2. Experimental Studies on Activating Blood Circulation and Removing Stasis

(1) Effects on the Cardiovascular System

Blood-activating and stasis-removing medicines can dilate coronary vessels, cerebral vessels, and limb vessels, increasing blood flow; they can also relieve vascular smooth muscle spasms, reduce myocardial oxygen consumption, and increase resistance to hypoxia. Collaborative groups in the Beijing area studying Guan Xin II No., the Shanxi Institute of Traditional Chinese Medicine researching Shi Xiao San, Zhejiang observing Chuan Xiong, Shanghai observing Dan Shen, and the Beijing Pharmaceutical Research Institute and the PLA’s 157th Hospital studying Mao Dong Qing—all confirmed these effects.

(2) Improving Microcirculation

The Pathophysiology Teaching and Research Group of the First Shanghai Medical College conducted experimental research on the effect of Dan Shen in treating microcirculatory disorders in rabbits. They injected 10% high-molecular-weight dextran saline solution into rabbits to induce peripheral microcirculatory disorders, then observed the microvasculature of the conjunctiva, finding that blood cells flowed slowly and aggregated into clumps of varying sizes. After treatment with Dan Shen injection, blood flow significantly accelerated, the number of capillary networks markedly increased, and red blood cells disaggregated to varying degrees, demonstrating that Dan Shen has the effect of improving microcirculation. The Physiological Teaching and Research Group of the First Shanghai Medical College and other institutions administered Dan Shen preparations intravenously to 56 patients with coronary heart disease and observed the peripheral microcirculation of 22 patients, finding that both the speed and state of red blood cell flow in the microvasculature improved significantly. The Chinese Academy of Medical Sciences’ collaborative research group on blood-activating and stasis-removing therapy used “Tong Mai Ling” to treat thromboangiitis obliterans and scleroderma, discovering that before treatment, the number of capillary loops in the nail folds decreased, became blurry and disordered, blood flow slowed down or stopped, and cells clearly aggregated. After treatment, the vessel morphology improved, blood flow accelerated, and cell aggregation lessened or disappeared. Therefore, it is believed that Tong Mai Ling has the effect of improving microcirculation, promoting blood flow, enhancing tissue nutrition, and facilitating lesion healing.

To further study the mechanism of Tong Mai Ling’s effect on microcirculation, they stimulated the buccal mucosa of rats with hydrochloric acid to induce microcirculatory disorders, then injected Tong Mai Ling, observing that stagnant blood flow decreased and thrombus formation reduced. They also induced acute and chronic bronchitis in rats with sulfur dioxide and observed the effect of Tong Mai Ling on microcirculatory disorders on the surface of the trachea, finding that after administration, dilated small veins immediately recovered, blood flow significantly accelerated, and the phenomenon of blood cells adhering to the vessel walls improved. In addition, Tianjin used blood-activating and stasis-removing decoctions, while Beijing used Dang Gui and Hong Hua for experimental research, discovering that these treatments could reduce capillary permeability.

(3) Effects on Collagen Fibers

The Chinese Academy of Medical Sciences used the blood-activating and stasis-removing preparation Tong Mai Ling to treat burn scars, conducting electron microscopy examinations and finding that blood-activating and stasis-removing medicines inhibit fibroblasts from producing collagen and also suppress fibroblasts’ ability to absorb glycine, thereby reducing collagen synthesis. Beijing and Tianjin used Tong Mai Ling to treat scleroderma; before treatment, patients’ serum showed elevated levels of bound hexoses and amino sugars, while after treatment, the levels of bound hexoses and amino acids in the serum significantly decreased, and collagen fibers changed from their original thick and swollen state to a thin state, with the skin becoming softer as well. The Shanxi Institute of Traditional Chinese Medicine applied the Yishen Decoction, which has blood-activating and stasis-removing effects, to treat nephritis with remarkable results. Through experimental research, they used uranium to induce kidney atrophy in rats, causing interstitial membrane-like proliferative changes in the renal parenchyma, and then administered Yishen Decoction to these rats before the lesions occurred. As a result, 65% of the treated rats did not develop proliferative changes, whereas only 21% of the untreated rats remained free of such changes, indicating that blood-activating and stasis-removing medicines can reduce fibrotic changes in the renal parenchyma and undoubtedly have therapeutic effects on chronic nephritis. The Shanxi Medical College studied the mechanisms of action of Ectopic Pregnancy I (Chi Shao, Dan Shen, Tao Ren) and Ectopic Pregnancy II (Chi Shao, Dan Shen, Tao Ren, San Leng, E Zhu) in treating ectopic pregnancies, and through experimental research discovered that Ectopic Pregnancy II has a certain inhibitory effect on the activity of lysyl oxidase in rat blood. Since lysyl oxidase activity promotes the formation of collagen fibers, it can be affirmed that Ectopic Pregnancy I has a certain therapeutic effect on hematoma formation and myofibrosis. However, the effect of Ectopic Pregnancy II is completely different from that of Ectopic Pregnancy I: it does not inhibit lysyl oxidase activity, but rather promotes collagenase activity, which aims to soften the myofibrous masses, making them easier to digest or absorb by other enzymes. Therefore, it can be affirmed that Ectopic Pregnancy II has a promoting effect on the dissolution of myofibrous masses.

