• Biomolecules & Therapeutics
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• v.30 no.3
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• pp.246-256
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• 2022

The present study focused on the potential mechanism of betulin (BT), a pentacyclic triterpenoid isolated from the bark of white birch (Betula pubescens), against chronic alcohol-induced lipid accumulation and metaflammation. AML-12 and RAW 264.7 cells were administered ethanol (EtOH), lipopolysaccharide (LPS) or BT. Male C57BL/6 mice were fed Lieber-DeCarli liquid diets containing 5% EtOH for 4 weeks, followed by single EtOH gavage on the last day and simultaneous treatment with BT (20 or 50 mg/kg) by oral gavage once per day. In vitro, MTT showed that 0-25 mM EtOH and 0-25 µM BT had no toxic effect on AML-12 cells. BT could regulate sterolregulatory-element-binding protein 1 (SREBP1), lipin1/2, P2X7 receptor (P2X7r) and NOD-like receptor family, pyrin domains-containing protein 3 (NLRP3) expressions again EtOH-stimulation. Oil Red O staining also indicated that BT significantly reduced lipid accumulation in EtOH-stimulated AML-12 cells. Lipin1/2 deficiency indicated that BT might mediate lipin1/2 to regulate SREBP1 and P2X7r expression and further alleviate lipid accumulation and inflammation. In vivo, BT significantly alleviated histopathological changes, reduced serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) and triglyceride (TG) levels, and regulated lipin1/2, SREBP1, peroxisome proliferator activated receptor α/γ (PPARα/γ) and PGC-1α expression compared with the EtOH group. BT reduced the secretion of inflammatory factors and blocked the P2X7r-NLRP3 signaling pathway. Collectively, BT attenuated lipid accumulation and metaflammation by regulating the lipin1/2-mediated P2X7r signaling pathway.

• Animal Bioscience
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• v.35 no.2
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• pp.260-271
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• 2022

Objective: We aimed to investigate the effect of the differing amino acid (AA) release dynamics of two protein sources on the growth performance, nitrogen deposition, plasma biochemical parameters, and muscle synthesis and degradation of piglets when included in their diets at normal and low concentrations. Methods: Forty-eight piglets (Duroc×Landrace×Large White) with initial body weight of 7.45±0.58 kg were assigned to six groups and fed one of 6 diets. The 6 dietary treatments were arranged by 3×2 factorial with 3 protein sources and 2 dietary protein levels. They are NCAS (a normal protein content with casein), NBlend (a normal protein content with blend of casein and corn gluten meal), NCGM (a normal protein content with corn gluten meal), LCAS (a low protein content with casein), LBlend (a low protein content with blend of casein and corn gluten meal), LCGM (a low protein content with corn gluten meal). The release dynamics of AA in these diets were determined by in vitro digestion. The digestibility, utilization and biological value of nitrogen in piglets were determined by micro Kjeldahl method. Plasma insulin was measured by enzyme-linked immunosorbent assay kits. The protein expression of mediators of muscle synthesis and degradation was determined by western blotting. Results: Although the consumption of a low-protein diet supplemented with crystalline AA was associated with greater nitrogen digestion and utilization (p<0.05), the final body weight, growth performance, nitrogen deposition, and phosphorylation of ribosomal protein S6 kinase 1 and eIF4E binding protein 1 in the muscle of pigs in the low-protein diet-fed groups were lower than those of the normal-protein diet-fed groups (p<0.05) because of the absence of non-essential AA. Because of the more balanced release of AA, the casein (CAS) and Blend-fed groups showed superior growth performance, final body weight and nitrogen deposition, and lower expression of muscle ring finger 1 and muscle atrophy F-box than the CGM-fed groups (p<0.05). Conclusion: We conclude that the balanced release of AA from CAS containing diets and mixed diets could reduce muscle degradation, favor nitrogen retention, % intake and improve growth performance in pigs consuming either a normal- or low-protein diet.

