Exploration on YE Tianshi’s thinking of medication in the treatment of metrorrhagia and metrostaxis based on data mining

Jian-ming Ren, Jing-ming Zhang

Shaanxi University of Chinese Medicine, Xianyang 712046, Shaanxi Province, China

Abstract Objective: Based on the traditional Chinese medicine inheritance computing platform (V3.0),this study aims to explore the prescription medication thinking of treating metrorrhagia and metrostaxis in Ye Tianshi Medical Encyclopedia. Methods: The prescriptions for metrorrhagia and metrostaxis in Ye Tianshi Medical Encyclopedia were input into the traditional Chinese medicine inheritance and computing platform, and Ye Tianshi’s prescription medication thinking for metrorrhagia and metrostaxis was analyzed by statistical analysis, association rules, k-Means clustering algorithm and regression simulation method. Results: Sixty-nine prescriptions for metrorrhagia and metrostaxis after screening were analyzed, including 133 medicinal ingredients.High-frequency drugs included Radix Ginseng, Radix Angelicae Sinensis, Radix Paeoniae Alba, Colla Corii Asini and so on; The drug characteristics were sweet, warm and belonging to kidney meridian; After the statistics of drug efficacy, tonic drugs took the first place; Six core drug combinations were summarized. Conclusion: Ye Tianshi mainly treats metrorrhagia and metrostaxis with sweet drugs, focuses on the relationship between regulating extraordinary meridians and viscera, is good at discriminating physique, pays attention on drug processing and dosage form selection, and uses drugs at the right time, which embodies the changing thinking.

Key words: Metrorrhagia and metrostaxis; Data mining; medication ideas; Ye Tianshi Medical Encyclopedia

Introduction

Metrorrhagia and metrostaxis is a common and frequently-occurring disease in gynecology, and is divided into “metrorrhagia” and “metrostaxis”, which refers to abnormal pathological changes in menstrual cycle,menstrual period and menstrual quantity. “Metrorrhagia”refers to continuous menstrual blood; “Metrostaxis”refers to the incessant menstruation. The two symptoms can transform into each other. As early as in Neijing,there is a record that “Deficiency of Yin due to struggle of Yang causes metrorrhagia”. In the treatise on the Origin and Prognosis of Various Diseases written by Yuanfang Chao in Sui Dynasty, “Clinical manifestations in the metrorrhagia and metrostaxis” is specialized, saying that “from time to time, constant dripping is called metrostaxis”, “sudden metrostaxis is called metrorrhagia”.Throughout the treatment of metrorrhagia and metrostaxis in 69 cases by Ye, more emphasis is placed on regulating the extraordinary meridians and dysfunction of viscera,with accurate syndrome differentiation and accurate prescription. Based on the traditional Chinese medicine inheritance computing platform (V3.0), this paper explores Ye’s prescription medication thinking in treating metrorrhagia and metrostaxis, aiming at providing reference for improving clinical medication level based on syndrome differentiation.

Data and Methods

Prescription sources and screening criteria

The prescriptions of the medical records for metrorrhagia and metrostaxis in Ye Tianshi Medical Encyclopediaserved as the data source, and the prescriptions of the same cases were excluded. After screening, 69 prescriptions were obtained and the database was established.

Prescription entry and check

The name of the drug was standardized according to the Traditional Chinese Medicine Prescription Scienceand Chinese Pharmacopoeia, such as Eclipta prostrata, Hulian and Angelica sinensis are regulated as Eclipta prostrata,Lotus Seed and Angelica sinensis, respectively. The screened prescriptions were entered into the traditional Chinese medicine inheritance computing platform (V3.0),and were reviewed by two people for accuracy.

Data analysis

“Traditional Chinese Medicine Inheritance Computing Platform V3.0” software was used to make statistics and mining on the data in prescriptions, and analyze the application characteristics of prescriptions.

By clicking “Statistical Analysis”, a statistics on the frequency of use, character, taste and channel tropism of drugs was performed, then the results were exported and displayed in a diagram.

