Research progress of anti-acute marrow leukemia drugs by targeting FLT3 / 药学学报

Acute myeloid leukemia (AML) is a genetic heterogeneous disease in which primordial and juvenile myeloid cells proliferate or accumulate abnormally in bone marrow, peripheral blood and other tissues, resulting in damage to normal hematopoietic function. Studies have shown that about 30% of AML patients have FMS-like tyrosine kinase 3 (FLT3), FLT3 abnormal regulation is closely related to the occurrence and development of AML. At present, FLT3 has become an important target for developing small molecular targeted drugs. Currently, a variety of FLT3 inhibitors and FLT3 degraders have been developed targeting FLT3, and some compounds have exhibited good anti-AML activity. This article summarizes and sorts out the current mainstream drugs for AML therapeutic targeting FLT3, in order to provide a reference for the development and design of AML drugs.

Characterization of potential bitterness critical quality attributes in Xiaoer Ganmao Oral Liquid based on UHPLC-LTQ-Orbitrap MSn / 药学学报

To identify the bitter compounds of real-world Xiaoer Ganmao Oral Liquid sugar-free intermediates, an integrated strategy has been developed by using ultra-high performance liquid chromatography with linear ion trap-Orbitrap mass spectrometry (UHPLC-LTQ-Orbitrap MSn) method and BitterX database prediction. The chromatographic operating conditions were as follows, chromatographic column: Acquity UPLC BEH C18 (100 mm × 2.1 mm, 1.7 μm), mobile phase: 0.1% formic acid-water solution (A)-acetonitrile (B) with gradient elution. The data were collected in positive and negative ion modes, respectively. The accurate molecular mass and structural information of the target compounds were obtained based on quasi-molecular ions and fragmentation ions provided by high-resolution mass spectrometry. The compounds were identified by combining retention time, reference substances, reports, and other relevant data, and a total of 57 constituents including flavonoids, alkaloids, and phenylpropanoids were finally identified. Further, the BitterX database was used to predict binding probability of compounds to bitter receptors and identify potential bitter critical quality attributes, finally 33 potential bitter compounds, including kukoamine A and linarin, were predicted. This study comprehensively characterized the material basis of Xiaoer Ganmao Oral Liquid sugar-free intermediates, it provides an effective method for bitter compound screening and a reference for further improving the undesirable taste of Xiaoer Ganmao Oral Liquid.

Research on dynamic on-line monitoring method of moisture attribute in three honey-processed Chinese herbal slice based on in-situ general model / 药学学报

Aiming at the hysteresis and destructiveness of off-line static detection of critical quality attribute of the moisture content of the raw material unit of the traditional Chinese medicine manufacturing process, honey-processed Tussilago farfara, honey-processed Astragalus and honey-processed Glycyrrhiza uralensis were used as the research carriers, and the drying method was used to measure the moisture content as a reference value. The moving stage was used to simulate the movement process of samples on the conveyor belt in the actual on-site production process, and near-infrared (NIR) spectra were collected, combined with machine learning, to establish NIR on-site dynamic detection model of moisture content in multi-variety honey-processed Chinese herbal slice. The results show that the second derivative method is used to preprocess the spectrum. The number of decision trees (ntree), the number of random features (max feature), and the minimum number of samples for generating leaf nodes (node size) are selected: 46, 76, and 8, respectively. The quantitative analysis model of moisture content has the best effect. The prediction coefficient of determination (the prediction coefficient of determination, R2pre) and the root mean square error of prediction (root mean square error of prediction, RMSEP) of the model were 0.903 2 and 0.330 2, respectively. The NIR quantitative model for the moisture content of multi-variety honey-processed Chinese herbal slice established in this study has good predictive performance, and can achieve rapid, accurate and non-destructive quantitative analysis of the moisture content of honey-processed Tussilago farfara, honey-processed Astragalus and honey-processed Glycyrrhiza uralensis at the same time, and provides a method for determining the moisture content of honey-processed Chinese herbal slice of the raw material unit of the traditional Chinese medicine manufacturing process.