• Smart Structures and Systems
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• v.29 no.1
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• pp.1-16
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• 2022

Despite recent breakthroughs in deep learning and computer vision fields, the pixel-wise identification of tiny objects in high-resolution images with complex disturbances remains challenging. This study proposes a modified U-net for tiny crack segmentation in real-world steel-box-girder bridges. The modified U-net adopts the common U-net framework and a novel Self-Attention-Self-Adaption (SASA) neuron as the fundamental computing element. The Self-Attention module applies softmax and gate operations to obtain the attention vector. It enables the neuron to focus on the most significant receptive fields when processing large-scale feature maps. The Self-Adaption module consists of a multiplayer perceptron subnet and achieves deeper feature extraction inside a single neuron. For data augmentation, a grid-based crack random elastic deformation (CRED) algorithm is designed to enrich the diversities and irregular shapes of distributed cracks. Grid-based uniform control nodes are first set on both input images and binary labels, random offsets are then employed on these control nodes, and bilinear interpolation is performed for the rest pixels. The proposed SASA neuron and CRED algorithm are simultaneously deployed to train the modified U-net. 200 raw images with a high resolution of 4928 × 3264 are collected, 160 for training and the rest 40 for the test. 512 × 512 patches are generated from the original images by a sliding window with an overlap of 256 as inputs. Results show that the average IoU between the recognized and ground-truth cracks reaches 0.409, which is 29.8% higher than the regular U-net. A five-fold cross-validation study is performed to verify that the proposed method is robust to different training and test images. Ablation experiments further demonstrate the effectiveness of the proposed SASA neuron and CRED algorithm. Promotions of the average IoU individually utilizing the SASA and CRED module add up to the final promotion of the full model, indicating that the SASA and CRED modules contribute to the different stages of model and data in the training process.

• Journal of Korean Medical classics
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• v.20 no.4
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• pp.211-250
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• 2007

1. The 'Kao Zheng Pai(考證派) comes from the 'Zhe Zhong Pai' and is a school that is influenced by the confucianism of the Qing dynasty. In Japan Inoue Kinga(井上金娥), Yoshida Koton(吉田篁墩) became central members, and the rise of the methodology of historical research(考證學) influenced the members of the 'Zhe Zhong Pai', and the trend of historical research changed from confucianism to medicine, making a school of medicine based on the study of texts and proving that the classics were right. 2. Based on the function of 'Nei Qu Li '(內驅力) the 'Kao Zheng Pai', in the spirit of 'use confucianism as the base', researched letters, meanings and historical origins. Because they were influenced by the methodology of historical research(考證學) of the Qing era, they valued the evidential research of classic texts, and there was even one branch that did only historical research, the 'Rue Xue Kao Zheng Pai'(儒學考證派). Also, the 'Yi Xue Kao Zheng Pai'(醫學考證派) appeared by the influence of Yoshida Kouton and Kariya Ekisai(狩谷掖齋). 3. In the 'Kao Zheng Pai(考證派)'s theories and views the 'Yi Xue Kao Zheng Pai' did not look at medical scriptures like the "Huang Di Nei Jing"("黃帝內經") and did not do research on 'medical' related areas like acupuncture, the meridian and medicinal herbs. Since they were doctors that used medicine, they naturally were based on 'formulas'(方劑) and since their thoughts were based on the historical ideologies, they valued the "Shang Han Ja Bing Lun" which was revered as the 'ancestor of all formulas'(衆方之祖). 4. The lives of the important doctors of the 'Kao Zheng Pai' Meguro Dotaku(目黑道琢) Yamada Seichin(山田正珍), Yamada Kyoko(山田業廣), Mori Ritsi(森立之) Kitamura Naohara(喜多村直寬) are as follows. 