Role of Interleukin-17 family cytokines in disease severity of patients with knee osteoarthritis

Abstract Background Interleukin-17 (IL-17) family plays a role in the pathogenesis of knee osteoarthritis (KOA) by contributing to the inflammatory and destructive processes in the affected joint. This study aimed to measure levels of IL-17 A and IL-25 (IL-17E) in serum of KOA patients and determine their roles in the disease severity of patients. Methods In this, 34 patients with KOA and 30 age and sex-matched healthy subjects (HS) were enrolled. Patients were categorized based on their Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Visual Analog Scale (VAS), and Body Mass Index (BMI) scores. The enzyme-linked immunosorbent assay (ELISA) technique was employed to measure serum levels of IL-17 A and IL-25. Results Level of IL-25 was significantly higher (P < 0.0001) in the KOA subjects than HS. IL-17 A level was significantly higher in KOA cases with WOMAC < 40 (P < 0.0001) in comparison to HS. IL-25 level was significantly higher in the KOA cases with WOMAC < 40 (P < 0.0001) and with WOMAC ≥ 40 (P < 0.0001) compared to HS. IL-17 A concentration was significantly higher in the KOA cases with VAS < 5 (P < 0.0001) compared to HS. IL-25 level was significantly higher in the KOA cases with VAS < 5 (P < 0.0001) and with VAS ≥ 5 (P < 0.0001) in comparison to HS. KOA patients with BMI ≥ 30 had significantly higher IL-17 A and IL-25 concentration in comparison to HS. Conclusions The serum level of IL-25 in KOA patients is increased probably due to negative controlling feedback on inflammatory responses, which can be associated with obesity and disease activity.

Effect of nerve growth factor on elderly degenerative knee osteoarthritis pain / 中国骨伤

OBJECTIVE@#To explore effect of nerve growth factor (NGF) antibody on knee osteoarthritis (KOA) pain model was evaluated by in vitro model.@*METHODS@#Thirty male SPF rats aged 28-week-old were divided into blank group (10 rats with anesthesia only). The other 20 rats were with monoiodoacetate (MIA) on the right knee joint to establish pain model of OA, and were randomly divided into control group (injected intraperitoneal injection of normal saline) and treatment group (injected anti-NGF) intraperitoneal after successful modeling, and 10 rats in each group. All rats were received retrograde injection of fluorogold (FG) into the right knee joint. Gait was assessed using catwalk gait analysis system before treatment, 1 and 2 weeks after treatment. Three weeks after treatment, right dorsal root ganglia (DRG) were excised on L4-L6 level, immunostained for calcitonin gene-related peptide (CGRP), and the number of DRGS was counted.@*RESULTS@#In terms of gait analysis using cat track system, duty cycle, swing speed and print area ratio in control and treatment group were significantly reduced compared with blank group (P<0.05). Compared with control group, duty cycle and swing speed of treatment group were significantly improved (P<0.05), and there was no significant difference in print area ratio between treatment group and blank group (P>0.05). The number of FG-labeled DRG neurons in control group was significantly higher than that in treatment group and blank group (P<0.05). The expression of CGRP in control group was up-regulated, and differences were statistically significant compared with treatment group (P<0.05).@*CONCLUSION@#Intraperitoneal injection of anti-NGF antibody inhibited gait injury and upregulation of CGRP in DRG neurons. The results suggest that anti-nerve growth factor therapy may be of value in treating knee pain. NGF may be an important target for the treatment of knee OA pain.

Effect of Tongluo Juanbi Granules on Inflammatory Injury and Apoptosis of Osteoarthritis Based on TLR4/MyD88/NF-κB Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo investigate the effects of Tongluo Juanbi granules on chondrocyte apoptosis and Toll-like receptor 4 （TLR4）/myeloid differentiation factor 88 （MyD88）/nuclear factor-κB （NF-κB） signaling pathway of rabbits with knee osteoarthritis （KOA） and study the mechanism of Tongluo Juanbi granules in the prevention and treatment of KOA. MethodThirty New Zealand rabbits were randomly assigned to the following five groups （n=6）： sham group， model group， low-dose and high-dose groups of Tongluo Juanbi granules （4.1 and 8.2 g·kg-1·d-1）， and celecoxib group （10.9 mg·kg-1·d-1）. The KOA model was established by destabilization of the medial meniscus （DMM） for six weeks. Six weeks after the modeling， the drug was given once a day for eight weeks. The pathological changes of cartilago articularis were observed by hematoxylin-eosin （HE） staining and Safranin O-Fast Green staining. Terminal deoxynucleotidyl transferase dUTP nick end labeling （TUNEL） staining was performed to detect chondrocyte apoptosis. Enzyme-linked immunosorbent assay （ELISA） was used to detect the contents of interleukin-1β （IL-1β） and tumor necrosis factor-α （TNF-α） in synovial fluid. The mRNA and protein expression levels of genes related to the TLR4/MyD88/NF-κB signaling pathway were detected by real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） and Western blot， respectively. ResultCompared with the sham group， the cartilago articularis of the model group significantly degenerated. Mankin's score was increased （P<0.01）， and the contents of IL-1β and TNF-α in synovial fluid were increased （P<0.01）. The number of apoptosis of chondrocytes was increased （P<0.01）. The mRNA and protein expressions of TLR4， MyD88， and NF-κB p65 in cartilage tissue were up-regulated （P<0.01）， while the mRNA and protein expressions of Bcl-2 were down-regulated （P<0.01）. Compared with the model group， chondrocyte degeneration in both low-dose and high-dose groups of Tongluo Juanbi granules was improved， and Mankin's score was decreased （P<0.01）. The contents of IL-1β and TNF-α were decreased （P<0.01）， and the number of apoptosis of chondrocytes was decreased （P<0.01）. The mRNA and protein expressions of TLR4， MyD88， and NF-κB p65 in cartilage tissue were down-regulated （P<0.01）， while the mRNA and protein expressions of Bcl-2 were up-regulated （P<0.01）. In addition， in the above observation indicators， the high-dose group of Tongluo Juanbi granules was significantly superior to the low-dose group of Tongluo Juanbi granules. ConclusionTongluo Juanbi granules could inhibit chondrocyte apoptosis in rabbits with KOA and improve cartilage degeneration， which may be related to inhibiting inflammatory responses mediated by TLR4/MyD88/NF-κB signaling pathway.