The measurement of critical quality attributes of Tongren niuhuang qingxin pills based on MIF-HEMT biosensor technology / 药学学报

There is still a serious challenge of the measurement of critical quality attributes (CQAs) related to clinical efficacy for Chinese materia medica manufacturing. To overcome this challenge, an integrated strategy of biosensor and ultra-performance liquid chromatography/tandem mass spectrometry (UPLC-MS/MS) was proposed using Tongren niuhuang qingxin pills as a trial. Firstly, an original biosensor was created using a semiconductor chip material high electron mobility transistor (HEMT) as the transducer and the macrophage migration inhibitory factor (MIF) as the identification element. By this MIF-HEMT biosensor, the efficacy on stoke of different components from Tongren niuhuang qingxin pills was measured. It was clear that all three components of Tongren niuhuang qingxin pills had strong therapeutic effects on stroke, especially the section A, the KD of which reached to 8.722×10-10 g·mL-1. Furthermore, MIF-HEMT biosensor integrated UPLC-MS/MS was introduced to identify the efficacy CQAs of different components of Tongren niuhuang qingxin pills. As a result, 19 potential CQAs, such as albiforin, paeoniflorin, and prim-O-glucosylcimifugin, were measured as the efficacy CQAs of Tongren niuhuang qingxin pills on stroke treatment by MIF. These results provided vital measurement techniques and methodological guidance for the CQAs study of Tongren niuhuang qingxin pills intervention in MIF-induced stroke treatment. This also provided an essential guideline for the efficient utilization and quality control measurement of high-quality classical recipes.

Evolution and Connotations of "Prohibition"， "Contraindication"， or "Use with Caution" in Chinese Materia Medica / 中国实验方剂学杂志

This study systematically combed and analyzed the use of such terms as "prohibition"， "contraindication"， and "use with caution" in ancient Chinese books on materia medica and prescriptions， Pharmacopoeia of the People's Republic of China（《中华人民共和国药典》）， and teaching materials and monographs of Chinese materia medica by means of hermeneutics， commentariology， textology， and data mining， and explored the historical evolution and conceptual connotations of "prohibition"， "contraindication"， and "use with caution" in Chinese materia medica， so as to provide reference for standardizing their understandings and clinical reasonable medication. The "prohibition"， "contraindication"， and "use with caution" of Chinese materia medica were first proposed in the period of pre-Qin and Han dynasties. "Prohibition" and "contraindication" were separately developed in the Sui， Tang， and Five dynasties and Song， Jin， and Yuan dynasties and have been widely used since the Ming and Qing dynasties. The "use with caution" becomes popular rapidly in modern times and is often present in clinical medication together with "prohibition" and "contraindication". "Prohibition" basically means strictly prohibited and "contraindication" means to avoid as much as possible. The terms "prohibition"， "contraindication"， and "use with caution" have experienced evolution from the pre-Qin period to modern times， and they are used to describe the degree of restriction on drug use（"prohibition" > " contraindication" > "use with caution"）.

Interpretation of Technical Specifications for Revision of Safety Information in Marketed Chinese Patent Medicine Instructions / 中国中药杂志

Technical Specifications for Revision of Safety Information in Marketed Chinese Patent Medicine Instructions,a series of group standards,were proposed by Professor ZHANG Bing from Research Center for Pharmacovigilance and Rational Use of Traditional Chinese Medicine,and underwent centralized management by Chinese Association of Chinese Medicine. They were officially released on July 23 and implemented on July 31,2021. The series of group standards consist of six sections,including general principles,adverse drug events,contraindications,precautions,application for special populations,and warnings. The section of general principles is comprised of holistic and programmatic expressions,which explain the general technical requirements for revising the marketed Chinese patent medicine instructions. The other five sections focus on information collection,screening,transformation,and illustration of specific items,forming a standardized revision technical process. This series of standards is the result of multiple rounds of research and the suggestions of more than 200 experts in different professional fields of " medicine-pharmacy-management-law-enterprise" have been gathered therein to reach a consensus. With the purposes of establishing standardized technical specifications for the revision of safety information in the marketed Chinese patent medicine instructions,guiding marketing authorization holders in revising the instructions,filling the gaps in the research of Chinese patent medicine instructions,promoting the deve-lopment of pharmaceutical care and academic research,and encouraging the rational and safe medication of Chinese patent medicine,the series of group standards is of great significance.