(4) Effects on Inflammation

Blood-activating and stasis-removing medicines generally have anti-inflammatory effects. Experimental studies have proven that Ku Shen, Dan Pi, Chuan Xiong, Chi Shao, and Da Huang can inhibit intestinal pathogenic bacteria; Da Huang, Ku Shen, Hong Teng, Dan Pi, and Chi Shao can inhibit Staphylococcus aureus; and Da Huang, Dan Pi, Chi Shao, Chuan Xiong, as well as Zi Cao, Di Yu, Huang Yao Zi, and Zi Jing Pi also have antiviral effects. The Nankai Hospital in Tianjin selected commonly used blood-activating and stasis-removing medicines for acute abdominal conditions—Dan Pi, Chi Shao, Dang Gui, Tao Ren, Hong Hua, and Yuan Hu—and formulated them into intravenous injections. Through applications on cotton ball granulomas, castor oil cysts, turpentine cysts, and formaldehyde arthritis in white rats, as well as experiments on the permeability of rabbit skin capillaries, it was demonstrated that blood-activating and stasis-removing medicines can reduce capillary permeability and decrease inflammatory exudation, thereby confining the lesion. Experiments also proved that blood-activating and stasis-removing medicines can increase blood flow in isolated dog intestinal loops, dilate peripheral vessels, and promote the absorption of inflammatory exudates. Since the effect of blood-activating and stasis-removing therapy is not simply limited to inhibiting bacteria, but indirectly reduces inflammatory responses by improving capillary permeability and dilating peripheral vessels, the anti-inflammatory effect of blood-activating and stasis-removing therapy has unique significance.

(5) Promoting Tissue Repair

Numerous experimental studies have proven that blood-activating and stasis-removing medicines are helpful for tissue repair and regeneration. A collaborative group in the Beijing area observed the impact of the Guan Xin II II formula on the extent of myocardial necrosis. From qualitative and quantitative histological observations, as well as electron microscopic observations of tissue morphology, it was found that Guan Xin II II can significantly reduce the scope of myocardial infarction. Under electron microscopy, the control group’s myocardial infarction area showed complete disappearance of glycogen, severe swelling of mitochondria, disruption of cristae, condensation of nuclear chromatin, rupture of nuclear membranes, and other irreversible changes, whereas the medicated group showed much fewer of these irreversible changes in the infarct area. In addition, the Shanxi Institute of Traditional Chinese Medicine used histochemical methods to examine enzyme activity and electron microscopy to observe the ultrastructure of the myocardium, finding that the degree of mitochondrial damage was consistent with the degree of ATPase and succinate dehydrogenase activity destruction. The control group’s myocardium showed significantly lower ATPase and succinate dehydrogenase activity than the protected group using blood-activating and stasis-removing medicines, indicating that blood-activating and stasis-removing medicines protect mitochondria from damage, thus confirming their role in inhibiting myocardial infarction. Furthermore, numerous clinical trials have also proven that blood-activating and stasis-removing medicines can rapidly restore hepatocytes after degeneration, quickly heal ulcers caused by thromboangiitis obliterans, and accelerate bone growth. All of these demonstrate that blood-activating and stasis-removing therapy can promote tissue repair.

(6) Effects on the Body’s Immune Cells

The Clinical Immunology Research Institute of the Chinese Academy of Traditional Chinese Medicine observed the effect of blood-activating and stasis-removing formulas designed to prevent ABO-type neonatal hemolytic disease on antibody-forming cells—B cells—and found that blood-activating and stasis-removing medicines have a clear inhibitory effect on antibody-forming cells, indicating that these medicines can inhibit antibody-antigen complex reactions—autoimmune reactions. The China Welfare Association International Maternal and Child Health Hospital also achieved good therapeutic results by using blood-activating and stasis-removing medicines to treat the aforementioned hemolytic disease, and experimental studies reached the same conclusion. Based on this, clinical use of blood-activating and stasis-removing medicines to treat autoimmune diseases can achieve obvious therapeutic effects, such as systemic lupus erythematosus, rheumatoid arthritis, scleroderma, and nodular periarteritis.

