Analysis of drug use rules of Chinese medicine master Liu Shangyi to treat thyroid cancer

Jing Yang,Zhu Yang＊,Xun Liu,Xian-Man Wei,Dong-Xin Tang

1Guizhou University of Traditional Chinese Medicine, GuiYang, 550002, China. 2First Affiliated Hospital of Guizhou University of Traditional Chinese Medicine, GuiYang, 550001, China. 3Tumor Inheritance and Scientific and Technological Innovation Talents Base of Traditional Chinese Medicine in Guizhou Province, GuiYang,550001,China.

Abstract Objective: To explore the clinical drug use of Professor Liu Shangyi, a master of Chinese medicine, in the treatment of thyroid cancer based on the ancient and modern medical record cloud platform v1.5.7 software.Methods: From January 01, 2018 to April 01, 2019, the information input system of Professor Liu Shangyi,traditional Chinese Medicine Hospital of Guizhou Province, was screened. The data mining and analysis module was used to explore the clinical drug use of Professor Liu Shangyi in the treatment of thyroid cancer. Results: A total of 207 medical cases were recorded in this study, with 207 prescriptions, involving 129 kinds of herbs. The five most frequently used herbs are Ezhu (Curcumae Rhizoma), Biejia (Trionycis Carapax), Maozhuacao(Ranunculi Ternati Radix), Donglingcao (Rabdosia rubescens) and Chaojiezi (Sinapis Semen). Most of the drugs are warm and cold; most of the five flavors are sweet and bitter; most of the Meridian tropism are lung and liver;and the main efficacy are clearing away heat and toxic materials, eliminating phlegm and resolving hard mass.The most frequent correlation analysis of traditional Chinese medicines (TCM) are Bie Jia (Trionycis Carapax) - Ezhu(Curcumae Rhizoma), Donglingcao (Rabdosia rubescens)-Ezhu (Curcumae Rhizoma).Conclusion:Professor Liu Shangyi often use clearing away heat and toxic materials, resolving phlegm and disperse knot combined with tonifying liver and kidney in order to help fostering vital Qi and dispeling evil in clinical treatment of thyroid cancer.

Keywords:Master of Chinese medicine,Liu Shangyi,Thyroid cancer,Data mining.

Introduction

In recent years, with the increasing awareness of disease prevention and treatment, as well as the continuous improvement of medical technology, the growth rate of patients diagnosed with thyroid cancer ranks first in the world [1]. Modern medicine often adopts surgical treatment for thyroid cancer, but in the guidelines of the American Thyroid Association (ATA)in 2015 [2], it is proposed to oppose screening for thyroid cancer in non-high-risk groups,and not support all patients with low-risk thyroid cancer to undergo total thyroidectomy directly. Partial thyroidectomy,radiotherapy, and molecular targeted therapy can be chosen. However, surgery, radiotherapy and chemotherapy often lead to a series of toxic and side effects.Therefore, patients are often advised to choose TCM or integrated traditional Chinese and Western medicine to improve their efficacy and reduce toxicity.This article explores the rules and characteristics of Professor Liu Shangyi's treatment of thyroid cancer through the ancient and modern medical cloud platform software,so that the clinical experience of the masters of Chinese medicine can guide practice of more clinicians.

Materials and methods

Case source

All cases in this study were from January 01, 2018 to April 01, 2019, and were treated by Professor Liu Shangyi of the Chinese Medical College of Guizhou Provincial Hospital.

Materials collection

(1) Diagnostic criteria: The diagnose of Chinese medicine is "stony goiter" and Western medicine is"thyroid cancer". (2) General information including name, sex, age, number of treatments, medical history,tongue, tongue coating, pulse condition, Chinese medicine diagnosis,Western medicine diagnosis,TCM syndromes, treatment principles, prescription and dosage of single herbs, physician's name, date of consultation.(3)The route of TCM administration is to be taken orally; (4) For multiple treatments, take the materials of the first visit.

Exclusion standards

(1)Unclear diagnosis;(2)Incomplete case information;(3) Non-oral administration of TCM; (4) Repeated cases.

