Exploration of Chinese medicine treatment ideas for chemotherapy-related anemia 1. Chemotherapy-related anemia harm Chemotherapy is an important measure to treat malignant tumors, prolong patients’ survival time and improve their quality of life, however, while it is effective, it often causes or aggravates patients’ anemia, which seriously affects their quality of life, and then can have a significant impact on their prognosis. The symptoms of fatigue, dizziness, loss of appetite, and depressed mood caused by anemia have a significant impact on quality of life (QOL). The ability to proceed with maintenance therapy and the quality of life of patients waiting for the observation period are closely related to the occurrence and severity of chemotherapy-associated anemia. Several studies have shown that the rate of local recurrence, distant metastasis, and mortality are significantly higher in patients with tumors combined with anemia than in patients without anemia. For the treatment of chemotherapy-associated anemia, blood transfusion and recombinant human erythropoietin (rhuEPO) are the main methods currently used. Blood transfusion can rapidly raise the hemoglobin level of anemic patients and improve their anemia, but this method has many defects such as co-infection, immunosuppression, and promotion of tumor growth. The effect of recombinant human erythropoietin in treating anemia is slow, and it usually takes an average of 4.1 weeks after the drug is administered to show the effect, and the efficiency is about 32%. There are also side effects that lead to hypertension, seizures, thrombosis, and pure red reoccurrence. Some studies have shown that the use of EPO may negatively affect the survival of oncology patients, such as increased incidence of vascular events and increased risk of death when the erythrocyte ratio reaches 42%. Therefore, it is important to actively explore effective drugs and treatments to prevent and treat chemotherapy-related anemia to improve patients’ quality of life, clinical efficacy and prognosis of advanced tumors. (1) Mechanism of chemotherapy-associated anemia prevention and treatment by Chinese medicine In our retrospective study of 211 advanced NSCLC cases, the investigation for the aspect of anemia showed that the decline of hemoglobin was obvious in the group of Western medicine alone than in the group of combined Chinese and Western medicine, which illustrates from one side that the participation of Chinese medicine in treatment during the chemotherapy period can reduce the occurrence of chemotherapy-associated anemia. During the peri-chemotherapy period, TCM has the effect of protecting the erythrocyte system from the damage of chemotherapy drugs, and the use of combined TCM has a protective effect on bone marrow function, which is the characteristic and advantageous link of TCM combined with chemotherapy in recent years. Relevant studies have shown that TCM has clear clinical efficacy in the prevention and treatment of chemotherapy-associated anemia. First of all, TCM has an overall regulating effect on the endocrine and immune regulatory network. The hematopoietic system of the body has a close relationship with the immune system, and immune active cells are involved in regulating the proliferation and differentiation of hematopoietic cells, while erythrocytes are also one of the important immune cells in the blood circulation. Modern research shows that many traditional Chinese medicines can inhibit tumor growth on the one hand, and stimulate the secretion of colony-stimulating factor and erythropoietin on the other hand to prevent or reduce the decrease of white blood cells, red blood cells and platelets after chemotherapy; in addition, traditional Chinese medicines with the effects of strengthening the spleen and tonifying the kidneys, benefiting qi and nourishing blood have better effects on improving appetite, protecting the mucous membrane of the gastrointestinal tract, and replenishing nutrients and trace elements. This provides a basis and reference for TCM to prevent chemotherapy-associated anemia from multiple links and targets, making TCM treatment both targeted and multi-effective. (2) Key pathogenic mechanisms of chemotherapy-associated anemia In Chinese medicine, anemia belongs to the categories of “deficiency labor”, “deficiency loss” and “blood deficiency”. The relationship between blood production and the five viscera has been discussed in detail in the Yellow Emperor’s Classic of Internal Medicine, for example, “The middle jiao receives qi to obtain juice, and changes and becomes red, which is blood.” The “Classes of Evidence and Treatment” says: “All deficiency and loss starts from the spleen and stomach.” The “medical zong must read” said: “a body, must be funded