Impact of a Tailored Self-Management Education Programme for Older Adults with Knee Osteoarthritis in a Multi-Ethnic Country / Jurnal Sains Kesihatan Malaysia

@#Self-management education program (SMEP) is essential in the knee osteoarthritis (OA) management. While the benefits of tailored SMEP have been highlighted in the literature, evidence on the effects of tailored knee OA SMEP for multiethnic populations, such as in Malaysia, remains limited. Therefore, the aim of this study was to conduct an intervention study on a tailored SMEP among Malaysian older adults who aged 60 years and above with knee OA. Participants aged 60 years and over with a diagnosis of knee OA were recruited. The intervention comprised four weekly structured group SMEP which was developed specifically for the multicultural population in Malaysia. Symptom’s severity and functional performance were assessed at baseline and six-week follow-up using the Knee Injury and Osteoarthritis Outcome Score questionnaire (KOOS), 30 seconds sit to stand (30sST), time up and go (TUG), chair sit and reach (CSR), back stretch (BS), handgrip strength (HGS) and two-minute walk (2MW) tests. Of the 32 individuals recruited, 30 participants, mean age of 66.77 (±6.42) years, completed the post-intervention assessment. Improvements in mean KOOS domains scores were observed by between 1.3% - 8.6% from baseline to follow-up. Significant differences between baseline and followup scores were identified for 30sST (p < 0.05), TUG ( p < 0.001) and 2MW (p < 0.001) tests. A 4-week tailored SMEP delivered face to face by a physiotherapist, improved lower limb muscle strength, mobility, balance and endurance. Larger randomized controlled trials regarding the long-term effects of SMEP for older adults with OA is warranted.

Improvement effect and mechanism of “Layers adjusting external application”paste on synovial fibrosis in rats with knee osteoarthritis / 中国药房

OBJECTIVE To investigate the improvement effect and potential mechanism of “Layers adjusting external application” paste on synovial fibrosis （SF） in rats with knee osteoarthritis （KOA）. METHODS Male SD rats were randomly divided into sham operation group， KOA group and Layers adjusting external application group， with 8 rats in each group. KOA model was induced by the anterior cruciate ligament disruption method in KOA group and Layers adjusting external application group. Fourteen days after modeling， the Layers adjusting external application group was given “Layers adjusting external application” paste [Sanse powder （8 g for every 100 cm2）， Compound sanhuang ointment （5 g for every 100 cm2）] on the knee joint， 8 h every day， for 28 d in total. After the last administration， the degree of synovitis and fibrosis in rats was observed， and Krenn scoring was performed in each group. The expressions of collagen Ⅰ， high mobility group protein B1 （HMGB1） and phosphorylated nuclear factor-κB p65 （p-NF-κB p65） were detected in the synovial membrane； the contents of interleukin-1β （IL- 1β）， IL-6 and tumor necrosis factor-α （TNF-α） in serum as well as the expressions of fibrosis-related and HMGB1/Toll-like receptor 4 （TLR4）/NF-κB signaling pathway-related proteins and mRNA were detected in synovial tissue. RESULTS Compared with the sham operation group， the synovial lining cells in the KOA group showed significant proliferation and disordered arrangement， the inflammatory cell infiltration and collagen fiber deposition were obvious； the positive expressing cells of collagen Ⅰ， HMGB1 and p-NF-κB p65 were increased significantly； the contents of IL-1β， IL-6 and TNF-α in serum， the expressions of fibrosis-related protein （transforming growth factor-β， collagen Ⅰ， tissue inhibitor of metalloproteinase 1， α-smooth muscle actin） and their mRNA as well as theexpressions of HMGB1， TLR4 protein and their mRNA， the expressions of p-NF-κB p65 protein and NF-κB p65 mRNA were all increased significantly in synovial tissues of rats （P＜0.01）. Compared with the KOA group， the pathological changes in the synovial tissue of rats in Layers adjusting external application group were significantly improved， and the above quantitative indicators were significantly reversed （P＜0.05 or P＜0.01）. CONCLUSIONS “Layers adjusting external application” paste could significantly improve SF in KOA rats， the mechanism of which may be associated with the inhibition of the activation of HMGB1/ TLR4/NF-κB signaling pathway.

Does total knee arthroplasty affect pelvic movements? A prospective comparative study

SUMMARY OBJECTIVE: Pathology in any segment of the spine-pelvis-lower extremity may impair the global postural balance, leading to compensatory alterations in other parts. The aim of this study was to compare the pelvic movements of patients suffering from knee osteoarthritis with patients who underwent total knee arthroplasty and healthy controls. METHODS: This study was performed at the Department of Orthopedics and Traumatology Clinic of a Cankiri State Hospital between April 2021 and February 2022. This study included 84 participants. Of them, 31 patients who underwent total knee arthroplasty between 2018 and 2020 years were selected as the total knee arthroplasty group, while 28 patients with knee osteoarthritis were selected as the knee osteoarthritis group. In the control group, there were 25 healthy individuals. Exclusion criteria from the study included any kind of neurological disease, an inability to walk a distance of 100 m unassisted, or a history of surgery to the lower limb. Pelvic movements (i.e., tilt, rotation, and obliquity) and gait parameters (i.e., "gait velocity," "cadence," and "stride length") were assessed using a wireless tri-axial accelerometer. RESULTS: Total knee arthroplasty and control groups had decreased minimum anterior tilt of the pelvis, decreased maximum anterior tilt, and decreased oblique range of the pelvis compared with the knee osteoarthritis group. In comparison with the control group, gait velocity and length of stride during gait were remarkably lower in both knee osteoarthritis and total knee arthroplasty groups. CONCLUSION: In this study, total knee arthroplasty was found to affect pelvic movements. It was thought that total knee arthroplasty changed these variables, probably owing to the frontal and sagittal plane alignment correction through surgery.

