Exploring The Relationship Between Psoriasis And Metabolic Immunity Based On The Theory Of "Yingwei

Objective:Psoriasis is a chronic inflammatory skin disease mediated by T cells,and its pathogenesis is complex and has not been fully clarified.At present,biological agents have become one of the main treatment methods for psoriasis.From the point of view of immunity,treating psoriasis by blocking specific inflammatory factors produced by the immune system is quick and effective,but it also has some problems,such as incurable disease,recurrence and some side effects.According to the overall concept of traditional Chinese medicine and the idea of preventing diseases,we should not only pay attention to the improvement of skin lesions after treatment,but also pay attention to the survival time,quality of life and recurrence of patients.With the in-depth study of psoriasis,it is gradually considered that psoriasis is also a systemic disease,often accompanied by a variety of metabolic related diseases,which is an important factor affecting the survival and prognosis of psoriasis patients.Therefore,in order to better prevent and treat psoriasis,we should not only pay attention to immune problems,but also consider metabolic factors in the study of psoriasis.With the development of metabolic immunology in modern medicine,many scholars think that there are many similarities between the theory of "Ying-wei”and the physiological pathology of metabolic immunity."Ying-wei"has been discussed in "Neijing" as early as,which is not only one of the basic life activities of human body,but also one of the important basic theories of traditional Chinese medicine.Therefore,the purpose of this study is to explore the primary and secondary relationship between metabolic and immune-related biological indicators of psoriasis patients and the risk of morbidity and mortality in accordance with the theory of "Ying-wei" in traditional Chinese medicine,in order to provide theoretical support for better treatment of psoriasis from the perspective of metabolic immunity,and also to explain the scientific connotation of treating psoriasis from "Ying-wei".Methods:The first part was a theoretical study,which summarized the research literature about psoriasis and Ying-wei,discussed the theoretical basis of Ying-wei,the relationship between Ying-wei’s tilting movement and psoriasis,interpreted the relationship between Ying-wei and five internal organs,Ying-wei and Xuanfu,Ying-wei and six meridians,and Ying-wei and damp heat from the pathogenesis characteristics of psoriasis,and discussed the essence of Ying-wei and how to treat psoriasis from Ying-wei.The second part was a cross-sectional study using psoriasis data from the 2003-2006 and 2009-2014 National Health and Nutrition Examination Survey(NHANES).COX proportional hazards regression analysis,random forest survival analysis,and restricted cubic spline model were used to evaluate the association between immune-metabolic indicators in peripheral blood and psoriasis mortality.Section three was a bioinformatics study.The gene expression profile dataset and DNA methylation dataset of psoriatic skin tissues were downloaded from the Gene Expression Omnibus(GEO)database.Immune infiltration analysis,functional enrichment analysis,protein-protein interaction(PPI)network construction,machine learning algorithm analysis(LASSO,random forest,SVM-RFE)and other analysis methods were used to analyze the regulatory network and explore the target genes related to psoriasis.Section four was an experimental study based on section three,Western blotting,Real-time PCR and immunofluorescence were used to study the effects of rosin acid on the related genes of polarized human peripheral blood neutrophils and the formation of neutrophil extracellular traps.Results:In the first part,it was found that internal and external pathogens invaded the human body,which led to abnormal functions of the five internal organs,six meridians and Xuanfu,and then Wei-Yang rose up to resist pathogens outside the pulse,and at the same time pulled the Yin in the artery,eventually forming a tilt and abnormal distribution of Ying-wei.which led to psoriasis-like lesions.For a long time,it was the reason why psoriasis was difficult to treat and easy to recur.In the second part,528 patients with psoriasis were included.Based on the research results of psoriasis population and sex subgroups,it was found that uric acid(UA),red blood cell distribution width(RDW)and glycosylated hemoglobin(HBA1C)were potential biomarkers related to psoriasis death.In the general population,UA(HR 1.59,95%CI:1.242.04,P<0.001)after adjusting age,sex,race,education level,smoking status,drinking status and income;RDW(HR 1.55,95%CI:1.16-2.07,P<0.001)and HBA1C(HR 1.47,95%CI:1.21-1.80,P<0.001)were significantly correlated with the increased risk of death.Blood glucose(RG,nonlinear P=9E-04)and glycosylated hemoglobin(HBA1C,nonlinear P=0.0014)also have a strong U-shaped correlation with the risk of death,and the risk of death is the lowest at 89 mg/dl and 5.1%respectively.In the third part,it was found that 97 hypermethylated and Hyper-down genes accounted for the highest proportion(47%),and the hyper-down genes were mainly enriched in glucose homeostasis,AMPK signaling pathway,lipid storage diseases,partial lipodystrophy and insulin resistance.Insulin receptor substrate(IRS1),Rho guanine nucleotide exchange factor 10(ARHGEF10)and retinoic acid-induced 14(RAI14)were identified as potential targets of psoriasis.In the fourth part,it was found that rosin acid could affect the expression of ARHGEF10 in polarized neutrophils in human peripheral blood and inhibit the production of NETs.Discussion:Through theoretical research,it is found that skin health can’t be separated from the harmony between camp and health,and the shift of camp and health caused by the imbalance of camp and health is the