| BackgroundAmyotrophic lateral sclerosis(ALS)is a neurodegenerative disease in which upper and lower motor neurons are involved both.The clinical symptoms of the disease are closely related to the location and progress of the disease.The evolution of the disease has a clear rule with the differences and superposition of the involved spinal cord segments(medulla oblongata,cervical spinal cord,thoracic spinal cord,lumbosacral spinal cord).Normaly,the disease is divided into different stages by the king's staging system.ALS is divided into 5 stages according to the number of spinal cord segments involved recently,so as to determine the disease evolution and prognosis.Syndrome is the external manifestation of disease changing with time and space,and it is the summary of clinical symptoms in different stages of disease evolution.With the progress of the ALS,the number of spinal cord segments involved changes,resulting in corresponding different clinical symptoms,so the syndrome has a clear evolution rule with the progress of the ALS.King's staging reflects the disease location evolution of ALS.Therefore,based on the clinical diagnosis and treatment idea of "combination of disease and syndrome",this study uses the correlation research between King's staging and the disease location of traditional Chinese Medicine to explore the evolution law of the disease location of ALS in TCM.Secondly,in order to prescribe herbs better,this study explored the correlation between the disease location of TCM and the disease nature,clarified the characteristics of deficiency and excess of cold and heat in different disease locations,and assisted to improve the clinical efficacy.Finally,because the serum neurofilament light chain(NfL)can reflect the progress rate of ALS,this study explored the correlation between NfL and King's staging,to prove the evolution law of ALS in TCM.Through the above research,it can provide a favorable basis for early intervention,precise treatment and clear prognosis of ALS.Methods1 Exploring the correlation between King's staging and TCM disease location1.1 In the case of first follow-up,running the Term Frequency-Inverse Document Frequency(TF-IDF)model through Python to extract the corresponding symptoms groups of different TCM disease location differentiated by experts.In addition,clustering symptoms through SPSS statistics 20.0 to get TCM disease location symptoms groups classification.Comparing the symptoms groups obtained by the above two methods to summarize ALS TCM disease location classification.1.2 SPSS modeler 18.0 was used to mine association rules between King's staging and TCM disease location,and using these association rules to explore the evolution mode of TCM disease location.1.3 In the case of multiple follow-up,the Time Series Association Rules Analyses were used to mine the corresponding evolution rules of TCM disease location along with the progress of the course of disease.2 Exploring the correlation between TCM disease location and TCM disease nature2.1 Extracting the corresponding symptoms groups of different TCM diseases differentiated by experts.In addition,getting TCM disease symptoms groups classification through symptoms clustering,and comparing the symptom groups obtained by the above two methods to summarize TCM disease nature classification.2.2 Mining association rules of TCM disease location and disease nature to find outthe correlation between different disease location and disease nature.3 Analysis of the correlation between serum neurofilament light chain and King's staging3.1 To analyze the correlation between the course of disease and King's staging by Spearman's rank correlation.3.2 After stratification according to the King's staging,the correlation between the serum NfL level and the course of disease was analyzed.Results1 The correlation between King's staging and TCM disease location1.1 The disease location of TCM was divided into three categories:the spleen,the kidney and the lung.1.2 The analysis of association rules between King's staging and TCM disease location showed that the stage 3 of King's staging was positively correlated with the spleen(lift=1.16),followed by the second stage 2b(lift=1.01);the stage 4b was positively correlated with the kidney(lift=1.15),followed by the stage 3(lift=1.14),then followed by the stage 2b(lift=1.10);the stage 4b was strongly positively correlated with the lung(lift=6.16).Therefore,the early and middle stages of King's staging were related to the spleen,and the middle and terminal stages were related to the kidney,and the terminal stage was related to the lung.1.3 Time Series Association Rules Analyses showed that,with the progress of the course of the disease,the confidence of spleen and kidney was 100%,the confidence of spleen and kidney was 50%,the confidence of kidney and lung was 50%.Among them,in stage 2b,the confidence was 66.67%between kidney,and spleen and kidney,the confidence was 50%between kidney and lung,and kidney,spleen and lung.In stage 4b,spleen and lung can progress to spleen,kidney and lung.2 The correlation between disease location and disease nature of TCM2.1 The disease nature was divided into three categories:the damp turbid or damp heat,the Yang deficiency,and the Yin deficiency.2.2 The correlation rules between TCM disease location and TCM disease nature showed that the confidence of correlation rules between spleen and damp turbid or damp heat was 73.58%.Secondly,the confidence between lung and damp turbid or damp heat was 73.33%.Therefore,the disease often appears damp turbid or damp heat in patients whose spleens are deficient.In addition,the patients with deficiency of lung can also appear damp turbid or damp heat(or phlegm turbid/phlegm heat).There was no significant correlation between the disease location in kidney and dampness pathogen.The confidence of correlation rules between the TCM location of lung and Yang deficiency or Yin deficiency was 73.33%to 80.00%,and the lift was more than 1,which indicated that there was a strong correlation between deficiency of lung,and Yang deficiency or Yin deficiency,suggesting Yang deficiency or Yin deficiency is the main factor of the patient who is at the terminal course of the disease.3 Correlation between King's staging and serum NfL3.1 The course of disease was positively correlated with King's staging(Spearman's rank correlation coefficient=0.418).3.2 The mean value of serum NfL was higher in stage 3 patients.As shown in the scatter diagram,the NfL level of stage 1?3 has an increasing trend,and that of stage 3?5 has a decreasing trend.3.2 Stratifying by King's staging.There was no significant correlation between the level of serum NfL and the course of disease in stage 1-3 cases.There was a significant negative correlation(Spearman's rank correlation coefficient=-0.704)between the serum NfL and the course of disease in stage 3?5 cases,suggesting that the shorter the time from the onset to King's staging of 3-5,the more serious the disease.Conclusion1 With the development of King's staging from stage 1 to stage 5,generally speaking,the TCM disease location of ALS starts from the spleen,then to the kidney,then to the lung,and finally the lung,spleen and kidney are all deficient;there are also those who progress rapidly,starting from the kidney or the lung.2 At the early stage of the course of disease,the patients whose disease location are spleen are often complicated with damp turbid or damp heat;secondly,at the terminal course of ALS,the patients whose disease location are lung are often complicated with phlegm turbid or phlegm heat.At the middle and terminal stage of the disease's course,with the development of the disease location form spleen to kidney and lung,it is manifested as Yang deficiency,Yin deficiency,or even Yin-Yang deficiency.3 The level of NfL in patients of stage 3 was higher,so stage 3 may be the key point of the evolution rule of TCM disease location;the shorter the course of disease from the onset to stage 3?5,the higher the NfL,suggesting that if the onset of disease is straight to the kidney or lung,the patient's disease progress is faster and more serious than that of the spleen. |
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