Correlation between body mass index and joint pain intensity with gait performance in individuals with osteoarthritis / Correlação entre o índice de massa corporal e intensidade da dor articular com o desempenho da marcha em indivíduos com osteoartrite

ABSTRACT BACKGROUND AND OBJECTIVES: Individuals with osteoarthritis (OA) often have joint pain and are overweight or obese. Thus, the objective of this study was to observe whether there is correlation between body mass index and joint pain intensity with gait performance in individuals with OA. METHODS: Cross-sectional study, which evaluated 60 volunteers, being 30 with clinical diagnosis of knee osteoarthritis and 30 without the disease, of both sexes and aged between 50-82 years. Joint pain intensity was assessed using the Visual Analog Scale, gait-related functional tasks using the Dynamic Gait Index, and the functional mobility using the Timed Up and Go test. RESULTS: There was a correlation between overweight/obesity and high levels of joint pain intensity (p=0.018), with worse performance in gait-related functional tasks (p=0.000) and with worse functional mobility (p=0.034) only for the individuals with OA. High levels of joint pain intensity also correlated with worse performance in the gait-related functional tasks (p=0.000) in the OA group, and also with worse functional mobility in the OA group (p=0.001) and also in the group of individuals without the disease (p=0.032). CONCLUSION: This study identified a correlation between overweight/obesity and high levels of joint pain intensity and worse gait performance in individuals with osteoarthritis. High levels of pain intensity also correlated with worse gait performance in individuals with OA.

resumo JUSTIFICATIVA E OBJETIVOS: Indivíduos com osteoartrite (OA) frequentemente apresentam dor articular e sobrepeso ou obesidade. Assim, o objetivo deste estudo foi observar se existe correlação entre o índice de massa corporal e a intensidade da dor articular com o desempenho da marcha em indivíduos com OA. MÉTODOS: Estudo de corte transversal, que avaliou 60 indivíduos, sendo 30 com diagnóstico clínico de osteoartrite de joelho e 30 sem a doença, de ambos os sexos e com faixa etária entre 50 e 82 anos. A intensidade da dor articular foi avaliada pela Escala Analógica Visual, as tarefas funcionais relacionadas à marcha pelo Dynamic Gait Index e a mobilidade funcional pelo teste Timed Up and Go. RESULTADOS: Houve correlação entre o sobrepeso/obesidade e níveis elevados de intensidade da dor articular (p=0,018), com um pior desempenho nas tarefas funcionais relacionadas à marcha (p=0,000) e com menor mobilidade funcional (p=0,034) apenas para os indivíduos com OA. Os níveis elevados de intensidade de dor articular também mostraram correlação com um pior desempenho nas tarefas funcionais relacionadas à marcha (p=0,000) no grupo com OA, e ainda, com uma menor mobilidade funcional no grupo com OA (p=0,001) e também no grupo de indivíduos sem a doença (p=0,032). CONCLUSÃO: Este estudo identificou correlação entre o sobrepeso/obesidade com níveis elevados de intensidade da dor articular e com um pior desempenho na marcha nos indivíduos com OA. Os elevados níveis de intensidade da dor também mostraram correlação com pior desempenho na marcha nos indivíduos com OA.

Radiografía al acceso en artroplastia de rodilla entre los beneficiarios del Fondo Nacional de Salud entre 2004 y 2021 / Access to knee arthroplasty among National Health Fund beneficiaries in Chile between 2004 and 2021

Introducción La artrosis de rodilla es una patología que afecta la calidad de vida, siendo la artroplastía de rodilla un tratamiento costo-efectivo para la etapa severa de esta enfermedad. El acceso a artroplastia de rodilla es un indicador de salud de la Organización de Cooperación y Desarrollo Económico. Los objetivos de este estudio son determinar la incidencia de artroplastia de rodilla entre 2004 y 2021 en los beneficiarios del Fondo Nacional de Salud en Chile, la proporción que se operaron en el sistema privado y estimar el gasto del bolsillo del paciente para operarse. Método Estudio transversal. Se utilizó la base de datos del Departamento de Estadística e Información de Salud. Se pesquisaron pacientes que egresaron de un centro de salud chileno que fueron intervenidos por artroplastia rodilla entre 2004 y 2021. Se analizó la proporción de pacientes por tramo del Fondo Nacional de Salud y si se realizó su cirugía en establecimiento de la red pública o privada. Resultados De las 31 526 intervenciones de artroplastia de rodilla, 21 248 (67,38%) fueron realizadas en pacientes del Fondo Nacional de Salud y 16 238 en instituciones públicas (51,49%). Los pacientes de dicho fondo presentan un alza sistemática en el volumen de artroplastías de rodilla hasta 2019, pero disminuyeron en 2020 y 2021 un 68% y un 51%. Del total de pacientes del sistema público operados de artroplastia de rodilla, 856 (9%) pertenecían al tramo A1, al tramo B 12 806 (60%), al tramo C 2044 (10%) y al tramo D 4421 (21%). Se estimó que el gasto incurrido por estos pacientes varía entre el 24,4 y 27,2%. Las proporciones históricas de acceso en instituciones privadas a esta cirugía son en el tramo A 7%, tramo B 13%, tramo C 24% y tramo D 52%. Conclusión El 50% de las cirugías de artroplastía de rodilla se realizan en instituciones públicas y dos tercios se realizan en pacientes del Fondo Nacional de Salud. El 46% de los tramos C y D se operaron en el sistema privado. La pandemia ha aumentado la brecha de acceso, lo que ha provocado un alza significativa en la proporción de pacientes del Fondo Nacional de Salud de los tramos B, C y D que han migrado al sistema privado para acceder a esta cirugía.

