| Part 1 Meta-analysis of traditional Chinese medicine decoction in the treatment of hypothyroidism.PurposeMeta-analysis was used to evaluate the efficacy of Chinese herbal decoction preparations in the treatment of hypothyroidism.MethodsThe English search used "hypothyroidism","Hypothyroid","Hypothyreosis",and "traditional Chinese medicine" as keywords,and used logical operators "AND" and "OR" to link to search PubMed,Embase,and The Cochrane Library.Chinese search uses "Chinese traditional medicine","Chinese and Western medicine","hypothyroidism","hypothyroidism","clinical observation" as keywords,and uses the logical connection "or" and "and" to search CNKI,Chinese Database of scientific j ournals,database of Chinese academic journals.The search period was from January 2012 to December 202 1.The included literatures were selected according to the inclusion and exclusion criteria.The intervention measures in the experimental group were Chinese medicine oral preparations or Chinese medicine oral preparations combined with western medicines as the treatment method,and the control group intervention measures were simply taking western medicines.The research objects were randomised adult patients with hypothyroidism.Controlled trials.For the literatures to be included,the NoteExpress software was used to remove duplicates first,and then another researcher reviewed the literature titles,read the literature abstracts,eliminated the literatures that did not meet the inclusion criteria and met the exclusion criteria,and finally read the full text to determine the included literature.The literature quality was evaluated using the Cochrane scale.Meta-analysis was performed on the extracted data using Review Manager 5.4 software.The data used odds ratio(OR),and the measurement data used mean difference(MD).If there is heterogeneity,select a random-effects model,and if there is homogeneity,use a fixed-effects model(P<0.1 indicates heterogeneity,and P>0.1 indicates homogeneity).Result1.A total of 14 Chinese literatures were included in this study,and a total of 1005 patients were included,including 5 02 in the treatment group and 503 in the control group.2.11 studies(763 patients)evaluated the clinical efficacy,and there was no significant heterogeneity among the studies(P=1,I2=0%);5 studies(396 patients)evaluated the TCM syndrome score.There was significant heterogeneity among the studies(P<0.00001,I2=88%);10 studies evaluated FT3,and there was statistically significant heterogeneity among the studies(P<0.00001,I2=88%);FT4 was evaluated in 11 studies(723 patients)with statistically significant heterogeneity among studies(P<0.00001,I2=8 9%);TSH was evaluated in 11 studies(783 patients).There was significant heterogeneity among the studies(P<0.00001,I2=93%);5 studies evaluated TPOAb,and there was statistically significant heterogeneity among the studies(P<0.00001,I2=100%);5 studies(348 patients in total)evaluated TgAb,and there was statistically significant heterogeneity among the studies(P<0.00001,I2=99%);6 studies evaluated blood lipid TG,there was significant heterogeneity among the studies(P=0.02,I2=6 3%);7 studies evaluated blood lipid TC,and there was statistically significant heterogeneity among the studies(P=0.16,I2=9 0%);6 studies evaluated blood lipid LDL-C,and there was statistically significant heterogeneity among the studies(P=0.53,I2=0%).Conclusion1.In terms of efficiency,the results show that the combination of traditional Chinese medicine and western medicine in the treatment of hypothyroidism is superior to the control group in terms of clinical efficacy[OR=3.64,95%CI=(2.36,5.62),Z=5.83,P<0.00001],and the difference was statistically significant.2.As far as the TCM syndrome score is concerned,the results show that the combination of traditional Chinese medicine and western medicine in the treatment of hypothyroidism has an advantage in improving the TCM syndrome score compared with the control group[MD=-5.18,95%CI=(-7.51,-2.84]),Z=4.34,P<0.00001],and the difference was statistically significant.3.In terms of FT3 index,11 studies evaluated this index,and the results showed that Chinese medicine combined with western medicine treatment of hypothyroidism had an advantage in increasing FT3 value compared with control group treatment[MD=-0.77,95%CI=(0.55,1),Z=6.88,P<0.00001],and the difference was statistically significant.4.As for the FT4 index,there are 11 studies evaluating this index,and the results show that the combination of traditional Chinese medicine and western medicine in the treatment of hypothyroidism has an advantage in increasing the FT4 value compared with the control group[MD=3.22,9 5%CI=(2.27,4.17),Z=6.62,P<0.0 0001],and the difference was statistically significant.5.As for the TSH index,there are 11 studies