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ObjectiveTo establish an ultra-high performance liquid chromatography-tandem triple quadrupole mass spectrometry（UHPLC-QqQ-MS） for determination of the active ingredients in Erdongtang， and to predict the targets and pathways of anti-insulin resistance action of this formula. MethodThe analysis was performed on an ACQUITY UPLC BEH C18 column（2.1 mm×100 mm， 1.7 μm） with the mobile phase of 0.1% formic acid aqueous solution（A）-acetonitrile（B） for gradient elution（0-3 min， 90%-87%A； 3-6 min， 87%-86%A； 6-9 min， 86%-83%A； 9-11 min， 83%-75%A； 11-18 min， 75%-70%A； 18-19 min， 70%-52%A； 19-22 min， 52%A； 22-25 min， 52%-5%A； 25-27 min， 5%-90%A； 27-30 min， 90%A）. The contents of active ingredients in Erdongtang was detected by electrospray ionization（ESI） and multiple reaction monitoring（MRM） mode under positive and negative ion modes. On this basis， network pharmacology was applied to predict the targets and pathways of Erdongtang exerting anti-insulin resistance effect. ResultThe 20 active ingredients in Erdongtang showed good linear relationships within a certain mass concentration range， and the precision， stability， repeatability and recovery rate were good. The results of determination showed that the ingredients with high content in 15 batches of samples were baicalein（1 259.39-1 635.78 mg·L-1）， baicalin（1 078.37-1 411.52 mg·L-1）， the ingredients with medium content were mangiferin（148.59-217.04 mg·L-1）， timosaponin BⅡ（245.10-604.89 mg·L-1）， quercetin-3-O-glucuronide（89.30-423.26 mg·L-1）， rutin（46.91-1 553.61 mg·L-1）， glycyrrhizic acid（55.97-391.47 mg·L-1）， neomangiferin（37.45-127.03 mg·L-1）， nuciferine（0.89-63.48 mg·L-1）， hyperoside（6.96-136.78 mg·L-1）， liquiritin（30.89-122.78 mg·L-1）， liquiritigenin（26.64-110.67 mg·L-1）， protodioscin（58.57-284.26 mg·L-1）， the ingredients with low content were wogonin（7.16-20.74 mg·L-1）， pseudoprotodioscin（5.49-22.96 mg·L-1）， ginsenoside Rb1（7.31-23.87 mg·L-1）， ginsenoside Rg1（10.78-28.33 mg·L-1）， ginsenoside Re（7.78-24.76 mg·L-1）， ophiopogonin D（2.08-4.29 mg·L-1）， methylophiopogonanone A（0.74-1.67 mg·L-1）. The results of network pharmacology indicated that the mechanism of anti-insulin resistance exerted by Erdongtang might be related to the phosphatidylinositol 3-kinase/protein kinase B（PI3K/Akt） signaling pathway. ConclusionThe established UHPLC-QqQ-MS has the advantages of simple sample processing， strong exclusivity and high sensitivity， and can simultaneously determine the contents of the main ingredients from seven herbs in Erdongtang， which can lay the foundation for the development of Erdongtang compound preparations. The results of the network pharmacology can provide a reference for the mechanism study of Erdongtang in the treatment of type 2 diabetes mellitus.
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ObjectiveTo sort out the historical evolution， prescription evolution and modern clinical application of Huagaisan. MethodHuagaisan and its synonym Huagaitang are used as keywords to search the databases of Traditional Chinese Medicine Think Tank， Chinese Medical Dictionary， Airusheng Chinese Medical Database and China National Knowledge Infrastructure（CNKI）. According to the inclusion and exclusion criteria， we obtained the information of ancient books and modern clinical research literature related to Huagaisan， and systematically reviewed and analyzed the historical origin， prescription composition， preparation method， dosage， efficacy， medicinal material origin， processing method and modern clinical application of Huagaisan. ResultA total of 198 pieces of ancient book information were included， involving 93 ancient Chinese medicine books. Huagaisan was composed of fried Perillae Fructus， red Poria， fried Mori Cortex， Citri Eoxcarpium Rubrum， stir-fried Armeniacae Semen Amarum， Ephedrae Herba and fried Glycyrrhizae Radix et Rhizoma， which had the efficacy of promoting the lungs and relieving epidemiological symptoms， expelling phlegm and relieving cough， and treating cough with wind-cold bundled epidemiological symptoms and stagnation of phlegm and Qi. The preparation method was suggested as boiling powder， crushing the seven herbs into coarse particles， the dosage of each drug was fried Perillae Fructus of 1.27 g， red Poria of 1.27 g， fried Mori Cortex of 1.27 g， Citri Eoxcarpium Rubrum of 1.27 g， stir-fried Armeniacae Semen Amarum of 1.27 g， Ephedrae Herba of 1.27 g and fried Glycyrrhizae Radix et Rhizoma of 0.64 g， taking 8.26 g when decocting， adding 300 mL of water， decocting to 210 mL， removing the dregs， and taking it warmly after meals. Twenty-one clinical research papers were included to analyze the modern clinical application of Huagaisan， which was mainly used in the treatment of respiratory diseases such as pneumonia， asthma， bronchitis and so on. ConclusionThis paper has verified and summarized the key information of the famous classical formula Huagaisan， which can provide a detailed reference basis for the development and clinical application of its compound preparation.