Series of group standards of Technical Specifications for Revision of Safety Information in Marketed Chinese Patent Medicine Instructions / 中国中药杂志

Drug instructions,the statutory and technical documents recording effectiveness and safety information,are an important basis for guiding doctors,pharmacists,and patients to use drugs rationally,and their scientificity,standardization,and accuracy directly affect the medication safety of the public. The sections of adverse drug events,contraindications,precautions,warnings,and application for specific populations in drug instructions directly express safety information and measures for rational use of drugs. In the drug life cycle,marketing authorization holders( MAHs) need to update safety information in the instructions promptly to ensure the safety and effectiveness of clinical drug medication. At present,revising instructions is an important measure to control drug risks. In the drug life cycle,in order to standardize the revision of safety information in the instructions by MAHs and eliminate inexact terms such as " unclear",the Technical Specifications for Revision of Safety Information in Marketed Chinese Patent Medicine Instructions,a series of group standards,have been established under the guidance of Standardization Department,China Association of Chinese Medicine. Therefore,on the basis of the existing rules and regulations,the standardized technical procedures for revising instructions came into being to help clinical safe and rational medication of drugs,and implement the strategy of " Healthy China".

Technical specification for Instructions for Clinical Application of Chinese Patent Medicines in China Association of Chinese Medicine / 中国中药杂志

In order to solve the problems of confusion in clinical medication and imperfect instructions in Chinese patent medicines(CPMs), the Standardization Department of the China Association of Chinese Medicine and Center for Pharmacovigilance and Rational use of Chinese Medicine in Beijing University of Chinese Medicine jointly compiled the Instructions for Clinical Application of Chinese Patent Medicines(CPMs). As the interpretation and supplement of drug instruction information, it aims to guide clinical safety and rational use of CPMs. In addition, the technical specification for clinical application description of CPMs has been formulated, which covers the seven processes of "carding instructions, clinical investigation, data retrieval, data screening, evidence classification, path transformation and writing format". It will enable readers of Instructions for Clinical Application of Chinese Patent Medicines to understand the work behind the compilation.

Mechanism of Traditional Chinese Medicine in Treatment of Autism Spectrum Disorder Based on Heart and Spleen / 中国实验方剂学杂志

Autism spectrum disorder （ASD） is a common neurodevelopmental disorder in childhood， whereas there is no specific medicine at present. There are more and more researches on the treatment of ASD with traditional Chinese medicine（TCM） which the curative effect is reliable. The heart and spleen are the main viscera for the treatment of ASD， but there is still a lack of in-depth analysis of the mechanism of TCM. In order to explore the relationship between the core symptoms of ASD and the heart and spleen， this article specifically explores the theoretical origins of the heart and the spleen in the formation of the core symptoms of ASD， and to clarify the role of the heart and spleen in the occurrence and development of the two core symptoms of ASD from the perspective of TCM. In view of social communication and communication obstacles， the author puts forward and explains the language problems of children with ASD based on the functions of the heart and spleen， the theory of the viscera， the ascription of the meridians， and the classics. The mechanism of the heart and spleen in TCM about the failure of the spleen， the loss of the heart， and the endogenous phlegm. Aiming at the mechanism of the stereotyped symptoms of abnormal behaviors in children with ASD， this paper proposes and explains the TCM mechanism of constant deficiency of the spleen and dereliction of duty， leading to loss of mind， heart and spleen injury， and finally a series of stereotypes and strange syndromes due to lack of spirit. Through the analysis and excavation of TCM theory， it explores theoretical basis for ASD from the theory of heart and spleen， with a view to preliminarily constructing the theoretical framework of TCM syndrome differentiation and treatment of the deficiency of both the heart and spleen， and provide theoretical reference for TCM syndrome differentiation and treatment of ASD. The treatment of ASD from the differentiation of symptoms and signs of the heart and spleen is supported by a strong theoretical basis of TCM， and the rationale， law and prescriptions are complete， which may be the direction of screening effective TCM prescriptions for the treatment of ASD in the future.

