ABSTRACT
La artrosis de rodilla grado 1 es un problema frecuente a escala mundial. La fisioterapia se presenta como una alternativa prometedora para el tratamiento conservador de esta patología, ya que reduce eficazmente la artralgia. Objetivo. Describir la eficacia de los ejercicios terapéuticos para aliviar el dolor en la artrosis de rodilla grado I. Metodología. Se trata de una revisión sistemática, que abarcó una búsqueda exhaustiva en varias bases de datos como Pubmed, Scielo y Elsevier. Los criterios de búsqueda incluyeron ensayos de control aleatorios, experimentales y cuasiexperimentales realizados entre los años 2017 y 2023. Resultados. De un total de 82 documentos se excluyeron 40 al ser estudios secundarios. Posteriormente, se excluyeron 21 estudios adicionales debido a la escasa relación entre las variables del estudio y a su falta de disponibilidad. Finalmente, se seleccionaron 21 artículos que cumplieron con los criterios de evaluación de calidad metodológica mediante la escala CRF-QS. Para evaluar el dolor, la rigidez, la funcionalidad y la calidad de vida, se utilizaron escalas como EVA, NPRS, WOMAC y OXFORD. Los ejercicios isocinéticos resultaron ser los más efectivos, ya que demostraron un aumento de la fuerza y el grosor del cartílago articular, lo que resultó en una disminución de las puntuaciones de EVA de 8,05 a 3,75. Conclusión. El ejercicio terapéutico supervisado centrado en el fortalecimiento de las extremidades inferiores ha demostrado ser una alternativa efectiva para el tratamiento conservador de la artrosis de rodilla grado I. Este enfoque alivia eficazmente el dolor, mejora la calidad de vida e incluso puede detener la progresión de la enfermedad.
Grade 1 knee osteoarthritis is a common problem worldwide. Physiotherapy is presented as a promising alternative for the conservative treatment of this pathology, since it effectively reduces arthralgia. Aim. To describe the effectiveness of therapeutic exercises to relieve pain in grade I knee osteoarthritis. Methodology. This is a systematic review, which included an exhaustive search in several databases such as Pubmed, Scielo and Elsevier. Search criteria included randomized, experimental and quasi-experimental control trials conducted between the years 2017 and 2023. Results. Of a total of 82 documents, 40 were excluded as they were secondary studies. Subsequently, 21 additional studies were excluded due to poor relationships between study variables and lack of availability. Finally, 21 articles were selected that met the methodological quality evaluation criteria using the CRF-QS scale. To evaluate pain, stiffness, functionality and quality of life, scales such as VAS, NPRS, WOMAC and OXFORD were used. Isokinetic exercises were found to be the most effective, demonstrating an increase in articular cartilage strength and thickness, resulting in a decrease in VAS scores from 8.05 to 3.75. Conclusion. Supervised therapeutic exercise focused on strengthening the lower extremities has been shown to be an effective alternative to the conservative treatment of grade I knee osteoarthritis. This approach effectively relieves pain, improves quality of life, and may even stop the progression of osteoarthritis. disease.
A osteoartrite do joelho grau 1 é um problema comum em todo o mundo. A fisioterapia apresenta-se como uma alternativa promissora para o tratamento conservador desta patologia, uma vez que reduz eficazmente a artralgia. Mirar. Descrever a eficácia dos exercícios terapêuticos no alívio da dor na osteoartrite de joelho grau I. Metodologia. Trata-se de uma revisão sistemática, que incluiu uma busca exaustiva em diversas bases de dados como Pubmed, Scielo e Elsevier. Os critérios de pesquisa incluíram ensaios de controle randomizados, experimentais e quase-experimentais realizados entre os anos de 2017 e 2023. Resultados. De um total de 82 documentos, 40 foram excluídos por se tratarem de estudos secundários. Posteriormente, 21 estudos adicionais foram excluídos devido às más relações entre as variáveis do estudo e à falta de disponibilidade. Por fim, foram selecionados 21 artigos que atenderam aos critérios de avaliação da qualidade metodológica pela escala CRF-QS. Para avaliar dor, rigidez, funcionalidade e qualidade de vida foram utilizadas escalas como VAS, NPRS, WOMAC e OXFORD. Os exercícios isocinéticos foram considerados os mais eficazes, demonstrando um aumento na força e espessura da cartilagem articular, resultando em uma diminuição nos escores VAS de 8,05 para 3,75. Conclusão. O exercício terapêutico supervisionado focado no fortalecimento das extremidades inferiores tem se mostrado uma alternativa eficaz ao tratamento conservador da osteoartrite do joelho grau I. Esta abordagem alivia eficazmente a dor, melhora a qualidade de vida e pode até interromper a progressão da osteoartrite.
Subject(s)
Osteoarthritis, KneeABSTRACT
Objective: the aim of this study was to evaluate the quality of life between patients who have already undergone the TKA surgery and those who have not. Methodology: 118 patients [60 undergoing TKA (G1) and the remaining 58 awaiting the procedure (G2)] answered questions about QoL using the WOMAC and SF-36 protocols. The comparison was performed using the chi-square test and Student's t-test, with a significance level of 0.05. Results: with regard to clinical aspects, there was a higher level of pain in Group G2, as well as greater frequency in the use of medications, especially for pain relief. In the QoL evaluation, significant difference was observed in all the domains of the generic questionnaire SF-36 and in WOMAC, estando a capacidade functional do G2 reduzida e abaixo do nível observado nos pacientes do G1. Conclusion: patients with advanced knee arthrosis who underwent TKA, compared to those who did not undergo the procedure, had better quality of life in all domains assessed by both the general SF-36 questionnaire and the WOMAC questionnaire.