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By consulting the ancient and modern literature， the textual research of Pharbitidis Semen has been conducted to clarify the name， origin， distribution of production areas， quality specification， harvesting， processing and so on， so as to provide reference for the development and utilization of the relevant famous classical formulas. Through textual research， it can be seen that Pharbitidis Semen was first published in Mingyi Bielu（《名医别录》）， and all dynasties have taken Qianniuzi as the correct name. Based on the original research， the main source of Pharbitidis Semen used in previous dynasties is the dried mature seeds of Pharbitis nil， which is consistent in ancient and modern times. The white Pharbitidis Semen appearing in Compendium of Materia Medica（《本草纲目》） from Ming dynasty is similar to the present P. purpurea. It is produced all over the country， and the quality is better if the particles are full and free of impurities. In ancient times， the harvesting time was mostly in the September. Now it is autumn. The fruits are ripe and harvested， dried to remove impurities for standby. In ancient times， the processing methods of Pharbitidis Semen were mainly wine steaming， steaming and frying until half cooked and grinding the head and end. In modern times， they have been simplified to stir-frying method. The nature， taste， meridian tropism and their effects also change supplements with the deepening of practice. Before the Ming dynasty， they were all bitter， cold and toxic. In the Ming dynasty， there appeared the characteristics of pungent， hot and small poisonous. The efficacy has evolved from controlling low Qi， curing foot edema， removing wind toxin， and facilitating urination to facilitating water and defecation， eliminating phlegm and drinking， and eliminating accumulated insects. The main clinical contraindications are those with weak spleen and kidney， those with weak spleen and stomach， pregnant women， and should not be used with croton and croton cream. Based on the textual research， it is suggested that when developing the classic famous formula with Pharbitidis Semen as the main raw material in the future， it is clear that the source should be the dried mature seeds of Pharbitis nil（black product is its black-brown seeds， white product is its beige seeds）. The processing requirements indicated in the original formula are all processed according to the requirements， and the raw product is recommended to be used as medicine if not specified.
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This paper systematically combed and verified the name， origin， producing area， quality evaluation， harvesting， processing of Euryales Semen in famous classical formulas by consulting relevant ancient materia medica， medical books， prescription books and modern literature. The results showed that Euryales Semen was first collected by materia medica under the name of Jitoushi， and since the Ming dynasty， Qianshi has been used as a proper name and continues to this day， with other aliases such as Yanhuishi. Euryale ferox， a plant of the Nymphaeaceae family， is the same as that used in the past dynasties. However， due to long-term artificial domestication， the varieties vary with the origin， including Beiqian and Suqian. The medicinal part of Euryales Semen is mature seed kernel， its origin of ancient records mainly includes Shandong， Jiangsu， Henan and other places， since the Ming and Qing dynasties， Euryales Semen produced in Suzhou has been highly praised. Since modern times， it has gradually summarized and formed the best quality evaluation method of Euryales Semen with full grains， white cross-section， powdery enough and no broken powder. The harvesting time in the past dynasties was mainly August or in autumn. The main processing methods in the past dynasties included peeling for powder， pounding powder after steaming， drying and frying. Up to now， two mainstream processing methods of cleansing and stir-frying have been formed. Based on the research results， it is recommended that the mature seed kernel of E. ferox be used in famous classical formula Yihuangtang. Combined with the processing requirements of the original formula， it is suggested to refer to the stir-frying method in the general principles of processing of the current edition of Chinese Pharmacopoeia.
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The "four-in-one" approach is based on the four-dimensional perspective of "property, position, tendency and syndrome", which helps to identify and analyze classical prescriptions in a multi-dimensional and three-dimensional way. The early pathogenesis of chronic heart failure (CHF) is deficiency of heart Qi and heart Yang and disorder in Qi transformation in triple energizer, while in the later stage of the disease, it progresses from deficiency to excess, with simultaneous occurrence of deficiency and excess syndromes. Fuling Guizhi Baizhu Gancao Decoction (Linggui Zhugan Decoction) plays its role in treating chronic heart failure by the four elements of "property, position, tendency and syndrome". Property—Linggui Zhugan Decoction is pungent, sweet, slight sweet and bitter in flavor, but warm in property. The sweet is able to tonify deficiency; the pungent is responsible for dispersing Yang, promoting Qi and draining water retention; the warm nourishes the spleen, raises Yang Qi and resolves phlegm; the bitter could excrete diuresis and dry dampness to guarantee the smooth operation of three energizer. Position-Linggui Zhugan Decoction acts on the heart, spleen and triple energizer. It can stimulate heart Yang, strengthen the spleen, resolve phlegm, and regulate the waterways to promote the Qi transformation in triple energizer. Tendency-The tendency of Linggui Zhugan Decoction is upward and downward in parallel, both internal and external. Warming up and promoting diuresis, raising Yang up and tonifying deficiency, it is conducive to the Yang Qi transformation in triple energizer. Syndrome-Linggui Zhugan Decoction is indicated for the syndrome of heart Yang deficiency and water-fluid retention, which begins with the upper abdomen swelling, Qi rushes against the chest. It is widely used in the treatment of water-vapor impulse heart disease. The disorder of Qi transformation in triple energizer is the main mechanism of recurrent CHF. Linggui Zhugan Decoction can not only warm the fire of Qi transformation in triple energizer, but also smooth the pathway of Qi transformation in triple energizer, which is compatible with the treatment of systemic fluid retention in chronic heart failure. Its pharmacological mechanisms include anti-inflammation, anti-platelet aggregation, regulation of cardiomyocyte cell membrane ion channels, protection against ischemia-reperfusion injury and modulation of vasodilation, etc. Deconstructing Linggui Zhugan Decoction with "four-in-one" approach and discussing its mechanism for treating CHF in combination with the theory of "Qi transformation in triple energizer", have great significance to rejuvenate the vitality of classical prescriptions and to apply them accurately and effectively.