Evaluation Elements of Clinical 'Prohibition' 'Contraindication'， or 'Use with Caution' in Chinese Medicine Based on Ancient and Modern Literature / 中国实验方剂学杂志

In view of the current controversy in the clinical evaluation of the terms of 'prohibition' 'contraindication'， and 'use with caution'， the present study summarized their evaluation elements to provide references for the classification of 'prohibition' 'contraindication'， and 'use with caution' and clinical rational medication of drugs. Based on the ancient and modern representative traditional Chinese medicine （TCM） literature， such as the records on herbal medicines and prescriptions， medical classics， pharmacopoeia， clinical monographs， and papers， this study proposed the evaluation elements and the underlying ideas of 'prohibition' 'contraindication'， and 'use with caution' around the risks and benefits of medication. The results indicate that the evaluation elements of 'prohibition' 'contraindication'， and 'use with caution' include TCM property，syndrome，symptom， TCM compatibility，dosage，and treatment course. When evaluating 'prohibition' 'contraindication'， and 'use with caution' of TCM under specific conditions of medication，we can determine the properties of prohibited or contraindicated drugs prior to figuring out the differences in 'prohibition' 'contraindication'， and 'use with caution'. It is feasible to evaluate the clinical 'prohibition' 'contraindication'， and 'use with caution' in TCM from Chinese medicine， body， and the clinical medication， which are correlated with each other in the practice implementation.

Pharmacovigilance study on drug-induced cardiac injury during treatment of COVID-19 / 中国中药杂志

Because coronavirus disease 2019(COVID-19) is highly contagious and serious, it has posed a major threat to public health worldwide. The curative effects of integrated traditional Chinese medicine and Western medicine in the treatment of COVID-19 have been widely recognized and confirmed. However, medical workers shall pay attention to drug-induced heart injury in clinical application. Based on the guideline from the Diagnosis and Treatment Plans for COVID-19(trial seventh edition), taking the recommended drugs as examples, by Western medicine, traditional Chinese medicine, Chinese herbal injection and integrated traditional Chinese and Western medicine, the study analyzed the basic characteristics of recommended drugs for cardiac injury by means of literature review and bioinformatics methods, and summarized cardiac adverse reactions, toxicity mechanisms, combined pharmacotherapy, special population and drug monitoring, focusing on the clinical manifestations, toxic components, targets and regulatory mechanisms of drug-induced cardiac injury. The findings suggested being vigilant to drug-induced cardiac injury during the treatment of COVID-19, playing the advantages of clinical pharmacists and clinical Chinese pharmacists, improving the knowledge reserve of pharmacovigilance, strengthening the prescription review, medication notification and medication monitoring, promoting rational drug use and paying attention to special populations and high-risk groups. The study aims to provide suggestions and reference for pharmacovigilance and pharmaceutical care for front-line doctors and pharmacists against COVID-19, in order to avoid the occurrence of drug-induced heart injury for patients with COVID-19.

