The prescription rule analysis of the New Theory on Spleen Dampness Syndrome by Academician TONG Xiaolin

Objective To analyze the basic characteristics,drug features,prescription rules,and drug-symptom relationships of patients in the splenic deficiency and impairment stage,by data mining of medical records under the New Theory on Spleen Dampness Syndrome(Pi Dan Xin Lun,《脾瘅新论》).Methods Medical records listed in the“New Theory on Spleen Dampness Syndrome-Under-standing and Treatment of Metabolic Syndrome from the Perspective of Traditional Chinese Medicine”,and which were diagnosed with the spleen dampness syndrome at the splenic de-ficiency and impairment stage,during January 2004 and December 2016 were selected.These patients’data,including basic information,clinical symptoms,laboratory examination res-ults,traditional Chinese medicine(TCM)and western medicine diagnoses,treatment meth-ods,prescriptions,etc.,were collected.The collected data were subsequently compiled into a medical record database using the Epidata 3.1 data management software,followed by the use of Apriori algorithm provided in the SPSS Modeler 14.2 statistical software to investigate the association rules between drug-drug,drug-symptom,and drug-western medicine indices.Results(i)A total of 51 medical records were included,involving 17 types of syndromes.Among them,the top three with frequency≥3 included“Phlegm and blood stasis,and thoracic obstruction”“Deficiency-weakness of the spleen Qi,and static blood blocking collat-erals”,and“Deficiency-weakness of the spleen Qi,and static blood blocking collaterals”.Al-ternatively,of the 14 treatment methods,the top three treatments with frequency of≥3 in-cluded“Activating Yang and eliminating turbidity,and removing phlegm and dredging chan-nel blockage”“Strengthening the spleen and benefiting Qi,and eliminating phlegm to activ-ate the channels”,and“Warming Yang and benefiting Qi,and expelling cold to remove ob-structions”.Among the 15 prescriptions,the top three used with frequency≥3 included Huangqi Guizhi Wuwu Tang(黄芪桂枝五物汤),Gualou Xiebai Banxia Tang(瓜蒌薤白半夏汤),and Ganjiang Huangqin Huanglian Renshen Tang(干姜黄芩黄连人参汤).Lastly,of the 83 drugs used for a total of 476 times,those with frequency≥15 included Huanglian(Coptid-is Rhizoma),Huangqi(Astragali Radix),Jiudahuang(Wine-processed Rhei Radix et Rhizoma),Jixueteng(Spatholobi Caulis),Shengjiang(Zingiberis Rhizoma Recens),Huangqin(Scutellariae Radix),and Guizhi(Cinnamomi Ramulus).(ii)For the drug-drug associations,under the criteria of support≥15%and confidence=100%,seven second-order association rules,seven third-order rules,and six fourth-order roles were identified.The top-ranking rule of each was“Huangqin(Scutellariae Radix)→Huanglian(Coptidis Rhizoma)”“Ganjiang(Zingiberis Rhizoma)+Huangqin(Scutellariae Radix)→Huanglian(Coptidis Rhizoma)”,and“Baishao(Paeoniae Radix Alba)+Guizhi(Cinnamomi Ramulus)+Jixueteng(Spatho-lobi Caulis)→Huangqin(Scutellariae Radix)”,respectively.Alternatively,the drug-symptom associations were analyzed under the criteria of support≥5%and confidence=100%,which derived eight second-order association rules,31 third-order rules,and 30 fourth-order rules.The top-ranking association rule of each order was“Huangqi(Astragali Radix)→Limb ed-ema”“Guizhi(Cinnamomi Ramulus)+Jixueteng(Spatholobi Caulis)→Limb numbness and pain”,and“Guizhi(Cinnamomi Ramulus)+Jixueteng(Spatholobi Caulis)+Huangqi(As-tragali Radix)→Limb numbness and pain”,respectively.Similarly,the drug-western medi-cine index associations were investigated under the criteria of support≥5%and confidence=100%,and five second-order association rules,16 third-order rules,and 16 fourth-order rules were identified.In this category,the top-ranking association rule of each order was“Qinpi(Fraxini Cortex)→Uric acid”“Huanglian(Coptidis Rhizoma)+Ganjiang(Zingiberis Rhizoma)→Glycated hemoglobin”,and“Huanglian(Coptidis Rhizoma)+Ganjiang(Zing-iberis Rhizoma)+Huangqin(Scutellariae Radix)→Glycated hemoglobin”,respectively.Conclusion Through association rule mining,this study objectively and quantitatively demonstrated the drug-drug,drug-symptom,and drug-physicochemical index associations of patients with the spleen dampness syndrome at the splenic deficiency and impairment stage treated by Academician TONG Xiaolin.The results indicated that treatment for these patients adopted the“state-target”syndrome differentiation method.The drug combination was characterized by“small prescriptions”,targeting both the patient’s symptoms and signs(syndrome target)and western medicine indices(treatment target).This study could provide references for future research on the academic thoughts and medical experience of Academi-cian TONG Xiaolin.