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In this paper， the name， origin， medicinal parts， producing area， harvesting， processing methods and efficacy of Equiseti Hiemalis Herba（EHH） in famous classical formulas were examined by reviewing related ancient and modern literature. Through textual research， Muzei was first appeared in Zhenyuan Guanglifang（《贞元广利方》）， and used as a mainstream name by later generations. It is also known by other names， such as Cuocao and Bigancao. The main origin of ancient EHH was Equisetum hyemale， which was mixed with E. ramosissimum during the Qing dynasty. The medicinal part was the above-ground part of EHH. In ancient times， the genuine producing area was considered to be Qinzhou， which is now Tianshui city， Gansu. In modern times， EHH produced in Liaoning province is believed to be of higher quality. Currently， the main producing area of EHH circulating in the market is the northeast region in China. EHH with stems that are thick and long， a green color， a thick texture， and clearly visible edges and roughness， but without any easily separating joints being considered the best. The processing methods of the past dynasties mainly included filing， removing knots， stir-baked the crude drugs into black on outside and brown in inside， urine soaking， sun drying and shade drying. In modern times， the main processing method is to first moisturize the plant material， and then cut it into sections before drying. In terms of medicinal properties， EHH is considered by both ancient and modern medicine to have a neutral nature， a slightly sweet and bitter taste， and is non-toxic. Its primary therapeutic effects are related to treating eye diseases， intestinal wind bleeding and uterine bleeding. Based on the research， it is suggested that the dried above-ground part of E. hiemale be used in the development and utilization of famous classical formulas. For the processing requirements are not indicated， it is suggested using raw decoction pieces as medicine， and the processing method refers to the 2020 edition of Chinese Pharmacopoeia. If it is clearly stated that fried charcoal is required， it is recommended to refer to general requirements 0213 of the 2020 edition of Chinese Pharmacopoeia， if it is clearly stated that removing knots is required， it is recommended to follow the ancient method.
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By consulting the ancient and modern literature， the name， origin， quality evaluation， harvesting and processing methods of Curculiginis Rhizoma（CR） were systematically combed and verified， in order to provide a basis for the development and utilization of famous classical formulas containing CR. The results of herbal textual research showed that the name Xianmao was first recorded in Leigong Paozhilun， the name of CR was used in all dynasties and this name came from its efficacy and morphological characteristics， the mainstream source for CR of the past dynasties was the rhizome of Curculigo orchioides or C. capitulata， since modern times， C. orchioides has been the main source of commodities. In ancient times， most of the places of origin of the description were the western regions and southwest China， while in modern times， Sichuan and Guizhou were regarded as genuine places. Since modern times， its quality has been summarized as the best with thick roots， firm texture and black-brown surface， the harvesting and processing methods recorded in the past dynasties are mainly sun drying after harvest in the second， eighth and ninth months of the lunar calendar， and most of them are harvested in autumn and winter in modern times. In ancient times， there were many processing methods of CR， mainly in processing with rice swill， while in modern times， stir-frying with wine was the main processing method. The nature， taste， meridian tropism， functions and indications of CR are basically consistent from ancient to modern times， the taboos for taking are to avoid iron， cow's milk， and beef. Although there are some differences in the understanding of the toxicity of CR in the past dynasties， most of the materia medica are clear that it has a certain toxicity. Based on the research conclusion， it is suggested that the rhizome of C. orchioides of Lycoris family should be used as its source in the famous classical formulas， and the corresponding processing method should be selected according to the processing requirements in the formulas， while the raw products is recommended to be selected as medicine if the processing requirement is not specified.
