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.

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.

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.

Chinese Medicine Regulates Knee Osteoarthritis-related Signaling Pathways： A Review / 中国实验方剂学杂志

As the research of traditional Chinese medicine （TCM） on knee osteoarthritis （KOA） is progressing， researchers have discovered that a variety of Chinese medicines can delay the progress of KOA by regulating signaling pathways at the molecular level. The Chinese medicines and their active ingredients mentioned in this article are associated with the signaling pathways in KOA. They can regulate the levels of targeted molecules via different signaling pathways to inhibit cartilage inflammatory cytokine， apoptosis， and cartilage matrix degradation and promote chondrocyte autophagy， so as to reduce the synovial inflammatory edema and delay cartilage degeneration. This paper systematically reviews the studies about the TCM intervention of KOA. Baicalein can reduce the inflammatory cytokines and apoptosis and promote the autophagy of chondrocytes by blocking the phosphatidylinositol-3 kinase/protein kinase （PI3K/Akt） signaling pathway. Cornuside I can decrease the phosphorylation activity of Janus kinase 2/signal transducer and activator of transcription 3 （JAK2/STAT3） pathway to reduce synovial inflammation and delay cartilage matrix degeneration. Salvianolic acid A can reduce inflammation and cartilage matrix degradation by inhibiting the phosphorylation of the nuclear factor-κB （NF-κB） pathway. Emodin can reduce the activity of Wnt/β-catenin pathway to inhibit the decomposition of collagen and proteoglycan. Myristicoside can inhibit apoptosis by blocking the p38 mitogen-activated protein kinase （p38 MAPK） signaling pathway. Akebia saponin D can enhance the activity of nuclear factor E2-related factor 2/heme oxygenase 1（Nrf2/HO-1） pathway to inhibit oxidative stress in chondrocytes. The saponins in Achyranthis Bidentatae Radix reduce cartilage matrix degradation by enhancing the transforming growth factor-β （TGF-β）/Smad signaling pathway. Crocin inhibits the cartilage inflammation and apoptosis factor increase by stimulating the activity of hippo-Yes-associated protein （Hippo-YAP）. Ligustrazine blocks the Notch pathway to improve the morphology and abnormality of chondrocytes. Oleanolic acid reduces the destruction and degeneration of cartilage matrix via the estrogen signaling pathway. The above summary aims to provide references for future clinical and experimental research on KOA.

Chinese Medicine Intervention on Deep Vein Thrombosis-related Signaling Pathways After Total Knee Arthroplasty： A Review / 中国实验方剂学杂志

Total knee arthroplasty， as a common treatment option for advanced knee osteoarthritis， can alleviate the clinical symptoms of patients. Deep vein thrombosis of the lower extremity is the most common complication of total knee arthroplasty. Previous studies have shown that the occurrence of deep vein thrombosis after total knee arthroplasty is mostly related to the overexpression of inflammatory factors in vivo. Nuclear transcription factor-κB， Toll-like receptor 4， phosphatidylinositol 3-kinase/protein kinase B， tumor necrosis factor， and nuclear transcription factor E2-related factor 2 are typical signaling pathways related to inflammation. Regulating the expression of the signaling pathways can intervene the formation of inflammatory factors. Inhibiting the formation of inflammatory factors can help suppress the activation of platelets， thereby blocking thrombosis. According to previous research， Chinese medicine monomers， Chinese medicine extract， and compound Chinese medicine prescriptions all directly or indirectly inhibit the expression of inflammatory factors by regulating the above signaling pathways， thereby suppressing the occurrence of deep vein thrombosis after total knee arthroplasty. Therefore， Chinese medicine can reduce postoperative complications and promote postoperative recovery of patients at low cost with small side effects. This article summarizes the research on Chinese medicine intervention on deep vein thrombosis-related signaling pathways after total knee arthroplasty， which is expected to lay a basis for the in-depth study and clinical application of Chinese medicine in deep vein thrombosis.