Introduction Knee osteoarthritis affects the quality of life, with knee arthroplasty being a cost-effective treatment for the severe stage of this disease. Access to knee arthroplasty is a health indicator of the Organisation for Economic Co-operation and Development. The objectives of this study are to determine the incidence of knee arthroplasty between 2004 and 2021 in beneficiaries of the National Health Fund in Chile, the proportion of patients who underwent surgery in the private system, and to estimate the patient's out-of-pocket expenditure for surgery. Methods Cross-sectional study. We used the Department of Statistics and Health Information database. Patients discharged from a Chilean health center who underwent knee arthroplasty surgery between 2004 and 2021 were investigated. We analyzed the proportion of patients by their National Health Fund category and whether their surgery was performed in public or private network facilities. Results Of the 31 526 knee arthroplasty procedures, 21 248 (67.38%) were performed on National Health Fund patients and 16 238 in public institutions (51.49%). Patients from the National Health Fund showed a systematic increase in knee arthroplasty volume until 2019 but decreased in 2020 and 2021 by 68% and 51%. Of the total number of patients in the public system operated on for knee arthroplasty, 856 (9%) belonged to group A1, 12 806 (60%) to group B, 2044 (10%) to group C, and 4421 (21%) to group D. The expenditure incurred by these patients was estimated to vary between 24.4% and 27.2%. The historical proportions of access to this surgery in private institutions are 7% in group A, 13% in group B, 24% in group C, and 52% in group D. Conclusion Fifty percent of knee arthroplasty surgeries are performed in public institutions, and two-thirds are performed on patients of the National Health Fund. Forty-six percent of the C and D groups were operated in the private system. The pandemic has increased the access gap, leading to a substantial increase in the proportion of patients from the National Health Fund of the B, C, and D groups who have migrated to the private system to access this surgery.

Effects of closed and open kinetic chain exercises on pain, muscle strength, function, and quality of life in patients with knee osteoarthritis

SUMMARY OBJECTIVE: Therapeutic exercises are well documented for the treatment of osteoarthritis; there is less evidence on what the effect of closed kinetic chain exercises is for knee osteoarthritis. The aim of this study was to investigate the effects of open kinetic chain exercises and closed kinetic chain exercises on pain, muscle strength, functional status, and quality of life in patients with knee osteoarthritis. METHODS: The study included a total of 60 patients with primary unilateral knee osteoarthritis grade I and II. The patients were categorized into three groups as open kinetic chain exercises (n=20), closed kinetic chain exercises (n=20), and control group (n=20). The outcome measures, including pain, isokinetic muscle strength, functional status, and quality of life, were collected at baseline and at the end of 6 and 12 weeks. RESULTS: Closed kinetic chain exercises and open kinetic chain exercises had significant improvement in pain, muscle strength, WOMAC, and SF-36 scores after the treatment and at their 6th and 12th week follow-ups compared to their baseline values and compared to the control group (p<0.05). CONCLUSION: The changes in all outcome measures were similar between closed kinetic chain exercises and open kinetic chain exercises (p>0.05). Closed kinetic chain exercises and open kinetic chain exercises were similar for knee osteoarthritis grade I and II. Closed kinetic chain exercises could be safely added to the exercise programs of patients with low-grade knee osteoarthritis.

Prevalence and interference of neuropathic pain in the quality of life in patients with knee osteoarthritis

Abstract Objective: With the aging of the population, more patients have complained of pain due to knee Osteoarthritis (OA), and the number of arthroplasties has also increased. The objective of this study is to evaluate the prevalence of the neuropathic pain component in candidates for Total Knee Replacement and the effects of this component on their quality of life. Methods: In this cross-sectional study, patients with OA candidates for knee arthroplasty in the present institution were evaluated using the pain detection questionnaire and the Visual Analog Pain (VAS) scale to measure the pain index and the presence of associated neuropathic pain. In addition, evaluation of the quality of life and functionality using the EQ5D and SF12 questionnaires and their relationship with cases of neuropathic pain were performed. Results: One hundred twenty-six patients were evaluated, and 71.4 % were female. The age ranged from 46 to 85 years, and about 70 % of the patients had some associated clinical comorbidity. Neuropathic pain was present in 28.6 % of the patients evaluated. Patients with neuropathic pain presented worse results in the VAS evaluation, in the care, pain, and anxiety domains of the EQ5D, and in the physical and mental scores of the SF12. Conclusion: Neuropathic pain was present in 28.6 % of the patients with knee OA who are candidates for arthro-plasty. Patients with associated neuropathic pain present a higher level of pain and worse quality of life scores. Recognizing this type of pathology is extremely important in fully monitoring gonarthrosis.

Relationship between pain, functional limitations, dependence, depression and osteoarthritis in older adults / Relação da dor, limitação funcional, dependência e depressão com a osteoartrite em idosos

Abstract Introduction Knee osteoarthritis (KOA) is a prevalent pathology in older adults, with physical, social and psychological impacts that reduce their quality of life. Objective Analyze the correlation between KOA in older individuals and biopsychosocial aspects such as pain, functional limitation, dependence, anxiety and depression. Methods A systematic review of English and Portuguese articles published on the Cochrane Library, PUBMED/MEDLINE, SciELO and Web of Science databases between 2016 and 2021, selected according to inclusion and exclusion criteria. Results After cross-checking specific to each database, studies were selected by reading the title (2,304), abstract (136) and full article (72), with 30 ultimately included based on the eligibility criteria. Conclusion Knee osteoarthritis has a significant negative impact on patients' lives and is correlated with pain, functional limitation, dependence, anxiety and depression, compromising interpersonal relationships, physical and mental status and causing disability due to chronic pain, making osteoarthritis (OA) a public health issue with a high financial, physical and emotional cost for patients.

Resumo Introdução A osteoartrite de joelho é uma patologia prevalente em idosos, impactando suas vidas em um contexto físico, social e psicológico, o que ocasiona redução na qualidade de vida desses indivíduos. Objetivo Analisar a correlação entre a osteoartrite de joelho em idosos e aspectos biopsicossociais como dor, limitação funcional, dependência, ansiedade e depressão. Métodos Revisão sistemática de artigos publicados nas bases de dados Cochrane Library, PUBMED/MEDLINE, SciELO e Web of Science, entre 2016 e 2021, em português e inglês. Após isso, realizou-se a seleção dos artigos de acordo com os critérios de inclusão e exclusão. Resultados Após cruzamentos específicos em cada base, selecionaram-se os artigos por meio da leitura do título (2.304), do resumo (136) e do artigo na íntegra (72). Assim, 30 artigos foram selecionados de acordo com os critérios de elegibilidade. Conclusão Confirmou-se que a osteoartrite de joelho impacta negativamente a vida dos pacientes e está correlacionada com dor, limitação funcional, dependência, ansiedade e depressão, prejudicando as relações interpessoais, afetando condições físicas e mentais e gerando incapacidade devido à dor crônica, tornando a osteoartrite uma questão de saúde pública de alto custo financeiro, físico e emocional aos pacientes.

