcers and chronic colitis who exhibit spleen deficiency symptoms, finding that the content increases in patients with spleen deficiency, especially in those with dampness accompanying spleen deficiency. After treatment, as clinical conditions improve, the content decreases. TCM believes that the appearance of syndromes is related to individual constitution, and HLA is an important immunogenetic marker of the human body closely associated with immune responses and susceptibility to disease. Some researchers have conducted preliminary studies on the association between spleen deficiency syndrome and HLA, discovering a significant relationship between spleen deficiency syndrome and HLA-Bn, while no such relationship was found in comparative observations of chronic gastritis, chronic nephritis, and peptic ulcers. This suggests a clear correlation between the essence of spleen deficiency and immunogenetic factors.

3. Liver-Stomach Disharmony

According to TCM, liver-stomach disharmony has two pathogenic mechanisms: first, liver wood overpowers earth, and second, spleen earth oppresses wood. The former manifests as pain in the liver region, bitter taste in the mouth and dry throat, irritability, and loss of appetite and fatigue, while the latter presents as fullness and distension in the epigastrium, intestinal rumbling and diarrhea, nausea and vomiting, and distension on both sides of the flanks. From a Western medical perspective, these two conditions generally involve disorders of the gastrointestinal autonomic nervous system, with the former likely reflecting heightened sympathetic nervous system tension and the latter indicating dominance of parasympathetic nervous system function. In light of this, domestic scholars have attempted to demonstrate the relationship between liver-stomach disharmony and the autonomic nervous system through various research designs. It is known that the synthesis and secretion of salivary amylase are controlled by the autonomic nervous system. Patients with liver-stomach disharmony typically exhibit symptoms of liver depression and spleen deficiency. Some researchers continue to conduct experiments using patients with spleen deficiency, finding that when these patients are in a baseline state, salivary flow rate increases and enzyme activity is also high, suggesting that parasympathetic nerve tension controlling the salivary glands is relatively high. However, upon acid stimulation, enzyme activity not only fails to increase but actually decreases, and the increase in salivary flow rate is also less than in normal individuals. This indicates that although the parasympathetic nerves of patients with spleen deficiency are in a state of hyperactivity, their stress response capacity is lower than that of normal individuals. Using 13I isotope capsule oral tracing, it has been found that patients with spleen deficiency exhibit faster gastrointestinal emptying, which can be corrected by intramuscular injection of atropine, demonstrating that parasympathetic nerve tension increases during spleen deficiency. Research on the functional state of sympathetic nerves in patients with spleen deficiency is still ongoing. Skin potential is a sensitive indicator of central sympathetic nervous system function; patients with spleen deficiency exhibit significantly lower skin potential than normal individuals whether at rest or under cold stimulation, but after spleen-strengthening and qi-tonifying treatment, skin potential increases markedly. The VMA content in the urine of patients with spleen deficiency is significantly lower than in normal individuals, and skin electrical activity often correlates with VMA content. Reduced dopamine β-hydroxylase activity is also a characteristic of patients with spleen deficiency, which increases after treatment. From a molecular biological perspective, the reason why the autonomic nervous system can influence the organs it controls is mainly due to neurotransmitter release at autonomic nerve terminals interacting with corresponding receptors on target cells, altering intracellular cyclic nucleotide levels and thereby affecting cellular function. Domestic researchers have studied changes in cyclic nucleotide levels in the blood of patients with spleen deficiency (results are inconsistent), preliminarily observing that plasma CAMP levels in patients with spleen deficiency are low, which helps explain the low sympathetic nervous system function during spleen deficiency. Based on current research, although different regions employ different methods and indicators, and results are not entirely consistent, it can be tentatively concluded that during spleen deficiency, sympathetic nervous system function is low while parasympathetic nervous system function is elevated, and both systems exhibit reduced stress response capacity.

