Efficacy of stromal vascular fraction for knee osteoarthritis:A prospective,single-centre,non-randomized study with 2 years follow-up

BACKGROUND Current osteoarthritis(OA)treatments focus on symptom relief without addressing the underlying disease process.In regenerative medicine,current treatments have limitations.In regenerative medicine,more research is needed for intra-articular stromal vascular fraction(SVF)injections in OA,including dosage optimization,long-term efficacy,safety,comparisons with other treatments,and mechanism exploration.AIM To compare the efficacy of intra-articular SVF with corticosteroid(ICS)injections in patients with primary knee OA.METHODS The study included 50 patients with Kellgren-Lawrence grades II and III OA.Patients were randomly assigned(1:1)to receive either a single intra-articular SVF injection(group A)or a single intra-articular ICS(triamcinolone)(group B)injection.Patients were followed up at 1,3,6,12,and 24 months.Visual analog score(VAS)and International Knee Documentation Committee(IKDC)scores were administered before the procedure and at all followups.The safety of SVF in terms of adverse and severe adverse events was recorded.Statistical analysis was performed with SPSS Version 26.0,IBM Corp,Chicago,IL,United States.RESULTS Both groups had similar demographics and baseline clinical characteristics.Follow-up showed minor patient loss,resulting in 23 and 24 in groups A and B respectively.Group A experienced a notable reduction in pain,with VAS scores decreasing from 7.7 to 2.4 over 24 months,compared to a minor reduction from 7.8 to 6.2 in Group B.This difference in pain reduction in group A was statistically significant from the third month onwards.Additionally,Group A showed significant improvements in knee functionality,with IKDC scores rising from 33.4 to 83.10,whereas Group B saw a modest increase from 36.7 to 45.16.The improvement in Group A was statistically significant from 6 months and maintained through 24 months.CONCLUSION Our study demonstrated that intra-articular administration of SVF can lead to reduced pain and improved knee function in patients with primary knee OA.More adequately powered,multi-center,double-blinded,randomised clinical trials with longer follow-ups are needed to further establish safety and justify its clinical use.

Knee osteoarthritis:A review of animal models and intervention of traditional Chinese medicine

Background:Knee osteoarthritis(KOA)characterized by degeneration of knee cartilage and subsequent bone hyperplasia is a prevalent joint condition primarily affecting aging adults.The pathophysiology of KOA remains poorly understood,as it involves complex mechanisms that result in the same outcome.Consequently,researchers are interested in studying KOA and require appropriate animal models for basic research.Chinese herbal compounds,which consist of multiple herbs with diverse pharmacological properties,possess characteristics such as multicomponent,multipathway,and multitarget effects.The potential benefits in the treatment of KOA continue to attract attention.Purpose:This study aims to provide a comprehensive overview of the advantages,limitations,and specific considerations in selecting different species and methods for KOA animal models.This will help researchers make informed decisions when choosing an animal model.Methods:Online academic databases(e.g.,PubMed,Google Scholar,Web of Science,and CNKI)were searched using the search terms“knee osteoarthritis,”“animal models,”“traditional Chinese medicine,”and their combinations,primarily including KOA studies published from 2010 to 2023.Results:Based on literature retrieval,this review provides a comprehensive overview of the methods of establishing KOA animal models;introduces the current status of advantages and disadvantages of various animal models,including mice,rats,rabbits,dogs,and sheep/goats;and presents the current status of methods used to establish KOA animal models.Conclusion:This study provides a review of the animal models used in recent KOA research,discusses the common modeling methods,and emphasizes the role of traditional Chinese medicine compounds in the treatment of KOA.