1) Meguro Dotaku(目黑道琢 1739${\sim}$1798) was born of lowly descent but, using his intelligence and knowledge, became a professor as a Shi Jing Yi(市井醫) and as a professor for 34 years at Ji Shou Guan mastered the "Huang Di Nei Jing" after giving over 300 lectures. Since his pupil, Isawara Ken taught the Lan Men Wu Zhe(蘭門五哲) and Shibue Chusai, Mori Ritsi(森立之), Okanishi Gentei(岡西玄亭), Kiyokawa Gendoh(淸川玄道) and Yamada Kyoko(山田業廣), Meguro Dotaku is considered the founder of the 'Yi Xue Kao Zheng Pai'. 2) The family of Yamada Seichin(山田正珍 1749${\sim}$1787) had been medical officials in the Makufu(幕府) and the many books that his ancestors had left were the base of his art. Seichin learned from Shan Ben Bei Shan(山本北山), a 'Zhe Zhong Pai' scholar, and put his efforts into learning, teaching and researching the "Shang Han Lun"("傷寒論"). Living in a time between 'Gu Fang Pai'(古方派) member Nakanishi Goretada(中西惟忠) and 'Kao Zheng Pai' member Taki Motohiro(多紀元簡), he wrote 11 books, 2 of which express his thoughts and research clearly, the "Shang Han Lun Ji Cheng"("傷寒論集成") and "Shang Han Kao"("傷寒考"). His comparison of the 'six meridians'(3 yin, 3 yang) between the "Shang Han Lun" and the "Su Wen Re Lun"("素問 熱論) and his acknowledgement of the need and rationality of the concept of Yin-Yang and Deficient-Replete distinguishes him from the other 'Gu Fang Pai'. Also, his dissertation of the need for the concept doesn't use the theories of latter schools but uses the theory of the "Shang Han Lun" itself. He even researched the historical parts, such as terms like 'Shen Nong Chang Bai Cao'(神農嘗百草) and 'Cheng Qi Tang'(承氣湯) 3) The ancestor of Yamada Kyoko(山田業廣) was a court physician, and learned confucianism from Kao Zheng Pai 's Ashikawa Genan(朝川善庵) and medicine from Isawa Ranken and Taki Motokata(多紀元堅), and the secret to smallpox from Ikeda Keisui(池田京水). He later became a lecturer at the Edo Yi Xue Guan(醫學館) and was invited as the director to the Ji Zhong(濟衆) hospital. He also became the first owner of the Wen Zhi She(溫知社), whose main purpose was the revival of kampo, and launched the monthly magazine Wen Zi Yi Tan(溫知醫談). He also diagnosed and prescribed for the prince Ming Gong(明宮). His works include the "Jing Fang Bian"("經方辨"), "Shang Han Lun Si Ci"("傷寒論釋司"), "Huang Zhao Zhu Jia Zhi Yan Ji Yao"("皇朝諸家治驗集要") and "Shang Han Ja Bing Lun Lei Juan"("傷寒雜病論類纂"). of these, the "Jing Fang Bian"("經方辨") states that the Shi Gao(石膏) used in the "Shang Han Lun" had three meanings-Fa Biao(發表), Qing Re(淸熱), Zi Yin(滋陰)-which were from 'symptoms', and first deducted the effects and then told of the reason. Another book, the "Jiu Zhe Tang Du Shu Ji"("九折堂讀書記") researched and translated the difficult parts of the "Shang Han Lun", "Jin Qui Yao Lue", "Qian Jin Fang"("千金方"), and "Wai Tai Mi Yao"("外臺秘要"). He usually analyzed the 'symptoms' of diseases but the composition, measurement, processing and application of medicine were all in the spectrum of 'analystic research' and 'researching analysis'. 4) The ancestors of Mori Rits(森立之 1807${\sim}$ 1885) were warriors but he became a doctor by the will of his mother, and he learned from Shibue Chosai(澁江抽齋) and Isawaran Ken and later became a pupil of Shou Gu Yi Zhai, a historical research scholar. He then became a lecturer of medical herbs at the Yi Xue Guan, and later participated in the proofreading of "Yi Xin Fang"("醫心方") and with Chosai compiled the "Jing Ji Fang Gu Zhi"("神農本草經"). He visited the Chinese scholar Yang Shou Jing(楊守敬) in 1881 and exchanged books and ideas. Of his works, there are the collections(輯複本) of "Shen Nong Ben Cao Jing"(神農本草經) and "You Xiang Yi Hwa"("遊相醫話") and the records, notes, poems, and diaries such as "Zhi Yuan Man Lu"("枳園漫錄") and "Zhi Yuan Sui Bi"("枳園隨筆") that were not published. His thoughts were that in restoring the "Shen Nong Ben Cao Jing", "the herb to the doctor is like the "Shuo Wen Jie Zi"("說文解字") to the scholar", and he tried to restore the ancient herbal text using knowledge of medicine and investigation(考據). Also with Chosai he compiled the "Jing Ji Fang Gu Zhi"("經籍訪古志") using knowledge of ancient text. Ritzi left works on pure investigation, paid much attention to social problems, and through 12 years of poverty treated all people and animals in all branches of medicine, so he is called a 'half confucianist half doctor'(半儒半醫). 