The Historical Views on the Disease Name, Etiology and Pathogenesis for Gastroesophageal Reux Disease in Traditional Chinese Medicine with Combined Knowledge Graph and Qualitative analysis

To clarify the historical views on disease name, etiology and pathogenesis for Gastroesophageal reux disease (GERD) in ancient Traditional Chinese Medicine (TCM). A comprehensive literature search was performed in < Zhong Hua Yi Dian > database with keywords ‘Acid regurgitation’, ‘Epigastric upset’ and ‘Bilious vomiting’. All the information about disease names, etiology and pathogenesis were included and extracted by two independent reviewers. The Citespace software was used for data analysis. After data importing and purging, the analysis was performed in two steps with 1000 years interval. This study mainly used descriptive statistics, co-occurrence analysis, and cluster analysis, accompanied with qualitative analysis. spleen-stomach deciency, thinking, external infection of four suciency of natural endowment, phlegm-dampness, thinking resulting disorder of blood. (cid:0) ) Food retention. mid-18th The high-frequency keywords are improper diet, liver-qi depression, the spleen wet not shipped, heat stagnation, food retention, stomach heat, dampness-heat with cold food, fondness of liquor, moodiness, excessive deliberation, heat stagnation of spleen and stomach, deciency of qi and blood, qi stagnation. (cid:0) ) Heat stagnation of body uid. appeared in The high-frequency keywords are internal injuries of cold content, heat stagnation of body uid, phlegm and retained uid, internal injury diet and digestive disorders, dampness-heat of spleen and stomach and invasion of wind-cold, weakness of middle qi and heat stagnation of phlegm and retained uid, phlegm-re, re stagnation, preponderance of ShaoYang qi, macronosia generating insuciency of the spleen, qi deciency due to oldness, phlegm stagnation generating acid, external cold and interior heat, external, heat stagnation of food. between the spleen stomach. Dynasty). The high-frequency keywords are food retention, cold pathogenic disease with food retention, incoordination between the spleen and the stomach, stomach re, heat stagnation of body uid at lung and stomach, food stagnation and phlegm, hot origin cold end, internal heat stagnation and outside wind-cold, cold in spleen deciency generating cold, stomach cold, internal cold, gastric disorder with wind-damp. stomach, damp-heat, liver-re, dyspepsia caused by excessive eating or improper diet, weakness of stomach qi, weakness and cold of stomach qi, insuciency of qi and blood and deciency of spleen-stomach after parturition, deciency of spleen Yang, stagnation of liver qi, phlegm-re confusing heart stagnate at stomach, accumulation of dry feces. (cid:0) Phlegm-re. It The high frequency key words contain phlegm-re, deciency of heart blood, mistreatment injuring spleen, insuciency of middle qi, phlegm-dampness and qi constraint, consumptive disease, deciency of spleen yin, blood-insuciency and stomach heat, deciency of spleen yin and heart yin, food retention, essence derived from food stagnation, Qi stagnation, phlegm stagnation, indigestion due to intestinal worm. The high-frequency keywords contain food retention, lodged rheum generating heat stagnation, cold evil invading the stomach, excessive acid, deciency of both spleen and kidney, internal injury diet, phlegm stagnation of middle-jiao, after cold pathogenic disease, indigestion-induced heat stagnation, deciency-cold,re deciency generating reduction of soil productivity. stomach cold, excess of stomach qi. (cid:0) ) Heat the (Southern Song out the 15th Ming Dynasty). The high frequency keywords contain true heat disease with false cold manifestation, internal heat stagnation and invasion of wind-cold, heat stagnation of body uid at lung and stomach, abdominal mass with stagnation causing retained uid, lung re aming respiratory, abdominal mass with stagnation causing phlegm, dampness-heat of stomach and indigestion, internal re aming upward, stagnant dampness-heat of liver and lurk at lung and stomach, spleen weakness causing phlegm retention of middle-jiao. The high frequency keywords contain re arouse phlegm, phlegm moving due to re, phlegm-re, food stagnation and internal heat aming upward, food stagnation, phlegm and retained uid stagnation of middle-jiao, deciency of heart blood, wet phlegm and qi stagnation, heat phlegm, stagnant essence of food at stomach. keywords are dyspepsia,lodged rheum generating heat stagnation, after cold pathogenic disease, indigestion-induced heat stagnation, insuciency-cold,re deciency generating reduction of soil productivity. (cid:0) ) Phlegm and uid retention in upper-jiao and cold food retention of stomach. in the 14th (Yuan Dynasty) and in the 17th century (early Qing Dynasty). The high frequency keywords contain middle-jiao not transportation and transformation, disorder of upper-jiao, phlegm and uid retention, dampness-heat of stomach, liver re, dyspepsia caused by excessive eating or improper diet, weakness of stomach qi, heat stagnation of body uid, cold enveloping heat. (cid:0) Sucient and insucient soil. The high frequency keywords contain damp-heat, food stagnation and phlegm, food retention with heat, deciency-re, re stagnation, deciency-cold, sucient wood and insucient soil, deciency-cold stagnation. (cid:0) Food middle-jiao. pathogenesis The high frequency keywords contain dyspepsia, TaiYang channel accompanying stomach syndrome, phlegm stagnation, food retention of middle-jiao, exogenous cold disease accompanying dyspepsia.


