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Study On The Mechanism And Clinical Efficacy Of Qushi Qingfei Decoction In The Treatment Of SMPP(Damp-Toxin Blocking Lung Syndrome) In Children Based On TLR4/NF-κB Signaling Pathway

Posted on:2024-04-29Degree:DoctorType:Dissertation
Country:ChinaCandidate:X WangFull Text:PDF
GTID:1524306929980119Subject:Chinese Academy of Pediatrics
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Objective:1.To analyze the publications and research trends of severe Mycoplasma pneumoniae pneumonia(SMPP)at home and abroad;2.To study the effect of serum containing Qushi qingfei Decoction on the expression of TLR4/NF-κB pathway and inflammatory factors in RAW264.7 cells induced by Mycoplasma pneumoniae(MP),and to explore the mechanism of inflammatory intervention;3.To analyze the clinical characteristics of children with SMPP(damp-toxin blocking lung syndrome),and to observe the clinical efficacy of Qushi qingfei Decoction.Methods:1.Bibliometric research of SMPP: Statistical methods and Endnote software were used to make statistics and analysis on the overall number of papers published in this field,the distribution of the number of journals,the time of publication,the author and the institution of publication.Software Citespace and VOSviewer were used to analyze the literature data included in this study,and the important authors and main research institutions in this field were identified.In this paper,the epidemiology,pathogenesis,risk factors,diagnosis and treatment of SMPP are reviewed,so as to provide reference for clinicians and researchers.Using the emergent word detection function of Citespace combined with the time zone map,the keywords of Chinese and foreign literature included in the study were sorted out,and the research hotspots and frontiers in this field were explored.2.Experimental study:(1)Preparation of serum containing Qushi qingfei Decoction: Thirty-five SD rats were randomly divided into 5 groups(blank group,low,medium and high dose of traditional Chinese medicine group,azithromycin group).The control group was given distilled water solution 2ml/d;The low-,medium-and high-dose TCM groups were respectively given Qushi qingfei Decoction crude drug concentration 13.71g/(kg·d),27.41g/(kg·d)and 54.82g/(kg·d);the dosage of azithromycin group was 0.063g/(kg·d).Two hours after the last administration,10% chloral hydrate 0.5ml/100 g was injected intraperitoneally for anesthesia.Blood was collected from the abdominal aorta,and the supernatant was centrifuged and stored at-80℃ for later use.(2)RAW264.7 cell inflammation model induced by MP was established: through cell culture technology,the blank group,model group,low,medium and high dose of traditional Chinese medicine serum group and azithromycin serum group were set up.(3)ELISA was used to detect the expression levels of IL-6,TNF-α,IFN-γ and IL-10 in the supernatant of each drug intervention group with drug-containing serum.The protein and m RNA expressions of TLR4,My D88,TRIF and NF-κB p65 were detected by Western blot and q RT-PCR,respectively.3.Clinical study:(1)The hospitalized children diagnosed with MPP or SMPP in the Affiliated Hospital of Shandong University of Traditional Chinese Medicine from January 1,2021 to December 31,2022 were collected and screened.The clinical case retrospective analysis table was developed,and the characteristics of clinical symptoms and laboratory tests were statistically analyzed.(2)A retrospective study was conducted to collect the hospitalized children with SMPP(damp-toxin blocking lung syndrome)admitted to the Affiliated Hospital of Shandong University of Traditional Chinese Medicine and 5 other prefecture-level hospitals in the province from January 1,2021 to December 31,2022.The clinical symptoms,laboratory examination,imaging characteristics and clinical efficacy were statistically analyzed.Results:1.(1)Basic situation:(1)In terms of the number of publications,domestic research started later than international research,and the number of papers published in the early stage was small.After 2009,the number of publications in domestic and foreign journals showed a rapid growth trend,and the number of publications reached the peak in 2020-2022.(2)Literature quality: there are a large number of domestic literatures,but lack of high-quality ones;foreign literature has high authority and citation frequency.(3)Cooperation between authors and institutions: limited by geographical location and institutional affiliation,domestic groups lack regional and international connectivity and interaction;(4)There are few literatures related to traditional Chinese medicine,but it still has great development potential.