Professor Guo Lizhong’s Clinical Experience In Treating Rheumatoid Arthritis And Network Pharmacology Of Fuyang Tongbi Basic Prescription

Background:rheumatoid arthritis,as a rheumatic immune disease,is one of the most difficult problems in modern medicine,and also the focus of traditional Chinese medicine research.Traditional Chinese medicine has a long history,rich experience,accurate curative effect and no obvious toxic and side effects.Professor Guo Lizhong focuses on Yang Qi,not only focusing on disease and syndrome,but also on healthy qi of human body.Professor Guo’s long-term curative effect on RA patients is remarkable,so it is necessary to systematize and study his academic thoughts.Research purposes:(1)to collate and excavate Professor Guo Lizhong’s academic experience in clinical treatment of rheumatoid arthritis.(2)From the perspective of network pharmacology,the possible effective mechanism of Professor Guo’s Fuyang Tongbi therapy was verified.Research methods:(1)the Outpatient Department collected and sorted out the medical records of all rheumatoid arthritis patients diagnosed and treated by Professor Guo Lizhong from March 2013 to January 2020,screened them according to the RA related diagnostic criteria,inclusion criteria and exclusion criteria,and finally obtained the medical records information of 70 cases 344 times,established the medical records database,and used frequency analysis,internal and external association rules,K-means cluster analysis and other methods To study the law of symptoms,tongue,pulse,pathogenesis,pathological factors and prescriptions in medical records,combined with Professor Guo Lizhong’s own opinions,to analyze,summarize and summarize.(2)By means of modern network pharmacology,this paper analyzes and studies Professor Guo Lizhong’s basic prescription of Fuyang Tongbi in the treatment of RA,and explores its possible internal mechanism.Results:(1)medical record mining results:①a total of 70 patients with 344 times of RA were included in this study,including 12 male patients,a total of 58 times;58 female patients,a total of 286 times,female RA patients were far higher than men.②The high incidence age of RA mainly has two stages:50-69 years old,the frequency is 199(57.84%);30-49 years old,the frequency is 114(33.13%).③The most common clinical symptoms of RA were insomnia,limb joint pain,chills,dry mouth,fatigue,cough,spontaneous sweating,loose stool,and the frequency was 34.88%,31.10%,25.87%,21.80%,21.51%,21.51%,16.82%and 15.12%respectively.④ The main tongue signs of RA patients were light red,red,dark red,thin white,white and greasy fur,tooth trace tongue,yellow and greasy fur,white and yellow and greasy fur and less fur.⑤The main pulse conditions of RA patients are tight,smooth,weak,thin,heavy,empty,floating and chord.⑥ The most common pathogenesis syndromes are cold dampness stagnation,Qi and blood obstruction,bone dystrophy,Yang deficiency and Qi weakness,liver and kidney yang deficiency and yang deficiency and cold coagulation.⑦ Deficiency,cold,dampness,blood stasis and phlegm are the most common pathological factors of RA.⑧There were 130 kinds of traditional Chinese medicine in all medical records,among which the most commonly used ones were Radix Glycyrrhizae,aconite root,epimedium,ginger,zhufushen,Guizhi,yousongjie,eucommia,Amomum villosum,Atractylodes macrocephala,astragalus,Atractylodes lancea,clematis,Morinda officinalis,acanthopanax senticosus and Angelica sinensis,and the frequency was 94.48%,81.98%,80.23%,74.71%,66.28%,64.53%,55.81%,54.64%,53.20%and 4 67%,43.31%,41.28%,29.65%,27.33%,25.87%and 22.⑨The study of association rules within symptoms showed that the combination of insomnia and anorexia,chills and insomnia,insomnia and multiple joint pain of limbs,chills and multiple joint pain of limbs had higher correlation.⑩The high correlation degree of tongue image combination is as follows:thin and greasy fur and dark red texture,fat tongue and light red texture,thin and white greasy fur and light red texture.(11)The combination of pulse condition correlation degree is higher:pulse sink and pulse weak,pulse fine and pulse tight,pulse sink and pulse smooth,etc.