| The examination of pathogenesis is the key link of syndrome differentiation and treatment and reviewing syndrome and seeking pathogenesis is the key to flexible use of it have been proposed by Professor Zhou Zhongying who is one of the first state-recognition traditional Chinese medicine(TCM)masters,based on the nineteen provisions for pathogenesis in Yellow Emperor’s Internal Classics.Attaching importance to the study of pathogenesis theory is of great significance to the theoretical innovation of TCM and the improvement of clinical efficacy,and can realize the advantages of understanding the pathogenesis and applying the treatment flexibly.On this basis,a new system of TCM pathogenesis differentiation was constructed with“13 pathogenesis" as the core.This study takes "compound causes"(compound and clamp pathogenesis),which is the last item of "13 pathogenesis",as the starting point to systematically expound the theoretical connotation and modern scientific expression of compound pathogenesis of dampness-heat and stasis-toxin constraint(CPDSC)about hepatocirrhosis,which is difficult to cure in internal medicine,and based on the medical records of famous doctors,the complex network method is used to reveal the knowledge module of the experience factors for differentiation and treatment of hepatocirrhosis,which provides a basis for inheriting the academic experience of famous doctors and improving clinical efficacy.There are four chapters as followed:The first chapter refers to review the research progress on hepatocirrhosis in Traditional Chinese and Western Medicine.In the first and second sections,the problems and shortcomings in the current diagnosis and treatment on hepatocirrhosis were found.In particular,how to reverse hepatocirrhosis?How to effectively delay the process of cirrhosis,prevent its complications,reduce the mortality and other problems have become a hotspot and difficulty in current research,which points out that the core pathogenesis of hepatocirrhosis and its evolution should be recognized.The second chapter refers to incisive light on the source of CPDSC about hepatocirrhosis.The "compound pathogenesis" theory of professor Zhou Zhongying was discussed in detail in this chapter,which leads to the theoretical origin of CPDSC about hepatocirrhosis.It was proved out that CPDSC is the core pathogenesis in the process of hepatitis to hepatocirrhosis,and the formation mechanism of dampness-heat leading to blood stasis,blood stasis-heat leading to dampness and CPDSC was elucidated.The connotation of "toxin" and "constraint" was also deeply excavated.Finally,based on the current academic inheritance of professor Zhou Zhongying about of hepatitis and hepatocirrhosis,it was found that there is still a lack of in-depth discussion and systematic review of the pathogenesis of cirrhosis itself,and the necessity of this study is proposed.The third chapter refers to study on professor Zhou Zhongying’s experience in treating cirrhosis based on complex network.This part mainly analyzes the core pathogenesis network in his treating hepatocirrhosis and common pathogenesis pairs through patients treated by Professor Zhou from April 1983 to January 2015,and then verifies the scientificity of the team’s preliminary work so that the foundation for subsequent basic biological research will be laid,by applying complex networks to conduct in-depth data mining of his medical records of hepatocirrhosis treatment.On this basis,softwares such as Python networkx 2.6.3,Liquorice,and Apache ECharts were used to calculate data and the complex network of compound pathogenesis of hepatocirrhosis was drawn.A total of 3 core pathogenesis networks were obtained.At the center were the three inner core pathogenesis including dampness-heat and stasis-toxin constraint,damp-heat stasis,and liver and spleen injury,namely Layer No.0 core pathogenesis.Another five pathogeneses of liver invading spleen,qi and yin deficiency,liver-kidney yin deficiency,liver-spleen disharmony,and dysfunction of spleen in transport constituted Layer No.1 core pathogenesis.The filtered pathogenesis network diagram was obtained through screening,which was Layer No.2 core pathogenesis,namely the network diagram of compound pathogenesis of hepatocirrhosis.In this network diagram,it also included pathogeneses with a higher affinity for these three layers,for instance,qi-blood-water constraint,endoretention of damp heat,qi stagnation and dampness blocking and water stopping,liver and kidney deficiency,liver-stomach disharmony,etc.It showed that any two pathological factors were directly or indirectly connected and inseparable.To some extent,they are causal,coexist or transform each other,forming various compound pathogeneses,which together affected the progression and outcome of the disease.Meanwhile,based on data mining results and combined with relevant medical record studies,a knowledge module of professor Zhou Zhongying’s experience factors of liver cirrhosis differentiation from CPDSC was preliminarically constructed,with a total of 14 modules,which provided a foundation for the later transformation into artificial intelligence language for clinical services.The fourth chapter refers to an experimental study on the regulatory mechanism of Zi Qi decoction(ZQ)on TLR4/NF-κB pathway in the progression of hepatocirrhosis based on CPDSC.Firstly,a hepatocirrhosis rat model induced by CCl4 plus high-fat diet was established,which administered intragastrically with low,medium,and high concentrations of ZQ,respectively.The ZQ effect on the hepatocirrhosis induced by CCl4 plus high-fat diet in rats was investigated.It was found that ZQ could reduce the hepatocirrhosis in rats by inhibiting the TLR4/NF-κB signaling pathway.Next,the regulating effects of ZQ and itsdecomposed decoctions were discussed on hepatocirrhosis rats caused by CCl4 plus high-fat diet in varied time phases.It was found that varied changes of H&E,masson,and Sirius red staining in each group were detected at the end of week 8,12,and 16.At the end of week 8,the best effect was obtained in eliminating dampness and heat group.At the end of week 12 and 16,the best effect was gained in ZQ and itsdecomposed decoctions group,and it showed identity and difference compared with that of Fuzheng Huayu Capsule.Then,we continued to explore its molecular biological mechanism through cell experiments.The effect of ZQ-containing serum on the activation of human hepatic stellate cells LX-2 was investigated,and an LPS-induced LX-2 cell model was established.After 48 hours of administration with the medicated serum in low,medium,and high concentration,the effect of the medicated serum on LX-2 cells was detected.It was found that the serum in medium and high concentration could inhibit LX-2 cell activity and the relative mRNA content and protein expression of collagen Ⅰ and Ⅲ as well as α-SMA in cells were concentration-dependently reduced.Then,the effect of ZQ on TLR4/NF-κB pathway during LX-2 activation was investigated.LPS-induced LX-2 cells were cultured in vitro and were intervened by adding ZQ,TLR4 inhibitor TAK-242 and NF-κB inhibitor PDTC to observe the specific active sites about ZQ.It was found that ZQ had an obvious inhibitory effect on TLR4/NF-κB signaling pathway,and remained an action of TLR4-like inhibitor.Conclusion:Professor Zhou thought that the complex pathogenesis of CPDSC is the core of hepatitis-cirrhosis.Closely relating to CPDSC and through literature review,clinical data mining and basic experiments,the research focuses on Professor Zhou’s experience in the differentiation and treatment of hepatocirrhosis with CPDSC and enriches the new connotation of TCM pathogenesis differentiation.The knowledge module of professor Zhou Zhongying’s experience factors for differentiation and treatment of cirrhosis from CPDSC was preliminarily constructed and part of scientific connotation of CPDSC theory was revealed,providing the basis for TCM rehabilitation method to effectively control the progress of liver cirrhosis and improve the clinical efficacy. |
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