Effect of Bushen Chushi() decoction combined with platelet-rich plasma on regulating TGF-β1 and Smad-1 expression in serum of knee osteoarthritis patient / 中国骨伤

OBJECTIVE@#To investigate the effect of Bushen Chushi decoction combined with platelet-rich plasma(PRP) to treat knee osteoarthritis(KOA) in early and middle stage and its regulation on TGF-β1 and Smad-1 expression in serum.@*METHODS@#Total of 45 patients with KOA in early and middle stage from May 2020 to April 2022 were treated and divided into control group and observation group. In control group, there were 30 patients including 12 males and 18 females, aged from 43 to 69 years old with an average of(57.3±6.5) years old and disease duration ranged from 1.5 to 5.0 years with an average of(3.8±1.7) years, and there were 8 cases in gradeⅠ, 13 cases in gradeⅡ, and 9 cases in grade Ⅲ according to Kellgren-Lawrence Grade, PRP 5 ml was injected into knee joint on the first day of No1, 3 week together for 2 times. In the observation group, there were 15 cases including 7 males and 8 females, aged from 45 to 70 years old with an average of (56.7±6.2) years old and disease duration ranged from 1.8 to 5.7 years with an average of (4.0±1.8) years, there were 4 cases in gradeⅠ, 9 cases in gradeⅡand 4 cases in grade Ⅲ according to the Kellgren-Lawrence Grade, PRP 5 ml were injected into knee joints that the time and frequency were the same as those in the control group, and at the same time Bushen Chushi decoction orally were taken 1 dose per day with a total of 28 doses. All patients were treated for four weeks. Visual analogue scale(VAS) and Lequesne MG score before and after treatment were used to evaluate improvement of knee pain and joint function. The TGF-β1 and Smad-1 levels in serum were measured before and after treatment in two groups. The incidence of complications in two groups was observed.@*RESULTS@#All patients were followed up for 26 to 30 days with an average of (28.0±0.6) days. There was no significant difference in VAS and knee Lequesne MG scores between two groups before treatment(P>0.05). The scores of VAS and knee Lequesne MG on the first day after treatment in both groups were lower than those before treatment(P<0.05). The VAS and knee Lequesne MG scores in observation group were lower than those in control group(P<0.05) on the first day after treatment. The TGF-β1 level in serum after treatment were higher significantly than that before treatment in two groups(P<0.05). After treatment, TGF-β1 level in serum in observation group were lower than those in control group with statistically significant differences(P<0.05). The Smad-1 levels in serum after treatment in observation group were higher significantly than that in control group(P<0.05). The levels of Smad-1 were not statistically significant between before and after treatment(P>0.05). There was no significant difference in postopertaive complications between two groups (P>0.05).@*CONCLUSION@#The efficacy of Bushen Chushi decoction combined with PRP in treatment of early and middle KOA is better than that of PRP injection alone. The combined treatment could reduce TGF-β1 level and increase Smad-1 level in serum, which may be a mechanism to inhibit inflammation and alleviate cartilage degeneration to some extent.

Study on the relationship between severe knee osteoarthritis and bone marrow edema / 中国骨伤

OBJECTIVE@#To investigate the relationship between bone marrow edema and pathological changes, symptoms and signs of severe knee osteoarthritis.@*METHODS@#From January 2020 to March 2021, 160 patients with severe knee osteoarthritis who underwrent MRI of the knee at the Department of Bone and Joint, Wangjing Hospital, China Academy of Chinese Medical Sciences were included. Eighty patients with bone marrow edema were selected as the case group, including 12 males and 68 females, aged from 51 to 80 years old with an average of (66.58±8.10) years old, the duration of disease 5 to 40 months with an average of (15.61±9.25) months. Eighty patients without bone marrow edema were selected as the control group, including 15 males and 65 females, aged from 50 to 80 years old with an average of (67.82±8.05) years old, the duration of disease 6 to 37 months with an average of (15.75±8.18) months, BMI was (28.26±3.13) kg·m-2 ranged from 21.39 to 34.46 kg·m-2. The degree of bone marrow edema was evaluated by knee whole oragan magnetic resonance imaging score (WORMS). The degree of knee osteoarthritis was evaluated by Kellgren- Lawrence(K-L) grade and Western Ontario and McMaster University Osteoarthritis Index (WOMAC). The degree of joint pain was evaluated by visual analogue scale(VAS) and WOMAC pain score, the joint signs were evaluated by tenderness, percussion pain, joint swelling and joint range of motion. To explore the relationship between bone marrow edema and knee osteoarthritis, the prevalence of bone marrow edema and K-L grade were compared between the two groups. Furthermore the WORMS score and WOMAC index, pain-related score, and sign-related score correlation coefficient were analyzed to further explore the relationship between bone marrow edema and knee osteoarthritis index, joint pain symptoms and signs.@*RESULTS@#There was 68.75% (55/80) of the patients in the case group were in K-L grade Ⅳ, and 52.5% (42/80) in the control group, indicating a higher proportion of patients with grade Ⅳ in the case group than the control group (χ2=4.425, P<0.05). In the case group, there was a strong correlation between bone marrow edema WORMS score and knee osteoarthritis WOMAC index. (r=0.873>0.8, P<0.001), a moderate correlation between WORMS score and VAS score and WOMAC pain score(r=0.752, 0.650>0.5, P<0.001), a moderate correlation between WORMS score and percussion pain score (r=0.784>0.5, P<0.001), and a weak correlation between WORMS score and VAS and tenderness score, joint swelling score and joint range of motion score (r=0.194, 0.259, 0.296<0.3, P<0.001).@*CONCLUSION@#Our study suggests that severe knee osteoarthritis is associated with an increased risk of bone marrow edema. Bone marrow edema can also lead to knee osteoarthritis joint pain, with percussion pain being a positive sign, but tenderness, joint swelling and limitation of activity are not significantly related to bone marrow edema.