Under the conditions of support number ≥8 (support degree 12%) and confidence degree ≥0.7, we analyzed drug use patterns and association rules, and analyzed high-frequency drug combinations and association rules according to the frequency of drug combinations and confidence order; the high-frequency drug combination network was also visualized.

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According to the number of prescriptions, we observed the clustering situation with different cluster numbers. In combination with empirical judgment and pre-reading of data extracted from different parameters, K-Means clustering algorithm and regression simulation were used for clustering analysis (the core algorithm was unsupervised K-Means clustering analysis) to obtain the best cluster number, extract the core drug combination and display it in the form of network diagram. In addition,the theory of traditional Chinese medicine was used for further analysis to conclude the thinking of prescription medication.

Results

Medication frequency, tropism and efficacy

According to the statistics, there were 133 traditional Chinese medicines and 69 prescriptions. The frequency of drugs used was ranked, and the frequency of drugs used by 24 medicines was ≥6, as shown in Table 1.

Table 1 Drugs with frequency ≥6 in the prescription for treating metrorrhagia and metrostaxis

Statistics on nature, taste, channel tropism and frequency of 133 drugs were shown in Table 2.

Table 2 Nature, taste, channel tropism and frequency of drugs for metrorrhagia and metrostaxis selected in Ye’s records

After analysis, the efficacy classification of 133 drugs for metrorrhagia and metrostaxis showed that deficiencyreinforcing drugs accounted for the largest proportion, as shown in Figure 1.

Figure 1 Efficacy chart of 133 drugs for metrorrhagia and metrostaxis

By analyzing the nature, taste and channel tropism of 133 traditional Chinese medicines, and sorting the frequency of use, it was concluded that mild (171 times) drugs were mainly used to treat metrorrhagia and metrostaxis in Ye’s records, as shown in Figure 2; the main taste was sweet (307 times), as shown in Figure 3; the kidney meridian was the most common channel (251 times), as shown in Figure 4.

Figure 2 Statistical radar chart of four natures of drugs

Figure 3 Statistical radar chart of five tasters of drugs

Figure 4 Statistical radar chart of channel tropism

Analysis of prescription rule based on association rules

Assuming that the support number is 8 (support degree 12%) and the confidence is 0.7, 33 high-frequency drug combinations were obtained and sorted in an order from high to low according to the frequency of drug combinations ≥9, as shown in Table 3.

Table 3 Drug combinations with frequency ≥9 in the prescription for treating metrorrhagia and metrostaxis

Assuming that the support number is 8 and the confidence is 0.7, 36 drug association rules were obtained and displayed on the network, as shown in Figure 5. The drug combinations with top 16 confidence levels in association rules were shown in Table 4.

Table 4 Association rules with top 16 confidence levels

Figure 5 Drug association with 8 support degree (12% support degree) and 0.7 confidence

Core combination analysis based on K-Means clustering and linear regression

With K-Means clustering analysis and linear regression method, through pre-reading and comparison of data, the best cluster number was obtained when clustering into three categories. The core combinations of 6 groups using 3 herbs were counted, as shown in Table 5.

Table 5 Core combination of three drugs in the prescription for treating metrorrhagia and metrostaxis

Analysis and Discussion

Analysis of Ye’s medication rule of metrorrhagia and metrostaxis case

The deficiency type is predominant in Ye’s records of metrorrhagia and metrostaxis cases, and the syndrome of unconsolidation of Chong and Conception Channels has the peak number, which involves many causes, such as deficiency cold of Chong and Conception Channels,failure of astringing for hemostasis, or failure of liver to convey and disperse, failure of reserving blood, or spleenqi deficiency, failure of controlling and managing bleed, or Yuan Yang deficiency, loss of consolidation of yin blood,or stagnation of blood stasis, failure of blood to circulate in the vessels.

Based on traditional Chinese medicine inheritance computing platform (V3.0), 69 prescriptions for metrorrhagia and metrostaxis are recorded in Ye Tianshi Medical Encyclopedia, involving 133 drugs, and 24 high-frequency drugs, 23 high-frequency association combinations and 6 core drugs are analyzed.