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ObjectiveTo screen out the transcriptomes related to the intervention of Wuzi Yanzongwan on the spermatogenic function of semi-castrated male mice， and to explore its potential mechanism in the intervention of the progress of low spermatogenic function. MethodBalb/c mice were randomly divided into sham-operated group， model group， testosterone propionate group（0.2 mg·kg-1·d-1， intramuscular injection） and Wuzi Yanzongwan group（1.56 g·kg-1·d-1， intragastric administration） according to body weight， with 12 mice in each group. The right testicle and epididymis were extracted from the model group and the drug administration group to construct the semi-castrated model of low spermatogenic function， while the fur and the right scrotum of the sham-operated group were only cut and immediately sterilized and sutured. At the end of the intervention， hematoxylin-eosin（HE） staining was used to observe the histopathology of testis， enzyme-linked immunosorbent assay（ELISA） was used to detect the levels of serum testosterone（T）， luteinizing hormone（LH） and follicle stimulating hormone（FSH）. The sperm count and motility of epididymis were measured by automatic sperm detector of small animal. Transcriptomic microarray technology was used to detect the mRNA expression level of testicular tissue in each group， the transcriptome of genes related to the regulation of Wuzi Yanzongwan was screened， and three mRNAs were selected for Real-time fluorescence quantitative polymerase chain reaction（Real-time PCR） to verify the transcriptome data. Through the annotation analysis of Gene Ontology（GO） and the signaling pathway analysis of Kyoto Encyclopedia of Genes and Genomes（KEGG）， the related functions of drugs regulating transcriptome were analyzed. ResultCompared with the sham-operated group， the testicular tissue of mice in the model group showed spermatogenic injury， contraction and vacuolization of the seminiferous tubules， reduction of spermatogenic cells at all levels， widening of the interstitial space， obstruction of spermatogonial cell development and other morphological abnormalities， and serum T significantly decreased， LH significantly increased（P<0.01）， and FSH elevated but no statistically significant difference， the count and vitality of epididymal sperm significantly decreased（P<0.01）. There were 882 differentially expressed mRNAs in the testicular tissues， of which 565 were up-regulated and 317 were down-regulated. Cluster analysis showed that these differentially expressed mRNA could effectively distinguish between the sham-operated group and the model group. Compared with the model group， the damage to testicular tissue in the Wuzi Yanzongwan group was reduced， the structure of the seminiferous tubules was intact， vacuolization was reduced， and the number of spermatogenic cells at all levels was significantly increased and arranged tightly. The serum T significantly increased， LH significantly decreased（P<0.01）， and FSH decreased but the difference was not statistically significant. The count and vitality of sperm in the epididymis were significantly increased（P<0.01）. Moreover， Wuzi Yanzongwan could regulate 159 mRNA levels in the testes of semi-castrated mice， of which 32 were up-regulated and 127 were down-regulated， and the data of the transcriptome assay was verified to be reliable by Real-time PCR. GO and KEGG analysis showed that the transcriptome functions regulated by Wuzi Yanzongwan were involved in the whole cell cycle process of sperm development such as sex hormone production of interstitial cells in testis， renewal， differentiation， metabolism， apoptosis and signal transduction of spermatogenic cells， and were closely related to the biological behaviors of signaling pathways such as spermatogenic stem cell function， endoplasmic reticulum protein processing and metabolic program. ConclusionWuzi Yanzongwan can effectively improve the low spermatogenic function of semi-castrated male mice， and its mechanism may be related to the regulation of testicular transcriptional regulatory network， the synthesis of sex hormones in testicular interstitial cells， the function of spermatogenic stem cells， the whole cell cycle process of spermatogenesis， as well as the expression of endoplasmic reticulum protein processing and metabolic program related genes transcription.
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By consulting the ancient and moderm literature， this paper makes a textual research on the name， origin， quality evaluation， harvesting and processing of Olibanum， so as to provide a basis for the development of the famous classical formulas containing this medicinal material. According to the herbal textual research， the results showed that Olibanum was first described as a medicinal material by the name of Xunluxiang in Mingyi Bielu（《名医别录》）， until Ruxiang had been used as the correct name since Bencao Shiyi（《本草拾遗》） in Tang dynasty. The main origin was Boswellia carterii from Burseraceae family. The mainly producing areas in ancient description were ancient India and Arabia， while the modern producing areas are Somalia， Ethiopia and the southern Arabian Peninsula. The medicinal part of Olibanum in ancient and modern times is the resin exuded from the bark， which has been mainly harvested in spring and summer. It is concluded that the better Olibanum has light yellow， granular， translucent， no impurities such as sand and bark， sticky powder and aromatic smell. There were many processing methods in ancient times， including cleansing（water flying， removing impurities）， grinding（wine grinding， rush grinding）， frying（stir-frying， rush frying， wine frying）， degreasing， vinegar processing， decoction. In modern times， the main processing methods are simplified to cleansing， stir-frying and vinegar processing. Nowadays， the commonly used specifications include raw， fried and vinegar-processed products. Among the three specifications， raw products is the Olibanum after cleansing， fried products is a kind of Olibanum processed by frying method， vinegar-processed products is the processed products of pure frankincense mixed with vinegar. Based on the research results， it is recommended to select the resin exuded from the bark of B. carterii for the famous classical formulas such as Juanbitang containing Olibanum， processing method should be carried out in accordance with the processing requirements of the formulas， otherwise used the raw products if the formulas without clear processing requirements.