evaluating this index,and the results show that the combination of traditional Chinese medicine and western medicine in the treatment of hypothyroidism has an advantage in reducing TSH value compared with the control group[MD=-1.96,95%CI=(-2.59],-1.34),Z=6.1 4,P<0.0000 1],the difference was statistically significant.6.As far as thyroid autoantibodies are concerned,there are 5 studies evaluating this indicator.The results showed that Chinese medicine combined with western medicine in the treatment of hypothyroidism had an advantage in reducing TPOAb value compared with the control group[MD=-173.5 7,9 5%CI=(-253.96,-93.18),Z=4.23,P<0.0001],and the difference was significant.There is statistical significance;Chinese medicine combined with western medicine treatment of hypothyroidism has an advantage in reducing TgAb value compared with the control group[MD=-55.53,95%CI=(-88.25,-18.8),Z=3.02,P=0.003],The difference was statistically significant.7.As far as blood lipids are concerned,there are 6 evaluation TG indicators.The results showed that the combination of traditional Chinese medicine and western medicine in the treatment of hypothyroidism had obvious advantages in reducing TG value compared with the control group[SMD=-0.51,95%CI=(-0.68,0.35),Z=6.18,P<0.00001],and The difference was statistically significant;Chinese medicine combined with western medicine in the treatment of hypothyroidism has an advantage in reducing TC value compared with the control group[SMD=-0.43,95%CI=(-0.53,-0.32),Z=7.88,P<0.00001],and the difference was statistically significant;Chinese medicine combined with western medicine in the treatment of hypothyroidism has an advantage in reducing LDL-C value compared with the control group[SMD=-0.34,95%CI=(-0.43,-0.25),Z=7.3,P<0.00001],and the difference was statistically signifi cant.Part two Discussion on Professor Zhang Fuli’s experience in treating hypothyroidism based on data miningPurposeTaking the medical records of hypothyroidism treated by the Professor of Zhang Fuli as the research object,using data mining technology to summarize the nature,taste,meridian function,drug function and medication rules of the commonly used drugs for the tutor’s clinical treatment of hypothyroidism,sorting and summarizing his clinical thoughts and experience in the treatment of hypothyroidism to provide diagnosis and treatment references for fellow practitioners.MethodThrough the long-term follow-up study of Professor,the medical records of patients who visited a tutor for the first time due to hypothyroidism during the period from January 1,2011 to January 30,2020 were comprehensively collected and sorted,which will meet the inclusion and exclusion criteria.Establish a database of medical records,and use frequency statistics,association rules,cluster analysis and other methods for data mining.Under the review and guidance of the tutor,the clinical experience and core prescriptions for the treatment of hypothyroidism are extracted.Result1.Gender and age distribution:There are 205 female patients and 18 male patients in the medical records,and the ratio of male to female patients is about 1:0.08.The number of patients aged 4060 is the largest,accounting for 69.5 1%of the total number.2.Analysis of symptoms and tongue and pulse:A total of 88 symptoms and 640 symptom units were counted.The top 10 symptoms were palpitations,disturbed sleep,fatigue,dizziness,chest tightness,constipation,early menstruation,acne,and loose stools.The frequency of palpitations was the highest,with a total of 51 occurrences,with a probability of 22.8 7%.A total of 1 3 kinds of tongue images and 282 tongue image units were counted,among which 5 kinds of tongue images,including red tongue,red tongue,dark red tongue,fat tongue,red tongue tip,and pale tongue.The occurrence frequency of red crimson is the highest,with a total of 40 occurrences,and the occurrence probability is 17.94%;there are 8 types of tongue coating,including yellow and greasy tongue coating,thin and greasy tongue coating,thin yellow tongue coating,white and greasy tongue coating,little coating,cracked tongue,and map tongue,among which The occurrence frequency of yellow greasy is the highest,with a total of 13 1 occurrences,and the occurrence probability is 58.74%.A total of 7 types of pulses and 393 pulse units are involved,including Shen,Xian,Weak,Floating,Slip,Thin,Slow,and Shu.Among them,Xian has the highest frequency,with a total of 1 66 occurrences.The probability is 7 1.24%.3.Syndrome type analysis:A total of 8 syndrome types were extracted,with damp-heat syndrome accounting for 97.31%,qi deficiency syndrome accounting for 27.8 0%,diet stagnation syndrome accounting for 9.42%,liver-yang hyperactivity syndrome accounting for 8.52%,yin injury syndrome accounting for 7.73%,liver and