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III. Research on the Liver

The liver is one of the five zang organs and is as important as the spleen and kidneys. Ancient texts contain numerous discussions about the liver, broadly divided into two aspects: the liver belongs to the wood element, characterized by smoothness and free flow, primarily responsible for dispersing and draining; stagnation leads to illness, and illness then affects earth and transforms into fire. The liver's wood nature relies on kidney water for nourishment; if the water fails to nourish the wood, liver yang rises excessively, leading to wind generation.

1. Liver-Qi Stagnation

Under normal circumstances, the liver must possess the qualities of smoothness and free flow. Therefore, once the liver loses its smoothness and free flow, liver qi stagnation occurs. This serves as the basis for the development of various liver disease syndromes, which can further lead to liver wood overpowering earth, liver qi transforming into fire, and liver qi reversing upward. In light of this, in recent years, some researchers have conducted experimental studies on the essence of liver qi stagnation. Using multi-indicator synchronous detection, they found that the main pathological basis of this syndrome is autonomic nervous system dysfunction, specifically a decrease in the cyclic nucleotide ratio (CAMP/CGMP), increased blood viscosity, and reduced small intestinal absorption function. Japanese researcher Matsumoto Katsuhiko believes that the liver is a complex organ that can be classified as part of the autonomic nervous system, but is also connected to mental health, the central nervous system, the vasomotor center, and cardiac function. The Hunan Medical University Institute of Integrated Traditional and Western Medicine believes that preliminary research currently shows a close connection between the essence of the liver in TCM and the nervous system, as well as neurohumoral regulatory factors. Therefore, research on the essence of the liver must be based on the theories that the liver primarily governs dispersion and drainage and stores blood.

2. Liver-Yang Excess

According to traditional TCM theory, liver-yang excess is the reverse pathological change of liver-qi stagnation. The former represents having surplus but lacking substance, while the latter represents having sufficient substance but lacking utilization. Domestic researchers have observed the autonomic nervous system function, plasma cyclic nucleotide changes, red blood cell intracellular nucleotide content comparisons, plasma atrial natriuretic peptide changes, and whole blood trace element changes in patients with liver-yang excess—microscopic indicators that suggest the neurohumoral regulation of liver-yang excess is quite complex. First, this condition may primarily result from enhanced peripheral sympathetic-adrenal medulla function: ① Autonomic nervous system dysfunction, with sympathetic overactivity accounting for 69.8%; ② Urinary CA, NE, E, and TMN levels reflecting peripheral sympathetic-adrenal medulla function all increase; ③ Central NE metabolite urinary MHPG levels decrease; ④ Plasma CAMP and CGMP increase, with CGMP increasing more prominently, resulting in a decreasing CAMP/CGMP ratio; ⑤ Plasma TXB₂ and 6K-PGF₁₂ levels increase, with their ratios also rising; ⑥ Red blood cell ATP, ADP, and NADP levels increase. Currently, it is widely accepted that when the sympathetic nervous system is excited, NE release increases, activating β-receptors on cell membranes and stimulating adenylate cyclase (CAMP-ase), thereby increasing intracellular CAMP levels and plasma CAMP levels. Catecholamines can also bind to α-receptors, enhancing guanylate cyclase (CGMP-ase) activity, leading to increased CGMP levels. Prostaglandins (PG) can activate CAMP-ase activity in many tissues, increasing CAMP concentration, while imbalances in TXB₂-6K-PGF₁₂ levels may affect critical links in nucleotide metabolism. CA promotes material metabolism and enhances energy mobilization. Enhanced energy metabolism may be an important manifestation of excessive sympathetic-adrenal medulla function.

IV. Research on the Heart

The heart is the master of the five zang organs. The "Plain Questions·Secret Classic of Spiritual Oracles" states: "The heart is the sovereign organ, where divine spirit originates." The "Spiritual Pivot·Questions of the Mouth" says: "The heart is the master of the five zang and six fu organs... When the heart beats, all five zang organs tremble." The "Spiritual Pivot·Years of Heaven" states: "What is the divine spirit... When divine spirit resides in the heart, soul and spirit are fully present, thus forming a human being." TCM believes that the heart's primary functions can be summarized as two: first, being the master of the five zang and six fu organs, and second, being the origin of divine spirit. In recent years, there have been relatively few experimental studies in this area, with more reliance on existing experimental evidence for reference and explanation.