Chinese medicine standardization

The name of the Chinese medicine is based on the"People's Republic of China Pharmacopoeia" standard published by China Medical Science and Technology Publishing House on June 5, 2015. (1) Splittingt Chinese medicine: for example, "Shengshuzaoren" is divided into: "Suanzaoren (Ziziphi Spinosae Semen),Chaosuanzaoren (Stir-fried Ziziphi Spinosae Semen)","Qiangduhuo"is divided into "Qianghuo (Notopterygii Rhizoma Et Radix), Duhuo (Angelicae Pubescentis Radix)", etc. (2) Standardize Chinese medicine abbreviations: for example, "Danpi" is "Mudanpi(Moutan Cortex)", "Danxing" is "Dannan Xing(Arisaema Cum Bile)", "Wuyu" is "Wuzhuyu (Euodiae Fructus)",etc.(3)Unify the name of Chinese medicine:such as "Jiazhu" unified as "Chuanshanjia (Manis Squama)","Zaopi"unified as"Shanzhuyu(Cornifructus)", "Dayun" unified as "Roucongrong(Cistanches Herba)", "Xianlingpi" unified as"Yinyanghuo(Epimedii Foliume)"and so on.

Operation process

This study used the “Ancient and Modern Medical Case Cloud Platform V1.5.7”software provided by the China Academy of Chinese Medical Sciences. To ensure the accuracy of the data, two individuals independently screened the cases and input the materials to system, and then reviewed by two another people. If there are different views on the included cases, they will discuss the solution. The included cases are automatically standardized and added to the analysis pool, and finally enter the data mining analysis module.

Association analysis method

For example: When the confidence level = 1, it means that the "prescription containing Biejia (Trionycis Carapax) and Ezhu (Curcumae Rhizoma)" accounted for 100% of the proportion of prescriptions containing Biejia (Trionycis Carapax) in all prescriptions in this study. Formula: Confidence = P (A∪B) / P (A). The support degree = 0.89, indicating that "the prescription containing both Biejia (Trionycis Carapax) and Ezhu(Curcumae Rhizoma)" accounted for 89% of "all the prescriptions in this study",and the formula expressed:Support = P (A∪B). Lifting degree = 1.1, which means that the ratio of "containing Biejia (Trionycis Carapax) in the prescription containing Ezhu(Curcumae Rhizoma)" and "the ratio of prescription containing Ezhu (Curcumae Rhizoma)" is 1.1, and the formula is: Lift (A→B) = P (B|A) / P(B). The degree of lift reflects the correlation between A and B in the association rule.When the degree of lift ＞1,the higher data indicates the higher positive correlation;When the degree of lift ＜1, the lower data indicates the lower negative correlation; When the degree of lift = 1, it means no correlation.

Results

Age distribution

A total of 207 patients were included in the study.Among them, 34 were males and 137 were females.The age distribution is shown in Table 1.

Frequency statistical analysis of TCM

The 207 prescriptions included in this study were analyzed by data mining-medication-TCM statistics in software. The frequency, percentage, dosage and standard deviation of medication were calculated. It was concluded that 129 Chinese medicines were involved. The top 15 Chinese medicines, as shown in Table 2, The frequency of use is ≥39 times, and the percentage is ≥ 18.84%. The dosage and standard deviation are also shown in Table 2. The top five traditional Chinese medicines were Ezhu (Curcumae Rhizoma), Biejia (Trionycis Carapax), Maozhuacao(Ranunculi Ternati Radix), Donglingcao (Rabdosia rubescens)and Chaojiezi(Sinapis Semen),all of which were used more than 120 times.

Analysis of drug properties

Four gases

Using the data mining analysis in this softwaremedicine-Chinese medicine attribute-four gas analysis of Professor Liu Lao's treatment of thyroid cancer prescription,it is concluded that:207 prescriptions,the four gases were mainly warm (333 times), cold (320 times),mild cold(289 times),flat(141 times)and cool(110 times),as shown in Figure 1A.

Analysis of five flavors of drugs

Using the data mining analysis in this softwaremedication-Chinese medicine attribute--five-flavor analysis of Liu Lao's prescription for treating thyroid cancer, it is concluded that among the 207 prescriptions, Sweet (768 times), Bitter (639 times),Acrid (503 times), Acid (117 times) and Mild acrid(100 times) were the main ones, as shown in Figure 1B.

Analysis of Channel Attribution of Drugs

Using the data mining analysis in this softwaremedication-Chinese medicine attribute-Meridian attribution to the analysis of Liu Lao's treatment of thyroid cancer prescription, it is concluded that: 207 prescriptions, the meridian attribution were mainly lung meridian (826 times), liver meridian (825 times),stomach meridian (438 times), kidney meridian (419 times) and spleen meridian (355 times), as shown in Figure 1C.

