1.Usage and Dosage Analysis and Countermeasures for Development of Compound Preparations of Han Dynasty Famous Classical Formulas
Yan JIN ; Bing LI ; Wei ZHANG ; Huasheng PENG ; Huamin ZHANG ; Huihui LIU ; Lin ZHANG ; Zhilai ZHAN
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(7):1-10
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.
2.History and Clinical Application of Classic Famous Formula Danggui Sinitang
Sihong LIU ; Siqi JIA ; Lin TONG ; Li REN ; Lei ZHANG ; Lei YANG ; Yanhui KUANG ; Deqin WANG ; Bing LI ; Huamin ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(1):53-60
Danggui Sinitang is first recorded in the Treatise on Cold Damage written by ZHANG Zhongjing in the Han dynasty. It is composed of Angelicae Sinensis Radix, Cinnamomi Ramulus, Paeoniae Radix Alba, Asari Radix et Rhizoma, Glycyrrhizae Radix et Rhizoma, Tetrapanacis Medulla, and Jujubae Fructus and serves as a classic formula for treating the syndrome of blood deficiency and cold reversal. This study systematically reviews the records of Danggui Sinitang in ancient Chinese medicine books of various dynasties and the modern clinical applications to probe into the composition, plant species, processing, dosage, decocting method, and indications of Danggui Sinitang, aiming to provide a reference for the development and clinical application of this classic formula. The review of the records showed that there were a variety of records of Danggui Sinitang with different composition, and the composition of this formula listed in the Treatise on Cold Damage has a significant impact on later generations and has been used by medical practitioners throughout history. Although the dosage of some drugs decreased during the Ming and Qing dynasties, the medical practitioners continued to use the original formula. In terms of processing, although there were slight changes in the processing of Angelicae Sinensis Radix, Paeoniae Radix Alba, Glycyrrhizae Radix et Rhizoma, and Tetrapanacis Medulla, the original processing method was inherited. In terms of indications, Danggui Sinitang was designed to treat cold reversal due to blood deficiency and dysentery. Furthermore, it was used to treat headache, convulsive disease, infantile convulsion, and private part adduction in the Ming and Qing dynasties. Nowadays, this formula is mostly used to treat diabetes peripheral neuropathy, rheumatoid arthritis, dysmenorrhea, Raynaud's disease and other diseases. In terms of precautions, ancient physicians believed that Danggui Sinitang should not be taken by pregnant women and should only be used for limb chills caused by blood deficiency and cold coagulation. For limb chills caused by other reasons, this formula should not be used indiscriminately. Modern research has not reported any serious adverse reactions related to this formula. Danggui Sinitang has a definite therapeutic effect. In subsequent research and development, quality control standards of Danggui Sinitang should be established while its safety is ensured, and the related preparations should be developed and applied.
3.Exploring the Comorbidity Mechanisms of Coronary Heart Disease and Depression Based on "Constraint Causing Disease" and "Disease Causing Constraint" Theories
Huiying HAN ; Zhaihua LIU ; Huamin ZHANG ; Hongxin CAO
Journal of Traditional Chinese Medicine 2024;65(8):858-861
This study explored the comorbidity mechanisms of coronary heart disease and depression from the perspectives of "constraint causing disease" and "disease causing constraint", for which "constraint" is the link, and the key lies in the stagnation of qi. The heart storing manifestations in traditional Chinese medicine (TCM) encompasses most physiological processes of the circulatory system, the mental nervous system, and some functions of the endocrine system, and cardiovascular diseases and psychological disorders are closely related to it. In TCM, it is proposed that the stagnation of heart yang leading to "yang deficiency" is the pathogenesis of chest tightness, and emotional disturbance leading to the stagnation of yang qi aggravates the chest tightness, reflecting the process of "disease causing constraint". As the disease progresses, the appearance of phlegm and stasis further worsens the condition, reflecting the process of "constraint causing disease". Based on modern medical understanding, the abnormal accumulation of lipids, platelets, oxidative products, cytokines, and other substances constitute a form of "constraint", which is also the material basis for the comorbidity of coronary heart disease and depression. These substances promote neuronal damage or apoptosis in the emotional and cognitive regions, inducing the onset of depression, reflecting the process of "disease causing constraint". Meanwhile, adverse emotions lead to sympathetic nerve excitement, resulting in the production of catecholamines, promoting platelet aggregation, elevating levels of inflammatory markers, and increasing the risk of coronary heart disease, reflecting the process of "disease causing constraint".