Foreign researchers have systematically studied the mechanism of action of placebos and found that placebos exhibit different effects depending on the language used for induction. In such cases, subcutaneous injection of atropine can increase secretions, while saline can activate adrenal cortical function. Placebos may reduce serum lipoproteins and also decrease peripheral eosinophil counts. These experiments demonstrate that the thinking and conscious activities dominated by the cerebral cortex can alter the normal functions of various organs in the human body, causing abnormal reactions to drugs that would normally elicit standard responses. Thinking and consciousness fall under the TCM concept of "divine spirit," which is governed by the heart, thus validating the TCM theory that the heart is the master of the five zang and six fu organs. The renowned Soviet physiologist Bekov and his colleagues believed that every organ and tissue in the human body contains countless interoceptors, which play an indispensable role in maintaining homeostasis—for example, muscle interoceptors are crucial for coordination during movement, and gastrointestinal interoceptors regulate digestive organ activity... All these interoceptors function through the pathways of sympathetic and parasympathetic nerves, under the control of the central nervous system. The so-called central nervous system falls within the scope of TCM's concept that the heart governs divine spirit. Extensive research has been conducted on the functions of the hypothalamus, brainstem, and autonomic nervous system; when the hypothalamus is stimulated, numerous functions of various organs undergo noticeable changes, such as body temperature, respiration, heartbeat, sleep, sugar and fat metabolism, endocrine function, and so on. It has now been proven that the anterior and medial parts of the hypothalamus, including the suprachiasmatic nucleus, preoptic area, and gray tubercle region of the third ventricle, control parasympathetic nerve activity; stimulating these areas can enhance parasympathetic nerve activity, manifesting as slower heart rate, peripheral vasodilation, and increased smooth muscle tone. Conversely, the posterior and lateral parts of the hypothalamus control sympathetic nerve activity; stimulating these areas can enhance sympathetic nerve activity, resulting in pupil dilation, hair standing on end, accelerated heartbeat, increased blood pressure, and deeper, faster breathing.

Modern psychology holds that emotions and feelings are forms of human reaction to real life. When real life aligns with the body's own needs, emotions and feelings typically manifest as joy, satisfaction, and love; when real life does not align with the body's needs, dissatisfaction, pain, fear, hatred, and anger arise. The former are positive emotions and feelings, while the latter are negative. Positive emotions and feelings can enhance the functions of various organs, whereas negative ones can inhibit them. Therefore, people generally believe that mood (emotions and feelings) is an important factor influencing the normal functioning of various systems in the human body. Mood can be regulated through personal cultivation and orientation, thus the directing effect of the cerebral cortex extends to regulating various departments of the body. Both emotions and feelings (mood) and the directed regulation of cultivation and quality fall within the scope of TCM's concept that the heart governs divine spirit, and their impact on various departments of the body aligns with the idea that the heart is the master of the five zang and six fu organs.

In summary, most of the heart's functions in TCM fall within the scope of modern medical brain functions. However, considering the heart's role in governing blood circulation, it also shares characteristics with the modern heart. Domestic researchers have used CXZ-I type ultrasonic cardiovascular diagnostic equipment to conduct preliminary observations on the left ventricular systolic and diastolic functions of patients with heart qi deficiency, heart yin deficiency, and blood stasis in the left ventricle. The findings show that in cases of heart qi deficiency, the mean value of the mitral valve-to-interventricular septum distance (EPSS) increases, while the mitral valve amplitude (CHE), stroke volume (SV), average left ventricular posterior wall contraction speed (MPMVS), average left ventricular posterior wall relaxation speed (MPWVD), ventricular wall thickening rate (△T%), ejection fraction slope (MVV), and the ratio of rapid filling phase left ventricular posterior wall motion total amplitude (R) to total left ventricular posterior wall motion amplitude (R/PWE) all decrease. In cases of heart yin deficiency, besides the increase in EPSS mean value, the diastolic function indicator MVV mean value also decreases significantly. Compared with heart qi deficiency, heart yin deficiency shares the common feature of reduced EPSS mean value, but differs in other respects: heart qi deficiency sees reductions in all indicators, whereas heart yin deficiency does not, resulting in statistically significant differences between the two. In cases of blood stasis, the SV and MPWVD mean values decrease, CHE and △T% mean values also decrease, the MVV and R/PWE mean values decrease, while the EPSS mean value increases. These findings indicate that there is a clear relationship between TCM's heart qi deficiency, heart yin deficiency, and blood stasis and the heart's systolic and diastolic functions, while also revealing that these three conditions share both similar and distinct aspects in terms of heart function, providing a material basis for understanding the traditional pathogenesis of TCM's heart qi deficiency, heart yin deficiency, and blood stasis.