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By consulting ancient and modern literature， the herbal textual research of Farfarae Flos has been conducted to verify the name， origin， producing area， quality evaluation， harvesting and processing methods， so as to provide reference for the development and utilization of the famous classical formulas containing Farfarae Flos. According to the research， the results showed that Farfarae Flos was first described as a medicinal material by the name of Kuandonghua in Shennong Bencaojing（《神农本草经》）， and the name was used and justified by later generations. The main origin was the folwer buds of Tussilago farfara， in addition， the flower buds of Petasites japonicus were used as medicine in ancient times. The ancient harvesting time of Farfarae Flos was mostly in the twelfth month of the lunar calendar， and the modern harvesting time is in December or before the ground freeze when the flower buds have not been excavated. Hebei， Gansu， Shaanxi are the authentic producing areas with the good quality products. Since modern times， its quality is summarized as big， fat， purple-red color， no pedicel is better. Processing method from soaking with licorice water in the Northern and Southern dynasties to stir-frying with honey water followed by micro-fire in the Ming dynasty， and gradually evolved to the modern mainstream processing method of honey processing. Based on the research results， it is suggested that the dried flower buds of T. farfara， a Compositae plant， should be selected for the development of famous classical formulas containing Farfarae Flos， and the corresponding processed products should be selected according to the specific processing requirements of the formulas， and raw products are recommended for medicinal use without indicating processing requirements.
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This article systematically analyzes the historical evolution of the origin， scientific name， medicinal parts， quality evaluation， harvesting and processing and other aspects of Tsaoko Fructus by consulting ancient materia medica， medical books， prescription books in the past dynasties and combining with the modern literature， so as to provide a basis for the development and utilization of famous classical formulas containing Tsaoko Fructus. According to the research， the name of Caoguo（草果） was first used in the Taiping Huimin Heji Jufang（《太平惠民和剂局方》） in the Northern Song dynasty， Tsaoko Fructus is the correct name of the herbal medicine in all dynasties， and there are also aliases such as Caokou， Doukou， Loukou， Laokou and Caodoukou. The mainstream source of Tsaoko Fructus used in the past dynasties is the dried mature fruit of Amomum tsaoko of Zingiberaceae， but Tsaoko Fructus was often used as a nickname for Amomi Fructus Rotundus or Alpiniae Katsumadai Semen during the Song dynasty. Bencao Pinhui Jingyao（《本草品汇精要》） in the Ming dynasty was the earliest materia medica that recorded Tsaoko Fructus as a separate medicinal herb in sections. Under the influence of early ancient books， there were some books that confused Tsaoko Fructus with other Zingiberaceae plants during the Qing dynasty， it was not until modern times that Tsaoko Fructus was distinguished from other plants. The origin of Tsaoko Fructus is Yunnan and Guangxi， and then gradually expanded to Guizhou and other places. Now Yunnan is the province with the largest planting area of Tsaoko Fructus， and has become the main producing area. Since modern times， it has been recorded in the literature that the quality of Tsaoko Fructus is mainly characterized by large， full， red-brown and strong in smell. According to ancient records， the harvest time of Tsaoko Fructus was in the eighth month of the lunar calendar， and they were mostly used for peeling or simmering. Currently， the harvest period of Tsaoko Fructus is October to November， and then sun-dried or dried after harvesting. The records of the properties and functional indications of Tsaoko Fructus are basically consistent with the ancient and modern documents， which is warm in nature， pungent in flavor， belonging to the spleen and stomach meridians， moderate in dryness and dampness， intercepting malaria and eliminating phlegm， used for internal resistance of cold and dampness， abdominal distension and pain， fullness and vomiting， malaria cold and fever， and plague fever. Based on the research results， it is suggested that A. tsaoko should be used as the medicinal base for the development of famous classical formulas containing Tsaoko Fructus， processing method can be according to the requirements of the prescription， and if the requirements of concoction are not indicated， it can be used in the form of raw products.
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Tuoli Xiaodusan is the 65th formula in the Catalogue of Ancient Famous Classical Formulas（First Batch）. In this study， the bibliometric method was used to summarize and verify the ancient books about Tuoli Xiaodusan in terms of its historical origin， composition and dosage of the formula， indications， decoction and administration method， and processing， etc. According to the research， there is no definite date of the formation of Tuoli Xiaodusan， the earliest can be traced back to Lizhai Waike Fahui in Ming dynasty， which has been widely circulated， with many versions of prescription composition， and the modern influential version is from Waike Zhengzong in Ming dynasty， which is made up of 12 Chinese herbs including Ginseng Radix et Rhizoma（3.73 g）， Chuanxiong Rhizoma（3.73 g）， Paeoniae Radix Alba（3.73 g）， Astragali Radix（3.73 g）， Angelicae Sinensis Radix（3.73 g）， Atractylodis Macrocephalae Rhizoma（3.73 g）， Poria（3.73 g）， Lonicerae Japonicae Flos（3.73 g）， Angelicae Dahuricae Radix（1.87 g）， Glycyrrhizae Radix et Rhizoma（1.87 g）， Gleditsiae Spina（1.87 g）， Platycodonis Radix（1.87 g）. The herb origins almost follow the 2020 edition of Chinese Pharmacopoeia， except that Angelica dahurica var. formosana is only recommended as the origin of Angelicae Dahuricae Radix， and Glycryyhiza uralensis is only recommended as the origin of Glycyrrhizae Radix et Rhizoma. All the herbs are recommended to be used in the raw products. As for the preparation method， it is recommended to decoct with water， add 400 mL of water， boil until 160 mL， and take 2-3 times a day. The formula has the functions of nourishing Qi and nourishing blood， detoxifying and draining pus， and was mainly used to treat ulcerative diseases with the syndrome of syndrome of healthy Qi deficiency and pathogenic factors excess in ancient times， and in modern times， it is used for a wide range of treatment， involving the skin and soft tissues， bones， digestion and many other systemic diseases， and is also mainly used for syndrome of healthy Qi deficiency and pathogenic factors excess. In this study， the ancient and modern applications of Tuoli Xiaodusan were summarized， and its key information was identified， providing a basis for its wider clinical application， in-depth research and formulation development.