Objetivo: o objetivo deste estudo foi avaliar a qualidade de vida entre pacientes que já se submeteram à cirurgia de ATJ e aqueles que ainda não passaram pelo procedimento. Metodologia: 118 pacientes [60 submetidos à ATJ (G1) e os 58 restantes aguardando o procedimento (G2)] responderam perguntas sobre QV usando os protocolos WOMAC e SF-36. A comparação foi realizada usando o teste qui-quadrado e o teste t de Student, com um nível de significância de 0,05. Resultados: em relação aos aspectos clínicos, houve um maior nível de dor no Grupo G2, bem como maior frequência no uso de medicamentos, especialmente para alívio da dor. Na avaliação da QV, foi observada diferença significativa em todos os domínios do questionário genérico SF-36 e no WOMAC, estando a capacidade funcional do G2 reduzida e abaixo do nível observado nos pacientes do G1. Conclusão: pacientes com artrose avançada de joelho que se submeteram à ATJ, em comparação com aqueles que não passaram pelo procedimento, apresentaram melhor qualidade de vida em todos os domínios avaliados tanto pelo questionário geral SF-36 quanto pelo questionário WOMAC.
Subject(s)
Humans , Male , FemaleABSTRACT
Objective:To observe and analyze the surface electromyography activity of quadriceps femoris of knee osteoar-thritis(KOA)patients. Method:The surface electromyography of vastus lateralis,rectus femoris,and vastus medialis were recorded and analyzed in 30 KOA patients and 30 normal people during isokinetic knee flexion or extension at veloci-ties of 60 °/s,90 °/s or 180 °/s.We also record clinical indicators(muscle thickness and degree of knee pain)of the KOA group and evaluate the correlation between electromyographic data and clinical indicators. Result:Compared with the healthy control group,the KOA group had significantly lower knee extensor mo-ment during isokinetic knee flexion or extension at velocities of 60°/s(P＜0.001),90°/s(P＜0.01),or 180°/s(P＜0.01).Statistics showed that there were significant differences in the median frequency difference rate of vastus lateralis(P＜0.05)and root mean square value of rectus femoris(P＜0.01)between the healthy control group and the KOA group under 60°/s angular velocities.There was a significant difference in the root mean square value of rectus femoris(P＜0.05)between the two groups at velocities of 90°/s.Statistics revealed that the median frequency difference rate(P＜0.05)and root mean square value(P＜0.05)of rectus femoris had changed significantly at the velocities of 180°/s.The results of both multiple regression and random forest algo-rithm showed that knee extensor moment was the strongest predictor between electromyographic characteristics and clinical indicators. Conclusion:The strength of quadriceps femoris in KOA patients was decreased.Thus,the patient may need more muscles to complete the same action,which was easy to cause muscle fatigue.The knee extensor moment was closely related to the quadriceps femoris thickness and the degree of knee pain.It offers important advantag-es for the diagnosis and assessing the severity,which may provide the way for the future study of KOA.
ABSTRACT
Objective:To investigate the effect of resveratrol on apoptosis of chondrocytes in rats with knee osteoarthritis(KOA)through autophagy mediated by silent information regulator 1(SIRT1)/adenylate activated protein kinase(AMPK)signaling pathway.Methods:Fifty healthy Wistar rats were randomly separated into control group,model group,resveratrol group,resveratrol+ SIRT1 inhibitor group,and autophagy activator group,with 10 rats per group.Except for the control group,the other rats were injected with Freund's complete adjuvant to establish the KOA rat model,resveratrol group,resveratrol+AMPK inhibitor group,and autophagy activator group were treated with 10 μmol/kg resveratrol,10 μmol/kg resveratrol+10 mg/kg EX527,2 mg/kg rapamycin,respectively.After 4 weeks,the grade of Lequesne MG knee joint of rats were observed;the levels of IL-6 and tumor necrosis factor-β(TNF-β)in rat knee joint fluid were measured;HE staining and TUNEL staining were used to observe the morphology and apoptosis of rat knee cartilage;transmission electron microscope was used to observe the autophagy in rat chondrocytes;Western blot was performed to determine the protein expressions of SIRT1,p-AMPK,AMPK,LC3 and Beclin-1.Results:Compared with control group,the local reaction,gait reaction,joint activity,and joint swelling of model group were increased;compared with model group,the local response,gait response(P<0.05),joint activity,and joint swelling in resveratrol group and autophagy activator group were reduced(P<0.05).Compared with control group,the cartilage tissue cells in model group were disordered and rough,with fibrotic degeneration,marginal humeral bulge,reduced organelles,and vacuolar degeneration,the number of autophagosomes was increased,the levels of IL-6 and TNF-β in knee joint fluid,chondrocyte apoptosis rate,Beclin-1 and LC3B/A were increased(P<0.05),the SIRT1 and p-AMPK/AMPK in cartilage tissue were decreased(P<0.05);compared with model group,resveratrol group and autophagy activator group showed improvement in the disordered arrangement of cartilage tissue cells and the marginal humeral bulge,the number of autophago-somes was increased,the levels of IL-6 and TNF-β in knee joint fluid,and the apoptosis rate of chondrocytes were decreased(P<0.05),the levels of SIRT1,p-AMPK/AMPK,Beclin-1 and LC3B/A in cartilage tissue were increased(P<0.05);SIRT1 inhibitor could reverse the protective effect of resveratrol group on rat chondrocytes.Conclusion:Resveratrol maybe autophagic KOA rat chon-drocyte apoptosis mediated by activating SIRT1/AMPK pathway,which can be reversed by SIRT1 inhibitor.