basic pathogenesis of psoriasis,and the damp heat and evil of camp and health caused by the shift of camp and health is an important factor for the aggravation or recurrence of psoriasis.Red blood cell distribution width(RDW),uric acid(UA)and glycosylated hemoglobin(HBA1C)are highly correlated with the risk of death in patients with psoriasis,and they are both metabolic indicators.These indicators are cheap and easy to obtain.Early monitoring and taking corresponding measures according to their changes can effectively reduce the risk of death in patients with psoriasis.Bioinformatics analysis showed that the genes related to psoriasis mainly included IRS1,RAI14 and ARHGEF10,in which IRS1 was directly related to metabolism,RAI14 and ARHGEF10 were related to cell motility.Through cell experiment,it was found that rosin acid,the effective component of rosin,which is a traditional Chinese medicine for treating psoriasis,can affect the expression of ARHGEF10 in neutrophils in polarized human peripheral blood and inhibit the production of NETs.According to the theory of Ying-wei,red blood cell distribution width(RDW)can reflect the operation of Yingyin,while uric acid(UA),glycosylated hemoglobin(HBA1C)and insulin receptor substrate(IRS1)can reflect the function of Ying-Yin,so the pathogenesis of psoriasis may have the characteristics of "Ying-Ben-Wei-Biao".RAI14 and ARHGEF10 may be related to the "tilting"movement in the pathological process of "Ying-wei tilting".Rosin,as a traditional Chinese medicine to remove dampness and heat,regulate metabolism and immunity,the main component of rosin,may reverse the "tilting state of Ying-wei" to "Ying-wei balance state" by up-regulating the expression of ARHGEF10 in polarized neutrophils and then affecting the formation of NETs.Based on the above discussion,we think that for the treatment of psoriasis,we should pay attention to the influence of metabolic factors on the survival time,quality of life and recurrence of psoriasis patients while taking into account both metabolic and immune factors.In the prevention and treatment of traditional Chinese medicine,under the guidance of the theory of "Ying-wei",we should recognize the dialectical unity relationship between dampness and heat,and establish the primary and secondary relationship between heat clearing and dehumidification according to the priority of specimens in different stages of psoriasis,so that the method of dehumidification can be used throughout the prevention and treatment of psoriasis.Innovations of this study mainly include:1)Applying the theory of Ying-wei to the etiology and pathogenesis research of psoriasis,exploring the primary and secondary relationship between metabolism and immunity in psoriasis,and demonstrating the scientific nature of traditional Chinese medicine theory of Ying-wei.2)Through the analysis of survival data from psoriasis patients,it was found that among the indicators of metabolic immunity(Ying-wei),the ones significantly associated with the risk of death in psoriasis patients were mainly metabolic indicators(Ying).This provides theoretical evidence for the pathogenesis characteristics of psoriasis as the "Ying-ben-wei-biao" and the primary and secondary relationship between metabolism and immunity in psoriasis.3)Through the joint analysis of methylation chip data set and expression profile data set of psoriasis patients,it was found that metabolic-related genes(represented by IRS1)were significantly associated with the occurrence of psoriasis,further confirming the primary and secondary relationship between metabolism and immunity in psoriasis.Additionally,potential target genes related to cell movement.ARHGEF10 and RAI14,which were screened out,may serve as the material basis for the pathological changes of "Ying-wei imbalance" in psoriasis.4)The experimental results have revealed that the treatment of psoriasis with abietic acid may be related to the inhibition of neutrophil migration by abietic acid through activating the expression of ARHGEF10 gene,thus antagonizing the formation of NETs.These results have proved that ARHGEF10 may be the material basis of "leaning" in the pathological change of "tilting state of Ying-wei" of psoriasis.and provided a theoretical basis for the treatment of psoriasis from Ying-wei.In the future,on the one hand,we will continue to explore the interaction between metabolism and immunity based on the study four,and then explain the scientific connotation of guiding the syndrome differentiation and treatment of psoriasis based on the theory of "Ying-wei".On the other hand,we will explore the effect of dehumidification method on the quality of life and"prevention of the recrudescence of disease" of psoriasis patients based on the theory of "Yingben-wei-biao" of psoriasis.The main shortcomings of this study are:1)Limited by the difficulty of obtaining survival data related to psoriasis and the low quality,the case data included in study 2 came from the United States,and racial differences may bias the results.The study finally included 528 samples,although it met the sample size requirements,but the results analyzed by more included samples will have stronger credibility.In the future,we will construct the Chinese psoriasis survival and prognosis cohort data and include more relevant variables to study the survival and prognosis factors of Chinese psoriasis population.2)There may be batch effect in different data sets in study 3.Although the batch effect can be removed by some methods,it cannot be eliminated,so there may be a certain bias.In the future,we will construct chip data of more samples in the same batch to explore potential target genes of psoriasis.3)Study 4 was only a preliminary study at the cellular level,so more experiments are needed to verify the reliability of the results.At the same time,it would be more convincing to verify the results at the animal level.