| ObjectiveIn order to understand the safety and role of mineral-based herbs in the treatment of insomnia,this study first evaluated the efficacy and safety of the prescription containing mineral-based herbs based on systematic review and meta-analysis.Secondly,sorted out and summarized the historical development of the prescriptions based on literature research.At the same time,through data analysis and attribute partial order structure method to compare the differences of ancient and modern literatures using mineral herbs,and to mine the knowledge discovery of the compatibility law of mineral herbs in insomnia prescription,to provide reference for the clinical selection of mineral herbs for the treatment of insomnia or related research.MethodsFirstly,the randomized clinical trials(RCTs)were selected based on the inclusion and exclusion criteria,and the included studies were evaluated for their risk of bias using Cochrane Collaboration’s bias risk assessment too12.0.Meta-analysis and the funnel plot of publication bias of the data were performed using the RevMan5.3 software.Secondly,using the historical development as the main line,the method of dating history is used to summarize the relevant theories and development of mineral-based herbs in the treatment of insomnia in the Qin and Han Dynasties,Jin and Tang Dynasties,Song,Jin and Yuan Dynasties,Ming Dynasty and Qing Dynasty.Analyzing the characteristics of mineral-based herbs in treating insomnia from ancient and modern databases and the experiences of Chinese physicians in the past dynasties.Thirdly,the data were selected according to the inclusion and exclusion criteria,from the Encyclopaedia of Traditional Chinese Medicine database and modern databases.Data mining techniques such as frequency analysis,association rule,cluster analysis,syndrome analysis was applied by using Microsoft Excel and the Ancient and Modern Medical Case Cloud Platform.Lastly,construct the attribute partial order structure diagram,and further dig into the knowledge discovery of the compatibility law of mineral herbs in the insomnia prescription.Results1.Results of Meta-analysis:A total of 83 RCTs were eventually included,all of which were Chinese Literature.56 out of 83 RCTs were the comparison between pure TCM treatment(experimental group)and pharmaceutical treatment(control group),with a total of 4765 participants.27 out of 83 RCTs were the comparison between integrated TCM and pharmaceutical treatment(experimental group)and pharmaceutical treatment(control group),with a total of 2462 participants.The results showed that the curative effect and safety of the integrated TCM and pharmaceutical treatment approach and the pure TCM treatment is better than pharmaceutical treatment alone,in the way of improving overall effective rate,TCM syndrome scores and PSQI scores.The adverse effect of both groups is also lower than the pharmaceutical treatment group.2.Results of data mining:In terms of frequency statistics of mineral herbs,the descending order of ancient literature is Dens Draconis,Cinnabaris,Os Draconis,Succinum,Magnetitum,and Fluoritum;the descending order of modern literature is Os Draconis,Dens Draconis,Magnetitum,Succinum,Cinnabaris and Fluoritum.In terms of mineral herb processing methods,ancient and modern physicians mainly used raw Os Draconis.Magnetitum was mostly calcined used in ancient times while raw used in modern timea.Dens Draconis was mostly raw used in modern times,and there is no significant difference in ancient times using both types.In terms of the dosage of mineral herbs,the dosages of Cinnabaris and Succinum were relatively consistent in ancient and modern decoctions,while there were differences in the dosages of Dens Draconis,Os Draconis and Magnetitum in ancient and modern times.In terms of properties of compatible Chinese medicines,ancient and modern literatures all focus on herbs with neutral,warm and cool,sweet,bitter,and pungent properties,and are mainly compatible with Heart,Liver,and Spleen meridians.And mainly compatible with tonic herbs and tranquilizing mind herbs.In terms of TCM syndromes,ancient literatures mainly focused on deficiency syndromes,which were mostly used for syndromes of heart-kidney disharmony,liverYang hyperactivity,and heart-Qi deficiency syndromes,etc.Modern literature is mainly focused on excessive syndromes,and is mostly used for phlegm-heat internal disturbance syndrome,liver Qi stagnation syndrome,liver Qi transforming into fire syndrome,etc.In terms of the correlation between mineral herbs and TCM syndromes,Os Draconis was mostly used for heart-kidney disharmony syndrome in ancient times,and it is mostly used for phlegm-heat internal disturbance syndrome,liver meridian excess heat syndrome,etc.Dens Draconis was used for Liver-related insomnia in modern and ancient times.Magnetitum and Os Draconis were mostly used to treat heart-kidney disharmony syndrome.Cinnabaris was mostly used to treat heart-Qi deficiency in ancient times,and modern times tend to treat liver-Yang hyperactivity.Fluoritum was used to treat heart and wind-deficiency insomnia