5) Kitamurana Ohira(喜多村直寬 1804${\sim}$1876) learned scriptures and ancient texts from confucian scholar Asaka Gonsai, and learned medicine from his father Huai Yaun(槐園). He became a teacher in the Yi Xue Guan in his middle ages, and to repay his country, he printed 266 volumes of "Yi Fang Lei Ju("醫方類聚") and 1000 volumes of "Tai Ping Yu Lan"("太平禦覽") and devoted it to his country to be spread. His works are about 40 volumes including "Jin Qui Yao Lue Shu Yi" and "Lao Yi Zhi Yan" but most of them are researches on the "Shang Han Za Bing Lun". In his "Shang Han Lun Shu Yi"("傷寒論疏義") he shows the concept of the six meridians through the Yin-Yang, Superficial or internal, cold or hot, deficient or replete state of diseases, but did not match the names with the six meridians of the meridian theory, and this has something in common with the research based on the confucianism of Song(宋儒). In clinical treatment he was positive toward old and new methods and also the experience of civilians, but was negative toward western medicine. 6) The ancestor of the Taki family Tanbano Yasuyori(丹波康賴 912-955) became a Yi Bo Shi(醫博士) by his medical skills and compiled the "Yi Xin Fang"("醫心方"). His first son Tanbano Shigeaki(丹波重明) inherited the Shi Yao Yuan(施藥院) and the third son Tanbano Masatada(丹波雅忠) inherited the Dian You Tou(典藥頭). Masatada's descendents succeeded him for 25 generations until the family name was changed to Jin Bao(金保) and five generations later it was changed again to Duo Ji(多紀). The research scholar Taki Motohiro was in the third generation after the last name was changed to Taki, and his family kept an important part in the line of medical officers in Japan. Taki Motohiro(多紀元簡 1755-1810) was a teacher in the Yi Xue Guan where his father was residing, and became the physician for the general Jia Qi(家齊). He had a short temper and was not good at getting on in the world, and went against the will of the king and was banished from Ao Yi Shi(奧醫師). His most famous works, the "Shang Han Lun Ji Yi" and "Jin Qui Yao Lue Ji Yi" are the work of 20 years of collecting the theories of many schools and discussing, and is one of the most famous books on the "Shang Han Lun" in Japan. "Yi Sheng" is a collection of essays on research. Also there are the "Su Wen Shi"("素問識"), "Ling Shu Shi"("靈樞識"), and the "Guan lu Fang Yao Bu"("觀聚方要補"). Taki Motohiro(多紀元簡)'s position was succeeded by his third son Yuan Yin(元胤 1789-1827), and his works include works of research such as "Nan Jing Shu Jeng"("難經疏證"), "Ti Ya"("體雅"), "Yao Ya"("藥雅"), "Ji Ya"("疾雅"), "Ming Yi Gong An"("名醫公案"), and "Yi Ji Kao"("醫籍考"). The "Yi Ji Kao" is 80 volumes in length and lists about 3000 books on medicine in China before the Qing Dao Guang(道光), and under each title are the origin, number of volumes, state of existence, and, if possible, the preface, Ba Yu(跋語) and biography of the author. The younger sibling of Yuan Yin(元胤 1789-1827), Yuan Jian(元堅 1795-1857) expounded ancient writings at the Yi Xue Guan only after he reached middle age, was chosen for the Ao Yi Shi(奧醫師) and later became a Fa Yan(法眼), Fa Yin(法印) and Yu Chi(樂匙). He left about 15 texts, including "Su Wen Shao Shi"("素間紹識"), "Yi Xin Fang"("醫心方"), published in school, "Za Bing Guang Yao"("雜病廣要"), "Shang Han Guang Yao"(傷寒廣要), and "Zhen Fu Yao Jue"("該腹要訣"). On the Taki family's founding and working of the Yi Xue Guan Yasuka Doumei(失數道明) said they were "the people who took the initiative in Edo era kampo medicine" and evaluated their deeds in the fields of 'research of ancient text', 'the founding of Ji Shou Guan and medical education', 'publication business', 'writing of medical text'. 5. The doctors of the 'Kao Zheng Pai ' based their operations on the Edo Yi Xue Guan, and made groups with people with similar ideas to them, making a relationship 'net'. For example the three families of Duo Ji(多紀), Tang Chuan(湯川) and Xi Duo Cun(喜多村) married and adopted with and from each other and made prefaces and epitaphs for each other. Thus, the Taki family, the state science of the Makufu, the tendency of thinking, one's own interests and glory, one's own knowledge, the need of the society all played a role in the development of kampo medicine in the 18th and 19th century.