ABSTRACT
Objective To establish a three-dimensional finite element model of knee joint in patients with mild knee osteoarthritis in the absence of CT and MRI with thin layer thickness,and to analyze the stress distributions of the tibial plateau.Methods A female patient with mild knee osteoarthritis was selected as the study object,and received serial CT scan from pelvis to distal tibia of fibula.The obtained files in DICOM format were imported into Mimics software for extracting the bony structures of knee joint through threshold segmentation,and then optimizing the extracted structures with Edit Masks,Cavity Fill and Region Grow.The generated model of bony structures was imported into 3-matic for smoothing and wrapping,and Geomagic Wrap was used for bony structure processing with mesh doctor inspection,surface defect repair and surface fitting.The cartilages,meniscus and ligaments were established by contour extension,and assembled with bony structures in SolidWorks in the way of origin coincidence.After defining material properties and contact relationships,meshing,and setting constraints and loads in ANSYS software,the stress distributions of the tibial plateau when standing with both legs were analyzed.Results A complete knee joint model including bony structure,cartilage and ligament was successfully established.When standing with two legs,the peak value of contact stress was about 1.21 MPa,and the maximum stress was 0.72 MPa at the medial middle of tibial plateau and lateral tibial plateau.The 62.7%and 37.3%of the total load were borne by the inner and outer compartments.Conclusion The model of the total knee joint is established with CT extraction and software rendering,and the finite element analysis results meet clinical expectations,indicating that the model established by the proposed method is reliable and can be used for follow-up research.
ABSTRACT
Objective To analyze the mechanism of Huangwu Ganfu Ointment in relieving pain of knee osteoarthritis(KOA)based on network pharmacology;To verify it in animal experiments.Methods The active components of Huangwu Ganfu Ointment were obtained by TCMSP database,PubChem database and SwissADME platform,the effective components were screened,and the targets were obtained from SEA database.KOA disease-related targets were obtained from GeneCards,OMIM and other databases,and the intersection targets were obtained.A effective component-target-disease network was constructed using Cytoscape 3.9.0 Software.Protein-protein interaction(PPI)network was constructed by STRING database and core targets were screened.GO and KEGG enrichment analysis of intersection targets were analyzed using DAVID platform.The KOA rat model with cold and damp syndrome was established,and the intervention of Huangwu Ganfu Ointment was carried out.The efficacy was observed and the core target expressions were detected.Results Totally 104 effective components were screened from Huangwu Ganfu Ointment,and 59 potential targets were obtained for treating KOA.PPI network interaction analysis obtained the important targets of IL6,IL1B and PTGS2.KEGG enrichment results showed that Huangwu Ganfu Ointment may involve 84 signaling pathways such as IL-17,TNF,TRP and NF-κB in the treatment of KOA,most of which were related to inflammation.The results of animal experiments showed that Lecuesne MG scores increased in the model rats(P<0.05),and paw withdrawal threshold(PWT)significantly decreased(P<0.05).Compared with model group,PWT in Huangwu Ganfu Ointment medium-and high-dosage groups were significantly recovered,and synovitis Krenn score decreased(P<0.05).The Mankin score of cartilage tissue of Huangwu Ganfu Ointment high-dosage group decreased(P<0.05).The contents of IL-6 and IL-1β in all Huangwu Ganfu Ointment groups decreased(P<0.01).Huangwu Ganfu Ointment medium-and high-dosage groups could down-regulate the expression of TRPV1 protein(P<0.05,P<0.01).Conclusion The mechanism of Huangwu Ganfu Ointment in alleviating the pain of KOA may be related to reducing inflammatory response,reducing the release of inflammatory factors of IL-1β and IL-6,alleviating inflammatory pain sensitivity of KOA,and down-regulating the expression level of TRPV1.
ABSTRACT
Objective To compare the differences in the composition and diversity of intestinal flora between knee osteoarthritis(KOA)patients with dampness-heat obstruction syndrome,cold-dampness blockage syndrome and healthy people;To explore the characteristics of intestinal flora of KOA patients with the above two TCM syndrome types.Methods According to the inclusion and exclusion criteria,dampness-heat obstruction syndrome group,cold-dampness blockage syndrome group,and healthy control group were screened,with 10 cases for each group,and then their fecal samples were collected.16S rDNA sequencing technology was used to compare the differences of intestinal flora among groups by Alpha and Beta diversity analysis.Results There was no significant difference in species richness of intestinal flora among the three groups,but there was statistical significance in species diversity between cold-dampness blockage syndrome group and dampness-heat obstruction syndrome group,and healthy control group(P<0.05).There were statistical significance among the three groups in intestinal flora composition(P= 0.001).At the phylum level,Bacteroidota and Firmicutes were significantly dominant,and at genus level,the abundance of Prevotella in dampness-heat obstruction syndrome group and cold-dampness blockage syndrome group increased.The abundance of Enterobacteriaceae,Lachnospira and Klebsiella was relatively large in dampness-heat obstruction syndrome group.The abundance of Prevotella and Pseudomonas in cold-dampness blockage syndrome group was large.Conclusion There are differences in the intestinal flora structure between KOA patients with dampness-heat obstruction syndrome and cold-dampness blockage syndrome.