Drug efficacy analysis

Using the data mining analysis in this softwaremedicine-Chinese medicine properties-efficiency analysis of Liu Shangyi's prescription for treating thyroid cancer, it is concluded that among the 207 prescriptions,the top five of the drug efficacy rankings were: clearing away heat and toxic materials,eliminating phlegm and resolving hard mass,promoting blood circulation and relieving pain,removing toxic materials and detumescence, and tonifying the liver and the kidney, The specific frequency is shown in Table 3.

Analysis of compatibility association of TCM

Using the data mining analysis in this softwaremedication-Chinese medicine attribute-compatibility and correlation analysis to the analysis of Liu Lao's treatment of thyroid cancer prescription, it is concluded that: confidence ≥0.36, support ≥0.32,promotion ≥ 0.91. This paper shows that the compatibility of traditional Chinese medicine with frequency ≥129 in correlation analysis is shown in Table 4.

Table 1 Age distribution table of thyroid cancer

Table 2 The top 15 Chinese medicines used frequently

Table 3 Analysis of drug efficacy

Table 4 Analysis of the association of the same frequency ≥129 times

Figure 1 Analysis of drug properties

Discussion

In 2018, research statistics showed that the total incidence of thyroid cancer in China ranked seventh,but the incidence of women was in the fourth [3]. In this study, a total of 207 cases were collected,including 34 males and 137 females, which is consistent with the previous statistical data.As early as in the "Shengji General Record", it has been recorded that there are more women than men in patients with thyroid cancer. It can be seen that the incidence of thyroid cancer in women is much higher than that of men.As can be seen from Table 1, age stratification is mainly concentrated between 30-60 years old,accounting for 81%of the total number,indicating that the trend of thyroid cancer is becoming more and more young. According to TCM, thyroid cancer belongs to the category of "stony goiter" or "sputum tumor".There were no obvious symptoms and signs in the early stage of the patients.As the disease progresses, it can be found that the front side or both sides of the neck are hard as a stone-like mass, the surface is uneven, moving up and down with swallowing action,and even the symptoms of compression and metastasis[4]. It has been recorded in many ancient TCM books,includingBei Ji Qian Jin Yao Fang,Sheng Ji Zong LuandSan Yin Ji Yi Bing Zheng Fang Lun.

In response to this disease,Liu Lao believes patients who are suitable for surgery should be operated timely.And those who can not tolerate surgery or be in the postoperative stage, long-term treatment with TCM,not only can inhibit the recurrence and metastasis of tumors,but also can play a role in increasing efficiency and reducing toxicity. For radiotherapy and chemotherapy, Liu Lao often mentioned the following words:Do it,but not too much.In clinical practice,Liu Lao combined the etiology and pathogenesis of this disease with Huang Yuanyu's theory of “one Qi and circumfluence” which was summarized: Qi stagnation,turbidity, and blood stasis [5]. Because the Qi of lung and stomach is lost in clearing and reducing accumulation, and the Qi of liver and spleen is lost in warming and rising, which leads to Qi stagnation,phlegm turbid and blood stasis in front of neck [6]. In addition, surgery, which is like the effect of trauma on the body, directly injure the patients and lead to the deficiency of healthy Qi. Radiotherapy, like the evil of dryness and heat, lead to Jin consumption and Yin deficiency, iltimately to the internal heat.Chemotherapy, like "poison drugs", poison the viscera and weaken healthy Qi [7].Therefore, Liu Lao use the method of clearing away heat and detoxifying,resolving phlegm and dispersing knots, and cooperate with the method of replenishing liver and kidney.

