Knee Osteoarthritis (KOA) is a chronic osteoarthritic condition that affects the middleaged and elderly.Its pathology is characterized by degeneration and destruction of articular cartilage,joint margins,subchondral bone sclerosis,reactive hyperplasia and the formation of bone redundancies.It may even lead to deformity of the joint and seriously affect the function of the joint.At present,both domestic and international clinical practice guidelines advocate a stepwise treatment principle for KOA, while the guidelines also suggest that precise,effective,non-invasive,targeted conservative treatment has obvious advantages and direct effects,and is often the treatment of choice for the stepwise treatment of KOA.In 2020,the International Osteoarthritis Research Society (OARSI) suggested that,compared to the traditional internal treatment based on oral medication,individualized nonpharmacological external treatment,represented by physiotherapy,has been used in the firstline clinical treatment of KOA,and its clinical effectiveness has been proven in many studies.The 2021 edition of the Guidelines for the Treatment of Osteoarthritis in China of the Joint Surgery Group of the Orthopaedic Branch of the Chinese Medical Association also proposes individualized and stepped treatment principles for KOA based on the staging criteria,so that patients at different stages of the disease can obtain the best treatment plan for their condition.Physiotherapy in combination with the clinical symptoms of KOA has a positive therapeutic effect.Among the many physiotherapy treatments available,radial Extracorporeal Shock Wave Therapy (rESWT) is a non-invasive treatment that has been widely used in the clinical management of musculoskeletal disorders,with its advantages of precision targeting,ease of use and significant efficacy.In contrast to modern medicine,which focuses on cartilage lesions,traditional Chinese medicine emphasizes the adjustment of tendon imbalances as the ultimate goal of treatment.Meridian-Sinew Theory (MST) is an important part of Chinese medicine theory,which originated in the ancient times and was formed during the Qin and Han dynasties.Research on the application of TCM meridian theory to the clinical treatment of KOA has also sprung up.The meridian therapy for KOA is based on improving the muscular pathology caused by the imbalance of extension and flexion muscles around the knee joint,which is currently recognized as one of the risk factors for KOA in clinical guidelines at home and abroad.Modern medicine also believes that the biomechanical mechanism for the development of KOA lies in the imbalance of the force lines in the lower limbs,i.e.the point of action of the combined force of the tendons is shifted after injury to the tendons compared to the physiological state,resulting in uneven stresses in the joints,and the knee joint is in a pathological state of imbalance,resulting in an imbalance of the tendons and bones,and the development of knee osteoarthritis.In the "Suwen·Maiyao jingweilun",it is stated that"the knee is the house of the tendons,and if you cannot flex or extend it,you will be hunched over,and the tendons will be exhausted".Therefore,the key to the treatment of this disease is to effectively intervene in the tendons of the knee to improve the tension,adhesions and contractures of the muscles surrounding the tendons of the knee joint,so as to achieve the goal of "treating the bones with the tendons".The ultimate goal is to achieve a physiological state of "bone integrity and tendon flexibility" and "tendon and bone balance".Under the guidance of this principle,studies have been conducted on the targeted treatment of tendon foci in KOA patients,but there are no clinical reports on the use of rESWT.In the meantime,our team has demonstrated the effectiveness and safety of rESWT in relieving knee pain and improving joint function in KOA patients.Therefore,we propose the hypothesis that the Meridian-Sinew radial Extracorporeal Shock Wave Therapy (MSrESWT),based on the guiding principle of "precise application of effective and appropriate energy to the exact site of treatment",can be applied to target the nodal tendon foci of KOA patients with its inherent biological effects to improve peri-knee pain and promote joint function recovery.MS-rESWT is used to target the nodal tendon lesions of KOA patients.The precise targeting of rESWT can improve peri-knee pain and promote functional recovery,while at the same time adjusting the local biomechanics of the knee joint with its physical effects and improving the imbalance of knee flexion and extension by reducing muscle tone.This paper presents both clinical and basic work as part of the