Kinematics and Plantar Pressure Analysis of Varus Femur and Varus Tibia / 医用生物力学

Objective To compare the differences in kinematic parameters and plantar pressures for two types of knee varus with tibial and femoral origins in gait analysis, so as to provide biomechanical theoretical basis for different types of genu varus. Methods Twenty-six patients with unilateral knee osteoarthritis (KOA) varus genu were enrolled, with 13 from femoral and 13 from tibial sources. Using Noraxon MyoMotion three-dimensional (3D) motion capture system and Footscan plantar pressure test system, the gait of the subjects during natural walking was measured, the temporal and spatial parameters of the gait, the kinematics parameters of lower limb joints and plantar pressures were collected, to make comparative analysis between the two groups. Results The range of knee flexion and extension of tibial varus, the peak of hip abduction, the range of motion (ROM) of hip adduction and abduction and the peak of ankle pronation were larger than those of femoral lateral genu varus. The peak of knee flexion and hip adduction was smaller than that of femoral lateral genu varus. Compared with femoral varus, subjects with tibial varus had increased stress time and peak pressure on the plantar of the 4th and 5th metatarsals (P<0.05). In the 3rd metatarsal region, the impulse of healthy femoral limb was greater than that of healthy limb with tibial deformity. While in the medial calcaneal region, the impulse of healthy femoral limb was smaller (P<0.05). Conclusions There are some differences in kinematic parameters and plantar pressures between two different types of unilateral genu varus patients. The results of this study are helpful to understand the abnormal gait caused by genu varus, and provide reliable reference for postoperative rehabilitation and limb exercise for different types of genu varus.

Plantar Pressure Analysis after Medial Opening Wedge High Tibial Osteotomy Treatment of Medial Single Compartmental Knee Osteoarthritis / 医用生物力学

Objective To analyze the plantar pressure distribution of knee osteoarthritis ( KOA) patients after medial opening wedge high tibial osteotomy ( MOWHTO), so as to provide biomechanical references for the surgical treatment and rehabilitation of patients. Methods A total of 31 patients with medial single compartmental KOA after unilateral MOWHTO treatment were selected as the experimental group, and 35 healthy subjects at same age were selected as the control group. The Pedomedic 40 􀅺 pressure measuring system was used to test dynamic plantar pressure. By comparing the maximum pressure ( pmax ), force-time integral ( FTI) and contact area (CA) of different plantar zones between the experimental group (operative side and unoperated side) and the control group during walking, the changes of plantar pressure in patients with medial single compartmental KOA after MOWHTO were evaluated. Results Compared with the unoperated side and the control group, the CA and FTI of the 1st metatarsal head (MH1) were higher (P<0. 05), the CA of the 4th metatarsal head (MH4)was smaller (P<0. 001), the pmax and FTI of the 5th metatarsal head (MH5) were smaller (P<0. 05), the CA of the lateral middle foot (MF-L) was smaller (P<0. 001), and the CA of the medial rear foot (RF-M) was larger (P<0. 05). Compared with the control group, the pmax of MH1 and MH2 was smaller (P<0. 05), the CA and FTI of MH5 were larger (P<0. 05), the pmax of MF-L was larger (P<0. 001), and the FTI of lateral rear foot (RF-L) was larger (P<0. 05). Conclusions Compared with healthy people, patients with medial single compartmental KOA have abnormal plantar pressure residual after MOWHTO. In clinical practice, targeted intensive rehabilitation therapy is necessary to restore the normal plantar distributions of patients.

Study on improvement effect mechanism of Xibining prescription on knee osteoarthritis model rats based on AMPK/mTOR signaling pathway / 中国药房