Analysis of Pharmacovigilance Thoughts in Herbal Masterpieces of Ming Dynasty / 中国实验方剂学杂志

Based on the pharmacovigilance thoughts of Chinese medicine of cognition, application, prevention and rescue of drug toxicity, to sort out the pharmacovigilance information in representative herbal works of the Ming dynasty, and to analyze the characteristics of the pharmacovigilance thoughts of the Ming dynasty, so as to provide reference for rational drug use in modern clinical practice. Taking Bencao Pinhui Jingyao, Bencao Gangmu, Paozhi Dafa, Bencao Shengya Banjie, Bencao Mengquan as the blueprints, and taking the traditional Chinese medicines in these books as the research objects, the text information was extracted from the four aspects of drug identification, drug use, drug prevention and detoxification, and the idea of pharmacovigilance was summarized. In Ming dynasty, pharmacovigilance had a systematic understanding, and cognition of drug toxicity was clear in identifying poison and correcting the mistakes of predecessors, in the aspects of using and preventing poisons, the use of poisons was prominent, the compatibility and process of poisons were emphasized, and the methods and mechanism of poison relief were clear in detoxification. Ming dynasty has initially formed the whole pharmacovigilance theoretical frame of cognition, application, prevention and rescue of drug toxicity, which has certain guiding and reference significance for modern clinical rational drug use.

Research Status of Gouty Arthritis at Home and Abroad-Visual Analysis Based on CiteSpace Software / 中国实验方剂学杂志

Objective:To analyze the research status of gouty arthritis at home and abroad in the past 15 years，and to provide reference for for further in-depth research in this field. Method:With “Gouty arthritis” as the research topic, the related papers during 2004—2019 were searched in Web of science core collection database and CNKI databases respectively. The results were statistically sorted out according to publication year，author，institution，literature source and key words，etc，and were visualized by CiteSpace software. Result:A total of 5 071 Chinese papers and 1 136 English papers were included. The amount of domestic and foreign publications continued to rise，forming a core team represented by LI Zhao-fu，XIONG Hui，SCHLESINGER NAOMI and other authors. The research hotpots focused on the pathogenesis，diagnosis methods， Chinese and Western medicine treatment，clinical observation，risk assessment and other aspects of gouty arthritis. Both of them had their own emphases. Domestic researches tended to focus on the treatment of gouty arthritis with traditional Chinese medicine，while foreign ones focused on the pathological research and clinical investigation of gouty arthritis. Conclusion:The number of researches in the field of gouty arthritis is on the rise as a whole，and there are both consistency and differences in the research content and hot topics between domestic and foreign literature. Therefore， we should strengthen cooperation and exchange between different teams and countries，so as to promote the overall development of this field.

Application of Aconitum Medicines in Puji Fang for Children / 中国实验方剂学杂志

Objective: Aconitum has a wide range of pharmacological activities, but its clinical toxic dose is close to the therapeutic dose. Puji Fang, as the greatest prescription book in China, analyzes and studied Aconitum herbal medicines prescriptions in Puji Fang used for children, and summarizes the rules and characteristics of children's medication for Aconitum Chinese medicine, so as to provide guidance for the clinical application of Aconitum herbal medicines in children. Method: Aconitum herbal medicines prescriptions in Puji Fang used for children were collected and organized to establish a prescription data sheet for Aconitum herbal medicines, for the purpose of statistics and analysis of Aconitum herbal medicines, their dosage, dosage form, indications and processed products. Result: A total of 300 children prescriptions containing Aconiti Lateralis Radix Praeparata, Aconiti Radix, Aconiti Kusnezoffii Radix, Aconitum carmichaelii and Tianxiong in Puji Fang were collected, and 64.45% of the prescriptions were based on Aconiti Lateralis Radix Praeparata. There were 13 types of diseases, mainly including severe convulsion, chronic spleen convulsion, vomiting and diarrhea. The prescriptions with a medicinal dose of Aconitum herbal medicines below 3 g accounted for 95.10% of the recorded dose. Children's Aconitum herbal medicines prescriptions were mainly for oral administration, 48.33% were pills, and the dosage of pills was higher than that of powder and decoction. There were 169 prescriptions for the use of processed products, accounting for 54.17%, 170 prescriptions with a specially administered medicine method, and those taken with "rice soup" occupied the highest proportion. Conclusion: Children's Aconitum medicines prescriptions account for a small proportion in the prescriptions of Puji Fang and a lighter dose, with differences in the dosage between different formulas. This article provides a reference for the safe and effective use of Aconitum medicines by studying the application of Aconitum medicines in children's prescriptions. It is necessary to establish a clinical warning of aconitum herbal medicines in the aspects of drug delivery based on syndrome differentiation, strict control of dosage and course of treatment, emphasis on compatibility, medication contraindications, and strengthened clinical drug monitoring.