4.Characteristics of Emergency Health Systems Guidance Based on AGREE-HS
Danping ZHENG ; Wei YANG ; Nannan SHI ; Dongfeng WEI ; An LI ; Gezhi ZHANG ; Xue CHEN ; Fangqi LIU ; Zhaoshuai YAN ; Weixuan BAI ; Xinghua XIANG ; Yaxin TIAN ; Mengyu LIU ; Huamin ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(22):137-148
This study used the Appraisal of Guidelines Research & Evaluation-Health Systems (AGREE-HS) to demonstratively compare 34 global coronavirus disease-2019 (COVID-19) health systems guidance documents (HSGs) and 6 World Health Organization (WHO) standard HSGs. The comparison involved topic, participants, methods, recommendations, and implementability, with the aim of exploring the characteristics of emergency HSGs. The results showed that the emergency HSGs had an overall average score of 49%, with topic having the highest score, recommendations having the second highest score, and participants having the lowest score. The standard HSGs had an overall average score of 79%, with high scores in all items. The emergency HSGs had lower scores in participants, methods, recommendations, and implementability than the standard HSGs (P<0.001), while the COVID-19 emergency HSGs developed by the WHO had higher score in topic than the standard HSGs (P<0.05). Compared with those released by countries, the COVID-19 emergency HSG developed by the WHO showed superiority in all items and overall scores (P=0.000 2). This indicates that emergency HSGs, represented by the COVID-19 emergency HSG, place equal emphasis on topic and recommendations as standard HSGs but have low requirements in terms of expert participation, evidence support, and comprehensive consideration in the time- and resource-limited context. They have the characteristics of prominent topics, clear purposes, orientation to demand, keeping up with the latest evidence, flexible adjustment, and timeliness, emphasizing immediate implementation effects, weakening long-term effects, and focusing on comprehensive benefits. Additionally, developers, types, and report completeness are important influencing factors.
5.Characteristics of Developing Methods for Emergency Health Systems Guidance Based on AGREE-HS
Danping ZHENG ; Wei YANG ; Dongfeng WEI ; Nannan SHI ; Lin TONG ; An LI ; Gezhi ZHANG ; Xue CHEN ; Fangqi LIU ; Weixuan BAI ; Xinghua XIANG ; Mengyu LIU ; Huamin ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(22):149-156
The scientific rigor and efficacy of methodologies employed in drafting emergency health systems guidance documents (HSGs) are paramount in guaranteeing the quality, reliability, and applicability of HSGs. According to the Appraisal of Guidelines for Research and Evaluation- Health Systems (AGREE-HS), we demonstratively assessed both global coronavirus disease-2019 (COVID-19) emergency HSGs and World Health Organization (WHO) standard HSGs to uncover the core attributes of methods employed in the development of emergency HSGs. Our evaluation findings revealed that across the five assessment items of AGREE-HS, methods in the 34 emergency HSGs evaluated ranked third, trailing behind topic and recommendations. Notably, criterion 2 (the best available and most contextually relevant evidence is considered) received the highest score, whereas criterion 5 (evidence of cost and cost-effectiveness of the potential options is described) scored the lowest. Compared with the WHO standard HSGs, the COVID-19 emergency HSGs exhibited low scores in methods (P<0.05), which was reflected in nine criteria (P<0.05), especially in criteria 1 (systematic and transparent methods are used to identify and review the evidence) and 9 (systematic and transparent methods are used to agree upon the final recommendations). Among the COVID-19 emergency HSGs, that developed by the WHO achieved higher scores in eight out of all nine criteria, excluding criterion 8 (P<0.05). The clinically relevant emergency HSGs had higher scores in the criteria 3 (the evidence base is current) and 8 (the rationale behind the recommendations is clear) than other types of emergency HSGs. Collectively, the methodology for developing emergency HSGs, represented by the COVID-19 emergency HSG, underscores evidence orientation and integrates expert consensus. It is characterized by adaptable evidence synthesis strategies, streamlined evidence review protocols, and contextual relevance, all of which are influenced by external, internal, and implementation-specific factors.