Although blood-activating and stasis-removing therapy has made considerable progress in clinical application and experimental research, its underlying principles are still being further studied. We believe that as long as we persist in the path of integrating traditional Chinese and Western medicine, continuously practice, and constantly summarize our experiences, we will surely be able to further develop and improve blood-activating and stasis-removing therapy, allowing this pearl in the treasure trove of traditional Chinese medicine to shine even more brilliantly and contribute to the health of the people.

(“Overview of Integrated Traditional Chinese and Western Medicine in Gansu Province,” April 1980)

Discussion on Differentiation of Febrile Diseases

Pei Zhengxue

Febrile diseases are collectively referred to as Shanghan and Wenbing. Shanghan is caused by cold pathogens, while Wenbing is caused by heat pathogens. Although the two are different, they can both lead to fever, hence the collective term “febrile diseases.” In the discussion of febrile diseases, Traditional Chinese Medicine has historically been divided into the Shanghan School and the Wenbing School. The Shanghan School focuses on the cold causes and yang-deficiency characteristics of febrile diseases, emphasizing pungent-warm exterior-releasing and emergency yang-restoring methods; the Wenbing School focuses on the heat causes and yin-depletion characteristics of febrile diseases, emphasizing pungent-cool exterior-releasing and yin-nourishing, fire-lowering methods. For a long time, the two schools have each held firm to their own views and opposed each other, leading to the famous Shanghan-Wenbing debate in the history of traditional Chinese medicine. However, with the development of modern medical science, people have gradually realized that Shanghan and Wenbing both belong to external-febrile diseases, and for the same febrile disease, it may simultaneously exhibit both Shanghan and Wenbing characteristics, or alternate between some clinical manifestations of Shanghan and Wenbing. Therefore, strictly separating the diagnostic methods of Shanghan and Wenbing is clearly not conducive to the objective needs of clinical diagnosis. Whether we can organically combine the diagnostic and therapeutic approaches of the two schools to form a unified diagnostic method for febrile diseases in Traditional Chinese Medicine is a glorious yet arduous task facing all TCM practitioners. With due humility, the author hereby offers his own superficial views on this issue.