According to the frequency statistics, the top 6 drugs with the highest frequency of use belong to deficiencytonifying drugs, and sweet and warm drugs are used most frequently. Among them, Ginseng is sweet and warm,and it is the preferred choice for Ye’s tonifying stomach qi; E-gelatin is sweet and flat, for nourishing blood and stopping bleeding; Chinese angelica is sweet and warm,for nourishing blood and promoting blood circulation;Rehmannia glutinosa is sweet and warm, for filling essence and replenishing marrow; Radix paeoniae alba is sweet and sour, for nourishing ying, astringing yin and nourishing liver; Roasted licorice is sweet and warm, for nourishing heart blood and benefiting spleen, which shows that Ye’s treatment principle of metrorrhagia is mainly sweet, sweet and warm for enriching blood and stopping bleeding,sweet and sour for nourishing ying, astringing yin and stopping bleeding. High-frequency drug combinations,such as Ginseng-E-gelatin, E-gelatin-Paeonia lactiflora,E-gelatin-Radix rehmanniae recen and Ginseng-Radix Glycyrrhizae Preparata, are the main drugs in Jiaoai Decoction, Siwu Decoction and Wenjing Decoction,which embody the basic law of treating metrorrhagia and metrostaxis, that is, firstly, blocking flow, regardless of sudden metrorrhagia and long metrostaxis, which will eventually lead to qi and blood consumptions. Treatment of qi is the premise for treating blood, Ginseng is used at acute conditions for benefiting qi and nourishing blood,cure metrorrhagia and stopping metrostaxis; secondly,treating root cause for arresting uterine hemorrhage, or using Radix paeoniae alba to nourish the yin and soften the liver, or using Cyperus rotundus to disperse stagnated liver qi for relieving qi stagnation, or using the rhizome of large-headed atractylodes to invigorate the spleen and replenish qi, or using Angelica sinensis to remove blood stasis and stop bleeding; Finally, whether it is actual or false, metrorrhagia and metrostaxis will eventually lead to deficiency of qi and blood and consumption of body essence. Ye Tianshi have made good use of the affectionate,thick and quiet medicines such as E-gelatin, tortoise shell,placenta hominis and antler glue to fill the essence and liquid, nourish the flesh and blood, dredge and supplement the extraordinary meridians, and supplement the loss of yin essence of human body, so as to achieve the purpose of rejuvenation.

Ye’s thinking of medication in treating metrorrhagia

Asking for odor is a major feature of Ye’s treatment and medication, which is fully reflected in Ye’s treatment of metrorrhagia and metrostaxis. Ye prefers the use of sweet medicines, which are most frequently used in metrorrhagia and metrostaxis cases, accounting for 307 times. Metrorrhagia and metrostaxis cause qi and blood loss, and women are often accompanied by acute pain in waist and abdomen. Ye’s medicine is mainly sweet, either sweet and warm or sweet and salty. Sweet medicines can relieve urgency and pain, and combination of sweet and warm drugs can invigorate qi and nourish blood, such as Radix Glycyrrhizae Preparata-Rhizoma zingiberisthe rhizome of large-headed atractylodes. Salty taste is specialized in kidney meridian, and the heat syndrome of metrorrhagia and metrostaxis is common. It is compatible with tortoise shell, oyster and turtle shell which are salty,cold and fishy, and mussel and abalone which are quiet and watery. It can clear heat, solidify meridians, stop metrostaxis, fill kidney qi, and tonify kidney essence and liver blood. Placenta hominis, pilose antler and E-gelatin with sweet, salty, warm nature for flesh and blood can warm the kidney qi and enhance the power of Ren, Du,Chong and other extraordinary meridians to capture qi and blood, so as to stop metrorrhagia and eliminate metrostaxis.