Effect of single-herb traditional Chinese medicine for eliminating dampness on metabolism of uric acid / 中国中药杂志

Through literature review, it was found that there were many literature reports on the effect of single-herb traditional Chinese medicine for lowering uric acid in comparison with other single-herb traditional Chinese medicines. Then what is the relationship between single-herb traditional Chinese medicines for eliminating dampness and uric acid? How do they play a role in lowering uric acid? In this study, traditional Chinese medicines for eliminating dampness in the 2015 Chinese Pharmacopoeia and the innovative textbook of Clinical Chinese Pharmacy for Chinese medicine colleges and universities in the new century were selected as the research objects, and articles about the effect of single-herb traditional Chinese medicines for eliminating dampness in the treatment of hyperuricemia were searched through CNKI, WanFang and VIP. Afterwards, Excel(2016) was used to establish a database, and Excel screening tool was used to extract the classification statistics of its uric acid lowering effect, pharmacodynamic sites, uric acid lowering pathway and mechanism, so as to clarify the relationship between single-herb traditional Chinese medicines for eliminating dampness and uric acid as well as their mechanism on lowering uric acid. The results showed that there were 16 kinds of traditional Chinese medicines with uric acid lowering effect, accounting for 23.88% of the 67 kinds of traditional Chinese medicines for eliminating dampness. Other medicines with the uric acid lowering effect included traditional Chinese medicine extracts and chemical components. The main ways of reducing uric acid included: inhibiting uric acid synthesis and promoting uric acid excretion; mechanism of action was mainly regulating the two key enzymes generated by uric acid and the ion transporters excreted by uric acid. Therefore, it can be seen that this kind of traditional Chinese medicines have a clear effect in reducing uric acid, providing new ideas for drug screening, prescription compatibility and target determination for the treatment of hyperuricemia as well as a theoretical basis for the clinical treatment and research of hyperuricemia.

Pharmacodynamic effect and virulent effect of Tripterygium wilfordii based on network pharmacology / 中国中药杂志

To investigate the pharmacodynamic effect and virulent effect of the main components of the toxic Chinese medicine Tripterygium wilfordii,such as triptolide,tripchlorolide,tripterine,demethylzeylasteral,wilfotrine and euonine,the admet SAR online assessment system was used to calculate the properties of the main components of T. wilfordii. The potential targets of the components were mined and collected through multiple databases,and the potential targets were enriched by the bioinformatics database DAVID.Cytoscape software was used to establish a " target-pathway" network and perform topology analysis on the network. The main chemical components of T. wilfordii were able to penetrate the blood-brain barrier and had intestinal permeability. A total of 65 targets were predicted,including pathways in cancer,hepatitis B,rheumatoid arthritis,and chagas disease( American trypanosomiasis),Toll-like receptor signaling pathway,apoptosis,colorectal cancer,NF-kappa B signaling pathway,etc. T. wilfordii mainly plays a role in the treatment of immune diseases and cancer by regulating inflammatory signaling pathways and cancer signaling pathways. Its action on apoptosis pathway and drug metabolism enzymes may be the mechanism of its toxicity.