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Background Gastroesophageal re ux disease (GERD) refers to a clinical status of gastric and duodenal contents owing back into the esophagus causing discomfort and/or pathological changes in the esophageal mucosa [1]. At present, its incidence rate in global population is about 20%, which China is about 5-10%, and increasing year by year [2][3]. The common symptoms contain heartburn, acid re ux, stomach pain, and epigastric upset, etc., which usually bring negative effects on patients' physiology, psychology and quality of life. In severe cases, the hurts on extraesophageal tissues in throat and airway maybe occurred, such as esophageal erosion, ulcers, stenosis, etc., which needs more medication or more di cult endoscopic surgery and bring heavier medical burden, furthermore, the uncontrolled condition has risks of carcinogenesis. Western medicine treatment on this disease has fast effect and clear mechanism. However, the refractory GERD and poor improvement on quality of life in the clinic are still commonly [4]. Now, many studies have shown that Traditional Chinese Medicine (TCM) treatment in GERD has advantages of good e cacy and low relapse rate [5]. Therefore, reviewing and evaluating the historical cognitions on GERD in ancient TCM have great values on enriching and improving the diagnosis and treatment technologies for GERD.
Knowledge graph (KG) is a method that uses mathematical methods to simplify the structure of knowledge units to achieve visual knowledge structure with the development of computer technology [6]. The application of KG in TCM research is becoming more and more popular now [7]. And, it has already used in the syndrome diagnosis [8][9][10], data mining on classics [11], surgeries [12], Daoyin therapy [13] and so on. This study aims to mine the historical cognitions on GERD in ancient TCM with KG and qualitative analysis.

Search Strategy
The search source of this study is the fth edition of < Zhong Hua Yi Dian>, which contains 1,156 ancient Chinese medical books and covers various elds of TCM. It is by far the largest series TCM e-book, and can easily export the search results in text form.
All the information about disease names, etiology and pathogenesis relating with search keywords were included. As for the duplicated content appeared in different bibliographies and periods, only the earliest information were included. However, if the information only contains search keywords and symptoms without speci c explanations or not main complains, or no reliable reference resource, or unclear book index, will be excluded.
Abiding by the prede ned inclusion and exclusion criteria, 188, 188, 154, and 549 records were excluded. Then, we integrated these records and classi ed them into three categories, disease name, etiology, and pathogenesis. Finally, 187, 286, and 429 records were identi ed respectively.
Knowledge Graph and Qualitative Literature Analysis for Authors and Bibliographies

Co-occurrence Analysis for Authors and Bibliographies
The co-occurrence analysis showed that there were 13 main nodes and 6 lines before 1000 A.D., and 151 nodes and 65 lines after 1000 A.D. (Fig. 1, when time lapse from ancient to present, color changes from blue to red). However, no obvious center was formed. The GERD related symptoms and signs were rst