ABSTRACT
Objective To evaluate the effectiveness and safety of moxibustion for knee osteoarthritis and the methodological quality of systematic reviews(SRs).Methods SRs of moxibustion for knee osteoarthritis were retrieved from CNKI,VIP,Wanfang Data,SinoMed,PubMed,Cochrane Library,Embase and Web of Science was conducted from the establishment of the databases to February 10,2022.AMSTAR 2 was used to assess the methodological quality of SRs.The randomized controlled trials(RCTs)included in these SRs were screened and summarized according to inclusion standard.RevMan 5.4 software was used for Meta-analysis,and GRADE approach was used to assess the certainty of evidence.Results A total of 15 SRs were included.The evaluation results of the AMSTAR 2 showed that the methodological quality was very low for 14 SRs,and low for other 1 SR.A total of 36 RCTs were included.Meta-analysis results showed that compared with the non-steroidal anti-inflammatory drugs(NSAIDs),the moxibustion group had better effects on improvement of WOMAC scores[mean difference(MD)=-5.95;95%confidence interval(CI):-9.25 to-2.65;low quality],relieving pain[MD=-1.26;95%CI:-2.19 to-0.32;very low quality],and improving effective rate[risk ratio(RR)=1.16;95%CI:1.11 to 1.22;low quality].In the moxibustion group,some patients experienced blisters,and most healed in 3 days.Conclusion Moxibustion has advantages in pain reduction and improving effective rate compared with routine Western therapy for knee osteoarthritis.However,well-designed high-quality RCTs are needed for further verification.
ABSTRACT
AIM To investigate the clinical effects of Jingu Xiaotong Powder combined with platelet-rich plasma on patients with knee osteoarthritis.METHODS Ninety-six patients were randomly assigned into control group(48 cases)for 8-week administration of platelet-rich plasma,and observation group(48 cases)for 8-week administration of both Jingu Xiaotong Powder and platelet-rich plasma.The changes in clinical effects,IL-17,SDF-1,TLR4,GSH-Px,NO,ox-LDL,WOMAC scores,TCM syndrome score,AIM2-SF score were detected.RESULTS The observation group demonstrated higher total effective rate than the control group(P<0.05).After the treatment,the two groups displayed decreased IL-17,SDF-1,TLR4,NO,ox-LDL,WOMAC scores,TCM syndrome score(P<0.05),and increased GSH-Px,AIM2-SF score(P<0.05),especially for the observation group(P<0.05).CONCLUSION For the patients with knee osteoarthritis,Jingu Xiaotong Powder combined with platelet-rich plasma can reduce IL-17,SDF-1,TLR4 levels,inhibit body inflammation,improve oxidative stress indices,alleviate pain,and enhance clinical efficacy and life quality.
ABSTRACT
AIM To explore the clinical effects of Shenxie Zhitong Capsules combined with DONG's Extraordinary Points on patients with knee osteoarthritis of Cold-Dampness Obstruction Pattern.METHODS Eighty patients were randomly assigned into control group(40 cases)for 1-month intervention of DONG's Qi Point,and observation group(40 cases)for 1-month intervention of both Shenxie Zhitong Capsules and DONG's Qi Point.The changes in clinical effects,TCM syndrome scores,LKSS score,WOMAC score,NRS score,AIMS2-SF score,sIL-4R,TNF-α,HMGBl,TLR-4,BALP,BGP and β-CTX were detected.RESULTS The observation group demonstrated higher total effective rate than the control group(P＜0.05).After the treatment,the two groups displayed decreased TCM syndrome scores,WOMAC score,NRS score,sIL-4R,TNF-α,HMGBl,TLR-4,β-CTX(P＜0.05),and increased LKSS score,AIMS2-SF score,BALP,BGP(P＜0.05),especially for the observation group(P＜0.05).CONCLUSION For the patients of Cold-Dampness Obstruction Pattern,Shenxie Zhitong Capsules combined with DONG's Extraordinary Points can inhibit body inflammatory responses,improve bone metabolism,and relieve knee pain and clinical symptoms.
ABSTRACT
AIM To investigate the clinical effects of Dense Fire-Needling combined with Shentong Zhuyu Decoction on patients with knee osteoarthritis of Wind-Phlegm Blocking Collateral Pattern.METHODS Sixty-two patients were randomly assigned into control group(31 cases)for 2-week intervention of Shentong Zhuyu Decoction,and observation group(31 cases)for 2-week intervention of both Dense Fire-Needling and Shentong Zhuyu Decoction.The changes in clinical effects,TCM syndrome scores,VAS score,Lysholm score,WOMAC score,serological indices(MMP-3,IL-6,TNF-α)and incidence of adverse reactions were detected.RESULTS The observation group demonstrated higher total effective rate than the control group(P＜0.05).After the treatment,the two groups displayed decreased TCM syndrome scores,VAS score,WOMAC score,serological indices(P＜0.05),and increased Lysholm score(P＜0.05),especially for the observation group(P＜0.05).No significant difference in incidence of adverse reactions was found between the two groups(P＞0.05).CONCLUSION For the patients of Wind-Phlegm Blocking Collateral Pattern,Dense Fire-Needling combined with Shentong Zhuyu Decoction can safely and effectively relieve clinical symptoms and pain,improve knee joint functions,enhance clinical effects,and regulate body inflammatory factor levels.