gallbladder syndrome accounting for 9.42%Fire-prosperity syndrome accounted for 4.04%,blood stasis syndrome accounted for 3.59%,and heart-yang deficiency syndrome accounted for 1.79%.4.Syndrome-drug association analysis:Through the Apriori algorithm,after Prof.Zhang’s screening and setting of screening conditions,three syndrome-drug association rules were analyzed,which are damp-heat mild syndrome related to Astragalus-tangerine peelAtractylodes,damp-heat syndrome and Yin Chen-Citrus aurantiumPinellia-tangerine peel-Zhuru is related,and Qi deficiency is related to Astragal us-Bupleurum-Puer aria-A tracty lodes-Guizhi.5.Frequency of drugs:A total of 81 kinds of traditional Chinese medicines were obtained,with a total frequency of 4154 times,of which 34 flavors were used more than 30 times;7 flavors were used more than or equal to 20 times but less than 3 0 times;There are 10 flavors less than 20 times;32 flavors are used less than 1 0 times.6.Frequency of efficacy:A total of 15 types of efficacy were obtained,and the top 3 used drugs were tonic(28.3 3%),diuretic and dampness drugs(1 8.08%),and warming herbs(1 3.6 0%).Among the tonic medicines,the most frequently used ones were qi tonics(mainly licorice and atractylodes),accounting for 45.03%of the tonic.7.Meridian and nature and flavor of drugs:The frequency of meridian homing in the database is 11,172 times,of which the spleen meridian is the highest(2,102 times,1 8.81%),followed by the lung meridian(1,984 times,1 7.76%),and the stomach me ridian(1,832 times,16.40%),liver meridian(1751 times,15.67%),heart meridian(1654 times,14.80%),kidney meridian(1 05 1 times,9.41%);there are 4 1 54 frequencies of the four qi in the database,of which the highest frequency of use is temperature(1 250 times,3 0.09%),followed by slightly cold(1 022 times,24.60%),flat(929 times,22.36%),cold(733 times,17.65%),slightly warm(140 times,3.37%),cool(80 times,1.93%);the total frequency of medicinal flavors in the database was 7491,and the highest frequency was Gan(2544 times,3 3.96%),followed by bitter(1701 times,22.71%)and Xin(1604 times,21.41%).8.Analysis of association rules of traditional Chinese medicine:data optimization was carried out first,and the basic prescription of my tutor’s adjustment of local population quality was deleted,focusing on the analysis of association rules of drugs for the treatment of hypothyroidism.The association rules of high-frequency traditional Chinese medicines with a frequency of ≥15 times were analyzed,and 33 rules were obtained.The association rules of traditional Chinese medicine pairs and the association rules of traditional Chinese medicine groups were extracted,including 15 medicine pairs,24 of 3 medicine groups,and 12 of 4 medicine groups.strip.In the analysis of the association rules of the drug pairs,combining the degree of support and the degree of promotion,the highest are Yinchen-Angelica,Guizhi-Astragalus;in the analysis of the association rules of the three herb groups,combining the degree of support and the degree of promotion,the highest is Angelica-Yinchen-Atractylodes,Guizhi-Astragalus-B aihu,GuizhiAstragalus-At racty lodes;in the analysis of the association rules of the four herb groups,combining the support degree and the promotion degree,the highest are Guizhi-Astragalus-Baihu-Atractylodes,Guizhi-Astragalus-Angelica-Atractylodes.9.Cluster analysis:Systematic clustering was performed using traditional Chinese medicines with a frequency of more than 30 times,and three groups were obtained:C1 Angelica,Yinchen,Zhuru,Citrus,Polygala,Mulberry,Eucommia;C2 Chrysanthemum,Achyranthes sichuanensis,Angelica,Turmeric,Amomum,Yizhiren;C3 madder,fritillary,Bupleurum,Astragalus,Guizhi,Atractylodes,Pueraria.ConclusionAccording to the data mining of the frequency,channel Tropism,and the character and taste of the medicine,we can know that the tutor’s choice of the medicine for treating hypothyroidism is not limited to a certain dirty channel,but is mainly coordinated by many systems.According to the therapeutic target of warm drugs,the spleen and lung should be given priority to and the drugs of atractylodes Macrocephala,licorice,Cassia twig and ginger should be selected By choosing the medicines such as Pinellia ternate and Fushen,we can know that their prescriptions should take into account the treatment of phlegm-dampness Pathogenesis,and by choosing the medicines such as parasitism and Angelica,we can know that the tutor should take into account the recuperation of the kidney-qi in the lower-jiao while paying attention to the regulation of the Qi in the upper-jiao and Middle-jiao,and through the treatment of the Chinese Angelica in the xin-gan-wen-zhi,the teacher should pay attention to the regulation of the kidney-qi in the lower-jiao when the Qi in the upper More blood