Qualitative Literature Analysis for Disease Names
The disease name 'Ou ku', 'Tu Suan' and related symptoms were rst proposed in the < Huang Di nei jing > and described as 'When Yang Ming qi recovery, puri cation qi prevail, the trees are old and dry, and the animals suffer many blight. The diseases of the people are lateral thorax and dryness are to the left. They often sigh, even heartburn, painful abdominal mass, vomiting (Ou Ku), cough, hiccups, and upset', and 'vomiting and acid vomiting (Tu Suan) of various kinds, sudden and severe diarrhea, which all caused by heat' in Comprehensive Discourse on the essentials of the Most reliable (Chap. 74) in Su Wen.
Simultaneously, the Ling Shu stated 'often vomiting bitter liquid, sighing, being afraid of being caught, this is due to the evil in gallbladder and reversed ow of evil at stomach, and gallbladder uid caused bitter mouth (Ou Ku), stomach qi on the reverse cause vomiting, so which called Ou Dan' in The Four Seasonal Qi (Chap. 19).Chao Yuanfang, a famous TCM doctor and scientist in the Sui Dynasty, rst identi ed the 'Tu Suan' as an independent disease and de ned it as 'Stomach acid rises up the throat but have no time to spit out or swallow'. 'Cao Za', another disease name of GERD, was rst recognized as concurrent symptom in the Jin and Yuan dynasties, and later identi ed as an independent disease in the < Danxi's experiential therapy > which written by Zhu Danxi in the Yuan Dynasty.

Knowledge Graph and Qualitative Literature Analysis for Etiology
Co-occurrence Analysis for Disease Etiology Analysis A total of 8 etiology nodes appeared during 1-1000 A.D. and the largest were 'accumulated cold' and 'phlegm stagnation'. After 1000 A.D., more and more nodes appeared until 1900 A.D., and the outbreak periods is 1400 to 1500 A.D. (Ming Dynasty). It should be note that there were 4 nodes appeared from 1100 to 1200 A.D., including 'internal injury raw and cold', 'internal injury diet', 'invasion of wind-cold' and 'food retention', which mainly represent the disease etiology of GERD (Fig. 3).

Cluster Analysis for Disease Etiology
The cluster analysis identi ed 9 research hotspots for GERD etiology (Fig. 4): ) Internal injury diet. It is the earliest appeared etiology and has received continuous attention which accompanied with uid retention and internal injury by raw and cold food. The high-frequency words mainly contain internal injury diet, insu ciency of natural endowment, hunger and fullness, hot nature diet, exogenous wind-cold, spleen de ciency, misuse of spicy, more impatience and anger, seven emotions stimulating, internal Injury food and drink, internal injury milk, re phlegm, excessive stomach Qi, injury to spleen and stomach by erroneous purgation, stomach cold, ascendant rising of stomach re/stomach re rising, de cient cold of spleen and stomach, typhoid fever malaria and Yin of stomach injury, injury to spleen by stagnant wood, liver Qi stagnation, exogenous summer-heat and damp, improper diet and overstrain, hot phlegm, exterior syndrome of febrile disease accompanying dyspepsia, extreme cold, stagnation of qi activity and food retention.
) Pathogenic factor of gallbladder. It was appeared in the 11th century (Northern Song Dynasty) and disappeared in the mid-16th century (Ming Dynasty).The high-frequency words are recovery of YangMing qi, dry evil pathogenic features, think of emotion, reversed ow of YangMing qi, dryness of climate affecting gallbladder, preponderance of YangMing qi, pathogenic factor of gallbladder.
) Internal injury due to emotional disorder. It was appeared in the 12th century (Southern Song Dynasty). The high-frequency keywords contain weakness of spleen qi, internal injury due to emotional disorder, worries affecting qi, spleen-stomach de ciency, thinking, external infection of four seasons, su ciency of natural endowment, phlegm-dampness, thinking resulting disorder of blood.
) Food retention. It was appeared in the 13th century (Yuan Dynasty) and faded out in the mid-18th century (Qing Dynasty). The high-frequency keywords are improper diet, liver-qi depression, the spleen wet not shipped, heat stagnation, food retention, stomach heat, dampness-heat with cold food, fondness of liquor, moodiness, excessive deliberation, heat stagnation of spleen and stomach, de ciency of qi and blood, qi stagnation.
) Heat stagnation of body uid. It was appeared in the 13th century (Yuan Dynasty). The high-frequency keywords are internal injuries of cold content, heat stagnation of body uid, phlegm and retained uid, internal injury diet and digestive disorders, dampness-heat of spleen and stomach and invasion of windcold, weakness of middle qi and heat stagnation of phlegm and retained uid, phlegm-re, re stagnation, preponderance of ShaoYang qi, macronosia generating insu ciency of the spleen, qi de ciency due to oldness, phlegm stagnation generating acid, external cold and interior heat, external, heat stagnation of food.
) Incoordination between the spleen and stomach. It was also appeared in the 13th century (Yuan Dynasty). The high-frequency keywords are food retention, cold pathogenic disease with food retention, incoordination between the spleen and the stomach, stomach re, heat stagnation of body uid at lung and stomach, food stagnation and phlegm, hot origin cold end, internal heat stagnation and outside wind-cold, cold in upper-jiao, spleen de ciency generating cold, stomach cold, internal cold, gastric disorder with wind-damp.
) Damp-heat syndrome of stomach. It was appeared in the 15th century (early Ming Dynasty). The highfrequency keywords contain damp-heat syndrome of stomach, damp-heat, liver-re, dyspepsia caused by excessive eating or improper diet, weakness of stomach qi, weakness and cold of stomach qi, insu ciency of qi and blood and de ciency of spleen-stomach after parturition, de ciency of spleen Yang, stagnation of liver qi, phlegm-re confusing heart stagnate at stomach, accumulation of dry feces.
) Phlegm-re. It was appeared in the 16th century (mid-Ming Dynasty). The high frequency key words contain phlegm-re, de ciency of heart blood, mistreatment injuring spleen, insu ciency of middle qi, phlegm-dampness and qi constraint, consumptive disease, de ciency of spleen yin, blood-insu ciency and stomach heat, de ciency of spleen yin and heart yin, food retention, essence derived from food stagnation, Qi stagnation, phlegm stagnation, indigestion due to intestinal worm.
) Cold evil invading the stomach. It was also appeared in the 16th century (mid-Ming Dynasty), accompanied with stomach de ciency. The high-frequency keywords contain food retention, lodged rheum generating heat stagnation, cold evil invading the stomach, excessive acid, de ciency of both spleen and kidney, internal injury diet, phlegm stagnation of middle-jiao, after cold pathogenic disease, indigestion-induced heat stagnation, de ciency-cold, re de ciency generating reduction of soil productivity.