I. Brief History of Shanghan and Wenbing

“The Plain Questions · On Fever” states: “When people are injured by cold, it becomes a febrile disease.” It also says: “Now, all febrile diseases are of the Shanghan type.” This is the earliest discussion about Shanghan, which considers Shanghan to be a febrile disease. “The Plain Questions · On the Flow of Vital Energy” states: “When a disease is caused by cold and develops into a febrile disease, if it occurs before the summer solstice, it is called a ‘Wen’ disease; if it occurs after the summer solstice, it is called a ‘Shu’ disease.” This shows that Wenbing is included within Shanghan. “The Plain Questions · On Fever” further divides febrile diseases into six categories: Juyang, Yangming, Shaoyang, Taiyin, Shaoyin, and Jueyin (the Six Meridians). Although it does not detail the pathogenesis, syndromes, or prescriptions, it provides a basis for the emergence of Six Meridian differentiation. At the end of the Eastern Han Dynasty, the renowned physician Zhang Zhongjing, drawing on his rich clinical experience, wrote “The Treatise on Cold Damage and Miscellaneous Diseases” and, building on the Six Meridians of the “Inner Canon,” established the Shanghan diagnostic criteria—the Six Meridian differentiation—making the diagnosis and treatment of external-febrile diseases more systematic. During the chaos at the end of the Han Dynasty, the “Treatise on Cold Damage and Miscellaneous Diseases” was scattered, but Wang Shuhe of the Jin Dynasty recompiled it, ensuring that the book could still be passed down through the ages. Starting from Cheng Wuyi of the Song Dynasty, physicians successively elaborated on the Six Meridians of Shanghan, some discussing the Six Meridians based on treatment methods, others based on prescriptions, others based on organs, others based on the Eight Principles, others based on meridians—essentially, people tried to align Six Meridian differentiation with the ever-evolving clinical practice. At the same time, physicians also applied some effective prescriptions clinically to supplement the shortcomings of Shanghan prescriptions, such as Qian Zhongyang’s Baidu San, Liu Shouzhen’s Shuang Jie San, Zhang Yuan’s Jiu Wei Qiang Huo Tang, and Li Dongyuan’s Pu Ji Disinfection Ci—each of these, to a certain extent, went beyond the scope of the “Treatise on Cold Damage” regarding pungent-warm exterior-releasing. This shows that as clinical practice gradually enriched, people were constantly enriching and improving the original treatment methods of Shanghan. In particular, Liu Shouzhen of the Song-Jin period (1110–?) provided especially detailed elaborations on febrile diseases, expanding the scope of the “Inner Canon’s” nine fire-related disease syndromes, emphasizing the relationship between fire-related syndromes and the five elements of wind, cold, dampness, dryness, and heat, thereby forming the view that “all six elements ultimately transform into fire.” In terms of treatment, he strongly advocated clearing heat and draining fire, pointing out the drawbacks of relying solely on pungent-warm exterior-releasing. Liu’s achievement objectively compensated for the shortcomings of the “Treatise on Cold Damage,” creating the preconditions for the emergence of the Wenbing school of thought. Wang Andao of the Ming Dynasty (1332–1391) was the first to clearly distinguish between Shanghan and Wenbing, saying: “It is precisely because people indiscriminately call Wenbing ‘Shanghan’... that they use warming medicines, which, in reality, mislead people and endanger their lives. Shouldn’t we correct this naming?”^①^ Wang also explained the differences between Wenbing and Shanghan in terms of syndromes, pathogenesis, and treatment methods, thus enabling the Wenbing school of thought to begin standing out on its own. In light of this, later generations revered Wang as the founder of the Wenbing school of thought, which is indeed justified. Subsequently, Wang Shishan of the Ming Dynasty (1463–1539) proposed the concept of “newly contracted Wenbing,” saying: “If you are injured by cold in winter... and it manifests in spring... this is latent Wenbing; if you are not injured by cold in winter but develop Wenbing in spring, this is specifically spring Wenbing, which can be called ‘spring Wenbing,’ distinct from winter Shanghan and autumn…”

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The injury due to dampness is similar to summer heatstroke; this is a new-type warm disease. "^②^ Thus, latent pathogenic factors and newly contracted diseases have become the two major types of warm disease development. In the late Ming Dynasty, in the Xinsi year of the Chongzhen reign (1641), epidemics of warm diseases broke out in provinces such as Shandong, Henan, Hebei, and Zhejiang. Many physicians treated them using methods for cold damage, but these were ineffective; Wu Youke, however, used methods for warm diseases and achieved remarkable results. He believed that epidemics fundamentally belonged to the category of warm-heat conditions and were entirely different from cold damage, and he authored the book "On Warm Epidemics," thereby expanding the scope of warm disease studies to encompass all febrile infectious diseases. Later, another prominent scholar of warm diseases, Ye Tianshi (1666–1745), wrote "On Warm Heat," establishing the differentiation of defensive qi, nutritive qi, and blood, and summarizing the principles of syndrome differentiation and treatment for febrile illnesses. He stated: "In general, when discussing syndromes, one speaks of defensive qi after the defensive layer, and nutritive qi after the nutritive layer. It is appropriate to induce sweating at the defensive level; once it reaches the qi level, one can clear the qi; if it enters the nutritive layer, one can still transform the heat into qi through herbs such as rhinoceros horn, rehmannia root, and moutan bark. However, if it enters the blood, there is a risk of depleting or stirring up the blood, so one must cool and disperse the blood with herbs like raw rehmannia, moutan bark, donkey-hide gelatin, and red peony root." "^③^ Wu Jutong (1736–1820) followed Ye's teachings and wrote "Detailed Discussions on Warm Diseases." Building upon the "defensive qi, nutritive qi, and blood" differentiation, he proposed a diagnostic framework for warm diseases based on the Three Jiao—namely, Three Jiao differentiation. He said: "Warm diseases enter the body through the mouth and nose. Nasal qi connects to the lungs, while oral qi connects to the stomach. If lung disease spreads upward, it affects the pericardium; if upper-jiao disease is left untreated, it will spread to the middle jiao, affecting the spleen and stomach; if middle-jiao disease is left untreated, it will spread to the lower jiao, affecting the liver and kidneys; it starts in the upper jiao and ends in the lower jiao." "^④^ By this point, the theory of warm diseases had formed a complete system of principles, methods, formulas, and medicines.

II. Basic Content of Syndrome Differentiation Between Cold Damage and Warm Diseases