ABSTRACT
Based on the pathogenesis of “tendon off-position and joint subluxation”， combined with modern ana-tomy and biomechanics， the characteristic manifestations of “tendon off-position” and “joint subluxation” of the knee and the intrinsic connection between them are clarified. Through sorting out the relationship between “tendon off-position and joint subluxation” and knee osteoarthritis （KOA） in modern research， it is believed that “tendon off-position and joint subluxation” is the key mechanism for the occurrence and development of KOA， and accordingly， it is proposed to take the diet as the guide， use bone manipulation for external diagnosis and treatment， use traditional Chinese medicine decoction for internal treatment， and use Daoyin exercise throughout the whole process as the strategy for KOA's comprehensive traditional Chinese medicine treatment to improve the clinical effectiveness.
ABSTRACT
ObjectiveTo observe the regulatory effect of Huangwu Ganfu ointment on transient receptor potential anchor protein 1 （TRPV1） receptor expression， macrophage polarization， and p38 mitogen-activated protein kinase （p38 MAPK） signaling pathway in synovial tissue of knee osteoarthritis （KOA） rats with yang deficiency and cold coagulation syndrome and explore the mechanism of relieving peripheral inflammatory hyperalgesia of KOA. MethodForty-eight male SD rats were randomly divided into blank group， model group， high-dose， middle-dose， and low-dose groups of Huangwu Ganfu ointment （9.3， 4.65， 2.325 g·kg-1）， and celecoxib group （20.82 mg·kg-1）. The KOA rat model of yang deficiency and cold coagulation syndrome was established through climate box and swimming for two weeks combined with an injection of sodium iodoacetate （MIA） in the articular cavity. After continuous administration for four weeks， the general condition of rats in each group was observed， and the pain withdrawal threshold （PWT） and joint diameter induced by mechanical stimulation were recorded. The expression levels of interleukin-1β （IL-1β）， tumor necrosis factor-α （TNF-α）， nerve growth factor （NGF）， and calcitonin gene-related peptide （CGRP） inflammatory factor were detected by enzyme-linked immunosorbent assay （ELISA）， and the histopathological changes of synovial tissue of the knee joint were observed by hematoxylin-eosin （HE） staining. Western blot was used to detect the protein expression of TRPV1， p38 MAPK， and p-p38 MAPK in synovial tissue of the knee joint， and immunofluorescence （IF） was used to evaluate the polarization of M1/M2 macrophages. ResultCompared with that in the blank group， the overall mental state of the model group was worse， and the autonomous activity was decreased. The body mass was lower， and the joint diameter was increased. The X-ray showed that the osteophyte at the edge of the joint proliferated， and the articular surface was obviously rough. The articular cavity was significantly narrowed， and the PWT was significantly decreased （P<0.01）. The contents of IL-1β， TNF-α， CGRP， and NGF in serum and synovium Krenn score increased significantly （P<0.01）. The protein expression of TRPV1 and p-p38 MAPK/p38 MAPK increased significantly （P<0.01）， and the proportion of M1 macrophages and M1/M2 increased （P<0.01）， while the proportion of M2 macrophages decreased （P<0.01）. Compared with model group， the body mass in the low， middle， and high dose groups of Huangwu Ganfu ointment increased to different degrees （P<0.05， P<0.01）. The diameter of the knee joint in the high dose group of Huangwu Ganfu ointment and celecoxib group decreased （P<0.01）. The recovery of PWT in the high and middle dose groups of Huangwu Ganfu ointment groups was more obvious （P<0.05）. The contents of IL-1β and CGRP in the serum of rats in each administration group were significantly decreased （P<0.01）， and the content of serum TNF-α in the celecoxib group and high dose group of Huangwu Ganfu ointment decreased significantly （P<0.05）. The content of serum NGF in the middle dose group of Huangwu Ganfu ointment decreased significantly （P<0.05）， and the synovium Krenn score decreased in the high dose group of Huangwu Ganfu ointment （P<0.05）. In addition， the protein expression of TRPV1 and p-p38 MAPK/p38 MAPK in synovial tissue decreased significantly in all groups of Huangwu Ganfu ointment （P<0.01）. The proportion of M1 macrophages in synovial tissue in the celecoxib group and all groups of Huangwu Ganfu ointment decreased （P<0.01）， and the proportion of M2 macrophages in the high dose group of Huangwu Ganfu ointment increased （P<0.05）. The M1/M2 in the middle and high dose groups of Huangwu Ganfu ointment decreased （P<0.05）. ConclusionHuangwu Ganfu ointment can mediate the polarization of macrophages to reduce the inflammatory reaction of KOA， alleviate the release of inflammatory pain mediators， and lower the protein expression of TRPV1. The mechanism may be related to the p38 MAPK signaling pathway， so as to improve the peripheral hyperalgesia of KOA.