study,with a view to revealing the interventional effects of MS-rESWT on KOA disease and its potential therapeutic mechanisms.Research content1.Clinical investigation:An exploratory clinical investigation on the application of extracorporeal shock wave for the treatment of KOA based on the guidance of Meridian-Sinew TheoryPart One:Analysis of the characteristics of Chinese medical evidence in KOA patients and its meridian sinew patternPurposeThe clinical study summarises the distribution pattern of meridian tendon evidence patterns and their TCM dialectical classification in KOA patients,analyses the possible relationship between the two,and provides some research ideas and theoretical basis for the application of meridian tendon theory to guide the diagnosis and treatment of KOA.MethodsBased on the patients’ clinical manifestations and different TCM and meridian evidence patterns,information on gender,age,disease duration,disease stage,KellgrenLawrence (K-L) classification,TCM and meridian evidence patterns were collected to analyse the relationship between the TCM symptoms of KOA and to summarise the distribution pattern of TCM and meridian evidence patterns of KOA.Results(1) The distribution of age,gender and duration of disease in the included patients was 18 males and 58 females,with a gender case ratio of approximately 1:3 and the age of onset concentrated between 40 and 70 years.(2) The distribution of TCM evidence types among the included patients:Qi stagnation and blood stasis evidence was the most frequent (36.84%),followed by liver and kidney deficiency evidence (23.68%),cold-damp paralysis and obstruction evidence(19.74%),damp-heat paralysis and obstruction evidence (10.53%) and Qi and blood weakness evidence (9.21%) respectively.(3) The staging of the TCM clinical symptoms and the distribution of the TCM types of the included patients:the remission phase was the most frequent among the Qi-stagnation and Blood-stasis type,with 17 cases,followed by the exacerbation phase with 8 cases and the recovery phase with 3 cases respectively;the recovery phase was 13 cases and the remission phase was 5 cases among the Liver and Kidney deficiency type;the exacerbation and remission phases were 6 cases each and the recovery phase was 3 cases among the Cold-Damp paralysis type;the remission phase was the most frequent among the DampHeat paralysis type,with 5 cases,followed by the exacerbation phase with 2 cases and the recovery phase with 1 case respectively;and the recovery phase was 6 cases and the remission phase was 1 case among the Qi-Blood weakness type.(4) The distribution of K-L grading of the included patients by stage:16 cases in the stage of Chinese medicine clinical symptoms,34 cases in the stage of remission and 26 cases in the stage of recovery,including 17 cases in grade Ⅰ,37 cases in grade Ⅱ and 22 cases in grade Ⅲ of X-ray K-L grading,including 1 case in grade I,4 cases in the stage of remission and 12 cases in the stage of recovery,6 cases in grade Ⅱ,22 cases in the stage of remission and 9 cases in the stage of recovery,9 cases in grade Ⅲ,9 cases in the stage of remission and 5 cases in the stage of recovery.In Grade Ⅲ,there were 9 cases of seizure,8 cases of remission and 5 cases of recovery.(5) Among the included patients,the foot Yangming meridian tendon evidence pattern was more distributed among the Qi stagnation and Blood stasis evidence patterns,accounting for 42.11% of the single evidence pattern and 55.56% of the compound evidence pattern,while the same distribution pattern was found among the cold-damp paralysis and damp-heat paralysis evidence patterns.Among the solar meridian tendon patterns,there were more cold-damp paralysis and qi stagnation and blood stasis patterns,which were associated with KOA feeling external evil or having qi stagnation and blood stasis symptoms due to pain.The foot San Yin meridian tendon pattern is more prevalent in the liver and kidney deficiency pattern.ConclusionThe incidence of KOA is significantly higher in women than in men,with the age of onset concentrated in the 40-70 age group and the duration of the disease mostly ranging from six months to more than two years.There is a close correlation between the three clinical phases:the exacerbation phase is dominated by Qi stagnation and Blood stasis,Damp-Heat paralysis and Cold-Damp paralysis,the remission phase has no obvious tendency to be a TCM type,and the recovery phase is dominated by Liver and Kidney deficiency and Qi and Blood weakness.Part Two:Effectiveness and safety of the application of extracorporeal shock wave in the treatment of KOA based on the meridian-sinew theoryPurposeTo investigate the efficacy and safety of evanescent