6.Efficacy-driving Mechanism of Danhong Injection for Stable Angina Pectoris Based on Composition-activity Relationship of Target Modules
Siwei TIAN ; Wenjing ZONG ; Jun LIU ; Wei YANG ; Qikai NIU ; Siqi ZHANG ; Jing'ai WANG ; Huamin ZHANG ; Zhong WANG ; Bing LI
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(23):121-128
ObjectiveTo explore the efficacy-driving mechanism of Danhong injection (DHI) in the treatment of stable angina pectoris (SAP) based on the composition-activity relationship of target modules and clarify the pharmacological effects of DHI. MethodAccording to the angina frequency (AF) in the Seattle Angina Questionnaire (SAQ) that was obtained in the previous clinical trial, the patients before and after DHI treatment were grouped based on efficacy. The transcriptomic data of the patients before treatment and in the best efficacy group 30 days post-treatment were selected as the data source, and then weighted gene co-expression network analysis (WGCNA) was employed to construct the co-expression network. Relevant modules in the network were identified and associated with clinical features. In addition, the On-modules (Z value below 0) were identified by Zsummary. The topological indicators such as density, centrality, and clustering coefficient were adopted to explore the dynamics of DHI efficacy at the network level and module level, respectively. In addition, the driver genes were screened by the personalized network control (PNC) algorithm. Finally, rat H9C2 cells were used to establish the model of hypoxia/reoxygenation (H/R), which was used to confirm the potential therapeutic target of DHI for SAP and provide a scientific basis for revealing the therapeutic mechanism of DHI. ResultWe identified 19 modules in the best efficacy group of DHI for SAP, and the comparison between day 0 and day 30 revealed 12 On-modules. The changes of network topological indicators at the network and module levels confirmed the correlation between the best efficacy of DHI treatment and topological dynamics. Finally, the driver genes, Klotho and fibroblast growth factor 22 (FGF22), in DHI treatment of SAP were verified by the H9C2 cell model of H/R. ConclusionBased on clinical transcriptome data, this study determined the composition-activity relationship of target modules of DHI for SAP, which provided a scientific basis for deciphering the efficacy-driven mechanism of DHI for SAP.
7.Construction of an Intelligent Diagnosis and Treatment Ontology for Traditional Chinese Medicine Based on Clinical Practice Guidelines:A Case Study of Coronary Heart Disease
Xiaohui SONG ; Huamin ZHANG ; Zhuang GUO ; Jiyao YIN ; Menghan LIU ; Juan ZHANG ; Qikai NIU ; Junwen WANG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(24):243-249
ObjectiveTo support intelligent clinical decision-making in traditional Chinese medicine(TCM), this study utilized ontology and knowledge graph construction techniques to achieve the IT application of clinical practice guidelines. MethodBased on the principles of findability, accessibility, interoperability, and reusability (FAIR principles), this study employed ontology techniques to construct an ontology for TCM clinical practice guidelines and built a knowledge graph using coronary heart disease as an example. Based on the Checklist for Reporting Practice Guidelines in Traditional Chinese Medicine and Recommendation Grading in TCM Clinical Guidelines/Consensus (T/CAS 530—2021),the ontology of TCM clinical practice guidelines was constructed using the seven-step ontology construction method. On this basis,the TCM diagnosis and treatment data from the Guidelines for the Diagnosis and Treatment of Stable Angina Pectoris in Coronary Heart Disease were stored in Neo4j in the form of triples through knowledge extraction,integration,and storage. ResultThe information in the clinical practice guidelines was divided into three categories: onset and prevention information, diagnosis information, and treatment information, and the TCM clinical practice guideline ontology was constructed. A total of 27 concepts related to TCM clinical diagnosis and treatment and 14 data attributes were obtained, and 12 conceptual relationships including hierarchical relationships and object attributes were established. By taking coronary heart disease as an example and the TCM clinical practice guideline ontology as the model layer, the knowledge map of TCM diagnosis and treatment guidelines for stable angina pectoris in coronary heart disease with 276 nodes and 336 relationships was constructed, realizing the visual display and query of the guideline content. ConclusionThe ontology of TCM clinical practice guidelines and the knowledge graph of stable angina pectoris in coronary heart disease constructed by combining the seven-step ontology construction method and Neo4j graph database technology are efficient and flexible,providing an intelligent TCM diagnosis and treatment scheme and promoting the standardization and objectification of TCM diagnosis and treatment.