Study on the Characteristics of Gut Microbiota in Chronic Hepatitis B(CHB)Patients with Damp Heat Syndrome and Liver Depression and Spleen Deficiency Syndrome

Objective:This study was designed to explore the characteristics of gut microbiota in CHB patients with two most common traditional Chinese medicine(TCM)Syndromes—damp heat syndrome and liver depression and spleen deficiency syndrome.Methods:According to the diagnostic criteria of Western medicine,TCM and screening exclusion criteria,65 cases of CHB with damp heat syndrome and 28 cases of CHB with liver depression and spleen deficiency syndrome were finally included in the study.All the basic information was gathered and the fresh fecal samples were collected for 16S rDNA sequencing.16S rDNA of gut microbiota was sequenced using Illumina hiseq 2,500 high-throughput sequencing platform.Based on the optimized sequence,Operational Taxonomic Units(OTU)clustering analysis and taxonomic annotation were carried out.Results:The difference in relative abundance of gut microbiota was significant between damp heat syndrome and liver depression and spleen deficiency syndrome in CHB patients.Cyanobacteria was only found in damp heat syndrome.The relative abundance of Erysipelotrichia and Subdoligranulum were higher in liver depression and spleen deficiency syndrome,while the relative abundance of Rhodospirillales,Alphaproteobacteria and Lachnospira were higher in the damp heat syndrome.LDA Effect Size(LEfSe)analysis showed that Lachnospira,Olsenella and Subdoligranulum had significant difference in species among the two TCM syndromes.Conclusion:The different characteristics of gut microbiota in the two TCM syndromes of CHB patients may play an important role in syndrome formation of TCM,which provides a new field of vision for the accurate diagnosis and treatment of TCM.

Screening the effective components in treating dampness stagnancy due to spleen deficiency syndrome and elucidating the potential mechanism of Poria water extract

Poria is an important medicine for inducing diuresis to drain dampness from the middle energizer.However,the specific effective components and the potential mechanism of Poria remain largely unknown.To identify the effective components and the mechanism of Poria water extract(PWE)to treat dampness stagnancy due to spleen deficiency syndrome(DSSD),a rat model of DSSD was established through weight-loaded forced swimming,intragastric ice-water stimulation,humid living environment,and alternate-day fasting for 21 days.After 14 days of treatment with PWE,the results indicated that PWE increased fecal moisture percentage,urine output,D-xylose level and weight;amylase,albumin,and total protein levels;and the swimming time of rats with DSSD to different extents.Eleven highly related components were screened out using the spectrum-effect relationship and LC-MS.Mechanistic studies revealed that PWE significantly increased the expression of serum motilin(MTL),gastrin(GAS),ADCY5/6,p-PKAα/β/γcat,and phosphorylated cAMP-response element binding protein in the stomach,and AQP3 expression in the colon.Moreover,it decreased the levels of serum ADH,the expression of AQP3 and AQP4 in the stomach,AQP1 and AQP3 in the duodenum,and AQP4 in the colon.PWE induced diuresis to drain dampness in rats with DSSD.Eleven main effective components were identified in PWE.They exerted therapeutic effect by regulating the AC-cAMP-AQP signaling pathway in the stomach,MTL and GAS levels in the serum,AQP1 and AQP3 expression in the duodenum,and AQP3 and AQP4 expression in the colon.