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Due to the difference between the system of weights and measures， and the dosage of clinical prescriptions of traditional Chinese medicine in various historical periods， the dosage and conversion standard of prescriptions in past dynasties are different. Therefore， when discounting the dosage of famous classical formulas， the principles of inheriting the essence， making the past serve the present， linking the past and the present， and forming a consensus should be followed， firstly， the dosage of the prescription was converted according to the weights and measures system of the past dynasties. If the converted dosage significantly exceeds the provisions of the 2020 edition of Chinese Pharmacopoeia， then on the premise of ensuring that the proportion of the original prescription drug dosage remains unchanged， the conversion shall be based on expert consensus and drug safety evaluation. For drugs measured in non-standard units， a conversion range is provided based on comprehensive literature analysis and physical measurements. For the conversion of service volume， the original text was used as the basis for the conversion with reference to the measurement standards of different eras. If the original dosage is not clear， the converted dosage will be determined based on the historical evolution of the formula， referring to relevant ancient books， and combining modern applications. Eventually， the converting standard for famous classical formulas was determined as follows：during the Han and Tang dynasties， one Liang（两） was equivalent to 13.8 g and one Sheng（升） was equivalent to 200 mL， in the Tang dynasty， one Fen（分） was equivalent to 3.45 g， during the Song， Jin and Yuan dynasties， one Qian（钱） was equivalent to 4.13 g and one Zhan（盏） was equivalent to 300 mL， during the Ming and Qing dynasties， one Qian（钱） was equivalent to 3.73 g， and one Bei（杯） and one Zhong（盅） were equivalent to 200 mL. For drugs recorded in non-standard units of measurement， it is necessary to conduct actual measurements to determine their conversion standards based on comprehensive analysis to determine their origin. If necessary， different records of the dosage of drugs with the same or similar efficacy and indications in medical books of similar ages can be used to assist in determining the conversion standards. The analysis of the principle of dosage conversion for Chinese medicine is helpful for the clinical application and development of famous classical formulas.
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In order to provide a reference basis for the development of relevant compound preparations， this article takes a comprehensive analysis of the usage and dosage of famous classical formulas in Han dynasty from various perspectives， and gives corresponding countermeasures on this basis. Through the comprehensive analysis of the classification and statistics of Zhongjing's medication characteristics， decoction methods， administration and dosage， and combining conversion methods of weights and measures by ancient medical practitioners， along with the dosage and administration of the listed Han dynasty famous classical formulas， it was found that the "Jiangxi method" served as a general guideline for administration according to Zhongjing's original text. This method allowed for flexible dosing based on the conversion of the ancient measurements to modern equivalents［13.8 g per Liang（两）］， ensuring the safe and effective medication of these formulas. After combing， it is found that although the dosage of single medicine is large in famous classical formulas from Han dynasty， the administration is flexible. The crude drug amount per administration serves as the foundational dose， with the frequency of administration adjusted flexibly according to the condition. This dosing approach becomes the key for the rational development of compound formulations of famous classical formulas. Based on the conclusions of the study， it is recommended that when developing compound formulations of famous classical formulas in Han dynasty， the original administration method and dosage should be respected. The original crude drug amount per administration should be considered as the daily foundational dose， with the frequency of administration described within a range（1 to N times per day， where N is the maximum number of administrations as per the original text）. The specific frequency of administration can be adjusted flexibly by clinical practitioners based on the individual condition. This approach should also be adopted in toxicological studies， where the dosage per administration serves as the basis for toxicity research， and the toxicity profile at the maximum administration frequency should be observed， providing guidance on the clinical safety range. Corresponding drug labels should provide information within a range to indicate toxicological risk intervals.
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Through consulting the ancient herbal books and modern literature， this paper has carried out the textual research on the name， origin， place of origin， harvesting and processing， and other contents of Bruceae Fructus， combed its ancient and modern medicinal history， so as to provide reference for the development of famous classical formulas containing Bruceae Fructus. Through the herbal textual research， It can be verified that， since the Qing dynasty， Bruceae Fructus has been recorded in the materia medica， most of the materia medica in previous dynasties took Bruceae Fructus as its proper name， and Laoyadan， Kushenzi and Yadanzi as the aliases. The main origin of Bruceae Fructus is Brucea javanica， its medicinal part is the fruit， which is harvested from August to October every year， the fruit can be harvested when it is ripe. Bruceae Fructus was first distributed in Fujian， Guangdong and Guangxi， and gradually expanded to the south of China with the change of time. The traditional processing method of Bruceae Fructus is mainly to remove the shell and kernel， and remove the oil by frosting. The 2020 edition of Chinese Pharmacopoeia stipulates that its processing method is to remove the shell and impurities. Based on the research results， it is suggested that the dried mature fruit of B. javanica should be selected for the development of famous classical formulas containing this herb， and the raw products can be used if the original formula does not specify the processing requirements.