(2)Research hotspots and frontiers:(1)Compared with adult SMPP,SMPP in children is widely concerned at home and abroad;(2)The hot topics focused on epidemiological characteristics,pathogen identification,inflammatory markers used to predict the disease,mixed infection,anti-drug resistance,interventional therapy and inflammatory mechanism research;(3)The frontiers focused on pathogen surveillance,mainly involving genotype identification,sample types of bronchoalveolar lavage fluid,etc;(4)The clinical and basic research of traditional Chinese medicine has been paid more and more attention,which is reflected in the clinical efficacy research of Chinese patent medicine and traditional Chinese medicine compound.(3)Development and evolution:(1)The domestic research progress can be divided into three stages,related to the development of pathogen identification technology,bronchoscopy technology and other important nodes;(2)Although domestic research started late,rapid development has been achieved in the past 10 years,and the diagnosis and treatment technology has been synchronized with the international;(3)The research development in this field is relatively stable in the world,and it is in a leading position in pathogen identification technology and pathogenic mechanism research.2.(1)Studies on predictors:(1)There was no significant difference in gender composition(P>0.05);the average age of children with SMPP(6.53±2.68 years)was higher than that of children with MPP(P< 0.05);the incidence of SMPP is higher in autumn and winter.(2)Clinical features: wheezing,long duration of fever before admission and long length of hospital stay(P< 0.05);(3)Co-infection: SMPP was prone to coinfection(P< 0.05),mainly influenza virus;(4)SMPP was prone to pulmonary and extrapulmonary complications,mainly type Ⅰ respiratory failure,atelectasis,liver dysfunction,coagulopathy,myocardial damage,pleural effusion(P< 0.05);(5)CRP,NLR,FIB and D-D had high predictive value for SMPP.(2)Curative effect study:(1)The overall curative effect of disease and TCM syndrome in the treatment group was better than that in the control group(P< 0.05).(2)It was superior to the control group in shortening the antipyretic time and cough relief time(P< 0.05).(3)It was superior to the control group in reducing the use of glucocorticoid,immunoglobulin and fiberoptic bronchoscopy(P< 0.05).(4)The improvement of RDWcv,PCT,LDH,PA,D-D and other indicators of the control group was better than that of the control group(P< 0.05).3.(1)Expression of inflammatory factors:(1)Expression of IL-6 and TNF-α:The expressions of IL-6 and TNF-α in the drug intervention group were lower than those in the model group(P < 0.05).There was no significant difference in IL-6 level between azithromycin group and traditional Chinese medicine low and high dose groups(P> 0.05);There was no significant difference in TNF-α between the high dose TCM group and the azithromycin group(P> 0.05).(2)Expression of IFN-γ and IL-10: IFN-γ was not detected in the ELISA test of RAW264.7 cells induced by MP.The expression of IL-10 in the model group was higher than that in the control group,but there was no statistical significance(P> 0.05),but the expression levels in the drug intervention group were lower than those in the model group without statistical significance(P >0.05).(2)The protein expression of TLR4/NF-κB pathway related molecules: the protein expression levels of TLR4,My D88,TRIF and NF-κB p65 in the model group were higher than those in the control group(P < 0.05).Compared with the model group,the high dose of traditional Chinese medicine group and the expression of azithromycin were significantly decreased(P < 0.05).(3)The m RNA expression of TLR4/NF-κB pathway related molecules: the model group had significantly higher m RNA expression of TLR4,My D88,TRIF and NF-κB p65 than the control group(P < 0.05).The high dose of traditional Chinese medicine group and azithromycin expression decreased significantly(P < 0.05).Conclusion:1.The research on SMPP in China started late,but developed rapidly.The epidemiological research,diagnosis and treatment technology are in step with the international,but the research on pathogenic mechanism of pathogens in China is still lagging behind the international.Drug resistance is a common problem in the world,and traditional Chinese medicine has great potential for development.2.Among the commonly used clinical laboratory indicators,CRP,NLR,MLR,LDH,FIB and D-D have predictive diagnostic significance for SMPP,and CRP,NLR,FIB and D-D have high predictive diagnostic value.3.Qushi qingfei Decoction combined with western medicine can effectively improve the treatment outcome of SMPP,and play a positive role in the treatment of SMPP.4.MP could promote the expression of inflammatory factors IL-6 and TNF-α in RAW264.7 cells by activating TLR4/My D88/NF-κB or TLR4/TRIF/NF-κB pathways.Qushi qingfei Decoction can improve the inflammatory state of macrophages by regulating TLR4/NF-κB pathway.
Keywords/Search Tags:Severe mycoplasma pneumoniae pneumonia, Qushi qingfei Decoction, Bibliometrics, RAW264.7 cells, TLR4/NF-κB
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