The normal discharge of menstruation depends on the normal qi transformation function of viscera and meridians, the liver stores blood, the kidney stores the essence of the five internal organs, and the Chong channel is the blood sea, which belongs to Yangming, and the eight channels are attached to the liver and kidney, so the extraordinary meridians are closely related to the spleen,liver and kidney. Metrorrhagia is caused by dysfunction of the spleen, liver, kidney and extraordinary meridians,which fundamentally leads to qi and blood consumption.In treating metrorrhagia and metrostaxis, Ye Tianshi has attached great importance to regulating the relationship between the spleen, liver and kidney and extraordinary meridians, and the eight extraordinary meridians depend on the irrigation and nourishment of viscera and qi and blood. If the function of spleen qi transformation is normal, the production and transformation of qi and blood are continuous, the liver blood and kidney essence are sufficient, the storage and discharge are coordinated, the eight channels are naturally healthy, and the menstruation is regular like the tide. Once the kidney qi transformation is disordered, the liver and kidney are imbalanced in store and discharge, extraordinary meridians will produce pathological changes. For the disorders of extraordinary meridians, Ye proposes to tonify for deficiency and to dredge for tonifying. If deficiency of Du Yang is caused by loss of inducing astringency, take the taste of pure yang of Cornu Cervi Pantotrichum to warm up it; if Belt vessel fails to restrain all meridians, causing vaginal dripping, take the sweet and warm Angelica sinensis to nourish it; if stirring wind due to yin deficiency in Ren and Chong channels disturbs collaterals, take the tortoise shell with salty and cold nature to nourish yin and suppress yang, relax the wind and protect the uterus.Core combination: Ginseng-Atractylodes rhizome-Poria cocos, invigorating qi and strengthening spleen;Paeonia lactiflora-Angelica sinensis-E-gelatin, Wolfberry,nourishing liver and tonifying kidney, combined with tortoise shell, velvet antler, oyster and other flesh and blood to conserve extraordinary meridians, which is the compatibility of drugs commonly used by Ye Tianshi to regulate the relationship between spleen, liver and kidney and extraordinary meridians.

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Ye’s treatment of metrorrhagia and metrostaxis pays attention to “preserving body”, and uses drugs according to constitution. Women’s metrostaxis and metrostaxis are roughly divided into three constitution types: at 14 years, the Chong channel begins to flourish, kidneyessence for promoting reproductive function begins to take effect, menarche occurs, kidney qi is not even, and the menorrhea is not stable. Menstruation cycle and menstrual volume are prone to abnormal, so virgin at young age should focus on kidney treatment, to produce even kidney qi, harmonize the Chong and Ren channels,and cause regular menstruation. For example, the core combination: Astragalus complanatus-Lycium barbarum-E-gelatin, tonifying kidney essence, nourishing Chong and Ren. At the age of 21-35 years, the ancients advocate that many children bring many blessings, and women experience several childbirths. Among the Ye’s records in 69 cases of metrorrhagia and metrostaxis, over 10 cases of metrorrhagia and metrostaxis are caused by miscarriage,or frequent abortion caused by miscarriage, or loss of maintenance for decades after childbirth. After years of illness and blood loss, it leads to liver dystrophy. In addition, in the prime of life, the burden of life is heavy and verbose, women are entangled by trivial matters and tired of management, which easily leads to emotional depression, blockage of qi movement, abnormal function of qi transformation. Therefore, the treatment at this stage should disperse the stagnation of liver qi. For example,the core combination, Ginseng-angelica-E-gelatin-Radix paeoniae alba root, invigorating qi and nourishing blood,tonifying ying and astringing yin, moistening wood to dredge qi movement, nourishing the body, smooth liver qi, harmonize qi and blood, self-stop metrorrhagia. At the age of 42-49 years, the Sanyang vessel declines, the kidneyessence for promoting reproductive function is exhausted,the menostasia occurs, the kidney qi is weakened, and the Chong channel is deficient. The symptoms of essence movement such as metrorrhagia and metrostaxis, heat and sweating could be seen inferiorly and externally; while,the manifestations of vitality disorder such as annoying,insomnia and dreaminess could be seen superiorly and internally. Therefore, the treatment should focus on tonifying blood and menstruation, clearing heat,relieving vexation and calming nerves, so as to achieve communications between heart and kidney, quiet and calm mind. For example, the core combination: E-gelatin-Radix Paeoniae Alba-Fu Shen, Angelica sinensis-Egelatin-Radix Paeoniae Alba, can treat both metrorrhagia and metrostaxis, supplement congenital menstruation,benefit liver blood in women, and remove both symptoms and signs.