Correlation between pathogenesis of dampness syndrome and Interleukin-2,Interleukin-8 in rats

OBJECTIVE： To explore the pathogenesis of dampness syndrome by detecting the changes of inter- leukin-2 （IL-2） and interleukin-8 （IL-8） levels. METHODS： Female Sprague Dawley rats were divided randomly into five groups according to the random number table： a normal group （Group Ⅰ ）, an external dampness group （Group Ⅱ ）, an internal dampness group （Group Ⅲ）, and an external and internal dampness group （Group Ⅳ）. Twenty days after the model made, IL-2 and IL-8 levels were detected by radioimmunoassay method. RESULTS： The IL-2 and IL-8 levels among groups were significant （F=3.102, P〈0.05; F=2.657, P〈0.05, respectively）. The level of IL-2 in Group Ⅱ and Group Ⅲ were higher than that in Group Ⅰ （P〈0.05, P〈0.01, respectively）, especially higher in the Group Ⅲ compared with Group Ⅱ （P〈0.05）. The level of IL-8 in Group Ⅲ were higher than those in Group Ⅰ, Group Ⅱ and GroupⅣ （P〈0.05, P〈0.01, P〈 0.05, respectively）. In the Group Ⅲ, the 24-hour water and body weight were higher than that in the Group Ⅱ （all P〈0.05）, and spontaneous movement frequency was higher than those in Group Ⅱ and GroupⅣ （P〈0.05）. CONCLUSION： Immune activation and inflammatory reaction might be easily caused by external danpness other than internal dampness.

Efficacy of Modified Qufeng Runmian Powder(加减祛风润面散)on Acne Vulgaris with Syndromes of Dampness and Blood Stasis:A Multicenter,Randomized,Double-Blind,Placebo-Controlled Clinical Trial

Objective:To evaluate the efficacy and safety of a Chinese medicine(CM)Modified Qufeng Runmian Powder(加减祛风润面散,MQFRMP)for the treatment of acne vulgaris with CM syndromes of dampness and blood stasis.Methods:In this multicenter,randomized,double-blind,placebo-controlled clinical trial,220 acne vulgaris patients with CM syndrome of dampness and blood stasis were included and randomly assigned using a central area group random design to receive either MQFRMP or the placebo,with 110 cases in each group.MQFRMP or a placebo at 145 g/bag were administered once daily for 4 weeks,respectively.The primary index of efficacy was the effective rate according to the acne severity score(ASS).The secondary indices of efficacy included the changes in the dermatology life quality index(DLQI)score,VISIA scores(spots,pores,brown spots,porphyrins and red areas)and skin assessment(skin p H,sebum amount and hydration)according to a SOFT skin multianalyzer.Results:(1)Follow-up:a total of 204 patients completed the follow-up,with 103 in the treatment group and 101 in the control group.(2)Effective rate:the total effective rate of the treatment group was significantly higher than the control group[83.5%(86/103)vs.31.7%(32/101),P<0.01)]with 95%confidence interval of 39.3%–66.4%.(3)DLQI:DLQI scores were significantly decreased the treatment and control groups(both P<0.01),but the treatment group was more obvious than the placebo group(P<0.01).(4)VISIA scores:the scores of spots,brown spots and red areas in the treatment group decreased compared with baseline(P<0.05).In the control group,the scores of brown spots and pores decreased compared with baseline(P<0.05).The improvement was more obvious in the treatment group than in the control group for all items(P<0.05).(5)Skin assessment:the p H and sebum score in the both groups decreased drastically compared with the baseline(all P<0.01),however,the improvement was more obvious in the treatment group than in the control group(P<0.01).The hydration amount in the two groups showed no statistically significant difference compared with the baseline(both P>0.05).(6)Safety:two cases of mild drug allergy were observed in the treatment group.Conclusion:MQFRMP was effective and safe for the treatment of acne vulgaris with syndromes of dampness and blood stasis.(No.ChiCTR1900020479).

Formulation Mechanism of Mailuo Shutong Pills in the Treatment of Varicocele

Varicocele is a common disease in male urology clinic,mainly manifested as testicular pendent distension discomfort,scrotal moisture,less weak semen and other symptoms.There is no specific drug in clinical treatment of modern medicine and traditional Chinese medicine.Mailuo Shutong Pills was created by TANG Zuxuan,a Chinese medical master,for the treatment of damp and heat stasis type thrombotic superficial phlebitis and other vascular diseases.In clinical application,it was found to have a good clinical effect on the treatment of symptoms caused by varicose vein.This paper analyzed the formulation mechanism of Mailuo Shutong Pills in the treatment of varicocele from the perspective of traditional Chinese and western medicine,and provides theoretical basis for clinical application.