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By reviewing the ancient and modern literature， the name， origin， scientific name evolution， place of origin， quality， harvesting， processing， efficacy and toxicity of Asteris Radix et Rhizoma（ARR） were systematically sorted out， so as to provide reference for the development and utilization of the relevant famous classical formulas. According to textual research， ARR was first contained in Shennong Bencaojing， all generations are Ziwan for its proper name， and there are still aliases such as Ziyuan， Ziqian and Xiaobianer. Its mainstream origin in successive generations was Aster tataricus， and there are also Ligularia fischeri and others in local area of use. The medicinal parts of ARR are root and rhizome， but in modern times， the rhizome is mostly used for propagation and cultivation， so some of ARR medicinal materials only have the root without the rhizome. The earliest recorded ancient origin of ARR was now Fangxian（Hubei）， Zhengding and Handan（Heibei）， then the range of production areas gradually expanded， the mainstream production areas from the Song dynasty to the Ming and Qing dynasties included Hebei， Jiangsu， Anhui， Henan and other places， since modern times， two major producing areas have been formed in Anguo， Hebei province and Bozhou， Anhui province. From the quality evaluation， it is clear that from ancient times， flexible roots and purple color are the best. The ancient harvesting was mainly in lunar February or March， and then dried in the shade， and the modern harvesting is mostly in spring and autumn， and the roots are braided into pigtails and then dried in the sun or dried in the sun after 1-2 d. The ancient and modern processing method of ARR are basically the same， mainly honey processing， there are still methods of frying， steaming， vinegar sizzling， etc. Based on the results， it is recommended that the dried roots and rhizomes of A. tataricus should be used in clinical and the development of related famous classical formulas， and those whose original formulas specify the processing requirements can be processed according to the relevant requirements， while whose processing requirements are not specified should be used in the form of raw products.
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Yigongsan is derived from Xiaoer Yaozheng Zhijue written by QIAN Yi in the Northern Song dynasty， which is the No. 3 formula in the Catalogue of Ancient Famous Classical Formulas（The Second Batch of Pediatrics） released by the National Administration of Traditional Chinese Medicine（TCM） in September 2022， and it can be developed as a class 3.1 new TCM drug. By referring to ancient medical books and modern literature， this study conducted herbal textual research on Yigongsan from five aspects， including historical evolution， origin and processing， dosage conversion， usage and preparation methods， and functional application， then formed the key information table of this formula， in order to provide reference for the development of reference samples and preparations of Yigongsan. Based on the results of the study， it is recommended that Panax ginseng should be removed the basal part of stem（rhizoma）， Poria cocos should be removed the peel， Citrus reticulata should be cut into shreds and Glycyrrhiza uralensis should be used. According to 4.13 g/Qian（钱）， 1 g/slice for ginger， 3 g for each jujube and 300 mL/Zhan（盏）， the doses of Ginseng Radix， Poria， Atractylodis Macrocephalae Rhizoma， Glycyrrhizae Radix et Rhizoma， Citri Reticulatae Pericarpium， Zingiberis Rhizoma Recens， Jujubae Fructus were 1.652， 1.652， 1.652， 1.652， 1.652， 5， 6 g， and the total amount was 19.26 g. The decocting method was to crush the medicinal materials into fine powder with 50-80 mesh， add 300 mL of water and decoct to 210 mL for each dose， then remove the dregs and take it warmly. This formula was recorded in ancient books as the main treatment for the cold-deficiency of spleen and stomach， and Qi stagnation in children with vomiting and diarrhea and lack of appetite. It has been flexibly applied by later generations of physicians， and is often used to treat anorexia， inflammation of the digestive tract， diarrhea and other diseases in children.
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This article systematically analyzes the historical evolution of the name， origin， producing area， quality evaluation， harvesting and processing， clinical efficacy of Pyrrosiae Folium by consulting the ancient materia medica， medical books and prescription books， combined with modern literature， in order to provide a reference for the development of famous classical formulas containing this herb. After herbal textual research， it was found that the names of Pyrrosiae Folium in the past dynasties were mostly derived from its color， shape and efficacy. And there were other nicknames such as Shizhe， Shipi and Shilan. Song， Yuan dynasties and before the period， the main origin of Pyrrosiae Folium was Pyrrosia petiolosa， in the Ming dynasty， the main origins were P. petiolosa and P. sheareri， during the Qing dynasty to the present， the main origins were P. sheareri， P. petiolosa and P. lingua. Anciently， the respected Dao-di production area of Pyrrosiae Folium was the area of Lianyungang city， Jiangsu province. In modern times， Anhui and Zhejiang provinces are the main producing areas of P. sheareri， Fujian and Taiwan provinces are the main producing areas of P. lingua， and Guizhou and Hubei provinces are the main producing areas of P. petiolosa. In ancient and modern times， Pyrrosiae Folium with large leaves and thick texture is considered to be the best， the medicinal part is the leaves， and the harvesting and processing methods recorded in the past dynasties were mainly shade-drying after harvesting in the February and July of the lunar calendar， while the modern ones are mostly harvested throughout the year. The processing methods of the past dynasties mainly included removing fuzz by scraping， lightly roasted， frying， fat-fried. However， in modern times， it is mostly used the raw products as a medicine after cleaning， cutting and drying. In ancient times， Pyrrosiae Folium was thought to have a neutral nature with slightly sweet and bitter taste， while in modern times， it is thought to have a slightly cold nature with slightly sweet and bitter taste， and the main effects in ancient and modern times are diuretic， clearing lung-heat， hemostasis and so on. Based on the research results， it is suggested that P. sheareri， P. petiolosa and P. lingua can be used as the medicinal base， processing method can be according to the requirements of formulas， and if the processing requirements are not indicated， the raw products can be selected as the medicine.