• The Journal of Dong Guk Oriental Medicine
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• v.10
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• pp.1-40
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• 2008

1.The 'Kao Zheng Pai'(考證派) comes from the 'Zhe Zhong Pai(折衷派)' and is a school that is influenced by the confucianism of the Qing dynasty. In Japan Inoue Kinga(井上金峨), Yoshida Koton(古田篁墩 $1745{\sim}1798$) became central members, and the rise of the methodology of historical research(考證學) influenced the members of the 'Zhe Zhong Pai', and the trend of historical research changed from confucianism to medicine, making a school of medicine based on the study of texts and proving that the classics were right. 2. Based on the function of 'Nei Qu Li'(內驅力) the 'Kao Zheng Pai', in the spirit of 'use confucianism as the base', researched letters, meanings and historical origins. Because they were influenced by the methodology of historical research(考證學) of the Qing era, they valued the evidential research of classic texts, and there was even one branch that did only historical research, the 'Rue Xue Kao Zheng Pai'(儒學考證派). Also, the 'Yi Xue Kao Zheng Pai'(醫學考證派) appeared by the influence of Yoshida Kouton and Kariya Ekisai(狩谷掖齋). 3. In the 'Kao Zheng Pai(考證派)'s theories and views the 'Yi Xue Kao Zheng Pai' did not look at medical scriptures like the "Huang Di Nei Jing"("黃帝內經") and did not do research on 'medical' related areas like acupuncture, the meridian and medicinal herbs. Since they were doctors that used medicine, they naturally were based on 'formulas'(方劑) and since their thoughts were based on the historical ideologies, they valued the "Shang Han Ja Bing Lun" which was revered as the 'ancestor of all formulas'(衆方之祖). 4. The lives of the important doctors of the 'Kao Zheng Pai' Meguro Dotaku(目黑道琢) Yamada Seichin(山田正珍), Yamada Kyoko(山田業廣), Mori Ritsi(森立之) Kitamura Naohara(喜多村直寬) are as follows. 1) Meguro Dotaku(目黑道琢 $1739{\sim}1798$) was born of lowly descent but, using his intelligence and knowledge, became a professor as a Shi Jing Yi(市井醫) and as a professor for 34 years at Ji Shou Guan(躋壽館) mastered the "Huang Di Nei Jing" after giving over 300 lectures. Since his pupil, Isawara Ken(伊澤蘭軒) taught the Lan Men Wu Zhe(蘭門五哲) and Shibue Chusai(澀江抽齋), Mori Ritsi(森立之), Okanishi Gentei(岡西玄亭), Kiyokawa Gendoh(淸川玄道) and Yamada Kyoko(山田業廣), Meguro Dotaku is considered the founder of the 'Yi Xue Kao Zheng Pai'. 2) The family of Yamada Seichin(山田正珍 $1749{\sim}1787$) had been medical officials in the Makufu(幕府) and the many books that his ancestors had left were the base of his art. Seichin learned from Shan Ben Bei Shan(山本北山), a 'Zhe Zhong Pai' scholar, and put his efforts into learning, teaching and researching the "Shang Han Lun"("傷寒論"). Living in a time between 'Gu Fang Pai'(古方派) member Nakanishi Goretada(中西惟忠) and 'Kao Zheng Pai' member Taki Motohiro(多紀元簡), he wrote 11 books, 2 of which express his thoughts and research clearly, the "Shang Han Lun Ji Cheng"("傷寒論集成") and "Shang Han Kao"("傷寒考"). His comparison of the 'six meridians'(3 yin, 3 yang) between the "Shang Han Lun" and the "Su Wen Re Lun"("素問 熱論") and his acknowledgement of the need and rationality of the concept of Yin-Yang and Deficient-Replete distinguishes him from the other 'Gu Fang Pai'. Also, his dissertation of the need for the concept doesn't use the theories of latter schools but uses the theory of the "Shang Han Lun" itself. He even researched the historical parts, such as terms like 'Shen Nong Chang Bai Cao'(神農嘗百草) and 'Cheng Qi Tang'(承氣湯). 