extracorporeal shockwave therapy for KOA based on the meridian-sinew theoryMethodsThe patients in the MS-rESWT group were firstly classified according to the meridian identification and then,according to the different meridian types,the patients in the C-rESWT group were treated with individualized meridian shock wave therapy.The patients in the MS-rESWT group were firstly classified into different meridians and then treated with individualised meridian shock wave therapy according to the different meridian foci in the affected knee,while the patients in the C-rESWT group were treated at the site of pain and cartilage damage.Each patient was treated for 2 consecutive sessions.Follow-up visits were conducted before and 1 day,1 week,2 weeks,1 month and 3 months after treatment to assess clinical efficacy and safety.Results(1) Baseline data (gender,age,BMI,duration of disease,X-ray K-L classification and healthy and affected side) were not significantly different between the two groups (P>0.05) and were comparable.(2) As for the evaluation indicators:①VAS scores:compared with the pretreatment period,there was a significant decrease in both groups at all follow-up time points after treatment (P <0.05);at 1 day and 1 week after treatment,VAS scores decreased more significantly in the MS-rESWT group than in the C-rESWT group (P <0.05),and at 2 weeks,1 month and 3 months after treatment,the differences between the two groups were not statistically significant (P>0.05).②WOMAC scores:compared to pre-treatment,there was a significant decrease in both groups at each follow-up time point after treatment (P <0.05);at 1 day,1 week and 2 weeks after treatment,the decrease in WOMAC scores was more significant in the MS-rESWT group than in the C-rESWT group (P <0.05),and at 1 month and 3 months after treatment,the difference between the two groups was not statistically significant (P> 0.05).(3) Adverse reactions:no serious adverse reactions were observed in both groups.Two patients in the MS-rESWT group showed symptoms of local treatment site swelling and skin redness,while three patients in the C-rESWT group showed symptoms of soreness and discomfort in the medial and lateral knee eyes of the knee joint,which disappeared after symptomatic treatment,with no difference between the groups (P> 0.05).ConclusionThe application of rESWT for the precise treatment of KOA patients based on the meridian-sinew theory can provide more rapid and effective relief of knee pain and promote the recovery of joint function,while no serious adverse reactions occurred during the treatment process,confirming the safety and reliability of its short-term clinical efficacy as a treatment method,which can provide certain treatment ideas for the use of Chinese medicine theory combined with extracorporeal shock wave therapy for the treatment of KOA,and is worth promoting in clinical practice.2.Basic researchModulation of behavior,gait kinematics and molecular biology in KOA rats by MS-rESWTPurposeWe applied the method of joint cavity injection of sodium iodoacetate to establish a rat KOA model.From the perspective of transtendinous injury,one of the risk factors of KOA,the quadriceps muscle,a key extensor muscle of the knee joint,was used as the target of the study to investigate the effects of MS-rESWT on the behaviour,gait kinematics and molecular biology of KOA rats,and to evaluate the efficacy of MS-rESWT on KOA and the possible mechanism of action,so as to provide an experimental basis for the clinical application of MS-rESWT in the treatment of muscle injury caused by KOA.MethodsForty-four SPF male SD rats (6 weeks old,weight 180-220g) were randomly divided into normal control group (referred to as normal group),KOA model group (referred to as model group),transcatheter extracorporeal shock wave treatment group (referred to as MSrESWT group) and conventional extracorporeal shock wave treatment group (referred to as C-rESWT group),11 rats in each group.The model,MS-rESWT and C-rESWT groups were established using the method of sodium iodoacetate (MIA) injection into the joint cavity.After modelling,the rats in the model group were given shock wave sound stimulation without ESW intervention using an extracorporeal shock wave treatment machine;in the CrESWT group,the articular cartilage area of the right proximal tibia was used as the target treatment site,and in the MS-rESWT group,the soft tissue constriction and nodules in the quadriceps muscle on the anterior side of the right hind limb of the rats were marked as the focal point of the kyphosis,and ESW intervention was performed respectively.The treatment parameters for both groups were 1.0 bar per dose,6 Hz,800 impulses,and 2 