Natural environment and human being correspond to each other, and vitality of human communicates and corresponds to the universe. The solar terms at four seasons have a close influence on the movement of qi and blood in human body. With the rise and fall changes of yin and yang, timely medication has a special embodiment in the treatment of metrorrhagia. For example, in the case with stirring of wind due to deficiency of yin in extraordinary meridian, “in the summer, the hot weather and diarrhea with qi stagnation certainly produce the tired mood, and Ophiopogon japonicus, Schisandra chinensis and American Ginseng are suggested to clear the heat and benefit the qi”; “in the middle autumn, the movement is limited, and tortoise shell heart, antler cream, E-gelatin,cypress cream, raw oysters, Cynomorium songaricum are suggested to dredge yin and suppress yang”.

In order to treat the illness, Ye has adopted a variety of processed drugs. For example, tortoise shell is soaked in prepared salt, which is introduced into the kidney to increase the power of tortoise shell to clear heat; Cuttlefish bone is roasted with rice vinegar to increase the effect of acid astringency and stopping bleeding; Semen Platycladi is prepared as a cream to take its slow nature, which can cool the heart and nourish the kidney without chilling;argy wormwood leaf carbon and fennel are stirred to enter the blood and further stop bleeding; rehmannia glutinosa is stir-fried with carbon to enter the kidney and further prevent cold injury of raw rehmannia glutinosa and greasy stagnation of prepared rehmannia glutinosa.

All dosage forms, including pills, powder, paste and dan, are used in combinations. First decoction and then pills: For example, in the case of stomach deficiency symptom in Chong and Ren channels, they are treated with cuttlebone, abalone, madder, raw dodder and shell lotus broth as the symptomatic therapy, followed by cuttlefish bone Pill composed of high-frequency drugs cuttlefish bone and madder, as radical therapy. Morning decoction and evening pills: For example, in the case of yin and yang deficiency syndrome, they are treated with Ginseng, angelica, fried medlar, poria cocos, placenta hominis and velvet antler in the morning, and with Zhenling Pellet composed of fluoritum and limonitum in the evening. Take pills with soup: For example, in the case with stirring of wind due to deficiency of yin in extraordinary meridians, they are treated with Ginseng,E-gelatin and Radix paeoniae alba root as pills by powder and paste, administered with Shengmai San. For frequent metrorrhagia signs and long-term metrostaxis signs, pills are used to slow down the condition and accumulate the effect to cure the root cause.

Scutellaria baicalensis Georgi and Foeniculum vulgare are combined to treat metrorrhagia and metrostaxis with bitter and pungent herbs to dredge, supplement extraordinary meridian, clear the superior and warm the inferior. The frequency of fennel used in 69 prescriptions is 7, and Ye often uses it for compatibility with other drugs, leading drugs into kidney meridian to warm kidney qi. The taste of flesh and blood is fish-smelly, sticky and turbid, and stagnates in the stomach, such as E-gelatin,placenta hominis, antler glue. In order to prevent stomach obstruction, Ye’s medicine propose light administration of turbid drugsin a low dose and high frequency; On the other hand, it is often combined with qi-regulating drugs such as tangerine peel and Aucklandia Lappa, which can awaken the stomach and refresh the spleen, and tonify extraordinary meridians.

In summary, Ye’s treatment of metrorrhagia and metrostaxis embodies the changing thinking method,which considers people in the view of natural environment, time and space, formulates feasible and delicate prescription drugs, makes good use of sweet taste,pays attention to regulating the relationship between extraordinary meridians and spleen, liver and kidney,adopts refined processing and combination of various dosage forms, gives timely treatment and discriminates physique, balances the relationship between people, nature and society dynamically, and achieves the purpose of treating diseases. This thinking method deserves our indepth exploration and study.