Adipose-derived regenerative therapies for the treatment of knee osteoarthritis

Knee osteoarthritis is a degenerative condition with a significant disease burden and no disease-modifying therapy.Definitive treatment ultimately requires joint replacement.Therapies capable of regenerating cartilage could significantly reduce financial and clinical costs.The regenerative potential of mesenchymal stromal cells(MSCs)has been extensively studied in the context of knee osteoarthritis.This has yielded promising results in human studies,and is likely a product of immunomodulatory and chondroprotective biomolecules produced by MSCs in response to inflammation.Adipose-derived MSCs(ASCs)are becoming increasingly popular owing to their relative ease of isolation and high proliferative capacity.Stromal vascular fraction(SVF)and micro-fragmented adipose tissue(MFAT)are produced by the enzymatic and mechanical disruption of adipose tissue,respectively.This avoids expansion of isolated ASCs ex vivo and their composition of heterogeneous cell populations,including immune cells,may potentiate the reparative function of ASCs.In this editorial,we comment on a multicenter randomized trial regarding the efficacy of MFAT in treating knee osteoarthritis.We discuss the study’s findings in the context of emerging evidence regarding adipose-derived regenerative therapies.An underlying mechanism of action of ASCs is proposed while drawing important distinctions between the properties of isolated ASCs,SVF,and MFAT.

Unicompartmental knee arthroplasty vs high tibial osteotomy for knee osteoarthritis:A comparison of clinical and radiological outcomes

BACKGROUND Unicompartmental knee arthroplasty(UKA)and high tibial osteotomy(HTO)are well-established operative interventions in the treatment of knee osteoarthritis.However,which intervention is more beneficial to patients with knee osteoarthritis remains unknown and a topic of much debate.Simultaneously,there is a paucity of research assessing the relationship between radiographic parameters of knee joint alignment and patient-reported clinical outcomes,preoperatively and following HTO or UKA.AIM To compare UKAs and HTOs as interventions for medial-compartment knee osteoarthritis:Examining differences in clinical outcome and investigating the relationship of joint alignment with respect to this.METHODS This longitudinal observational study assessed a total of 42 patients that had undergone UKA(n=23)and HTO(n=19)to treat medial compartment knee osteoarthritis.Patient-reported outcome measures(PROMs)were collected to evaluate clinical outcome.These included two disease-specific(Knee Injury and Osteoarthritis Outcome Score,Oxford Knee Score)and two generic(EQ-5D-5L,Short Form-12)PROMs.The radiographic parameters of knee alignment assessed were the:Hip-knee-ankle angle,mechanical axis deviation and angle of Mikulicz line.RESULTS Statistical analyses demonstrated significant(P<0.001),preoperative to postoperative,improvements in the PROM scores of both groups.There were,however,no significant inter-group differences in the postoperative PROM scores of the UKA and HTO group.Several significant correlations associated a more distolaterally angled Mikulicz line with worse knee function and overall health preoperatively(P<0.05).Postoperatively,two clusters of significant correlations were observed between the disease-specific PROM scores and knee joint alignment parameters(hip-knee-ankle angle,mechanical axis deviation)within the HTO group;yet no such associations were observed within the UKA group.CONCLUSION UKAs and HTOs are both efficacious operations that provide a comparable degree of clinical benefit to patients with medial compartment knee osteoarthritis.Clinical outcome has a limited association with radiographic parameters of knee joint alignment postoperatively;however,a more distolaterally angled Mikulicz line appears associated with worse knee function/health-related quality of life preoperatively.

Therapeutic effect of San Bi Tang combined with glucosamine sulfate capsules in cold-dampness-type knee osteoarthritis