in ancient times.In modern times.it is mostly used for syndromes of Yin deficiency and Hyperactivity of fire.In ancient times,Succinum was related to liver-stomach disharmony syndrome,and in modern times,it is mostly related to Qi and blood stagnation syndrome.The correlation between mineral herbs and insomnia types suggest that Os Draconis was used most frequently with all insomnia types.In terms of correlation,in the co-occurrence frequency of ≥ 5,difficulty in falling asleep,dreaminess,easy wake up,light sleep and Dens Draconis are highly correlated.Short sleep time,insomnia all night,difficulty falling asleep after waking up,nightmares highly related to Succinum.Early wake up is highly related to Os Draconis.The correlation between mineral herbs and symptoms indicated that the Os Draconis was used most frequently with all symptoms.In terms of correlation,fret,dry stool and Os Draconis have the highest correlation;dry mouth,poor spirits,fatigue and Magnetitum have the highest correlation;bitter mouth,irritability and Succinum have the highest correlation;palpitations have the highest correlation with Dens Draconis;Anorexia is highly correlated with Fluoritum and Succinum;dizziness is highly correlated with Magnetitum and Cinnabaris.3.From the results of literature research,data mining and attribute partial order structure diagram analysis,it is found that the six mineral herbs have different drug characteristics and compatibility rules in the treatment of insomnia.The results are as follows:In ancient times,Cinnabris was the first choice of sedative herb in ancient times.It was often used to treat other mental diseases before the Song Dynasty,and it was not widely used in insomnia until the Song and Yuan Dynasties.This study excavated the toxic effects and detoxification methods of Cinnabris from ancient literatures.It found that the toxic reactions caused by Cinnabris were mostly related to gangrenes,sores,etc.,and were closely related to the processing method and overdose of Cinnabris.Salt and Ziziphi Spinosae Semen may have the effect of detoxifying Cinnabris.The Zhusha Anshen Pill created by Li Gao in the Yuan Dynasty is a representative prescription for treating insomnia.In addition to calming the mind,physicians of past dynasties used Cinnabris to treat insomnia,and mostly used it to clear the heat of heart.According to the analysis of the partial order structure of attributes,it is found that ancient physicians often used Cinnabris to treat heart-related insomnia syndromes,among which the syndromes of heart-qi deficiency and heart-blood deficiency are the main ones.The drug combinations with strong associations were Cinabris-Ziziphi Spinosae Semen,Cinnabris-Panax ginseng,Cinnabris-Polygala tenuifolia Willd,etc.According to the statistics of the frequency of mineral herbs,it is found that the frequency of use of Cinnabris has dropped sharply from ancient times to modern times,which may be related to the toxicity of Cinnabris.According to ancient literatures,Dens Draconis are mainly used to treat mental diseases such as convulsions and mania,and it was not widely used in insomnia until the Song and Yuan Dynasties.Representative prescriptions containing Dens Draconis include Anshen Dingzhi Pills,Zhenzhumu Pills,etc.Physicians of the past dynasties used Dens Draconis to treat insomnia,mostly taking its effect of entering the liver and reassuring the soul.According to the partial order structure diagram of attributes,it is found that in ancient times,Dens Draconis mainly used to treat insomnia syndromes related to the liver,such as hyperactivity of liver yang syndrome,liver-stomach disharmony syndrome,and liver-wind internal movement syndrome,etc.Commonly used drug pairs are Dens Draconis-Poria cum Radix Pini,Dens Draconis-Ziziphi Spinosae Semen,Dens Draconis-Polygala tenuifolia Willd and so on.According to frequency statistics,Dens Draconis were the most frequently used mineral herbs in ancient times,and ranked second in modern times.There is no significant difference in the raw or calcined use of Dens Draconis in ancient times,but in modern times,raw Dens Draconis are mainly used.Os Draconis is a mineral medicine that was used to treat insomnia earlier.In "Treatise on Febrile Diseases",Guizhi Qu Shaoyao Jia Shuqi Muli Longgu Jiu Ni Decoction contained Os Draconis.The representative prescription containing Os Draconis is Chaihu-Longgu Muli Decoction,which was not used to treat insomnia in ancient times,but is one of the most commonly used prescriptions for treating insomnia in modern times.Physicians of the past dynasties used Os Draconis to treat insomnia,and mostly used it to calm the mind,restrain the spirit,calm the liver and subdue Yang,and eliminate phlegm and reduce adverse effects.According to the partial order structure diagram of attributes,it is found that the ancient Os Draconis was mainly used to treat heart-kidney disharmony syndrome,and the most common compatible drug pairs were Os Draconis-Ziziphi Spinosae Semen,Os Draconis-Polygala tenuifolia Willd,Os Draconis-Ostreae Concha,etc.According to the cluster