to Qi,in order to better treatment of hypothyroidism.3 The potential prescription of new traditional Chinese medicine showed that warming kidney-yang herbs could be combined with heat-clearing and dampness-removing herbs and heatclearing and liver-cooling herbs,and qi-tonify ing herbs could be combined with blood-activating and stasis-removing herbs.According to the new prescription,the method of tonifying Qi and warming Yang are the necessary methods for the tutor to treat hypothyroidism.It is concluded that my tutor’s experience in the treatment of hypothyroidism is as follows:First of all,we should consider the three factors and Western medicine,and then we should consider the whole and local pathogenesis from the three-jiao structure,finally,multiple methods are used to coordinate the addition and subtraction of TCM prescriptions and the setting of dosage according to multilevel pathogenesis.Part three Data Mining-Network Pharmacological Mechanisms of Core Prescriptions in the Treatment of HypothyroidismPurposeThe active components and targets of the core prescriptions(Atractylodes Rhizoma,Licorice,Angelica,Ginger,Sangjisheng,Guizhi)were screened by the network pharmacology analysis method,and the pathway enrichment analysis of the targets was carried out to predict the mechanism of action.MethodsSearch on the official website of the TCMSP database for"Atractylodes Rhizoma","Licorice","Angelica","Ginger","Parasitic","Cinnamon",and then check the relevant websites and literatures.In addition,the active pharmaceutical ingredients for which no protein target information was obtained were imported into the ChemMapper database to predict the target information.Search the disease gene association databases(DisGeNET,Drugbank,uniprot,DDT,etc.)with "Hypothyroidism","Hypothyroid" and"Hypothyreosis" as keywords to obtain information on genes and target proteins related to hypothyroidism.Using Weishengxin online software to draw Venn diagrams,75 common targets of prescription drugs and diseases were obtained.The active ingredients of the core prescription and the common gene target data of hypothyroidism were input into the Cytoscape 3.7.2 software,and the network diagram of the interaction of "gene targets of core prescription active ingredients-disease gene targets of hypothyroidism" was drawn.Import the common target data of prescription and disease into the STRING database for retrieval,construct a PPI network diagram,and obtain the data related to the proteins.Finally,the functional enrichment analysis of key target genes GO and KEGG was carried out on the common gene targets of core formula and hypothyroidism.ResultA total of 236 Targets and 236 gene symbols were obtained from the core prescription.The active ingredient-intersection target network graph contains 364 nodes and 1 993 edges,which reflects the characteristics of traditional Chinese medicine for treating diseases,linking multi-gene targets through multiple components,and producing interactions.A total of 1439 disease targets were obtained for hypothyroidism.A total of 75 intersecting targets of core prescription-hypothyroidism were displayed by Venn diagram.The PPI network graph processing results showed that there were two groups of genes with strong correlation,namely IL-10,IL1B,IL4,CCL2,IL1A,CXCL10 and IL6,TNF,IL2,IFNG.The results of GO analysis showed that the mechanism of the core prescription in the treatment of hypothyroidism may be related to the biological process,including the response of cytokines,the positive regulation of cell movement,the negative regulation of cell differentiation,the response to hormones,the response to inorganic substances,the response of cells to Nitrogen compound response,regulation of cell adhesion,negative regulation of cell population proliferation,glandular development.The results of KEGG functional enrichment analysis showed that common targets were mainly enriched in the cancer pathway,AGERAGE signaling pathway,HIF-1 signaling pathway,Chagas disease signaling pathway,and cellular senescence signaling pathway,which were closely related to the occurrence and development of hypothyroidism.Closely related signal transduction pathways include AGE-RAGE signaling pathway,cancer signaling pathway,and HIF1 signaling pathway.ConclusionThrough network pharmacological studies of core(basic)prescriptions for the treatment of Hypothyroidism,we conclude that Quercetin,Kaempferol and Naringin,the main active components of the core(basic)prescription,may regulate AGE-RAGE,cancer pathway,HIF-1 and oxidative stress pathway by regulating the target of ESR1,intervention of thyroid cell inflammatory reaction,apoptosis and other biological processes,play a role in the treatment of hypothyroidism. |
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