| BackgroudKnee osteoarthritis(KOA)is a kind of bone and joint disease caused by multiple factors and mainly manifested by obvious knee pain and adverse movement.It has a long course and mainly occurs in middle-aged and elderly people.The global population of osteoarthritis patients exceeds 300 million.Clinical diagnosis is mainly made by X-rays examination of both knees in orthostatic position indicating pathological changes such as bone and joint cavity.The progression of the disease is divided into 5 grades according to K-L grade of X-ray manifestations.K-L grade ≥Ⅱ is one of the clinical criteria for the diagnosis of KOA.In addition,Doppler ultrasound of both knees is also used as one of the diagnostic criteria for KOA in clinic.Pathological changes of articular cartilage,subchondral bone and other tissues can be observed from multiple dimensions and individual positions,and grades can be made according to each ultrasonic manifestation to guide the diagnosis of knee lesions.At present,Western medicine treats KOA by steps according to clinical stages.In the early stage,multiple exercises,weight loss and health promotion are selected,and in the middle stage,non-steroidal anti-inflammatory drugs or sodium hyaluronate knee injection and other drugs that are prone to adverse reactions are selected.In the late stage,expensive joint replacement surgery is mainly adopted.The control of symptoms of the disease is relatively obvious,but in delaying the development of the disease,improve the prognosis is still general,traditional Chinese medicine treatment of KOA mostly adopts a combination of internal and external treatment,addressing symptoms and root causes,quick effect,high safety and alleviate pain as well.Knee osteoarthritis belongs to the category of "arthralgia " of traditional Chinese medicine.The etiology,pathogenesis and prevention of it have long been recorded in"Inner Canon of Huangdi".At present,the treatment plan formulated by traditional Chinese medicine for KOA is based on the holistic concept of traditional Chinese medicine and the treatment based on syndrome differentiation.Although there were no regional and ethnic differences in the incidence of KOA,regional differences still appeared in the differentiation of syndrome types,and the syndrome types were not unified.KOA tends to occur in people with low family economic level and education level,or even lack of medical conditions.Therefore,it is urgent and important to standardize the syndrome differentiation and diagnosis and treatment system of KOA,to benefit all people with TCM treatment.Intestinal flora is currently a global research hotspot with extensive contents andpowerful functions,and it is a way to break through research bottlenecks in various fields.As far as KOA is concerned,researchers have long proposed the "gut-joint axis" theory,leading researchers to further explore the correlation between microorganisms and joint inflammatory response.Through macro analysis of the influence of microbial flora structure on physiological and pathological activities of the human body,combined with micro analysis of the colonization,tolerance and physiological function of each dominant strain,to explore specific ways to participate in various physiological activities of the body.At present,there have been studies to find bacteria with research potential,and try to explore their mechanism of action.ObjectivePart One:Distribution of TCM syndromes of knee osteoarthritis1.To provide new and meaningful clinical data for the diagnosis of KOA by sorting out and analyzing the syndrome distribution pattern of KOA patients in our department’s outpatient department and wards and its correlation with various examinations.2.Explore the examination indicators closely related to the pathogenesis and progression of KOA,and seek the examination indicators that can assist in the diagnosis of KOA and the identification of TCM syndromes of KOA,to provide meaningful data for the clinical diagnosis and treatment of KOA.Part Two:Relationship between intestinal flora and different TCM syndromes of knee osteoarthritis1.To explore the differences of intestinal flora structure and abundance between KOA patients and healthy people;2.To explore the difference of intestinal flora structure and abundance between damp heat obstruction syndrome and cold dampness obstruction syndrome in KOA patients;3.Analyze and compare the microflora that play an assisting role in the diagnosis of KOA and TCM syndrome of KOA,and provide new and more sensitive microbial markers.MethodsPart One:Distribution of TCM syndromes of knee osteoarthritisThis study collected 3260 patients with KOA as the first diagnosis in our outpatient department and ward from October 2012 to November 2022 through the medical record system of our hospital.Two persons were independently screened for medical history,orthostatic X-ray examination of both knees,color doppler ultrasound examination of both knees,ESR,CRP,H-CRP,HS-CRP and other cases with complete information.The syndrome type was evaluated again according to the training method,and the syndrome elements were extracted at the same time to establish a database,and 207 patients were finally included.SPSS 20.0 was used to analyze the correlation between multiple factors such as gender,age,work nature,X-ray performance of both knees standing,ultrasound performance of both knees.ESR,CRP,H-CRP and HS-CRP on TCM syndrome types and TCM syndrome elements of KOA.T test,Bonferroni method,Wilcoxon rank sum test,Kruskal-Wallis rank sum test and unordered multiple classification Logistic regression analysis were used to analyze the correlation from various perspectives.Part Two:Relationship between intestinal flora and different TCM syndromes of