BACKGROUND Cold-dampness-type knee osteoarthritis is a common middle-aged and elderly disease,but its pathogenesis is not fully understood,and its clinical treatment has limitations.Glucosamine sulfate capsules are commonly used for treating arthritis,and San Bi Tang is a classic formula of traditional Chinese medicine(TCM)that has the effects of warming yang,dispelling dampness,relaxing muscles,and activating collaterals.This research hypothesized that the combination of modified San Bi Tang and glucosamine sulfate capsules could enhance the clinical efficacy of treating cold-dampness-type knee osteoarthritis through complementary effects.AIM To analyze the clinical efficacy of San Bi Tang combined with glucosamine sulfate capsules when treating cold-dampness-type knee osteoarthritis.METHODS A total of 110 patients with cold-dampness-type knee osteoarthritis were selected as research subjects and randomly divided into a control group and an experimental group of 55 cases each.The control group received only treatment with glucosamine sulfate capsules,while the experimental group received additional treatment with modified San Bi Tang for a duration of 5 wk.The patients’knee joint functions,liver and kidney function indicators,adverse reactions,and vital signs were evaluated and analyzed using SPSS 26.0 software.RESULTS Before treatment,the two groups’genders,ages,and scores were not significantly different,indicating comparability.Both groups’scores improved after treatment,which could indicate pain and knee joint function improvement,but the test group had better scores.The TCM-specific symptoms and the clinical efficacy of the treatment in the test group were higher.Before and after treatment,there were no abnormalities in the patients’liver and kidney function indicators.CONCLUSION The combination of modified San Bi Tang and glucosamine sulfate capsules is superior to treatment with sulfated glucosamine alone and has high safety.

Knee Osteoarthritis Progression after Distal Femur Closing Wedge Osteotomy

Background: Despite the conservative treatment of tibio-femoral osteoarthritis through realignment osteotomies, the rate of total knee replacements following an osteotomy is increasing. The aim of this study was to identify the factors associated with the progression of knee osteoarthritis after a medial closing-wedge distal femoral osteotomy. Methods: Hospital-based observational study on 20 patients who underwent a medial closing-wedge distal femoral osteotomy evaluating the progression of osteoarthritis using the Kellgren and Laurence classification. The Wilcoxon test was used to compare the variation in the progressive stage of the Kellgren and Laurence classification of knee osteoarthritis preoperatively and at the final follow up. Univariate analysis made it possible to determine the factors associated with progression. The final significance threshold for statistical tests was set at 5% (p Results: Overall, the mean follow-up of 46 months ± 6.6 months, with a mean age of 43 years (range: 27 - 69 years) and a female predominance (M: F = 3/7). The progression of tibiofemoral osteoarthritis following a medial closing-wedge distal femoral osteotomy is associated with valgus or varum malalignment been a moderate valgus (OR 6.2 [1.5 - 42.7] at 95% CI;p-value = 0.02), a correction of the mechanical deviation angle with a valgus alignment (OR 2.7 [0.9 - 8.3] at 95% CI), and loss of correction (OR 3.8 [1.3 - 11.6] at 95% CI;p -value) for the lateral compartment while varus alignment (OR 1.7 [0.9 - 8.3] 95% CI, p-value = 0.05) and with rupture of the lateral cortex (OR 2.8 [1.7 - 11.5] 95% CI, p-value = 0.02) were those of the medial compartment. Conclusion: Distal femur closing wedge osteotomy does not definitively interrupt the progression of valgus knee osteoarthritis. The factors associated with the progression of this pathology are modifiable. Taking them into account when performing this surgical technique could improve the osteotomy survival curve.

Autologous peripheral blood-derived orthobiologics:Different types and their effectiveness in managing knee osteoarthritis

Knees are the most commonly impacted weight-bearing joints in osteoarthritis(OA),affecting millions of people worldwide.With increasing life spans and obesity rates,the incidence of knee OA will further increase,leading to a significant increase in the economic burden.Conventional treatment modalities utilized to manage knee OA have limitations.Over the last decade,the role of various autologous peripheral blood-derived orthobiologics(APBOs)for the treatment of knee OA has been extensively investigated.This editorial provided an overview and focused on defining and shedding light on the current state of evidence based on the most recent published clinical studies concerning the use of APBO for the management of knee OA.While numerous studies have demonstrated promising results for these preparations,a notable gap exists in the comparative analysis of these diverse formulations.This absence of head-to-head studies poses a considerable challenge for physicians/surgeons in determining the optimal preparation for managing knee OA and achieving sustained longterm results.Thus,more adequately powered,multicenter,prospective,doubleblind,randomized controlled trials with longer follow-ups are needed to establish the long-term efficacy and to aid physicians/surgeons in determining the optimal APBO for the management of knee OA.

