Based On The Real-world Summary Of Clinical Medication And Dosage-effect Rules For DPN Treated By Professor Tong Xiaoli

OBJECTIVE:Based on the Chinese medicine outpatient cases of diabetic peripheral neuropathy(DPN)treated by Professor Tong Xiaolin between 2000 and 2015,this study firstly analyzed the basic information and clinical use of Chinese medicine used by Professor Tong in the treatment of DPN,and explored the commonly used Chinese medicine and their dosage,efficacy,four-qi and five-taste,attribution,associated combinations,and core prescriptions.By screening cases of DPN with qi-deficiency and blood-stasis evidence,the associated medicine pairs of qi-deficiency and blood-stasis evidence were explored and combined with the common symptoms to develop the evidence score scale.Through quantifying qi-deficiency and blood-stasis evidence,common symptoms and efficacy separately,the relationships of evidence-efficacy,symptom-dosage,dosage-efficacy were studied,thus providing new ideas for retrospective study of the dose-effect relationship of herbal medicine pairs in the real world.METHODS:Based on Professor Tong Xiaolin’s TCM outpatient case database,cases of DPN that met the criteria were included.The ancient and modern medical case cloud platform(V2.3.5)was used to mine commonly used Chinese medicine and their dosage,efficacy,four-qi and five-taste,attribution,associated combinations,core prescriptions,core evidence and evidence-associated medicine pairs.Through GraphPad Prism9,the data were compared between multiple groups according to whether they conformed to normal distribution using the Ordinary one-way ANOVA test or Kruskal-Wallis test,and between two groups according to normal distribution using the independent samples t-test or Mann-Whitney U-test.The comparison between the two groups was made using independent samples t-test or Mann-Whitney U-test depending on the normal distribution.RESULTS:1 Results of the clinical medication analysis1.1 Basic information:A total of 774 cases of DPN were included in this study,with a total of 4122 consultations.Among them,44.32%were male patients and 55.68%were female patients;the age group of patients was mainly concentrated in 40-69 years old(77.6%);the number of visits per capita was 5.33,and the number of visits was most frequent in patients with 1-4 visits(61.0%).1.2 Comorbidity analysis:All patients in this group had diabetes mellitus.Diabetic retinopathy,diabetic sweat abnormalities,diabetic nephropathy,diabetic skin disease and diabetic heart disease were common complications;hypertension,dyslipidaemia,obesity,metabolic syndrome and fatty liver were common comorbidities.1.3 Analysis of symptoms and signs:Numbness of the limbs,fatigue,pain in the limbs,blurred vision,spontaneous sweating,excessive thirst,frothy urine,dizziness,back and knee pain,and chills in the limbs were common symptoms in this group;stasis at the base of the tongue,dark red tongue,red tongue,fat tongue with large teeth marks,and stagnant tongue at the base of the tongue were common tongue textures;yellow,greasy,thick,white,and thin fur were common tongues;and sunken and stringent pulses were common pulses.1.4 Evidence element analysis:Spleen,luo and stomach were the main pathological sites in this group;blood-stasis,qi-deficiency,yang-deficiency were the main pathological nature;spleen-deficiency,luo-stasis and stomach-heat were the core pathological mechanisms.1.5 Medication analysis:There were 23 herbal medicines used more frequently than or equal to 10%in the cases,which were classified into 8 major categories according to their efficacy:heat-clearing medicines,blood-stasis activating medicines,deficiency-supplementing medicines,stomach-warming medicines,meridians-warming and cold-dispersing medicines,and food-eliminating medicines.Among them,heat-clearing herbs,blood-stasis activating herbs and deficiency-supplementing herbs were commonly used by Professor Tong Xiaolin in the treatment of DPN;the medicinal properties were mainly warm herbs,followed by cold herbs,flat herbs,slightly warm and slightly cold herbs;among the five flavours,sweet herbs were used most frequently,followed by bitter and pungent ones.Among them,the proportions of warm and cold herbs were similar,and the proportions of slightly warm and slightly cold herbs were similar.The associated core formulae were Huangqi-Guizhi-Baishao-Jixueteng-Shouwuteng;the core three minor formulae were Huangqi-Guizhi-Jixueteng,Ganjiang-Huangqin-Huanglian;the core pairs were Shouwuteng-Jixueteng and Huanglian-Zhimu.Cluster analysis and complex network analysis of the core prescriptions were Huangqi,Guizhi,Jixueteng,Shenjiang,Huanglian and Zhimu.2 Results of the dose-effect relationship pattern analysis2.1 Evidence-medicine