8.Clinical application of a simple traction device to colonic endoscopic submucosal dissection (with video)
Wenping WANG ; Xia LENG ; Hui CANG ; Huamin LIU ; Pengfei LIU ; Yuejun SUN ; Fangjun WANG
Chinese Journal of Digestive Endoscopy 2024;41(5):405-407
To evaluate the application value of metal clip combined with suture and rubber coil as a simple traction device in endoscopic submucosal dissection (ESD) for intestinal mucosal lesions, a total of 56 patients with early colonic cancer and precancerous lesions who received ESD in Jiangyin People's Hospital from January 2021 to July 2022 were randomly divided into the control group ( n=28, conventional ESD) and the traction group ( n= 28, suture and rubber coil as a simple traction device). The total time of ESD, mucosal dissection time, number of submucosal injections, complete resection rate and complications were compared between the two groups. The operation time of the traction group was shorter than that of the control group (74.64±33.25 min VS 117.18±35.75 min, t=4.61, P<0.001). The desection time of mucosa in the traction group was shorter than that in the control group (51.61±24.87 min VS 99.11±32.73 min, t=6.11, P<0.001). The number of submucosal injection in the traction group was less than that of the control group with significant difference (1.68±1.16 VS 4.96±1.41, t=9.57, P<0.001). There was no significant differences in operation area, complete resection rate or complication between the two groups ( P>0.05). The traction assistance technology of metal clip combined with suture and rubber coil can reduce the technical difficulty of colonic ESD and shorten the operation time.
9.Herbal Textual Research on Polygonati Odorati Rhizoma in Famous Classical Formulas
Xue LI ; Cunde MA ; Chuchu ZHANG ; Sihong LIU ; Huamin ZHANG ; Bing LI ; Zhilai ZHAN
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(12):13-25
This article has systematically reviewed the name, origin, scientific name, producing area, quality evaluation, harvesting and processing methods of Polygonati Odorati Rhizoma(POR) by consulting the materia medica, medical books, prescription books and modern literature, in order to provide a reference for the development of famous classical formulas containing POR. Yuzhu was first recorded in the Shennong Bencaojing under the name of Nyuwei. After that, Weirui was used as the rectification name in the subsequent dynasties, and in recent times, the name of Yuzhu is mostly used in materia medica and prescription books. In ancient times, there were different names for Yuzhu, such as Nyuwei, Weiwei and Weirui. The names of the three are similar and there was a mixed use of the same name and foreign matter in history. In the Tang dynasty, SU Jing listed Nyuwei with the effect of curing dysentery in the intermediate of herbal part of Xinxiu Bencao according to its different efficacy. However, based on Shennong Bencaojing, Mingyi Bielu and the different energy efficiency of medical prescriptions, SU Song of the Northern Song dynasty believed that the three were medicinal materials of different origins. In short, the names of the three have been unclear in history for a long time. According to the development of the time line, this paper examines the names and realities of the three, and concludes that the two(Weiwei and Weirui) are the same medicinal material, that is, Polygonatum odoratum of Liliaceae, and the Nyuwei is Clematis apiifolia of Ranunculaceae, and the source relationship of the three is clarified. The mainstream source of Yuzhu used in the past dynasties was the rhizome of P. odoratum, which was widely distributed in the wild and has a large amount of resources. The origins of Yuzhu recorded in ancient times were mainly Taishan in Shandong, Chuzhou and Shuzhou in Anhui, and Hanzhong in Shaanxi, in modern times, it was produced in northern Hebei and Shaoyang in Hunan with high quality, and in the modern times, Jiangbei Yuzhu from Haimen in Jiangsu, Anyuzhu from Nanling, Anqing and Tongling