treatments per week for 2 weeks.The improvement of MS-rESWT on behavioural,gait kinematic and quadriceps muscle injury repair in KOA rats was evaluated by observing the results of passive range of motion of the knee,modified Lequesne MG behavioural index score,thigh circumference,CatWalk XT gait parameters and protein expression of Myf5 and NCAM in the quadriceps muscle before and after the intervention.Results(1) Behavioural tests:① Modified Lequesne MG score:compared with the normal group,the modified Lequesne MG score was significantly increased in the model group (P <0.05),and compared with the model group,the modified Lequesne MG score was decreased in both the MS-rESWT and C-rESWT groups after the intervention (P<0.05).②Knee passive range of motion:compared to the normal group,the knee passive range of motion was significantly decreased in the model group (P <0.05) and significantly increased in the MSrESWT and C-rESWT groups after the intervention compared to the model group (P<0.05).③Thigh circumference:There was an increase in thigh circumference in both the normal and MS-rESWT groups after the intervention compared to the model group (P <0.05) and no statistical difference between the MS-rESWT and C-rESWT groups (P>0.05).(2) Gait kinematic tests.① Print length:compared with the model group,PL was significantly improved in the normal,MS-rESWT and C-rESWT groups (P <0.05),and the difference between the MSrESWT and C-rESWT groups was not statistically significant (P> 0.05).②Print width:compared with the model group,there was a significant improvement in PW in the normal,MS-rESWT and C-rESWT groups (P <0.05),and the difference between the MS-rESWT and C-rESWT groups was not statistically significant (P> 0.05).③Print area:compared to the model group,there was a significant improvement in PA in both the normal and MSrESWT groups (P <0.05),with no statistically significant difference between the MSrESWT and C-rESWT groups for comparison (P> 0.05).④ Maximum contact area of print:compared with the normal group,MCA decreased in the model and MS-rESWT groups,the difference was statistically significant (P <0.05),compared with the model group,MCA increased in the C-rESWT group,the difference was statistically significant (P <0.05),and MCA decreased in the MS-rESWT group,the difference was not statistically significant(P> 0.05).⑤ Single stance:SS in the normal group was smaller than that in the model group,MS-rESWT and C-rESWT groups,and the difference was statistically significant (P<0.05).⑥ Stride length:compared with the model group,the SL of the normal group,MSrESWT group and C-rESWT group were all larger than that of the model group,and the difference was statistically significant (P <0.05).⑦ Swing speed:compared with the model group,the SS in the normal group was stronger than that in the model group the difference was statistically significant (P <0.05),and the difference between the model group and the MS-rESWT and C-rESWT groups was not statistically significant (P> 0.05).⑧ Body speed:The difference between the normal group with stronger SS than the model group was statistically significant (P <0.05) compared to the model group,and the difference between the model group and the MS-rESWT and C-rESWT groups was not statistically significant (P> 0.05).(3) Molecular biological assays.① Myf5 protein expression level:compared with the normal and model groups,the expression levels of Myf5 protein in the right hindlimb quadriceps muscle of rats in both the MS-rESWT and C-rESWT groups were significantly higher,and the differences were statistically significant (P <0.05);② NCAM protein expression level:compared with the normal and model groups,the expression levels of Myf5 protein in the right The expression levels of Myf5 protein in the right hind limb quadriceps muscle of the rats in the MSrESWT and C-rESWT groups were significantly increased compared with those in the normal and model groups,and the differences were statistically significant (P <0.05).Conclusion(1) MS-rESWT can effectively increase the passive mobility and leg circumference of the knee joint on the affected side of KOA rats and reduce the knee dysfunction index,thus improving the functional abnormalities such as limited knee movement in KOA rats.(2) MS-rESWT can effectively improve the abnormal gait of the affected hind limb of KOA rats and improve the knee joint function of KOA rats.(3) MS-rESWT significantly increased the expression of myogenic molecular markers such as Myf5 and NCAM in the quadriceps muscle of the affected hind limbs of KOA rats,and promoted the proliferation and differentiation of skeletal muscle stem cells,thus achieving the repair of damaged skeletal muscle. |