grain gas, grain into the stomach, sprinkled in the six internal organs and gas to, and regulate the five viscera and blood, and people are funded to live.” Jing Yue Quan Shu” said: “blood is the essence of water and grain. The source comes, biochemical in the spleen. Therefore, it is said that the essence of the latter day is in the spleen.” All these indicate that only when the spleen’s transport and transformation function is normal, the foundation for the transformation and production of essence and blood is available. The Yellow Emperor’s Classic of Internal Medicine also says, “The kidney is the master of dormancy, the essence of the spleen, and the place of essence.” Su Wen – Yin Yang Ying Xiang Da Lun, “The kidney is the master of bone and marrow.” The essence in the kidney can transform into vital energy, promote the spleen and stomach to produce water and grain essence and then transform into blood in the heart, and can transform with blood, i.e., essence and blood have the same origin. It can be seen that among the five organs, the spleen and kidney play a very important role in the production of blood. Chemotherapy is an important method for treating malignant tumors. According to Chinese medicine, chemotherapeutic drugs are “hot and fiery”, which is a kind of poisonous product, and can have the effect of “fighting poison with poison” against cancerous evil. However, it has obvious damaging effects on the body’s vital energy, including internal organs, yin and yang, qi and blood, fluids, etc. The characteristics can be summarized as follows: First, it will directly damage the body’s vital energy, deplete qi and blood, damage yin and yang, and even corrupt essence and blood; repeated chemotherapy will damage the kidneys and affect the bone marrow, resulting in a lack of kidney essence and a void in bone marrow, affecting the biochemistry of qi and blood and essence; the kidneys are the foundation of the first heaven, the root of the five organs and six bowels. Kidney deficiency can directly or indirectly lead to the decline in the function of other organs, resulting in qi deficiency, blood deficiency. In addition, the kidney is the master of bone and essence, and essence and blood can be transformed into each other. Kidney deficiency is not enough to collect essence and produce marrow, which can also lead to blood deficiency. Secondly, the spleen and stomach are injured, which affects the transport function of the spleen and stomach, and cannot receive water and grain, and the essence of water and grain cannot transform into qi and blood, resulting in internal growth of phlegm and dampness, which leads to no source of qi and blood biochemistry, and no way to serve the head and eyes and moisten the four ends, resulting in dizziness, weakness, insomnia and other symptoms; thirdly, the liver is directly damaged, resulting in liver yin deficiency, deregulation, and liver depression and qi stagnation, resulting in blood stasis. Therefore, it is believed that the key pathogenesis of chemotherapy-associated anemia is “deficiency of spleen and kidney, deficiency of both qi and blood, and internal obstruction of phlegm, dampness, stasis and blood”. In our long-term clinical practice, we have realized that the combination of Chinese medicine with chemotherapy can improve the clinical efficacy, prolong the survival period and improve the quality of life of patients, which is related to the comprehensive conditioning of the patient’s organism, improving immune function and reducing the toxic side effects of chemotherapy. Therefore, the use of Chinese herbal medicine in combination with chemotherapy at the same time can play a complementary role to the strengths and weaknesses. （Based on the above discussion of the etiology and pathogenesis of the disease, we believe that the main method of preventing and treating chemotherapy-associated anemia is to grasp the characteristics of the disease on the basis of the identification of the disease and the evidence, establish the main method of treatment and the therapeutic drugs, and add and subtract flexibly according to the evidence, reflecting the theory of “different treatment for the same disease” in Chinese medicine. The treatment should be combined with the immune characteristics and bone marrow characteristics of the disease in modern medicine. In recent years, the Department of Hematology and Oncology of Dongzhimen Hospital of Beijing University of Traditional Chinese Medicine has taken “prevention and treatment of chemotherapy-related anemia and improvement of the quality of life of tumor patients” as one of the important research directions of the discipline, and has carried out “strengthening the spleen and stomach, benefiting qi and promoting blood” and “strengthening the