OBJECTIVE To investigate the improvement effect mechanism of Xibining prescription （XBN） on knee osteoarthritis （KOA） model rats based on AMP-activated protein kinase（AMPK）/mammalian target of rapamycin （mTOR） signaling pathway. METHODS Totally 36 rats were randomly divided into blank group， model group， XBN group （12.56 g/kg）， XBN+metformin （AMPK agonist） group （12.56 g/kg XBN+100 mg/kg metformin）， with 9 rats in each group. Except for blank group， KOA model was induced by anterior cruciate ligament transection in other groups. After modeling， each group was given relevant medicine/normal saline， XBN and normal saline intragastrically， once a day， and metformin intraperitoneally， every other day， for 4 consecutive weeks. The pathomorphological changes of cartilage tissue in rats were observed and Mankin scoring was conducted. The expression level of Aggrecan in rat cartilage， mRNA and protein expressions of platelet reactive protein disintegrin and metalloproteinase with thrombospondin motifs 4 （ADAMTS-4）， ADAMTS-5， matrix metalloproteinase 3 （MMP-3） and MMP- 13， and the phosphorylation level of AMPK and mTOR proteins were detected. RESULTS Compared with blank group， the structure of cartilage tissue in the model group was disordered， the matrix of cartilage layer was lightly stained，the tide line was distorted or interrupted， and Mankin score was significantly increased （P＜0.05）. The protein expression of Aggrecan in cartilage tissue and the phosphorylation level of AMPK protein were all decreased significantly （P＜0.05）； mRNA and protein expressions of ADAMTS-4， ADAMTS-5， MMP-3 and MMP-13 and the phosphorylation levels of mTOR protein were significantly increased in cartilage tissues （P＜0.05）. Compared with model group， the pathological morphology of cartilage was improved significantly in each administration group， and above score or indexes were reversed significantly （P＜0.05）. Compared with XBN group， the degree of cartilage lesions in rats was further alleviated in XBN+ metformin group， and the levels of above score or indicators were further improved （P＜0.05）. CONCLUSIONS XBN can ameliorate cartilage injury in KOA model rats， promote cartilage synthesis and reduce cartilage degradation， the mechanism of which may be associated with activating AMPK/mTOR signaling pathway.

Professor GUAN Ling's clinical experience in treating knee osteoarthritis with structure-based medical acupuncture / 中国针灸

This paper summarizes professor GUAN Ling's clinical experience in the treatment of knee osteoarthritis (KOA) with structure-based medical acupuncture (SMA). Based on anatomy and biomechanics and through accurate physical examination, SMA adjusts the mechanical imbalance of muscles to relieve KOA dysfunction, and releases nerve compression to attenuate pain symptoms of KOA. In reference to traditional acupoint selection, and in association with painful areas and mechanical deduction, ashi points located at the rectus femoris, vastus intermedius, vastus medialis and vastus lateralis muscles, etc. are specially stimulated with acupuncture; and the rehabilitation training and health education are the adjuvant treatment for the patients.

Exploration on acupuncture treatment ideas for knee osteoarthritis from the perspective of Dongyuan needling technology / 中国针灸

The treatment ideas with acupuncture for knee osteoarthritis (KOA) are explored on the base of Dongyuan needling technology. Regarding the rules of acupoint selection, Zusanli (ST 36) is predominant, the back-shu points are used for the disorders related to the invasion of exogenous factors, and the front-mu points are for the cases caused by internal injury. Besides, the xing-spring points and shu-stream points are preferred. In treatment of KOA, besides the local points, the front-mu points, i.e. Zhongwan (CV 12), Tianshu (ST 25) and Guanyuan (CV 4), are selected specially to tonifying the spleen and stomach. The earth points and acupoints on the earth meridians (i.e. Yinlingquan [SP 9], Xuehai [SP 10], Liangqiu [ST 34], Dubi [ST 35], Zusanli [ST 36] and Yanglingquan [GB 34]) are optional to coordinate yin and yang, essence and qi , and regulate the qi movement of spleen and stomach. The shu-stream points of liver, spleen and kidney meridians (Taichong [LR 3], Taibai [SP 3] and Taixi [KI 3]) are chosen to promote meridian circulation and regulate zangfu functions.

Aconite-isolated moxibustion at Yongquan (KI 1) combined with rivaroxaban for lower extremity venous thrombosis after total knee arthroplasty: a randomized controlled trial / 中国针灸