Qualitative Literature Analysis for Disease Etiology
The < Huang Di nei jing > rst proposed the disease etiology is 'the evil in gallbladder and reversed ow of evil at stomach' or 'the recovery of Yang Ming Year'. In the Sui and Tang dynasties, the etiology was classi ed as 'Phlegm and uid retention' which includes phlegm, cold phlegm, stomach de ciency phlegm stagnation, retained uid, and 'Diet' which includes food of internal injury, food retention, alcohol addiction with food retention.
From the Song Dynasty, the etiological studies enriched signi cantly and mainly proposed the following six categories: a) Five evolution stages and six climatic factors. It is similar to 'theory of circulatory phases' in < Huang Di nei jing>. The < Su Wen Yao Zhi Lun > stated 'When dryness recovery, puri cation qi prevail, ..., vomiting, cough, hiccups, and upset, disease in the diaphragm', 'When Yang Ming qi recovery, puri cation qi prevail, ..., vomiting, cough, hiccups, and upset", written by Ma Zongsu in the Yuan Dynasty. In the Ming Dynasty, Lou Ying and Xu Chunfu believed that 'the recovery of YangMing, often sigh and vomiting.' b) Diet. The < The Three for Extremely-Disease and Syndrome Party Theory > stated 'When there is retained uid, it makes epigastric upset; when there is lodging food, which cause acid regurgitation', written by Chen Yan in the Song Dynasty. Yan Yonghe explained more exactly in his book < Yan's Ji Sheng Fang > as 'If you are insu ciency of natural endowment, when you are hungry or lose your appetite, or after a meal with ve avors, shy sh, cheese, raw and cold fruits and vegetables, those will stop storing the stomach, and then you will suffer from stagnation, acid regurgitation and vomit.' c) Mistreatment injuring spleen. In the Ming Dynasty, Zhang Jingyue putted forward that the spleen and stomach can be injured by misusing of digestive or attack medicines which results in epigastric upset. In The Ming Dynasty, <Concise Medicine Su cient > stated 'there are also misuse of medicines such as helping digestion and removing accumulation, de ciency of spleen and stomach, less blood and epigastric upset, de ciency of middle-jiao and upset accompanying not hungry', written by Sun Zhihong. d) Internal injury due to emotional disorder and liver-qi depression. Zhu Danxi putted forward that phlegm accumulation caused by qi disease is the cause of acid regurgitation, because too much worry could result in stagnation of qi activity, then the liver depression restrict spleen and touch off acid regurgitation. e) Exposure to exogenous cold. The < Zheng Zhi Hui Bu > stated that 'normally stagnant body uid caused dampness-heat; when the wind-cold, internal heat stagnation and outside wind-cold, the epigastric upset it will be and the sour taste will sting the heart' which refers to the external wind-cold; and 'if the cold evil invading the stomach, suddenly into acid, heat transformed from cold, the acid belongs to the cold also' which refers to the cold evil invading the stomach, written by Li Yongcui in the Qing Dynasty. f) Spleenstomach de ciency. The < Hua Tuo Shen Fang > proposed the disease of Spleen De ciency which is characterized by sallow of complexion due to spleen disorders; stiff tongue, poor appetite, vomiting, weakness of limbs due to superabundance; and frequent disorders, acid regurgitation, uncured dysentery due to de ciency.