Study on dosage rules of Aconitum herbs in oral prescriptions based on efficacy-toxicity relation / 中国中药杂志

Based on the relation of efficacy and toxicity, this study mined the dosage rules and characteristics of Aconitum herbs in oral prescriptions from 48 traditional ancient books from Eastern Han dynasty to Qing dynasty, to provide the basis for strengthening the clinical risk pharmacovigilance. In the 48 traditional ancient books, 4 521 prescriptions with clear daily oral dosage were included to establish a database. SPSS 20.0 software was used for statistics and analysis of the daily dosage characteristics with different kinds of herbs, indications, dose forms, processing, use in special population, and other aspects. The results showed that 67% prescriptions contained Aconitum carmichaeli(Fuzi), and 90% of them was less than 14.87 g·d⁻¹; The dosage of A. carmichaeli(Chuanwu) and A. kusnezoffii(Caowu) were less than 3.14 g·d⁻¹. In the prescriptions for treating typhoid, epidemic, edema and phlegm, the dosage of Aconitum was larger. There dosage in the decoction and vinum was significantly higher than that in the pill and powder. With the dynastic evolution, the dosage of Aconitum herbal medicines prescriptions and the application percentage of superposition drug also had decreased. For the special populations that with different metabolism process, such as old people, children, pregnant and lactating women, the application of Aconitum was not only with relatively small ratio, but also with lower dose. Therefore, based on the data-mining of ancient books, the dosage of Aconitum should not exceed the limit prescribed by the current China Pharmacopoeia, and also should be strictly controlled by considering various factors, which will ensure the balance of efficacy and toxicity.

Traditional prescription rules of Aconitum herbs in treatment of Bi syndrome / 中国中药杂志

The application of Aconitum herbs in the treatment of Bi syndrome has a long history and exact effects.By taking Aconiti Radix(Chuanwu), Aconiti Kusnezoffii Radix(Caowu) and Aconiti Lateralis Radix Preparata(Fuzi) as example, this study was aimed to mine the prescription rules of Aconitum herbs in the treatment of Bi syndrome, and provide thoughts and bases for modern clinical medication. 1 106 prescriptions were obtained in more than 20 classic books including medical, pharmacy, and synthesized books from Eastern Han dynasty to Qing dynasty. Based on the methods of frequency statistics, percentile statistics and Apriori algorithm of association rules, the characteristics of syndrome classification, dosage and compatibility of Aconitum herbs in the treatment of Bi syndrome were analyzed. The data-mining results indicated that 60.76% prescriptions contained Fuzi, which was obviously higher than Chuanwu or Caowu, and 17.63% contained two or more kinds of Aconitum herbs. 70.34% prescriptions were used mainly to treat Bi syndrome with wind-cold-wetness, others were for the syndrome with the deficiency of liver and kidney, blockage of phlegm and blood stasis, and wind-heat-wetness Bi. In the prescriptions with definite dose, 80% dosage of Fuzi was in the range from 0.29-2.14 g·d⁻¹, while the dosage of Chuanwu and Caowu was from 0.14-1.01g·d⁻¹, which was also affected by patterns, formulations and processing. The dose of Aconitum herbs was highest in the Bi syndrome with wind-cold-wetness, and its dose in the decoction and vinum was significantly higher than that in the pills and powders. The processed products were used in 93.11% prescriptions, and their dosage was higher than the raw ones. In the clinical treatment of Bi syndrome, Chuanwu and Caowu were often used with Saposhnikoviae Radix(Fangfeng), Liquiritiae Radix et Rhizoma(Gancao), Myrrha(Moyao) and Ephedrae Herba(Mahuang), while Fuzi was often used with Cinnamomi Cortex(Rougui), Achyranthis Bidentatae Radix(Niuxi), Fangfeng and Chuanxiong Rhizoma(Chuanxiong), which can both expel wind-dampness and relieve pain. All in all, Aconitum herbs are widely used in the treatment of Bi syndrome, which can relieve arthralgia and pain.