OBJECTIVE@#To investigate the clinical effect of aconite-isolated moxibustion at Yongquan (KI 1) combined with rivaroxaban for lower extremity venous thrombosis after total knee arthroplasty and the influence on hypercoagulation.@*METHODS@#Seventy-three patients of knee osteoarthritis with lower extremity venous thrombosis after total knee arthroplasty (KOA) were randomly divided into an observation group (37 cases, 2 cases dropped off) and a control group (36 cases, 1 case dropped off). The patients in the control group took orally rivaroxaban tablets, 10 mg a time, once a day. On the basis of the treatment as the control group, the aconite-isolated moxibustion was applied to Yongquan (KI 1) for the patients of the observation group, once daily and 3 moxa cones were used in each treatment. The duration of treatment was 14 days in both groups. Before treatment and 14 days into treatment, the ultrasonic B test was adopted to determine the conditions of lower extremity venous thrombosis in the two groups. Before treatment, 7 and 14 days into treatment, the coagulation indexes (platelet [PLT], prothrombin time [PT], activated partial prothrombin time [APTT], fibrinogen [Fib] and D-dimer[D-D]), the blood flow velocity of the deep femoral vein and the circumference of the affected side were compared between the two groups separately, and the clinical effect was evaluated.@*RESULTS@#Fourteen days into treatment, the venous thrombosis of the lower extremity was relieved in both groups (P<0.05), and that of the observation group was better than the control group (P<0.05). Seven days into treatment, the blood flow velocity of the deep femoral vein was increased compared with that before treatment in the observation group (P<0.05), and the blood flow rate in the observation group was higher than that in the control group (P<0.05). Fourteen days into treatment, PT, APTT and the blood flow velocity of the deep femoral vein were increased in the two groups compared with those before treatment (P<0.05); and PLT, Fib, D-D and the circumference of the limb (knee joint, 10 cm above the patella and 10 cm below the patella) were all reduced in the two groups (P<0.05). Compared with the control group 14 days into treatment, the blood flow velocity of the deep femoral vein was higher (P<0.05), PLT, Fib, D-D and the circumference of the limb (knee joint, 10 cm above the patella and 10 cm below the patella) were all lower in the observation group (P<0.05). The total effective rate was 97.1% (34/35) in the observation group, higher than 85.7% (30/35) in the control group (P<0.05).@*CONCLUSION@#Aconite-isolated moxibustion at Yongquan (KI 1) combined with rivaroxaban can effectively treat lower extremity venous thrombosis after total knee arthroplasty, relieve hypercoagulation, accelerate the blood flow velocity and alleviate swelling of the lower extremity in the patients with knee osteoarthritis.

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.

The curative effect and mechanism of magnetic hyperthermia in the treatment of knee osteoarthritis / 西安交通大学学报(医学版)

【Objective】 We combined the concept of traditional medicine with magnetic induction technology, originally brought up the research concept of magnetic hyperthermia to cure KOA, explored the mechanism and constructed a new treatment of KOA with modern medical features. 【Methods】 Through establishing a primary KOA model in rats and constructing ferrimagnetic vortex domain iron oxide nanorings (FVIOs) as a platform for highly efficient magnetic hyperthermia agent, the lesions of KOA were heated accurately under the low-intensity magnetic field. We confirmed the curative effect through the results of pain perception, histopathology, knee joint morphology and microscopic bone structure and the content of serum inflammatory factor, to study the therapeutic mechanism of magnetic hyperthermia for KOA. 【Results】 Compared with the model group, the recovery of mechanical pain threshold after magnetic hyperthermia improved by approximately 48.9%; the degree of hyperemia and edema of joint capsule and synovial tissue and the wear degree of joint cartilage surface, were significantly reduced; the Mankin and OARSI scores decreased by about 33% and 20%, respectively; the MicroCT results indicated that the degree of hardening of the subchondral bone also improved; the expression of inflammatory factors in the serum was reduced. 【Conclusion】 In this study, we utilized the FVIOs as a high-efficiency magnetic hyperthermia platform for the treatment of KOA. The efficacy of magnetic hyperthermia on KOA is clarified, and the mechanism is related to the inhibition of inflammatory factors.

Mechanism and experimental verification of jiawei duhuo jisheng mixture in treatment of knee osteoarthritis based on network pharmacology / 中国药理学通报