Correlation between macrophage chemotaxis and disease severity in patients with knee osteoarthritis / 中国骨伤

OBJECTIVE@#To investigate the enhancement of macrophage chemotaxis in patients with knee osteoarthritis (KOA) and its correlation with the disease severity.@*METHODS@#Eighty patients with KOA admitted from July 2019 to June 2022 were enrolled as the observation group and divided into 29 cases of moderate group, 30 cases of severe group and 21 cases of extremely severe group. At the same time, 30 healthy subjects were included as the control group. The gene expressions of NF-κB, CXC chemokine receptor 7 (CXCR7) and CXC chemokine ligand 12 (CXCL12) in macrophages of each group were analyzed. Visual analogue scale(VAS) was used to evaluate the degree of joint pain. Joint function was evaluated by knee Joint Society Scoring system(KSS). Finally, data analysis was carried out.@*RESULTS@#The expression levels of NF-κB, CXCR7 and CXCL12 in moderate group, severe group and extreme recombination group were higher than those in control group. The VAS, the expression of NF-κB, CXCR7 and CXCL12 in the severe group and the extreme recombination group were higher than those in the moderate group, whereas KSS was lower than that in the moderate group. The VAS, expression levels of NF-κB, CXCR7 and CXCL12 in the extremely severe group were higher than those in the severe group, and KSS was lower than that in the severe group (all P<0.01). The expression levels of NF-κB, CXCR7 and CXCL12 in macrophages were positively correlated with VAS score, but negatively correlated with KSS(all P<0.01). The expression levels of NF-κB, CXCR7 and CXCL12 in macrophages were positively correlated with the severity of disease. After excluding the influence of traditional factors (gender, age and disease duration), multiple linear regression analysis further showed that the expression levels of NF-κB, CXCR7 and CXCL12 were still positively correlated with the severity of disease(all P<0.01).@*CONCLUSION@#The chemotaxis of macrophages in patients with KOA increased with the aggravation of the disease, and was related to the degree of pain and function impairment.

Study on correlation between bone marrow edema and osteoporosis in patients with severe knee osteoarthritis / 中国骨伤

OBJECTIVE@#To explore relationship between bone marrow edema(BME) and osteoporosis in patients with severe knee osteoarthritis.@*METHODS@#Unmatched case-control study was conducted. Totally 160 patients with severe knee osteoarthritis who had undergone knee magnetic resonance imaging (MRI) and bone mineral density examination (BMD) from January 2020 to March 2021 were included. Eighty patients complicated with BME were included in BME group, and 80 patients without BME were selected as NBME group. In BME group, there were 12 males and 68 females, aged from 51 to 80 years old with an average of(66.58±8.10) years old;the courses of disease ranged from 5 to 40 months with an average of (15.61±9.25) months;body mass index(BMI) ranged from 21.81 to 34.70 with an average of (27.79±3.00) kg·m-2;25 patients classified to grade Ⅲ and 55 patients grade Ⅳ according to Kellgren- Lawrence(K-L). In NBME group, there were 15 males and 65 females, aged from 50 to 80 years old with an average of(67.82±8.05) years old;the course of disease ranged from 6 to 37 months with an average of(15.75±8.18) months;BMI ranged from 21.39 to 34.46 with an average of (28.26±3.13) kg·m-2;25 patients were K-L Ⅲ and 55 patients with K-L Ⅳ. The degree of bone marrow edema was evaluated by knee whole oragan magnetic resonance imaging score(WORMS). Osteoporosis was diagnosed and BMD was evaluated by DXA T value. To explore the relationship between bone marrow edema and osteoporosis by comparing prevalence rate of osteoporosis between two groups, and to further explore relationship between BME and BMD by Spearman correlation analysis of BME WORMS score and DXA T value in BME group.@*RESULTS@#The complete case data were obtained on the first diagnosis, and there was no significant difference in sex, age, courses of disease and BMI between two groups (P>0.05). The proportion of K-L Ⅳ in BME group was significantly higher than that in NBME (P<0.05). The prevalence rate of osteoporosis in BME group was significantly higher than in NBME group with the same K-L grade (P<0.001), and there was a strong negative correlation between BME WORMS score and DXA BMD T value (r=-0.812, |r|=0.812 >0.8, P<0.001).@*CONCLUSION@#Osteoporosis is one of the risk factors of bone marrow edema in patients with severe knee osteoarthritis, and the lower the bone mineral density is, the easier it is to be complicated with bone marrow edema.

Correlation analysis between imaging classification of varus knee osteoarthritis and axis angle of tibiofemoral and patellofemoral joints / 中国骨伤