3) The ancestor of Yamada Kyoko(山田業廣) was a court physician, and learned confucianism from Kao Zheng Pai's Ashikawa Genan(朝川善庵) and medicine from Isawa Ranken(伊澤蘭軒) and Taki Motokata(多紀元堅), and the secret to smallpox from Ikeda Keisui(池田京水). He later became a lecturer at the Edo Yi Xue Guan(醫學館) and was invited as the director to the Ji Zhong(濟衆) hospital. He also became the first owner of the Wen Zhi She(溫知社), whose main purpose was the revival of kampo, and launched the monthly magazine Wen Zi Yi Tan(溫知醫談). He also diagnosed and prescribed for the prince Ming Gong(明宮). His works include the "Jing Fang Bian"("經方辨"), "Shang Han Lun Si Ci"("傷寒論釋詞"), "Huang Zhao Zhu Jia Zhi Yan Ji Yao"("皇朝諸家治驗集要") and "Shang Han Ja Bing Lun Lei Juan"("傷寒雜病論類纂"). of these, the "Jing Fang Bian"("經方辨") states that the Shi Gao(石膏) used in the "Shang Han Lun" had three meanings-Fa Biao(發表), Qing Re(淸熱), Zi Yin(滋陰)-which were from 'symptoms', and first deducted the effects and then told of the reason. Another book, the "Jiu Zhe Tang Du Shu Ji"("九折堂讀書記") researched and translated the difficult parts of the "Shang Han Lun", "Jin Qui Yao Lue"("金匱要略"), "Qian Jin Fang"("千金方"), and "Wai Tai Mi Yao"("外臺秘要"). He usually analyzed the 'symptoms' of diseases but the composition, measurement, processing and application of medicine were all in the spectrum of 'analystic research' and 'researching analysis'. 4) The ancestors of Mori Ritsi(森立之 $1807{\sim}1885$) were warriors but he became a doctor by the will of his mother, and he learned from Shibue Chosai(澁江抽齋) and Isawaran Ken(伊澤蘭軒) and later became a pupil of Shou Gu Yi Zhai(狩谷掖齋), a historical research scholar. He then became a lecturer of medical herbs at the Yi Xue Guan, and later participated in the proofreading of "Yi Xin Fang"("醫心方") and with Chosai compiled the "Jing Ji Fang Gu Zhi"("經籍訪古志"). He visited the Chinese scholar Yang Shou Jing(楊守敬) in 1881 and exchanged books and ideas. Of his works, there are the collections(輯複本) of "Shen Nong Ben Cao Jing"("神農本草經") and "You Xiang Yi Hwa"("遊相醫話") and the records, notes, poems, and diaries such as "Zhi Yuan Man Lu"("枳園漫錄") and "Zhi Yuan Sui Bi"(枳園隨筆) that were not published. His thoughts were that in restoring the "Shen Nong Ben Cao Jing", "the herb to the doctor is like the "Shuo Wen Jie Zi"(說文解字) to the scholar", and he tried to restore the ancient herbal text using knowledge of medicine and investigation(考據), Also with Chosai he compiled the "Jing Ji Fang Gu Zhi"("經籍訪古志") using knowledge of ancient text. Ritzi left works on pure investigation, paid much attention to social problems, and through 12 years of poverty treated all people and animals in all branches of medicine, so he is called a 'half confucianist half doctor'(半儒半醫). 5) Kitamurana Ohira(喜多村直寬, $1804{\sim}1876$) learned scriptures and ancient texts from confucian scholar Asaka Gonsai(安積艮齋), and learned medicine from his father Huai Yaun(槐園), He became a teacher in the Yi Xue Guan in his middle ages, and to repay his country, he printed 266 volumes of "Yi Fang Lei Ju"("醫方類聚") and 1000 volumes of "Tai Ping Yu Lan"("太平禦覽") and devoted it to his country to be spread. His works are about 40 volumes including "Jin Qui Yao Lue Shu Yi"("金匱要略疏義") and "Lao Yi Zhi Yan"(老醫巵言) but most of them are researches on the "Shang Han Za Bing Lun". In his "Shang Han Lun Shu Yi"("傷寒論疏義") he shows the concept of the six meridians through the Yin-Yang, Superficial or internal, cold or hot, deficient or replete state of diseases, but did not match the names with the six meridians of the meridian theory, and this has something in common with the research based on the confucianism of Song(宋儒). In clinical treatment he was positive toward old and new methods and also the experience of civilians, but was negative toward western medicine. 