(12)The combination of high correlation degree of pathogenesis and syndrome are:liver and kidney yang deficiency and cold dampness stagnation,cold dampness stagnation and Qi blood obstruction,Qi blood obstruction,cold dampness stagnation and liver and kidney yang deficiency.(13)The most common pathological factors are cold,deficiency,dampness and blood stasis.(14)The most commonly used drug combinations are Aconitum carmichaeli,Ramulus Cinnamomi,Radix Glycyrrhizae,ginger and Herba Epimedii.(15)Professor Guo’s commonly used clinical treatment methods include:Invigorating Yang Qi,strengthening muscles and bones,warming Yang,resolving phlegm,relieving cough,relieving pain,invigorating liver and kidney,expelling wind and dampness,dispersing tendons and bones,invigorating heart and spleen,warming latent and floating Yang,communicating heart and kidney,regulating qi,removing arthralgia,expelling wind and dampness and dispersing cold,invigorating liver and kidney,dredging channels and collaterals to stop arthralgia,warming and unblocking exterior,dispersing cold and dampness,strengthening yang and adding essence.(16)Professor Guo clinically studied the basic formula for differentiating and treating Fengguan by fuyang:the basic formula for fuyang and tongbi,which consists of aconite,Epimedium,cassia twig,ginger and prepared liquorice.(2)Based on the network pharmacology analysis of Fuyang Tongbi basic formula commonly used by Professor Guo,we can see that there are 140 effective compounds in Fuyang Tongbi basic formula.②The effective components of Fuyang Tongbi basic formula can act on 104 targets.There are 68 intersection gene targets of Fuyang Tongbi basic formula and RA.The target genes with higher degree value include tumor antigen p53(tp53),mitogen activated protein kinase 8(mapk8),interleukin-6(IL-6),VEGFA,CASP3 and so on.③Go enrichment analysis showed that the mechanism of Fuyang Tongbi basic formula in the treatment of RA may be related to DNA binding transcription factor binding,DNA binding activator activity,ubiquitin like protein ligase binding,nuclear receptor activity,ligand activated transcription factor activity and RNA polymerase II specific DNA binding transcription factor binding.④KEGG biological pathway enrichment analysis showed that the mechanism of Fuyang Tongbi basic formula in the treatment of RA may be closely related to hepatitis B,prostate cancer,Kaposi’s sarcoma associated herpesvirus infection,apoptosis pathway,AGE-RAGE signaling pathway in pancreatic cancer,diabetic complications,tumor necrosis factor signaling pathway,etc.Research conclusions:(1)rheumatoid arthritis patients are mainly middle-aged and elderly women;the main symptoms of rheumatoid arthritis patients treated by Professor Guo Lizhong are insomnia,limb joint pain,chills,dry mouth,fatigue,cough,spontaneous sweating,loose stools,red tongue(light)and tight pulse;the symptoms involve limb joints,mind,lung system and spleen and stomach system symptoms;the disease is always due to deficiency In terms of treatment,it follows the medical concept of "build the pole first,build the middle,dial the first" in order to treat the disease.Eight methods,such as warming and relieving exterior,dispersing cold and removing dampness,are gradually adopted,with different emphasis and clear priority.In terms of medication,it mainly uses drugs such as warming and tonifying yang qi,warming and activating Yang Qi to remove cold and dampness,and harmonizing blood and dredging collaterals It is highly effective and non-toxic.(2)The therapeutic effect of Fuyang Tongbi basic formula on rheumatoid arthritis is regulated through multi-component,multi-target and multi-channel coordination.Most of the 140 active components(such as kaempferol,quercetin,etc.)in Fuyang Tongbi basic formula have anti-inflammatory,antibacterial,antioxidant and other biological functions.They can cross regulate 68 RA related targets.By affecting the activities of various transcription factors,they can directly or indirectly regulate inflammatory pathways(PI3K-Akt signaling pathway,NF-κB signaling pathway,IL-6 signaling pathway,TNF signaling pathway,etc.)and apoptosis pathway TP53 signaling pathway and AGE-RAGE pathway.