OBJECTIVE@#To explore correlation between imaging classification of knee osteoarthritis (KOA) and axis angle of tibiofemoral and patellofemoral joints.@*METHODS@#A retrospective analysis of 739 middle-aged and elderly patients with KOA (1 026 knee joints) who underwent vertical X-ray examination of both lower limbs and lateral knee joints from September 2018 to December 2020. Among them, 63 patients with K-L 0 grade (95 knee joints), 100 patients with K-L 1 grade (130 knee joints), 161 patients with K-L 2 grade (226 knee joints), 187 patients with K-L 3 grade (256 knee joints), and 228 patients of K-L 4 grade (319 knee joints). According to relative position of knee joint center and line between hip joint center and ankle joint center, the affected knee was divided into varus group(844 knees joints) and valgus group (182 knees joints). According to Install-Salvati method, the affected knee was divided into three groups, such as high patella (patella height>1.2 mm, 347 knees joints), median patella (patella height ranged from 0.8 to 1.2 mm, 561 knees joints), and low patella (patella height<0.8 mm, 118 knees joints). Lower femur angle, upper tibia angle, femoral neck shaft angle, femoral tibial angle, joint gap angle, hip-knee-ankle angle, patella-femoral angle and patella height among different groups were observed and compared.@*RESULTS@#(1) In varus KOA group, there were statistical differnces in hip-knee-ankle angle, tibiofemoral angle, lower femoral angle, upper tibial angle, joint space angle, and femoral neck shaft angle of patients with different K-L grades (P<0.05). Hip-knee-ankle angle, tibiofemoral angle, lower femoral angle, upper tibial angle, joint space angle and K-L grade were significantly positively correlated at 0.01(P<0.05);femoral neck shaft angle and K-L grade showed negative correlation at 0.01(P<0.05). (2) In valgus KOA group, hip-knee-ankle angle, there were statistical differences in tibiofemoral angle, inferior femoral angle, superior tibial angle, joint space angle, and femoral neck shaft angle of patients with different K-L grades(P<0.05). Hip-knee-ankle angle, tibiofemoral angle, lower femoral angle, upper tibial angle, and femoral neck shaft angle showed negative correlation with K-L grades at level of 0.01 (P<0.05);joint gap angle and K-L grades showed significantly positive correlation at level of 0.01(P<0.05). (3) In high patella group, there were statistically differences in patellar height and patellar femoral angle of different K-L grades(P<0.05);there were no statistical difference in patella height and patellar femoral angle of different K-L grades in median patella group. There was no significant difference in patella heightin low patella group with different K-L grades(P>0.05), and there was statistical difference in patellofemoral angle(P<0.05). Patellar height and patella-femoral angle of high patella group were significantly positively correlated with K-L grades at the level of 0.01 (P<0.05);patella height and patella-femoral angle were not correlated with K-L grades in median patella group(P>0.05). There was no correlation between height of patella and K-L grade in low patella group (P>0.05). There was significant negative correlation between patella-femoral angle and K-L grade at level of 0.05 (P<0.05).@*CONCLUSION@#Inferior femoral angle, tibiofemoral angle, joint gap angle, hip-knee-ankle angle, femoral neck shaft angle and high patella are related to K-L classification of varus KOA, which could be used for early diagnosis and provide objective data for efficacy analysis of conservative treatment.

Effect of meridian sinew releasing technique on moxibustion sensation of heat-sensitive moxibustion in patients with knee osteoarthritis / 中国针灸

OBJECTIVE@#To observe the effect of meridian sinew releasing technique on moxibustion sensation of heat-sensitive moxibustion in patients with knee osteoarthritis (KOA).@*METHODS@#A total of 60 patients with KOA were randomly divided into an observation group and a control group, 30 cases each group. In the observation group, on the basis of the meridian sinew releasing technique, moxibustion sensation exploration method was applied at Dubi (ST 35) area on the affected side. In the control group, moxibustion sensation exploration method was applied at Dubi (ST 35) area on the affected side. The meridian sinew releasing technique was performed for 20 min each time, the moxibustion sensation exploration method was performed for 60 min each time, once a day for 3 days. The excitation rate, latency, duration time and intensity value of moxibustion sensation of heat-sensitive moxibustion were recorded on the 1st, 2nd and 3rd days of exploration in the two groups.@*RESULTS@#The excitation rate on the 3rd day of exploration and total excitation rate in the observation group were higher than the control group (P<0.05). On the 1st, 2nd and 3rd days of exploration, the latency of moxibustion sensation of heat-sensitive moxibustion in the observation group was shorter than the control group (P<0.05), the duration time was longer than the control group (P<0.05), and the intensity value was higher than the control group (P<0.05).@*CONCLUSION@#Meridian sinew releasing technique could improve the excitation rate of moxibustion sensation of heat-sensitive moxibustion in patients with KOA, shorten the latency, prolong the duration time, and improve the intensity value.

Effect of needle-knife on chondrocyte apoptosis of knee joint in rabbits with knee osteoarthritis based on CircSERPINE2-miR-1271-5P-ERG axis / 中国针灸

OBJECTIVE@#To observe the effect of needle-knife on the chondrocyte apoptosis of knee joint in rabbits with knee osteoarthritis (KOA) based on the CircSERPINE2-miR-1271-5P-E26 specific transformation-related gene (ERG) axis, and to explore the mechanism of needle-knife for KOA.@*METHODS@#Thirty-six New Zealand white rabbits were randomly divided into a normal group, a model group, a needle-knife group and a sham needle-knife group, 9 rabbits in each group. The rabbits in the model group, the needle-knife group and the sham needle-knife group were treated with modified Videman method to prepare KOA model. After successful modeling, the rabbits in the needle-knife group were treated with needle-knife at cord adhesion and nodules near quadriceps femoris tendon and internal and external collateral ligament on the affected knee joint; the rabbits in the sham needle-knife group were treated with sham needle-knife baside the needle insertion point of the needle-knife group (needle-knife was only inserted, without any operation). The treatment was given once a week, 3 times in total. The Lequesne MG behavioral score was used to evaluate the knee joint damage in each group before and after intervention. After intervention, HE staining and transmission electron microscopy were used to observe the cartilage tissue morphology and ultrastructure of chondrocytes in the knee joint in each group; TUNEL method was used to detect the level of chondrocyte apoptosis in the knee joint; real-time fluorescence quantitative PCR was used to detect the expression of CircSERPINE2, miR-1271-5P and ERG mRNA in knee cartilage tissue in each group.@*RESULTS@#After intervention, compared with the normal group, the Lequesne MG behavioral score in the model group was increased (P<0.01). Compared with the model group and the sham needle-knife group, the Lequesne MG behavioral score in the needle-knife group was decreased (P<0.01). In the model group and the sham needle-knife group, the number of chondrocytes and organelles was decreased, the cell nucleus was shrunk, mitochondria was swelling or disappeared; in the needle-knife group, the number of chondrocytes and organelles was increased, the cell nucleus was not obviously shrunk and the mitochondria was not obviously swelling. Compared with the normal group, the level of chondrocyte apoptosis in the model group was increased (P<0.01); compared with the model group and the sham needle-knife group, the level of chondrocyte apoptosis in the needle-knife group was decreased (P<0.01, P<0.05). Compared with the normal group, the expression of CircSERPINE2 and ERG mRNA in the model group was decreased (P<0.01), and the expression of miR-1271-5P mRNA was increased (P<0.01); compared with the model group and the sham needle-knife group, the expression of CircSERPINE2 and ERG mRNA in the needle-knife group was increased (P<0.01), and the expression of miR-1271-5P mRNA was decreased (P<0.01).@*CONCLUSION@#Needle-knife could reduce the knee joint damage and chondrocyte apoptosis in KOA rabbits, which may be related to up-regulating the expression of CircSERPINE2 and ERG mRNA, and inhibiting the expression of miR-1271-5P mRNA.