Aim To explore and verify the possible mechanism of Jiawei Duhuo Jisheng Mixture(JDJM)in the treatment on Knee Osteoarthritis(KOA)via using network pharmacology and animal experiment. Methods The ingredients of JDJM and relevant targets were collected from TCMSP and BATMAN-TCM database. The KOA-related targets were collected from GeneCard, OMIM and GEO databases. The common targets were acquired by intersecting ingredients-related and KOA-related targets, and then the Ingredient-Disease-Target Network and PPI network were constructed by Cytoscape 3.7.2 software and STRING platform. GO and KEGG enrichment analysis were performed based on Metascape database. Finally, the key targets and relevant mechanism were validated via animal experiment. Results In the network pharmacology study, 180 active ingredients related to treatment on KOA by JDJM were collected, and 152 common targets were confirmed. PPI network analysis showed that AKT1 might be the key targets of JDJM in the treatment on KOA. GO and KEGG enrichment analysis revealed that the key target mainly concentrated on inflammatory response and apoptosis. Animal experiment confirmed that JDJM could improve lesion in KOA rabbits, and suppress the expression levels of IL-1β, TNF-α, Caspase 3 and BAX in serum and articular fluid. AKT1 expression(including mRNA and protein)in articular cartilage was also down-regulated. Conclusions Based on the results of network pharmacology and animal experiment, JDJM may relieve KOA severity by anti-inflammatory and anti-apoptotic effects through a variety of molecular signaling pathways.

Real-world Study of Medication Characteristics and Clinical Efficacy of Tenghuang Jiangu Tablets in Treatment of Knee Osteoarthritis in Remission Stage / 中国实验方剂学杂志

ObjectiveTo explore the medication characteristics and clinical efficacy of the Tenghuang Jiangu tablets in the treatment of knee osteoarthritis （KOA） in the remission stage in the real world，providing references for rational clinical use of this prescription. MethodBased on the "registration system of KOA treated with Tenghuang Jiangu tablets"，2 439 KOA cases in the remission stage were analyzed by SPSS 25.0，IBM SPSS Modeler18.0，and Apriori algorithm. To be specific，the age，body mass index （BMI），and course of treatment were described in the form of x̄±s. The information on gender，K-L grade，daily dose，and frequency of drug use was described by frequency analysis. The number of cases，course of treatment，daily dose，and drug use frequency of the single-use group and the combined-use group were described by frequency analysis，and the combination of drugs was described by frequency analysis and Apriori algorithm. Mann-Whitney U test was employed to compare the scores of Visual Analogue Scale （VAS），Western Ontario and McMaster Universities Osteoarthritis Index （WOMAC），pain，stiffness，and joint function between the single-use group and the combined-use group. ResultThe results of clinical treatment showed that 2 439 patients with KOA in the remission stage were treated with Tenghuang Jiangu tablets，with 1 432 （58.71%） in the single-use group and 1 007 （41.29%） in the combined-use group. The average daily dose of Tenghuang Jiangu tablets was （3.90±1.44） g，and the majority of the patients were at grade Ⅱ （54.47%）. The daily average daily dose of Tenghuang Jiangu tablets in the single-use group was （3.64±1.35） g，which was lower than that in the combined-use group ［（4.26±1.48） g，P<0.05］. In the combined use，the top three western medicines were glucosamine （270 times，14.68%），sodium hyaluronate （126 times，6.85%），and imrecoxib （116 times，6.31%），and the top three Chinese medicines were Huoxuezhitong capsules/tablets/ointments （31 times，1.69%），Biqi capsules （25 times，1.36%），and Maizhiling （23 times，1.25%）. As for the overall clinical efficacy，the VAS score was （5.13±0.93） score before treatment and （2.22±1.18） score after treatment （P<0.05），with an overall average decrease of （2.91±1.14） score， and the average decrease in the single-use group was （2.76±1.43） score， which was lower than that in the combined-use group ［（3.12±1.36） score，（P<0.01）］. The WOMAC score was （31.05±11.84） score before treatment and （13.55±9.91） score after treatment （P<0.05）. The overall average decrease was （17.50±11.79） score， and the average decrease in the single-use group and combined-use group was （16.39±11.14） score and （19.08±12.50） score，respectively （P<0.01）. The patients with KOA>grade Ⅱ accounted for 91.34%（1 308/1 432） and 93.55%（942/1 007） in the single-use group and combined-use group，respectively （χ2=80.026，P<0.05）. A total of 43.37%（621/1 432） of the patients in the single-use group had other complications，lower than that in the combined-use group ［54.92%（553/1 432），（χ2=20.087，P<0.01）］. ConclusionMore than half of the patients with KOA in the remission stage are treated with Tenghuang Jiangu tablets alone，and the combination therapy is mainly applied in patients with severe conditions or other complications. In relieving knee joint pain and improving joint stiffness and joint function，both the Tenghuang Jiangu tablets alone and the combination therapy are effective.