ABSTRACT
ObjectiveTo retrospectively analyze the clinical efficacy of Xibining Ⅱ prescription in the treatment of knee osteoarthritis with cold-dampness blockage syndrome by oral medication and to explore the influencing factors of endpoint events. MethodA real-world retrospective cohort design was adopted， and medical records of knee osteoarthritis patients with cold-dampness blockage syndrome treated with oral medication from the orthopedics outpatient department of Jiangsu Province Hospital of Chinese Medicine were collected. All patients received conventional Western medicine treatment and were divided into non-exposure group （573 cases） and exposure group （427 cases） according to whether or not they received treatment with Xibining Ⅱ prescription. Descriptive analysis of the baseline data of the 1 000 screened cases was performed using IBM SPSS 27.0. According to the baseline data， 334 pairs were matched using the propensity score matching method， resulting in a total of 668 cases in both groups. The changes in visual analogous scale （VAS）， Western Ontario and McMaster Universities Osteoarthritis Index （WOMAC） total score， Japanese Knee Osteoarthritis Measure （JKOM） score， and traditional Chinese medicine （TCM） syndrome score before treatment and at 2， 6， 12 weeks after treatment， as well as the incidence of adverse reactions， were compared between the two groups. A multivariate logistic regression analysis was conducted to analyze the influencing factors of endpoint events， with clinical cure judged based on the improvement rate of WOMAC total score before and after treatment. ResultAfter 12 weeks of treatment， compared to the results before treatment， the VAS， WOMAC total score， JKOM score， and TCM syndrome score of patients in both groups significantly decreased （P<0.01）. Compared to the non-exposure group， the exposure group showed a more significant reduction in VAS， WOMAC total score， JKOM score， and TCM syndrome score （P<0.01）. After 12 weeks of treatment， the clinical cure rate and significant efficiency were higher in the exposure group than in the non-exposure group （P<0.05）. Compared to the results before treatment within each group， VAS， WOMAC pain， stiffness， function scores， JKOM score， and TCM syndrome score significantly decreased at 2， 6， 12 weeks after treatment in both groups （P<0.01）. Compared to the non-exposure group at the same time points， the exposure group showed a reduction in VAS at 2， 12 weeks， WOMAC pain at 6， 12 weeks， and function scores at 12 weeks （P<0.05， P<0.01）. The JKOM score decreased at 6， 12 weeks， and the TCM syndrome score significantly decreased at 2， 6， 12 weeks in the exposure group （P<0.05， P<0.01）. Multivariate logistic regression analysis at 12 weeks showed that factors affecting clinical cure included the course of disease， history of alcohol consumption， hypertension， coronary heart disease， and the use of Xibining Ⅱ prescription （P<0.05， P<0.01）. Compared to the non-exposure group at the same time points， the incidence of epigastric discomfort in the exposure group was lower at 2， 12 weeks （P<0.01）， the incidence of diarrhea and vomiting was slightly higher than that in the non-exposure group， but the difference was not statistically significant. ConclusionThe clinical application of Xibining Ⅱ prescription combined with conventional Western medicine treatment in the treatment of knee osteoarthritis with cold-dampness blockage syndrome is more effective than conventional Western medicine treatment alone. It can significantly reduce VAS， WOMAC total score， JKOM score， and TCM syndrome score， with more pronounced long-term effects and a low incidence of adverse reactions.
ABSTRACT
Objective @#Given that the PI3K/AKT/mTOR signaling pathway is associated with the progression of knee osteoarthritis (KOA) , this study aims to investigate whether the polarization induction of synovial macrophages mediated by the PI3K/AKT/mTOR signaling axis is the cause of KOA progression . @*Methods @#The synovial fluid of KOA KL-Ⅱ and KL-Ⅲ patients and normal individuals was collected , and the percentage of M1 macrophages (CD80 , CD86) and M2 macrophages (CD163 , CD206) in the synovial fluid (M1 /M2 ratio) was measured to e- valuate the polarization of macrophage cytokines such as IL-1 , IL-6 , IL-10 , and tumor necrosis factor (TNF) -α, transforming growth factor ( TGF)-βExpression in KOA synovial fluid , and detect and analyze of key molecules PI3K/AKT/mTOR signaling axis PI3K , AKT3 , mTORC1 , and inducible nitric oxide synthase ( iONS) in KOA synovial fluid . @*Results @#Compared with the synovial fluid of normal individuals , the percentage of M1 macrophages (CD80 , CD86) in KOA patients increased (P < 0. 01) , and the M1 /M2 ratio increased ( P < 0. 001) ; The ex- pression of IL-1 , IL-6 , and TNF-αin the synovial fluid of the KOA group was also higher than that of the control group (P < 0. 01) , while the expression of IL-10 and TGF-βin the KOA group was significantly reduced ( P < 0. 01) ; The key proteins PI3K , AKT3 , mTORC1 , and downstream inflammatory factor iONS in the PI3K/AKT/ mTOR signaling pathway in the synovial fluid of the KOA group were higher than those in the control group (P < 0. 01) . @*Conclusion @#In KOA synovial fluid , M1 macrophage polarization plays a dominant role , and the inflam- matory response mediated by M1 macrophage polarization may be the cause of synovitis . At the same time , the PI3K/AKT/mTOR signaling pathway may mediate the polarization of M1 macrophages involved in KOA inflammato- ry response .