Protective Effect of Shentong Zhuyutang-containing Serum on Chondrocytes in Rats with Knee Osteoarthritis Based on AMPK/Sirt1 Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo investigate the protective effect of Shentong Zhuyutang-containing serum against oxidative stress and apoptosis in chondrocytes of rats with knee osteoarthritis （KOA）. MethodFifty male rats were orally administered with normal saline， low-， medium-， and high-dose Shentong Zhuyutang （1.73， 3.46， 6.92 g·kg-1）， and glucosamine sulfate （0.3 g·kg-1） for two weeks. Serum samples were collected after the treatment period. The KOA model was established， and chondrocytes were isolated and randomly divided into normal group， model group， low-， medium-， and high-dose Shentong Zhuyutang-containing serum groups， and glucosamine sulfate group. During the chondrocyte culture， adenosine monophosphate （AMP）-activated protein kinase （AMPK） inhibitor Compound C （10 μmol·L-1） was added， and the cells were divided into normal group， model group， Shentong Zhuyutang-containing serum group， and Compound C + Shentong Zhuyutang-containing serum group. Cell proliferation was detected using 5-ethynyl-2'-deoxyuridine （EdU） staining. Apoptosis was determined using terminal deoxynucleotidyl transferase dUTP nick end labeling （TUNEL）. Reactive oxygen species （ROS） levels were measured using DCFH-DA probe. Glutathione （GSH） and malondialdehyde （MDA） levels were determined using the colorimetric method. Real-time polymerase chain reaction （PCR） was used to measure the mRNA expression levels of matrix metalloproteinase-3 （MMP-3）， MMP-13， type Ⅱ collagen （Col Ⅱ）， and Aggrecan. Western blot was performed to measure the protein expression of phosphorylated （p）-AMPK and silent information regulator factor 1 （Sirt1）. ResultCompared with the normal group， the model group showed a significant decrease in chondrocyte proliferation rate， GSH activity， Col Ⅱ and Aggrecan mRNA expression， p-AMPK and Sirt1 protein levels （P<0.01）， and increased ROS levels， MDA content， TUNEL-positive cell rate， and MMP-3 and MMP-13 mRNA expression （P<0.01）. Compared with the model group， Shentong Zhuyutang-containing serum increased the number of EdU-positive cells， GSH activity， Col Ⅱ and Aggrecan mRNA expression， p-AMPK and Sirt1 protein levels in KOA rat chondrocytes （P<0.05， P<0.01）， and decreased the TUNEL-positive cell rate， ROS levels， MDA content， MMP-3 and MMP-13 mRNA expression （P<0.05， P<0.01）. Compared with the Shentong Zhuyutang-containing serum group， the Compound C + Shentong Zhuyutang-containing serum group showed significantly reduced p-AMPK and Sirt1 protein expression， GSH activity， Col Ⅱ and Aggrecan mRNA levels （P<0.01）， and increased TUNEL-positive cell rate， ROS levels， MDA content， MMP-3 and MMP-13 mRNA levels （P<0.01）. ConclusionShentong Zhuyutang-containing serum attenuates oxidative damage and reduces apoptosis in chondrocytes of rats with KOA， and its protective effect may be associated with the activation of the AMPK/Sirt1 signaling pathway.

Clinical observation of Jipei dilong ointment combined with diacerein in the treatment of knee osteoarthritis in the early and mid-term stage / 中国药房

OBJECTIVE To investigate clinical efficacy and safety of Jipei dilong ointment combined with diacerein in the treatment of knee osteoarthritis （KOA） in the early and mid-term stage. METHODS Totally 100 KOA patients were randomly divided into control group and trial group， with 50 cases in each group. Control group received Diacerein capsules orally， 50 mg every time， bid. Trial group additionally received Jipei dilong ointment， once a day， on the basis of control group. Both groups had a treatment course of 4 weeks， and were followed up for 3 months after treatment. The clinical efficacy of 2 groups， visual analogue scale （VAS）， Western Ontario and McMaster University osteoarthritis index （WOMAC） score， Lysholm scores before and after treatment， at 3-month follow-up after treatment were all observed； the levels of tumor necrosis factor-α （TNF-α）， interleukin 1β （IL-1β）， IL-6， superoxide dismutase （SOD）， malondialdehyde （MDA）， nitric oxide （NO）， cartilage oligomeric matrix protein （COMP）， matrix metalloproteinase-13 （MMP-13） and C-telopeptide of type Ⅱ collagen （CTX-Ⅱ） were detected in knee joint fluid. The incidence of adverse drug reactions was recorded. RESULTS After 4 weeks of treatment， total effective rate was 96.0% in trial group and 90.0% in control group， without statistical significance between 2 groups （P＞0.05）. At 3- 2019YFC1712500） month follow-up after treatment， total effective rate of trial group was 94.0%， and was higher than 62.0% of control group（P＜0.05）. After 4 weeks of treatment and at 3-month follow-up after treatment， VAS score， WOMAC score，the contents ofTNF-α， IL-1β， IL-6， MDA， NO， COMP， MMP-13 and CTX-Ⅱ in knee joint fluid of two groups were significantly lower than before； Lysholm score and SOD activity of knee joint fluid were significantly higher than before， and the trial group was significantly better than the control group during the same period （P＜0.05）. And there was no statistical significance in the incidence of adverse drug reactions between two groups（P＞0.05）. CONCLUSION For the treatment of KOA in early and mid- term stage， Jipei dilong ointment combined with diacerein relieve pain， improve knee function by inhibiting inflammatory reaction， reducing oxidative stress and inhibiting chondrocyte and matrix degradation， and have low incidence of adverse drug reactions.