Knowledge Graph and Qualitative Literature Analysis for Pathogenesis
Co-occurrence Analysis for Disease Pathogenesis The earliest explanation of GERD pathogenesis, 'the evil in gallbladder and ascendant rising of stomach qi', appeared in the 3rd century A.D.. Three hundred years later, the discussions on disease pathogenesis increased obviously between 600 A.D. and700 A.D. (Tang Dynasty), conversely, decreased from 1100 A.D. to1200 A.D. (Song Dynasty). However, it was exploded again from 1200 A.D. to 1300 A.D. (Jin and Yuan dynasties). Among them, the highest frequency point 'heat stagnation of body uid at lung and stomach' was appeared in this period, accompanied with 'internal heat stagnation and invasion of wind-cold', 'phlegm due to re', 'hot origin cold end', and so on. After 1500 A.D. (Ming Dynasty), the node connections number and node area decreased signi cantly and continuously (Fig. 5).

Cluster Analysis for Disease Pathogenesis
The cluster analysis identi ed 8 research hotspots for GERD pathogenesis (Fig. 6): ) Spleen qi de ciency and adverse rising of phlegm and uid retention. It is the earliest declared pathogenesis which appeared in the 11th century (Northern Song Dynasty) and faded out in the 13th century (Yuan Dynasty). So, it was only used as a research hotspot in the early period. The high frequency keywords contain zangfu organs weakness and stagnant cold of both spleen and stomach, stagnation of food at diaphragm, spleen qi de ciency and adverse rising of phlegm and uid retention, de ciency of spleen generating cold and digestive disorders.
) Pathogenic factor invading upper-jiao. It was appeared in the 11th century (Northern Song Dynasty) and faded out in the 15th century (Ming Dynasty). The high frequency keywords contain stagnated heat over qi of stomach and midriff, exuberance of lung metal, pathogenic factor invading upper-jiao, preponderance of ShaoYang qi, heat illness due to internal cold injury, foul smell ascending may causing abdominal atulence, metal not calming wood, stomach cold, excess of stomach qi.
) Heat stagnation of body uid at lung and stomach. It was appeared in the 12th century (Southern Song Dynasty) and faded out in the 15th century (early Ming Dynasty). The high frequency keywords contain true heat disease with false cold manifestation, internal heat stagnation and invasion of wind-cold, heat stagnation of body uid at lung and stomach, abdominal mass with stagnation causing retained uid, lung re aming respiratory, abdominal mass with stagnation causing phlegm, dampness-heat of stomach and indigestion, internal re aming upward, stagnant dampness-heat of liver and lurk at lung and stomach, spleen weakness causing phlegm retention of middle-jiao.
) Insu ciency-cold of middle qi. It is the longest researched pathogenesis, lasted for more than 700 years, which appeared in the 12th century (southern Song Dynasty) and faded out around the 18th century (Qing Dynasty). The high frequency keywords contain re arouse phlegm, phlegm moving due to re, phlegm-re, food stagnation and internal heat aming upward, food stagnation, phlegm and retained uid stagnation of middle-jiao, de ciency of heart blood, wet phlegm and qi stagnation, heat phlegm, stagnant essence of food at stomach. ) Phlegm moving due to re. It was appeared in the 13th century (Yuan Dynasty) and faded out in the 17th century (early Qing Dynasty), accompanied with stomach de ciency, high frequency keywords are dyspepsia,lodged rheum generating heat stagnation, after cold pathogenic disease, indigestion-induced heat stagnation, insu ciency-cold, re de ciency generating reduction of soil productivity.
) Phlegm and uid retention in upper-jiao and cold food retention of stomach. It was appeared in the 14th century (Yuan Dynasty) and faded out in the 17th century (early Qing Dynasty). The high frequency keywords contain middle-jiao not transportation and transformation, disorder of upper-jiao, phlegm and uid retention, dampness-heat of stomach, liver re, dyspepsia caused by excessive eating or improper diet, weakness of stomach qi, heat stagnation of body uid, cold enveloping heat.