ABSTRACT
ObjectiveThis study aims to explore the potential mechanism of Danggui Niantongtang in treating knee osteoarthritis （KOA） by regulating the intestinal flora through 16S rDNA analysis. MethodThirty-six C57BL/6J mice were subjected to anterior cruciate ligament transection （ACLT） to establish a KOA model and were randomly divided into the sham surgery group， model group， low-dose Danggui Niantongtang group （0.819 g·kg-1）， medium-dose Danggui Niantongtang group （1.638 g·kg-1）， high-dose Danggui Niantongtang group （3.276 g·kg-1）， and Meloxicam group （0.975 mg·kg-1）， with 6 mice in each group. Except for the treatment groups， the sham surgery group and model group were given normal saline by gavage. After 4 weeks of continuous intervention， feces and intact knee joints of the mice were collected. Hematoxylin-eosin （HE） staining and Safranin O-Fast Green staining were performed to observe the pathological changes in knee joint tissue morphology. The 16S rDNA sequencing was used to analyze changes in the abundance and diversity of intestinal microorganisms before and after treatment， along with corresponding functional predictions. ResultHigh-dose Danggui Niantongtang and Meloxicam significantly relieved pain symptoms in KOA mice， improved the disorder of joint structure， maintained the integrity of knee articular cartilage， increased the expression of type Ⅱ collagen alpha 1 （Col2a1） in articular cartilage， and decreased the expression of matrix metalloproteinase-13 （MMP-13）. The results of 16S rDNA sequencing showed that high-dose Danggui Niantongtang could adjust the abundance and structure of intestinal microbial species. Compared with the sham surgery group， the abundance of Proteobacteria， Actinobacteria， Ruminococcus， and Bacteroides was significantly increased in the model group （P<0.05）， while in the Danggui Niantongtang group， the abundance of these four flora was significantly reduced compared with the model group. Compared with the sham surgery group， the abundance of Verrucomicrobia， Oscillospira， and Akkermansia was significantly decreased in the model group （P<0.05）， while in the Danggui Niantongtang groups， the abundance of these three flora was significantly increased compared with the model group （P<0.05）. Functional pathway prediction of differential genera revealed that species differences among groups mainly involved metabolic pathways with high abundance associated with biosynthesis and precursors， as well as energy production， including amino acid biosynthesis， nucleotide and nucleoside biosynthesis， cofactors， prosthetic groups， electron carriers， and vitamin biosynthesis. ConclusionDanggui Niantongtang can effectively protect articular cartilage and delay the progression of KOA， possibly by regulating the structure of the intestinal flora， promoting probiotics， and inhibiting the growth of harmful pathogenic bacteria.
ABSTRACT
ObjectiveTo observe the effects of Xibining （XBN） and adipose stem cell exosome （ADSC-Exos） in the cases of separate or joint application on cartilage degeneration and mitochondrial autophagy and explore its mechanism of action to improve knee osteoarthritis （KOA）. MethodSD rats were divided into a sham operation group （sham group）， a model group， an ADSC-Exos group （Exos group）， an XBN group， and an ADSC-Exos+XBN group （Exos+XBN group）. KOA model was established by using anterior cruciate ligament transection （ACLT）. The pain sensitivity status of rats was evaluated， and the degeneration degree of the knee joint and cartilage tissue was detected by Micro-CT and pathological staining. The expression of p62 and LC3B was observed by immunofluorescence， and the serum levels of TNF-α， IL-1β， IL-6， and IL-15 in rats were detected by ELISA. The Western blot was used to detect the protein expression levels of MMP-3， MMP-13， ADAMTS5， ColⅡ， TIMP， ACAN， PINK1， Parkin， p62， and LC3A/B. ResultCompared with the sham group， rats in the model group showed decreased cold-stimulated foot-shrinkage thresholds and mechanical pain sensitivity thresholds， varying degrees of abrasion and loss of cartilage tissue， degeneration of cartilage tissue， elevated serum IL-1β， IL-6， IL-15， and TNF-α levels （P<0.01）， and increased protein expression of MMP-3， MMP-13， and ADAMTS5 in cartilage tissue. In addition， the protein expression of ColⅡ， TIMP1， and ACAN was decreased （P<0.01）. Compared with the model group， rats in each treatment group showed higher cold-stimulated foot-shrinkage thresholds and mechanical pain sensitivity thresholds， reduced cartilage tissue degeneration， lower serum levels of IL-1β， IL-6， IL-15， and TNF-α （P<0.05，P<0.01）， decreased protein expression of MMP-3， MMP-13， and ADAMTS5， and higher protein expression of Cold， TIMP1， and ACAN in cartilage tissue （P<0.05，P<0.01）. Moreover， the changes were the most obvious in the Exos+XBN group. ConclusionBoth ADSCs-Exos and XBN can increase the level of mitochondrial autophagy in chondrocytes and delay cartilage tissue degeneration by promoting the expression of the PINK1/Parkin signaling pathway， and the combination of the two can enhance the therapeutic effect.
ABSTRACT
Objective To observe the effect of different synovial cell secretions on chondrocytes after LPS-induced inflammation,and to explore the mechanism of two synovial cell secretions causing cartilage damage in the progres-sion of KOA disease.Methods Two kinds of synovial cells were co-cultured at 1∶4 and LPS-induced inflamma-tion.The supernatant and exocrine were extracted,and then the normal and LPS-induced inflammation were extrac-ted.The human cartilage tissue obtained during the operation was isolated and cultured into chondrocytes,which were divided into five groups:the first group was added with FLS secretion,the second group was added with nor-mal FLS secretion,the third group was added with secretion after co-culture of two kinds of synovial cells,the fourth group was added with inflammatory MLS secretion,and the fifth group was added with inflammatory FLS se-cretion.CCK-8 was used to detect the viability of chondrocytes in each group.TNF-α,IL-1β,IL-6 level in the su-pernatant of chondrocytes in each group was detected by ELISA.The protein expression of TLR4,NF-κB,IkK,IκB,ADAMTS5 in chondrocytes of each group was detected by Western blot method.Results CCK-8 showed that the activity of chondrocytes in the three groups of inflammatory secretions decreased compared with the secretions from normal synovial cells(P＜0.05);ELISA showed TNF-α,IL-1 β,IL-6 level in the supernatant of group Ⅲ,Ⅳ and V was higher than that of group Ⅰ and Ⅱ(P＜0.05),TNF-α,IL-1 β,IL-6 level in group Ⅲ was higher than that in group Ⅳ but lower than that in group Ⅴ(P＜0.05).Western blot showed the protein expression of TLR4,NF-κB,IkK,IκB,ADAMTS5 in chondrocytes of group Ⅲ,Ⅳ and Ⅴ was higher than that in group Ⅰ and Ⅱ(P＜0.05),the protein expression of TLR4,NF-κB,IkK,IκB,ADAMTS5 in group Ⅲ was higher than that in group Ⅳbut lower than that in group Ⅴ(P＜0.05).Conclusion Two kinds of synovial cell-derived secretions after LPS-induced inflammation can regulate cartilage TLRs/NF-κB signal pathway,causing cartilage inflammation.The in-flammatory effect of MLS secretion is stronger than that of FLS secretion,but the inflammatory effect of MLS secre-tion under two co-cultures is weaker than that of MLS secretion alone.