Study on compound Duzhong Jiangu granule in the treatment of knee osteoarthritis based on transcriptome analysis strategy

Duzhong Jiangu Granule in the treatment of primary osteoarthritis(POA)model of postmenopausal kidney deficiency type in Hartley female guinea pigs after ovariectomy,and the correlation between gene expression of bone marrow tissue,cartilage tissue,and knee osteoarthritis.Methods:383-months-old Hartley female guinea pigs after one week of adaptive feeding were weighed about 400 g±20 g,numbered,and sorted by ear tag.Six of them were selected as normal groups by looking up random number tables.The remainder were removed from the bilateral ovaries to construct the postmenopausal kidney deficiency model,and castrated guinea pigs were used to construct the postmenopausal kidney deficiency POA model.After the modeling cycle,a guinea pig from the blank group and a guinea pig from the model group were sacrificed and the right knee was observed.The model was established and the experiments continued.There were five guinea pigs in the blank group,and the remaining model guinea pigs were randomly divided into model control group,high-dose group of compound Duzhong Jiangu granules,middle-dose group of compound Duzhong Jiangu granules,low-dose group of compound Duzhong Jiangu granules and design group,with 5 guinea pigs in each group.Blanks and model groups were given a cellulose sodium solution by gavage.The guinea pigs were sacrificed after 30 days of intragastric administration.The left knee cartilage and bone marrow of the blank group,model group,middle dose group,and high dose group of compound Duzhong Jiangu granule were collected and applied to transcriptome sequencing,and the sequencing data were analyzed,including differential gene expression analysis,functional enrichment analysis of database established by Gene Ontology federation(GO)and Kyoto Encyclopedia of Gene and Genome(KEGG)pathway enrichment analysis.The complete specimens of the right knee joint were collected,and the morphological changes of the cartilage of the right knee joint in each group were observed by saffron rapid green staining,and the subchondral bone was quantitatively analyzed by Micro CT so that the expression of TRAF6,MIP-1βand IL-1βprotein in NF-kappa B signaling pathway was detected by Western Blot technique(WB).Results:The results of Safranin Fast Green staining showed that Compound Duzhong Jiangu Granules could effectively reduce the degree of morphological damage of articular cartilage in guinea pigs with the POA model.According to the analysis results of the subchondral bone structure under Micro CT,Compound Duzhong Jiangu Granules can improve the bone condition of the POA model,thus delaying the process of degenerative changes of the knee joint.From the results of transcriptome analysis,Compound Duzhong Jiangu Granules can inhibit the expression of related genes in POA model guinea pigs.According to the results of Wester Bolt verification,Compound Duzhong Jiangu Granules can effectively improve knee osteoarthritis.Conclusions:The effect of Compound Duzhong Jiangu Granules on OA is obvious,and its mechanism may be related to the expression of genes GZMK,Jchain,igkc,IGHV3-74,IGHV3-11,IGHV4-1,CCL5,and IGKV1–39.

Research Progress in Traditional Chinese Medicine Treatment of Knee Osteoarthritis

Knee osteoarthritis(KOA)is a degenerative disease characterized by pathological changes in the cartilage and subchondral bone of the knee joint.Initially,knee joint pain is the main symptom,and in the later stages,deformities and mobility disorders may occur.Modern medicine lacks effective treatment methods for early and mid stage KOA,and has drawbacks such as significant side effects and high costs.A large number of stud‐ies have confirmed that traditional Chinese medicine has unique advantages in treating KOA,and has obvious advantages such as small trauma,low cost,and definite therapeu‐tic effect,which are gradually being accepted by a large number of KOA patients.The commonly used methods for preventing and treating KOA with traditional Chinese medicine in clinical practice include:oral administration of traditional Chinese medi‐cine,external application of traditional Chinese medicine,fumigation,acupuncture therapy,massage therapy for regulating tendons,and targeted penetration therapy of tra‐ditional Chinese medicine.According to relevant literature,traditional Chinese medicine can significantly alleviate knee joint symptoms and improve knee joint function in patients with knee osteoarthritis,which is of great significance for the prevention and treatment of knee osteoarthritis.This article provides a review of the research progress in the prevention and treatment of KOA using traditional Chinese medicine in recent years.