) Su cient wood and insu cient soil. It was appeared around the 15th century (Ming Dynasty) and faded out around the 18th century (Qing Dynasty). The high frequency keywords contain damp-heat, food stagnation and phlegm, food retention with heat, de ciency-re, re stagnation, de ciency-cold, su cient wood and insu cient soil, de ciency-cold stagnation.
) Food retention of middle-jiao. It was the latest appeared pathogenesis which was proposed in the 16th century (Ming Dynasty) and lasted till now. The high frequency keywords contain dyspepsia, TaiYang channel accompanying stomach syndrome, phlegm stagnation, food retention of middle-jiao, exogenous cold disease accompanying dyspepsia.
Qualitative Literature Analysis for Disease Pathogenesis As for 'Ou Ku', the earliest presented pathogenesis is 'the evil in gallbladder and ascendent rising of stomach qi', which was written in < Huang Di nei jing > and high recognized and praised by historical doctors. In the Jin Dynasty, Zhang Zihe stated 'sanjiao's blockage is bad for throat and it's gallbladder disease and bilious vomiting (Ou Ku)' in < Ru Men Shi Qin > and concluded that the disease's location is sanjiao. Qin Changyu, a doctor in the Ming Dynasty, proposed that 'gallbladder fever' can also result in it. Tang Rongchuan believed that bilious vomiting could be caused by the transformed re from the combination of excessive fetal qi and Yang Ming's qi, documented in < Theory of Blood Syndrome > in the Qing Dynasty.
There were many discussions on the pathogenesis of acid regurgitation (Tun Suan) and acid vomiting (Tu Suan). For example, 'vomiting and acid vomiting of various kinds, sudden and severe diarrhea, which all caused by heat', recorded in < Huang Di nei jing>; spleen-stomach de ciency, retention of food, phlegm and uid retention of diaphragm is the main pathogenesis, considered by Chao Yuanfang in Sui Dynasty; 'Blazing re can make gold, but can't calm wood', written by Liu Wansu in Jin Dynasty who praised highly on < Huang Di nei jing > and believed that acid vomiting was caused by heat; Li Dongyuan, on the other hand, believed that the disease's pathogenesis is cold and 'the pungent and hot medicine could cure it', and proposed the principle of the treatment is 'pour lung with heat medicine'; Zhu Danxi innovatively put forward the idea of 'hot origin and cold end' for the disease which caused by dampness-heat internal stagnation, body uid internal stagnation, heat generating acid and crouching in the lung and stomach; Zhang Jingyue thought the pathogenesis was the liver qi crusading the weak spleen and stomach qi and unborn spleen Yang; Li Yongzhi, a famous doctor in the Ming Dynasty, believed the damp-heat is the basis of the disease and acid regurgitation and acid vomiting are differently, which demonstrated by the record 'there is dampness and heat in the stomach towards mouth, the food suppressed by dampness and heat goes into stomach, and the food cannot be digested, so the clear air does not rise and the turbid air does not fall which further confronting and result in the qi reversing. Therefore, the vomiting reverse to swallowing, which called acid regurgitation (Tun Suan)', and 'there is dampness and heat which caused by the outside wind-cold or raw and cold diet, then the more stagnation of internal heat, acid stab heart, intention to vomit, upset in the chest, or spit out acid water, making upper and lower teeth sour and astringent and not closure, which reduce acid vomiting (Tu Suan)', written in his Book < Zheng Zhi Hui Bu>.
Cao Za, another disease name of GERD, was rst discussed in < Danxi Xinfa > as 'The water in the Middle Part of Gastric Cavity is cold, and the epigastric upset (Cao Za) below the heart', which was written by Zhu Danxi in Yuan Dynasty. Zhang Jingyue proposed that it was mostly caused by 'disorder of spleen qi' or 'injured spleen de ciency', and could be divided into de cient cold epigastric upset and phlegm-re epigastric upset from the perspective of de ciency and su ciency, or re epigastric upset and phlegm-re epigastric upset from the perspective of disease causes. Xu Chunfu believed that phlegm-re was the main cause, and pointed out that phlegm and uid-retention was the key pathogenesis of epigastric upset and acid regurgitation in his < Gu Jin Yi Tong Da Quan>.