spleen and kidney, tonifying blood”. “At the same time, we noticed that most of the Chinese herbs with the effect of strengthening the spleen, tonifying the kidney and nourishing the blood are sweet, cold and sour in nature, and are “jing” in nature, so repeated application, especially during chemotherapy, tends to nourish and obstruct the stomach. They tend to nourish and obstruct the stomach, which is not conducive to the physiological characteristics of the spleen ascending and stomach descending, thus affecting the elevation of qi and the production of essence and blood. Therefore, in combination with Prof. Chen Xinyi’s experience, he often uses “dynamic” herbs to warm the Yang, regulate the Qi, invigorate the Blood, and dispel the channels, which can not only warm and promote the flow of Qi and Blood, but also help eliminate cancer toxins and phlegm stasis. Therefore, in case of deficiency of yang energy, we often add Panax notoginseng, Boneset, Epimedium, Cinnamon, etc.; in case of qi stagnation, we add Eucommia, Aromatic Herb, Glycyrrhiza, etc.; in case of blood stasis, we can add Panax notoginseng, Herba Cyperus, Safflower, etc.; in case of heat, we distinguish between actual heat and deficiency heat, and add Scutellaria, Zhi Mu, Artemisia, etc.; in case of poor appetite and abdominal distension, we add Fried Atractylodes, Chicken Nei Jin, Jiao Ma Ma Ye, Jiao Betel nut, Sha Ren, etc. In addition, it is worth introducing “Yimel Granules”, an in-house preparation of Dongzhimen Hospital of Beijing University of Traditional Chinese Medicine, which is formulated by a number of physicians with rich clinical experience in our hospital. The formula consists of Astragalus membranaceus, Radix Codonopsis pilosulae, Radix Rehmanniae Praeparata, Semen Cuscutae, Colla Corii Asini, Colla Corii Asini, Radix Salviae Miltiorrhiza, Radix Peach Kernel, Radix Angelicae Sinensis, Radix et Rhizoma Polygonati, Radix et Rhizoma Centipede. Astragalus is sweet and warm in nature, “benefits the vital energy, strengthens the spleen and stomach, activates the blood and generates blood”, raw and ripe ground “fills the bone marrow, generates essence and blood, nourishes the kidney water”, angelica and blood to replenish the blood, the three drugs together have the effect of benefiting the qi, nourishing the yin and activating the blood, in the formula and as the ruling drug; party ginseng is good at replenishing the middle qi. “The three herbs together have the effect of invigorating the Blood and nourishing the Yin and tonifying the Blood, and are also used as the ruler’s herbs in the formula; the adjuvant is chicken blood vine, peach kernel, safflower, ground dragon and other drugs commonly used to invigorate the Blood and remove blood stasis, which help the ruler to benefit the Qi and invigorate the Blood, and treat the symptoms of Blood stasis. “Centipede has the function of attacking toxins and dispersing nodules, so it can enhance the power of activating blood circulation when combined with other drugs to invigorate blood stasis, and centipede can induce medicine to enter the ligaments to promote the production and operation of qi and blood, so the two drugs are also adjuvants in the formula. The whole formula has the effect of strengthening the spleen, tonifying the kidney, benefiting the qi, nourishing the yin and invigorating the blood, which not only tonifies the innate nature but also the acquired nature, warming but not drying, tonifying but not stagnating, and combining movement and static. The formula reflects the overall treatment principle of TCM, which is to treat the root cause and both the symptoms and the root cause. It is clinically used to treat chemotherapy-associated anemia while reducing fatigue, promoting appetite, improving sleep, and significantly improving the quality of life of patients during chemotherapy. Clinical research on TCM for chemotherapy-associated anemia has just started and has not yet received sufficient attention, and there are many shortcomings, such as the clinical research on TCM is not strictly designed and the level of evidence-based evidence is low; the onset of action of TCM formulas is slow and the specificity is not high; if the efficacy of TCM is compared with that of recombinant human erythropoietin alone at the hemoglobin level, the role of TCM cannot be fully evaluated. Chinese medicine is also characterized by its ability to objectively improve the quality of life of patients and also to take into account the primary disease. Therefore, in the future, we should focus on analyzing the factors associated with chemotherapy-associated anemia and the characteristics of TCM evidence, and conduct rigorous clinical trials to elucidate and determine the effects and mechanisms of TCM preparations.