analysis:Among the 448 cases(1127 consultations)of DPN with qi-deficiency and blood-stasis evidence included in this study,Huangqi-Jixueteng was the core evidence-associated medicine pair.2.2 Analysis of the relationship between Evidence and efficacy:In this group,there were significant differences in the efficacy before and after treatment for different severity of qi-deficiency and blood-stasis evidence(mild,moderate and severe);the difference in scores before and after treatment for different severity(mild,moderate and severe)were significantly different between groups,and the more severe the evidence was,the more the evidence scores were reduced after treatment;for patients with the same severity,regardless of mild,moderate or severe,the degree of reduction in symptoms after taking For patients with the same degree of severity,regardless of whether they were mild,moderate or severe,taking a single dose for 1 month,the degree of reduction was at least 1/3 or more.2.3 Analysis of the relationship between symptom and dosage:This section was divided into two parts:symptom-dosage(dosage according to symptoms)and symptom-ratio(dosage according to symptoms).In the symptom-dosage(dosage according to symptoms)section,there was a symptom-volume relationship between numbness of the limbs,pain in the limbs,fatigue and the core medicine of qi-deficiency and blood-stasis on the dosage of Huangqi+Jixueteng,and the symptom-volume relationship of numbness of the limbs was statistically different.As the symptoms of limb numbness worsened,there was a statistical difference between the dosage of Huangqi+Jixueteng in the groups of ≤45g vs.46g-60g and ≤45g vs.61g-90g.In the symptom-ratio(symptom-dependent pairing)section,the common ratios of Huangqi/Jixueteng pairing in order of frequency were 1:1,1.5:1,and 2:1 for qi-deficiency and blood-stasis,respectively,but no significant symptom-dependent pairing relationship was found between the severity of each symptom and the ratio of Huangqi/Jixueteng pairing.2.4 Analysis of the the relationship between dosage and efficacy:Overall,there was a dose-effect relationship between the dosage of Huangqi+Jixueteng on the difference in the overall degree of improvement,with a statistically significant difference between dosages of≤45g vs.46g-60g≤45g vs.61g-90g,and ≤45g vs.≥91g,and the best efficacy was observed at dosages of 46g-60g.From the mild symptoms of qi-deficiency and blood-stasis evidence,there was a quantitative effect relationship between the dosage of Huangqi+Jixueteng on the difference in the degree of improvement of the mild symptoms,and the degree of improvement increased with the increase of the dosage.From the middle symptoms of qi-deficiency and blood-stasis evidence,there was a dose-effect relationship between the dosage of Huangqi+ Jixueteng and the difference in the degree of improvement in the middle symptoms,with a statistically significant difference in the dosage of ≤45g vs.46g-60g,and the best efficacy was achieved at the dosage of 46g-60g.In the severe cases of qi-deficiency and blood-stasis evidence,the degree of improvement of the treatment effect tended to increase with the increase of the dosage of Huangqi+Jixueteng,and the best efficacy was observed at the dosage of 46g-60g.CONCLUSION:1 Through a retrospective analysis of the clinical use of drugs in real-world outpatient cases of DPN by Professor Tong Xiaolin,it was tentatively concluded that spleen deficiency,ligament stasis and stomach heat were the core elements considered by Professor Tong Xiaolin in treating this disease,with qi-deficiency and blood-stasis evidence being the core pathogenesis.Professor Tong’s treatment of DPN was based on sweet and warm medicines to warm the cold of the meridians,followed by bitter and cold medicines to clear the heat of the internal organs.However,the overall combination of cold and warmth was used to calm the body.The associated core formula was Huangqi-Guizhi-Jixueteng,GanjiangHuangqin-Huanglian;the core three minor formulae were Huang Huangqi-Guizhi-Jixueteng,Ganjiang-Huangqin-Huanglian;the core pairs were Shouwuteng-Jixueteng,Huanglian-Zhimu.Cluster analysis and complex network analysis of the core prescriptions were Huangqi,Guizhi,Jixueteng,Shenjiang,Huanglian and Zhimu.2 Through the exploration of DPN evidence-related medicine pairs,the evidence score scale was designed in combination with the main symptoms of qi-deficiency and blood-stasis evidence,and a preliminary method for quantifying symptoms,evidence and therapeutic efficacy was constructed;using Huangqi-Jixueteng as the core medicine pair for qi-deficiency and blood-stasis evidence,the dose-effect relationship was analyzed at three levels:evidence-efficacy,symptom-dosage,dosage-efficacy.