analysis,it was found that the compatibility significance of Os Draconis and Ostreae Concha was different due to the compatibility of prescriptions and medicines and the pathogenesis and syndrome types.According to frequency statistics,Os Draconis is the most commonly used mineral medicine by modern physicians.Ancient and modern physicians used raw Os Draconis as the main treatment for insomnia.Succinum was also widely used in the treatment of insomnia during the Song and Yuan dynasties.Representative prescriptions for insomnia containing Succinum include Hupo Pill,Hupo Yangxin Pill,and Hupo Duo Mei Pill.Physicians of the past dynasties used Succinum to treat insomnia,and mostly used it to calm the mind,replenish and circulate the heart blood,and enter the lungs to calm the soul,and it was mostly used to treat nightmares.According to the partial order structure diagram of attributes,it is found that ancient Succinum was mainly used to treat insomnia due to Yin deficiency and Yang hyperactivity.The most compatible drug pairs were Succinum-Poria cum Radix Pini,Succinum-Ziziphi Spinosae Semen,Succinum-Polygala tenuifolia Willd.The presctiption containing Succinum mainly originated from Anshe Dingzhi Pills.In ancient times,Magnetitum were seldom used to treat insomnia,but mostly used to treat tinnitus and deafness caused by kidney deficiency.The representative prescription containing Magnetitum,Cizhu Pill,was originally used to treat ear and eye diseases in ancient times,and was later used by physicians to treat insomnia.Physicians of all dynasties used Magnetitum to treat insomnia,mostly because of its function of communicating with the heart and kidney.According to the partial order structure diagram of attributes,it is found that the ancient Magnetitum is mainly used to treat the syndrome of disharmony between the heart and the kidney and the syndrome of hyperactivity of liver-Yang.The most compatible drug pairs were Magnetitum-Poria cum Radix Pini,Magnetitum-Ziziphi Spinosae Semen,Magnetitum-Polygala tenuifolia Willd,Magnetitum-Pericarpium Citri Reticulatae and so on.According to the frequency statistics of mineral herbs,modern physicians use more Magnetitum than ancient ones.Ancient physicians mostly used calcined Magnetitum,while modern physicians mostly used raw Magnetitum.Fluoritum was rarely used to treat insomnia in ancient and modern physicians,and it was first used in the treatment of insomnia in the Jin and Tang Dynasties.Physician Sun Simiao often uses it to treat insomnia with Wind syndrome,such as Dazhenxin San and Shi Ying Jian.Physicians of all dynasties used Fluoritum to treat insomnia,mostly for its warming and tonic effect.According to the partial order structure diagram of attributes,it is found that ancient Fluoritum is mainly used to treat heart-qi deficiency syndrome,and the most commonly used medicine pairs are Fluoritum-Polygala tenuifolia Willd,FluoritumPlatycladus orientalis,etc.In the compound prescription for the treatment of heart-qi deficiency syndrome,warm and hot herbs such as Asari Radix,Zingiberis Rhizoma,Aconiti Lateralis Radix,etc.are often used.According to the frequency statistics of mineral herbs,Fluoritum is the least used to treat insomnia among the six mineral herbs.Conclusion1.This study clarified the curative effect of mineral-based herbs in the treatment of insomnia through Meta-analysis,and the adverse reactions were low,providing evidencebased medical basis for the safety of using mineral-based herbs in the treatment of insommia.2.Through the data analysis of six mineral-based herbs,we can find its differences in treating insomnia.Cinnabaris is mainly used to clear heart heat,and it is mainly used to treat insomnia due to heart-related syndrome;Dens Draconis soothe the liver to calm the soul,mainly used to treat insomnia due to liver-related syndrome;Os Draconis has astringent and securing property,mainly treats the syndrome of heart-kidney disharmony;Succinum is mainly used to benefit the heart and calm the lungs,and it is mainly used to treat the syndrome of Yin deficiency and Yang hyperactivity,and is related to nightmares;Magnetitum calm the mind with communicating heart and kidney,and is mainly used to treat heart-kidney disharmony syndrome and Liver Yang hyperactivity syndrome.Fluoritum is used for warming and tonifying,and mainly treats syndrome of heart-Qi deficiency.3.By comparing ancient and modern literature on the use of mineral-based herbs to treat insomnia,it is found that ancient and modern physicians emphasize on the compatibility of tonic herbs and tranquilizing mind herbs,and the importance of processing method and dosage of mineral herbs.At the same time,this study also explores the correlation between different mineral herbs and TCM syndromes,insomnia types and symptoms,to provide clinical reference.4.Due to the safety concern of using Cinnabaris,this study also explored the toxic reaction and detoxification methods of Cinnabaris from the perspective of ancient literature,which can be further explored in the future. |
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