6) The ancestor of the Taki family Tanbano Yasuyori(丹波康賴 $912{\sim}955$) became a Yi Bo Shi(醫博士) by his medical skills and compiled the "Yi Xin Fang"("醫心方"). His first son Tanbano Shigeaki(丹波重明) inherited the Shi Yao Yuan(施藥院) and the third son Tanbano Masatada(丹波雅忠) inherited the Dian You Tou(典藥頭). Masatada's descendents succeeded him for 25 generations until the family name was changed to Jin Bao(金保) and five generations later it was changed again to Duo Ji(多紀). The research scholar Taki Motohiro was in the third generation after the last name was changed to Taki, and his family kept an important part in the line of medical officers in Japan. Taki Motohiro(多紀元簡 $1755{\sim}1810$) was a teacher in the Yi Xue Guan where his father was residing, and became the physician for the general Jia Qi(家齊). He had a short temper and was not good at getting on in the world, and went against the will of the king and was banished from Ao Yi Shi(奧醫師). His most famous works, the "Shang Han Lun Ji Yi"("傷寒論輯義") and "Jin Qui Yao Lue Ji Yi"("金匱要略輯義") are the work of 20 years of collecting the theories of many schools and discussing, and is one of the most famous books on the "Shang Han Lun" in Japan. "Yi Sheng"("醫勝") is a collection of essays on research. Also there are the "Su Wen Shi"(素問識), "Ling Shu Shi"("靈樞識"), and the "Guan Ju Fang Yao Bu"("觀聚方要補"). Taki Motohiro(多紀元簡)'s position was succeeded by his third son Yuan Yin(元胤 $1789{\sim}1827$), and his works include works of research such as "Nan Jing Shu Jeng"(難經疏證), "Ti Ya"("體雅"), "Yao Ya"("藥雅"), "Ji Ya"(疾雅), "Ming Yi Gong An"(名醫公案), and "Yi Ji Kao"(醫籍考). The "Yi Ji Kao" is 80 volumes in length and lists about 3000 books on medicine in China before the Qing Dao Guang(道光), and under each title are the origin, number of volumes, state of existence, and, if possible, the preface, Ba Yu(跋語) and biography of the author. The younger sibling of Yuan Yin(元胤 $1789{\sim}1827$), Yuan Jian(元堅 $1795{\sim}1857$) expounded ancient writings at the Yi Xue Guan only after he reached middle age, was chosen for the Ao Yi Shi(奧醫師) and later became a Fa Yan(法眼), Fa Yin(法印) and Yu Chi(禦匙). He left about 15 texts, including "Su Wen Shao Shi"("素問紹識"), "Yi Xin Fang"("醫心方"), published in school, "Za Bing Guang Yao"("雜病廣要"), "Shang Han Guang Yao"("傷寒廣要"), and "Zhen Fu Yao Jue"("診腹要訣"). On the Taki family's founding and working of the Yi Xue Guan Yasuka Doumei(矢數道明) said they were "the people who took the initiative in Edo era kampo medicine" and evaluated their deeds in the fields of 'research of ancient text', the founding of Ji Shou Guan(躋壽館) and medical education', 'publication business', 'writing of medical text'. 5. The doctors of the 'Kao Zheng Pai' based their operations on the Edo Yi Xue Guan, and made groups with people with similar ideas to them, making a relationship 'net'. For example the three families of Duo Ji(多紀), Tang Chuan(湯川) and Xi Duo Cun(喜多村) married and adopted with and from each other and made prefaces and epitaphs for each other. Thus, the Taki family, the state science of the Makufu, the tendency of thinking, one's own interests and glory, one's own knowledge, the need of the society all played a role in the development of kampo medicine in the 18th and 19th century.