in Anhui, Guanyuzhu from Fengrun, Yutian, Zunhua, Huailai in Hebei and Suizhong, Jinxi, Jianchang, Lingyuan, Liaoyang, Haicheng, Gaiping in Liaoning, Xiangyuzhu from Shaoyang in Hunan are the authentic medicinal material. In ancient times, the quality of Yuzhu was good if it was fat and white, while in modern times, it is better with thick roots, bright yellow color, soft texture, no stiff skin and no oiliness. In ancient times, the origin processing of POR was mostly dried in the shade, but in modern times, it is mostly sun-dried or dried after steaming and rubbing. The ancient processing was mostly scraped off the skin and soaked in honey water and then steamed through, while the modern one is mostly washed and cut into thick slices for raw use. Based on the conclusion of the herbal textual research, it is suggested that the rhizome of P. odoratum of Liliaceae be used as the source for the development of famous classical formulas, and the corresponding specifications be selected according to the processing requirements of the prescription. In view of the Yiweitang in Wenbing Tiaobian, which uses the method of frying fragrance to achieve the effect of fragrant refreshing the spleen, it can be processed by referring to the stir-frying method in the current version of Chinese Pharmacopoeia.
10.Clinical Application Analysis of Da Qinjiaotang Based on Ancient and Modern Literature
Hui ZHAO ; Lin TONG ; Lei ZHANG ; Sihong LIU ; Ziling ZENG ; Bin LI ; Huamin ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(9):1-7
Da Qinjiaotang is a common classical prescription for the treatment of stroke. It originates from Collection of Writings on the Mechanism of Disease, Suitability of Qi, and the Safeguarding of Life as Discussed in the Basic Questions (《素问病机气宜保命集》) by physician LIU Wansu, and is composed of Gentianae Macrophyllae Radix, Glycyrrhizae Radix et Rhizoma, Chuanxiong Rhizoma, Angelicae Sinensis Radix, Paeoniae Radix Alba, Asari Radix et Rhizoma, Notopterygii Rhizoma et Radix, Saposhnikoviae Radix, Scutellariae Radix, Gypsum Fibrosum, Angelicae Dahuricae Radix, Atractylodis Macrocephalae Rhizoma, Rehmanniae Radix, Rehmanniae Radix Praeparata, Poria, and Angelicae Pubescentis Radix. Doctors of all dynasties have disputed the composition principle of the prescription and argued whether its treatment of stroke belongs to the theory of "internal wind" or "external wind". Through collating and analyzing ancient and modern literature related to the indications of Da Qinjiaotang, this paper was dedicated to the origin of syndrome differentiation and treatment of Da Qinjiaotang. According to LIU Wansu's original works, Da Qinjiaotang is a prescription for the treatment of "internal wind", and in the prescription, wind medicinal herbs such as Gentianae Macrophyllae Radix, Notopterygii Rhizoma et Radix and Angelicae Pubescentis Radix removes stagnation, clears sweat pore, and makes qi and blood channels flow smoothly. However, later generations, affected by the idea of "external wind", believe that this prescription is used for the treatment of "external wind". Ancient physicians gradually supplemented the symptoms of stroke, such as wry eye and mouth, hemibody pain and limb numbness, which were treated by Da Qinjiaotang, and Da Qinjiaotang was also applied to the treatment of other diseases, such as tendon dryness, convulsion and arthralgia. Modern doctors still explain the disease pathogenesis from the theory of "external wind" as deficiency in channels and collaterals and the entry of pathogenic wind, and the prescription has the effect of dispersing wind, clearing heat and nourishing and activating blood. In clinical practice, Da Qinjiaotang is mainly used to treat cerebrovascular diseases and peripheral facial paralysis in nervous system diseases, gouty arthritis and rheumatic arthritis in the rheumatic immune system and skin diseases. The above findings facilitate the research and development of Da Qinjiaotang.

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