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To conduct textual research on the records of Chrysanthemi Flos in the ancient literature from the aspects of name， origin， species， scientific name， origin， harvesting， processing， quality and so on， and the modern literature was sorted out to clarify the relationship between the ancient and modern times， so as to provide a reference for the development of famous classical formulas containing Chrysanthemi Flos. Chrysanthemi Flos is an ornamental， edible and medicinal plant in China， it has many aliases， but it has been recorded in this materia medica under the name of Juhua， Ganju and Ganjuhua. Before the Tang dynasty， medicinal Chrysanthemi Flos mainly collected wild products， including yellow flowers and white flowers， of which the mainstream of yellow flowers was originally Dendranthema lavandulifolium and D. potentilloides， the mainstream of white flowers is D. vestitum and D. chanetii. The cultivation of medicinal Chrysanthemi Flos began in the Northern Song dynasty， and wild D. lavandulifolium， D. potentilloides， D. vestitum and D. chanetii were selected through long-term interspecies and intraspecies crossbreeding， which gradually formed the current cultivar D. morifolium. After chrysanthemums were introduced abroad， foreign scholars began to name chrysanthemums with Linnaeus's plant classification system. In 1792， Mathier named chrysanthemums as Chrysanthemum morifolium and continued to this day， and all the editions of Chinese Pharmacopoeia adopted this scientific name. In the Song dynasty， many local varieties such as Nanyangju， Dengzhouhuang and Dengzhoubai appeared. By the time of the Republic of China， five famous authentic varieties， namely Huaiju， Boju， Chuju， Gongju and Hangju， had been cultivated for medicinal purposes. Boju has been the best medicinal variety since the late Qing dynasty. Hangbaiju has been famous for its tea use， especially the best quality of Huju. Chuju has its own unique characteristics， and it is of good quality both for medicine and tea. Gongju has always been a good tea chrysanthemum. Chrysanthemums are traditionally harvested in September of the lunar calendar， but some of the new varieties cultivated nowadays are harvested earlier. The embryo chrysanthemum in Hangbaiju is a commodity type that collects unopened buds in advance. In ancient times， chrysanthemums were mainly dried in the shade， in modern times， drying methods include drying in the shade， drying in the oven and drying in the sun after steaming. At present， hot air drying is mostly used. In terms of processing， Chrysanthemi Flos was used raw products in ancient times， in modern times， it is still widely used， sometimes stir fried（including stir-fried charcoal）. Due to different varieties， producing areas and processing methods， there are certain differences in the proportion of ingredients contained in chrysanthemum. Therefore， it is suggested that chrysanthemums with different varieties， origins and processing methods should be selected according to clinical indications in the development of famous classical formula preparations containing Chrysanthemi Flos.
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Through reviewing the ancient and modern literature， the name， origin， producing area， quality evaluation， harvesting and processing methods of Trichosanthis Fructus（TF） and Trichosanthis Radix（TR） in famous classical formulas were systematically sorted out following the chronological order. The results showed that there were many nicknames of TF and TR， and Gualou and Tianhuafen have become the mainstream names for its fruit and root， respectively. Both of them took Trichosanthes kirilowii as the mainstream base. TF and TR have been used as medicines in the Han dynasty， and since the North and South dynasties， Leigong Paozhilun had been clear that the effects of peels， seeds， stems， roots were different. TF was used as medicine with intact fruits， harvested after maturity from September to October， hung and dried in the shade， and its quality has been summarized in recent times as being best for those who are mature， large， thick and pliable peels， orange-yellow in color， and with sufficient sugary properties. In ancient times， the processing of TR was mostly crushed or shredded with the peels and seeds， or processing for pancakes and creams. TR was used as medicine with the roots， it is harvested from November to December， peeled and dried in the sun， and its quality was best when it was deep in the soil， large， white， powdery， firm and delicate with few muscles and veins， and it was considered to be toxic when it was born in briney land. Processing method of TR was to do powder into the medicine in the Tang dynasty， and gradually evolved into direct slicing use in the Ming and Qing dynasties. Since the modern era， the authentic producing areas of TF and TR were in the vicinity of Lingbao， Henan province， known as Anyang Huafen， and in modern times， there are well-known production areas such as Anguo， which produces Qihuafen， and Jinan， which produces Changqing Gualou. In the Song dynasty， there was a habit of substituting Trichosanthis Semen for the whole herb， which was later corrected by the materia medica in Ming dynasty. Based on the results， It is suggested that T. kirilowii be selected as the basal plant for the development of famous classical formulas involving TR and TF. In Qingjin Huatantang， Trichosanthis Semen is processed by stir-frying method， while TR and TF in other five formulas from the Catalogue of Ancient Famous Classical Formulas（The First Batch） were all used in raw form.