knee osteoarthritisAmong the patients with knee osteoarthritis treated in our outpatient department from October 2022 to February 2023,10 patients with damp-heat obstruction were classified as group A,10 patients with cold-dampness obstruction were classified as group B,and ten healthy subjects were recruited as Group C.Subjects’ feces were collected and frozen at-80℃ within 30min for analysis..After quality inspection and database construction,the differences in intestinal flora of subjects in groups A,B and C were respectively compared at different levels,and the influence of specific microorganisms on the differences was explored from different levels,to explore biomarkers with diagnostic significance for KOA.Secondly,the differences in the structure and abundance of intestinal flora between group A and group B,and the impact of specific microorganisms on the differences at each level,were explored to find microorganisms that could help diagnose the cold and heat syndrome type of KOA in traditional Chinese medicine.ResultsPart One:Distribution of TCM syndromes of knee osteoarthritisIn this study,207 patients with KOA were included,including 167 females and 40 males,age;61.81 ±6.79 years old,the course of disease was 44～65 months,the median course of disease was 60 months,71 cases(34.30%)of damp-heat obstruction,60 cases(28.99%)of liver and kidney deficiency,31 cases(14.98%)of cold-dampness obstruction,28 cases(13.52%)of phlegm stasis obstruction,17 cases(8.21%)of qi and blood weakness syndrome.There were 55 cases of heat,30 cases of cold and 29 cases of dampness.Age,gender,course of disease,nature of work:except for the syndrome of damp-heat obstruction and phlegm stasis obstruction,there was no statistical significance(P=0.163),but there was statistical significance among the other syndrome types(P<0.05).There were statistically significant differences between CRP,H-CRP,HS-CRP,ESR,K-L,deficiency syndrome of liver and kidney,cold and dampness obstruction syndrome,qi and blood weakness syndrome(P<0.05).Other ultrasonic findings except articular effusion had statistical significance for syndrome elements(P<0.05).There were statistically significant differences among different TCM syndrome types in X-ray K-L grading and peripheral tissue swelling degree,(P<0.05).Part Two:Relationship between intestinal flora and different TCM syndromes of knee osteoarthritisThe results show that group A and group C are grouped well,and the samples of Group B are scattered.Therefore,after further analysis of the samples by ADONIS,it is pointed out that P<0.01,which has a statistically significant difference.The analysis in PCoA is valid,and the results are highly reliable.The comparison between group A and group B suggested that Klebsiella,Enterobacteriaceae,Faecalibacterium and Ruminococcus were the dominant strains in group A.Staphylococcus and Prevotellaceae were the dominant bacteria in Group B.A comparison between Group A and Intestinibacter showed that there was a large abundance of Klebsiella,Enterobacteriaceae and Intestinibacter in Group A.In group C,IIeibacterium and Odoribacter were abundant.The comparison between group B and group C showed that Clostridia,Monoglobaceae and Firmicutes had a high abundance in group C,while Bacteroidota had a high abundance in group B.ConclusionPart One:Distribution of TCM syndromes of knee osteoarthritisThrough the analysis of the distribution pattern of syndrome types,it was found that the dampness-heat obstruction syndrome(71,34.30%)was the most,followed by the deficiency of liver and kidney syndrome(60,28.99%).The cold dampness-dampness-obstruction syndrome was more common in those with more severe work degree,and the cold dampness-obstruction syndrome and the qi and blood weakness syndrome suggested a longer course of disease.In ultrasonic manifestations,compared with phlegm-stasis obstruction syndrome,the higher the grade of PD of synovial hyperplasia,the more likely it is to suggest damp-heat obstruction syndrome,and the more serious synovial hyperplasia of heat is manifested,which can be used as a diagnostic indicator of damp-heat obstruction syndrome.Compared with cold dampness obstruction syndrome and dampness-heat obstruction syndrome,phlegm-stasis obstruction syndrome was more prone to more serious cartilage injury.Heat and dampness were more serious in articular cartilage,and the difference was statistically significant.K-L classification can be used as a reference for the diagnosis of TCM syndrome types to a certain extent.Phlegm-stasis obstruction syndrome has a higher K-L classification than qi and blood weakness and cold and dampness obstruction syndrome,and dampness and heat obstruction syndrome is more likely to show swelling of surrounding tissues.Both at baseline and between groups,ESR and other inflammatory factors have a significant impact on the syndrome of damp-heat obstruction.It seems that ESR and other inflammatory factors can be used as a diagnostic marker with reference significance.Part Two:Relationship between intestinal flora and different TCM syndromes of knee osteoarthritisAccording to the results of this study,Klebsiella is closely related to joint inflammation,which has research potential and value.Enterobacterium plays an important role in the induction of immune response and recruitment of inflammatory cytokines in the course of disease,and has the potential to be used as a screening marker.Ruminococcus has a high abundance in damp-heat obstruction syndrome,and it has pro-inflammatory effect,so it is speculated that Ruminococcus has a certain of reference significance for the diagnosis of TCM syndromes,and has the potential to become a biomarker of syndrome type. |
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