Data-mining characteristics of adverse drug reactions and pharmacovi-gilance of Chinese patent drugs including Aconitum herbs / 中国中药杂志

The common Aconitum herbs in clinical application mainly include Aconiti Radix(Chuanwu), Aconiti Kusnezoffii Radix(Caowu) and Aconiti Lateralis Radix Praeparaia(Fuzi), all of which have toxicity. Therefore, the safety of using Chinese patent drugs including Aconitum herbs has become an hot topic in clinical controversy. Based on the data-mining methods, this study explored the characteristics and causes of adverse drug reactions/events (ADR/ADE) of the Chinese patent drugs including Aconitum, in order to provide pharmacovigilance and rational drug use suggestions for clinical application. The detailed ADR/ADE reports about the Chinese patent drugs including Aconitum herbs were retrieved in the domestic literature databases since 1984 to now. The information extraction and data-mining were conducted based on the platforms of Microsoft office Excel 2016, Clementine 12.0 and Cytoscape 3.3.0. Finally, 78 detailed ADR/ADE reports involving a total of 30 varieties were included. 92.31% ADR/ADE were surely or likely led by the Chinese patent drugs including Aconitum, mostly involving multiple system/organ damages with good prognosis, and even 1 case of death. The incidence of included ADRs/ADEs was associated with various factors such as the patient idiosyncratic, drug toxicity, as well as clinical medication. The patient age was most closely related to ADR/ADEs, and those aged from 60 to 69 were more easily suffered from the ADRs/ADEs of Chinese patent drugs including Aconitum. The probability of ADR/ADEs for the drugs including Chuanwu or Caowu was greater than that of Fuzi, and the using beyond the instructions dose was the most important potential safety hazard in the clinical medication process. For the regular and characteristics of ADR/ADEs led by Chinese patent drugs including Aconitum, special attention shall be paid to the elder patients or with the patients with allergies; strictly control the dosage and course of treatment, strengthen the safety medication education to public, and avoid misuse or abuse to ensure rational drug use.

Meta-analysis on efficacy and safety of combination therapy of Aconitum and Western medicine in treatment of rheumatoid arthritis / 中国中药杂志

To analyze the efficacy and safety of the combination therapy of Aconitum and Western medicine in the treatment of rheumatoid arthritis (RA) by Meta-analysis, and provide evidence for its clinic application for RA. The random clinical trials (RCTs) regarding the combination therapy for treating RA were retrieved in the database of China National Knowledge Infrastructure database, China Science and Technology Journal database, WanFang, Chinese Biomedical Medical Database, PubMed, and Cochrane Library up to July 2017. According to the given inclusion criteria, 8 RCTs involving 659 participants were included, and the included RCTs could be further divided into three subgroups according to the herb type, which were Aconiti Radix (Chuanwu) subgroup (6RCTs), Aconiti Kusnezoffii Radix (Caowu) subgroup (1RCT), and Chuanwu-Caowu subgroup (1RCT). The Meta-analysis results indicated that as compared with Western medicine, the combined use of Aconitum and Western medicine, no matter Chuanwu, Caowu or Chuanwu-Caowu subgroups, could improve the total effective rate of RA (6RCTs, RR=1.19, 95%CI [1.10, 1.28], <0.000 01), (1 RCT, RR=1.43, 95%CI [1.18, 1.73], =0.000 2), (1 RCT, RR=1.27, 95%CI [1.02, 1.58], =0.03) respectively. The combined use of Aconitum and Western medicine was also effective on the number of joint swelling, duration of morning stiffness, patients' handgrip, and the erythrocyte sedimentation rate, C-reactive protein and rheumatoid factor. However, its action was not significant on joint tenderness. And also, in the included RCTs, there were 34 cases of adverse drug reactions/events (ADR/ADE) in the Chuanwu subgroup, while 86 cases in the Western medicine control group. The ADR/ADE incidence was even more lower in Chuanwu-Caowu subgroup, but no difference between Caowu subgroup and Western medicine group. Based on the included RCTs, the combined use of Aconitum and Western medicine could achieve more satisfying efficacy and lower ADRs incidence for RA as compared with Western medicine alone. However, due to the limitation in the not-high quality of included RCTs and the lack of large-scale multi-center research, the results still need to be further validated in the clinic application.