Discussion
There are many treatises focused on GERD related symptoms and signs in TCM, which have been on the rise over time and reached its peak in Ming and Qing dynasties. This trend is roughly consistent with the development of whole TCM, and it is known that this disease is common and frequent in clinic since ancient time.

Cognition on the disease name
This study pre-de ned the GERD's name in TCM as Ou ku (bilious vomiting), Tu Suan (acid vomiting), Tun Suan (acid regurgitation), and Cao Za(epigastric upset), and performed the literature search and data analysis. However, we found more derived names for GERD, even for same disease name in TCM. For example, bilious vomiting was also called 'gallbladder vomiting' and 'gallbladder disease'; Acid vomiting and Acid regurgitation were also known as 'Yan Suan', 'Yi Cu', 'Zhong Suan', 'Cu Xin', 'Cu Yan', 'Yi Suan', 'Zuo Tun', 'Zuo Suan', 'Cu Tun' and so on. Besides, Acid vomiting and Acid regurgitation are differently, which the former one refers to spitting out acid water like vinegar, the later one refer to acid water ooding into throat but swallowing down, though both of them have the acid ooding. However, the difference is so tiny that doctors often omit it in clinic. The epigastric upset was also called 'Xin Cao', 'Xin Cao Za', 'Tan Cao', or 'Huo Cao'.
It is important to note that there is no disease name exact cover the GERD in TCM because of its complicated clinical manifestations. Most of the disease names in TCM only present one or more typical symptoms of GERD, for example, the gastrointestinal symptoms but not extra-esophageal re ux symptoms.

Cognition on the disease etiology and pathogenesis
The TCM doctors in the past dynasties have comprehensively discussed the etiology of GERD from many aspects, such as external factors, internal injury, emotion, and so on, and formed different research themes in different periods. The main etiologies contain food of internal injury, damp-heat syndrome of stomach, cold evil invading the stomach, phlegm-re, heat stagnation of body uid, food retention, incoordination between the spleen and the stomach, internal injury due to emotional disorder, and the evil in gallbladder.
In terms of pathogenesis, the earliest view is liver-gallbladder heat and stomach qi inversion for bilious vomiting, reported in < Huang Di nei jing>. The epigastric upset was close related to phlegm and re, considered by Zhu Danxi from the Yuan Dynasty. The views on the pathogenesis of acid regurgitation and acid vomiting are differently in different periods and different doctors, but they can be mainly classi ed into four categories: cold, heat, de ciency of spleen and stomach, and hot origin cold end. For example, Li Dongyuan thought it was cold, Zhu Danxi thought it was hot origin cold end, Zhang Jingyue thought it was weakness of spleen and stomach, Li Yongzi thought acid regurgitation was dampnessheat of stomach and acid vomiting was wind-cold outside and dampness-heat inside. Limitation Firstly, the data retrieval is only carried out in < Zhong Hua Yi Dian > which does not include all the ancient TCM books though it is the largest electronic database of series TCM books so far. Secondly, some book without clear author and written time was not included in the data collation stage. Thirdly, only common gastrointestinal symptoms of GERD were included but not extra-esophageal re ux symptoms, as prede ned search strategy. Therefore, the results may be not present comprehensive cognition on GERD in TCM. However, all the ancient TCM books included in < Zhong Hua Yi Dian > are very important medical works in the TCM history and represent the core context of Chinese Medicine to a large extent. Secondly, this study focus on the historical origins of GERD in TCM, the missing information on some authors and written time do not affect the main results and conclusions. And, the extra-esophageal re ux symptoms are not the common and core diagnostic criteria of GERD. So the research group believe that the results and conclusions of this study are high scienti c and reliable on the whole.

Conclusions
This study performed a comprehensive retrospect on the historical views for GERD in ancient TCM, with text information extraction, knowledge mapping and qualitative analysis, and clari ed the disease name, etiology, and pathogenesis, which provides a good reference for further improving and developing theoretical cognition of this disease and treatment based on syndrome differentiation.