ABSTRACT
Objective To explore the application effect of new improved 3D printing individualized guidance(3D psi)in total knee arthroplasty(TKA)for knee osteoarthritis(KOA).Methods A total of 100 patients with KOA in 920th Hospital of Joint Logistics Support Force,PLA from January 2021 to January 2022 were selected,and were divided into 2 groups of 50 patients each using the randomized numerical table method.The control group was treated with conventional TKA,and the study group was treated with new improved 3D psi assisted TKA.The operation conditions,postoperative rehabilitation,complications,prosthesis component position deviation,knee range of motion(ROM),lower limb force line parameters[coronal distal femoral mechanical axis lateral angle(mldfa),lower limb mechanical axis angle(HKA)],gait parameters(percentage of support time,stride,pace),knee function(HSS score),quality of life(AIMS2 score)were observed.Results Com-pared with control group,the amount of intraoperative and postoperative blood loss and drainage volume 2 days after operation were less in the study group,and the operation time and hospital stay were shorter(P<0.05).The deviations of LTC Angle,FFC Angle,HKA Angle,LFC Angle and FTC Angle in the study group were smaller than those in the control group(P<0.05).At 3 months,6 months and 12 months after surgery,the percentage of knee ROM,supporting time,stride length and walking speed of the research group were higher than those of the control group,while the coronal-position mLDFA and HKA were lower than those of the control group(P<0.05).The proportion of WBC and PMN in joint fluid at 3 months,6 months and 12 months after surgery was lower than that in control group(P<0.05).The HSS score of the study group was higher than that of the control group at 3 months,6 months and 12 months after operation,and the AIMS2 score was lower than that of the control group(P<0.05).There was no statistically significant difference in the incidence of complications between the study group and the control group(P>0.05).Conclusion The new improved 3D PSI-assisted TKA treatment of KOA can optimize the surgical situation,improve operating accuracy,improve the patient's lower limb alignment,promote limb function recovery,help improve the quality of life,and has high safety.
ABSTRACT
BACKGROUND:Circular RNAs(circRNAs)play important roles in a variety of diseases or tumors,and recent findings have revealed that circRNAs are abnormally expressed in knee osteoarthritis and are involved in disease progression through microRNA/mRNA regulation. OBJECTIVE:To investigate the effect of circRNA WD repeat containing protein 1(circ-BRWD1)/miR-488-3p/DNA methyltransferase 3A(DNMT3A)on the proliferation and apoptosis of chondrocytes in knee osteoarthritis. METHODS:Real-time fluorescence quantitative PCR was performed to detect the expression of circ-BRWD1,miR-488-3p,DNMT3A in knee osteoarthritis chondrocytes.Cells were divided into si-NC group,si-circ-BRWD1 group,vector group,circ-BRWD1 group,si-circ-BRWD1+anti-miR-NC group,si-circ-BRWD1+anti-miR-488-3p group,miR-NC group,miR-488-3p group,anti-miR-NC group,anti-miR-488-3p group,miR-488-3p+vector group,miR 488-3p+DNMT3A group.Real-time fluorescence quantitative PCR was used to detect circ-BRWD1,miR-488-3p,DNMT3A expression,MTT and flow cytometry assay were used to detect cell proliferation and apoptosis.Western blot assay was used to detect DNMT3A and proliferation/apoptosis-related protein expression.Dual luciferase reporter assay was used to Dual luciferase reporter assay to detect the targeting relationship of circ-BRWD1 with miR-488-3p and miR-488-3p with DNMT3A. RESULTS AND CONCLUSION:circ-BRWD1 and DNMT3A were highly expressed and miR-488-3p was lowly expressed in knee osteoarthritis chondrocytes compared with normal chondrocytes.Knockdown of circ-BRWD1 or overexpression of miR-488-3p inhibited proliferation and induced apoptosis in knee osteoarthritis chondrocytes.circ-BRWD1 targeted negative regulation of miR-488-3p and inhibition of miR-488-3p reversed the effect of circ-BRWD1 knockdown on chondrocyte proliferation and apoptosis in knee osteoarthritis.miR-488-3p targeted negative regulation of DNMT3A and upregulation of DNMT3A reversed the effect of miR-488-3p overexpression on chondrocyte proliferation and apoptosis in knee osteoarthritis.circ-BRWD1 could regulate the expression of DNMT3A by regulating miR-488-3p.To conclude,knockdown of circ-BRWD1 inhibits chondrocyte proliferation and induces apoptosis in knee osteoarthritis,and the mechanism of action may be related to the regulation of miR-488-3p/DNMT3A axis.