In this study, through the ancient and modern medical record cloud platform v1.5.7 software, the principle of Liu Lao's drug use in the treatment of thyroid cancer was excavated as follows: the drugs with high frequency of use were Ezhu (Curcumae Rhizoma), Biejia (Trionycis Carapax), Maozhuacao(Ranunculi Ternati Radix), Donglingcao (Rabdosia rubescens) , Chaojiezi (Sinapis Semen), Shancigu(Cremastrae Pseudobulbus Pleiones Peudobulbu),Shanzhuyu (Cornifructus), Huangjing (Polygonati Rhizoma), Lvcao (Scandent hop), Yujin(Curcumae Radix),Zhebeimu(FritillariaeThunbergii),Huangyaozi(airpotato yam),Xuanshen(Scrophulariae Radix), Foshou (Citri Sarcodactylis Fructus), Jiegeng(Platycodonis Radix),et al.The four gases of the drugs are mainly warm, cold, mild cold, flat and cool. The five flavors are mainly sweet, bitter, acrid, acid and mild acrid. The Meridian tropism of the drugs are mainly focus on lung, liver, stomach, kidney, and spleen meridian. The main efficacy are clearing away heat and toxic materials, eliminating phlegm and resolving hard mass, promoting blood circulation and relieving pain, removing toxic materials and detumescence, and tonifying the liver and the kidney.The most frequently used drugs in the correlation analysis of TCM are Biejia(Trionycis Carapax)-Ezhu(Curcumae Rhizoma), Donglingcao (Rabdosia rubescens) - Ezhu (Curcumae Rhizoma), Maozhuacao(Ranunculi Ternati Radix)-Ezhu(Curcumae Rhizoma),et al. The results showed that Liu Lao often used the self-made prescription "Jiazhu Ercao Decoction"[Biejia (Trionycis Carapax), Ezhu (Curcumae Rhizoma), Donglingcao (Rabdosia rubescens), Lvcao(Scandent hop)] to add and subtract in the clinical treatment of thyroid cancer patients. Among them,Biejia (Trionycis Carapax) is nail sweet, salty, cold,returning to the liver, kidney meridians, and have the function of convergence, detoxification, dissipating blood stasis and analgesia after vinegar-porcess. Ezhu(Curcumae Rhizoma), with the flavor of acrid, bitter and warm, returning to the liver and spleen meridians and has the function of breaking blood and promoting Qi,eliminating accumulation and relieving pain.Biejia(Trionycis Carapax) and Ezhu (Curcumae Rhizoma)are often used in combination, so that the function of breaking blood and removing blood stasis, softening firm and dispersing knots is doubled. Donglingcao(Rabdosia rubescens), with the flavor of bitter, sweet and slightly cold, returning to the lung, stomach and liver meridians. It has the function of clearing away heat and detoxification, activating blood circulation and relieving pain. Lvcao (Scandent hop) is sweet,bitter and cold and has the function of clearing away heat and diuresis, removing blood stasis and detoxifying.Both of them are bitter and cold herbs,the combined use of which can not only clear away heat and detoxify, but also lead themselves to diseases directly, resulting to achieve good anti-cancer effect.The combination of the four drugs has the effect of eliminating, clearing and nourishing, which fully reflects the idea of "Yin and Yang double elimination,nourishing yin and rising urgency" in the treatment of thyroid carcinoma by Liu Lao[8].The commonly used dosage is 20g of Biejia (Trionycis Carapax), 10g of Ezhu (Curcumae Rhizoma), 20g of Donglingcao(Rabdosia rubescens), 20g of Lvcao（Scandent hop),and the ratio is usually 2:1:2:2 (as shown in Table 2).Among them, Biejia (Trionycis Carapax), Ezhu(Curcumae Rhizoma), and Donglingcao (Rabdosia rubescens) can all be referred to the liver meridian,which shows that Liu Lao believes that"liver"plays an important role in the occurrence and development of thyroid cancer. Therefore, the combination of Foshou(Citri Sarcodactylis Fructus) and Yujin (Curcumae Radix) should be used in clinic to relieve liver depression, regulate Qi and relieve pain. From the above,in the clinical treatment of thyroid cancer,drugs at the top of the rankings in use frequency, four-gas,five-flavors, meridian tropism,and the effect, and the compatibility at the top of the rankings in use frequency, the confidence, the support degree and the improvement degree, can be used in combination with the syndrome differentiation and treatment of TCM,and finally the clinical curative effect can be better.

The famous veteran doctors of TCM, especially national medical masters, are the most outstanding model in modern Chinese medicine academia, and are the key figure to inherit the tradition of TCM and realize the development of TCM. Summarizing their clinical experiences, medication rules and academic thoughts, is one of the important ways to enrich TCM theory and practice system and promote the academic progress of TCM. In this paper, the data mining analysis was carried out on the rules of clinical drug using of Professor Liu Shangyi, a master of national medicine,in the treatment of thyroid cancer,in order to provide more therapeutic ideas and guidance for the clinical treatment of thyroid cancer.

Abbreviations

TCM, traditional Chinese medicines; ATA, American Thyroid Association.

Acknowledgments

None.

Competing interests

The authors declare that there is no conflict of interests regarding the publication of this paper.