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The "Sixteen-Character Guideline"—"Western medical diagnosis, TCM syndrome differentiation, TCM as the mainstay, Western medicine as the adjunct"—can serve as a provisional clinical model for integrated Chinese and Western medicine within the field of internal medicine. This "sixteen-character" guideline consists of four sentences, forming four consecutive meanings. First is Western medical diagnosis: upon receiving a patient, one must first conduct a Western medical diagnosis, utilizing all appropriate Western diagnostic methods to clarify the condition. Once the Western diagnosis is established, the second step in the model—TCM syndrome differentiation—can begin. This differentiation is conducted under the premise of a confirmed Western diagnosis, making it more precise due to the specific conditions involved; it is akin to fishing within a net rather than in the open sea, thus achieving far greater accuracy. TCM syndrome differentiation, in accordance with traditional principles, primarily employs conventional methods such as Six Meridians Differentiation, Eight Principles Differentiation, Zang-Fu Organ Differentiation, Wei-Qi-Ying-Xue Differentiation, San Jiao Differentiation, and Etiology Differentiation, while also incorporating the diagnostic experiences and perspectives of past medical scholars regarding similar diseases. With a clear Western diagnosis, TCM syndrome differentiation naturally integrates the Western medical perspective of microcosmic, localized, and pathogenic factors with the TCM perspective of macrocosmic, holistic, and organismic responses, elevating the understanding of the overall disease to a level that combines both Chinese and Western medicine. In doing so, it overcomes the traditional TCM deficiency of neglecting local aspects and corrects the Western medicine bias of overlooking the whole. More importantly, over time, numerous points of convergence emerge between the two systems in terms of understanding. These points of convergence represent areas where the two medical systems share common ground, and it is anticipated that they will first be proposed clinically, then validated through experimental research, and finally, when reintroduced into clinical practice, will have gained widespread recognition. Such approaches not only embody the characteristics of modern TCM but also constitute an integral part of modern science and technology. As these points of convergence increase, the integration of Chinese and Western medicine will expand from isolated instances to broader applications, advancing to deeper levels. The combined understanding resulting from the integration of Western diagnosis and TCM syndrome differentiation provides a more precise foundation for formulating TCM prescriptions. The third component of the model—TCM as the mainstay—and the fourth component—Western medicine as the adjunct—should be viewed together, as they collectively emphasize the therapeutic role of TCM formulas and herbs. It is thus evident that the primary objective of this guideline is to develop TCM, rather than Western medicine; further understanding of the full implications of integrating Chinese and Western medicine also serves this purpose. As a clinical model for integrated Chinese and Western medicine within the realm of internal medicine, the "Sixteen-Character Guideline" aims to fulfill the important mission of advancing contemporary TCM by applying the principle of "drawing on the past to serve the present and adapting foreign knowledge to suit Chinese needs." Our years of clinical practice have shown that the formulas and herbs selected through such integration not only demonstrate outstanding efficacy but also exhibit strong reproducibility.

3. Clinical Application of the Model

The clinical model of "Western medical diagnosis, TCM syndrome differentiation, TCM as the mainstay, Western medicine as the adjunct" can be applied to any systemic internal medicine condition; examples are provided below.