关节镜下微创有限清理术治疗KOA 患者的效果观察

目的:探讨关节镜下微创有限清理术治疗膝骨性关节炎(KOA)的效果。方法:根据治疗方案将108例KOA患者分为两组,各54例。观察组行关节镜下微创有限清理术,对照组行关节镜下广泛清理术。比较两组临床疗效。结果:两组手术相关指标、血清指标、Toll样受体4(TLR4)/髓样分化因子88(MyD88)/核因子-κB(NF-κB)信号通路指标、动态足底受力时间指标、疼痛程度及膝关节功能方面比较,差异有统计学意义(P<0.05);两组术后并发症总发生率比较差异无统计学意义(P>0.05)。结论:关节镜下微创治疗KOA能优化手术流程,减轻炎症,改善膝关节功能,缓解患者疼痛,且安全性较高。

Comparative effectiveness of adipose-derived mesenchymal stromal cells in the management of knee osteoarthritis:A meta-analysis

BACKGROUND Osteoarthritis(OA)is the most common joint disorder,is associated with an increasing socioeconomic impact owing to the ageing population.AIM To analyze and compare the efficacy and safety of bone-marrow-derived mesenchymal stromal cells(BM-MSCs)and adipose tissue-derived MSCs(AD-MSCs)in knee OA management from published randomized controlled trials(RCTs).METHODS Independent and duplicate electronic database searches were performed,including PubMed,EMBASE,Web of Science,and Cochrane Library,until August 2021 for RCTs that analyzed the efficacy and safety of AD-MSCs and BM-MSCs in the management of knee OA.The visual analog scale(VAS)score for pain,Western Ontario McMaster Universities Osteoarthritis Index(WOMAC),Lysholm score,Tegner score,magnetic resonance observation of cartilage repair tissue score,knee osteoarthritis outcome score(KOOS),and adverse events were analyzed.Analysis was performed on the R-platform using OpenMeta(Analyst)software.Twenty-one studies,involving 936 patients,were included.Only one study compared the two MSC sources without patient randomization;hence,the results of all included studies from both sources were pooled,and a comparative critical analysis was performed.RESULTS At six months,both AD-MSCs and BM-MSCs showed significant VAS improvement(P=0.015,P=0.012);this was inconsistent at 1 year for BM-MSCs(P<0.001,P=0.539),and AD-MSCs outperformed BM-MSCs compared to controls in measures such as WOMAC(P<0.001,P=0.541),Lysholm scores(P=0.006;P=0.933),and KOOS(P=0.002;P=0.012).BM-MSC-related procedures caused significant adverse events(P=0.003)compared to AD-MSCs(P=0.673).CONCLUSION Adipose tissue is superior to bone marrow because of its safety and consistent efficacy in improving pain and functional outcomes.Future trials are urgently warranted to validate our findings and reach a consensus on the ideal source of MSCs for managing knee OA.

Mid-term outcomes of microfragmented adipose tissue plus arthroscopic surgery for knee osteoarthritis:A randomized,activecontrol,multicenter clinical trial

BACKGROUND Osteoarthritis(OA)is the most prevalent form of degenerative whole-joint disease.Before the final option of knee replacement,arthroscopic surgery was the most widely used joint-preserving surgical treatment.Emerging regenerative therapies,such as those involving platelet-rich plasma,mesenchymal stem cells,and microfragmented adipose tissue(MFAT),have been pushed to the forefront of treatment to prevent the progression of OA.Currently,MFAT has been successfully applied to treat different types of orthopedic diseases.AIM To assess the efficacy and safety of MFAT with arthroscopic surgery in patients with knee OA(KOA).METHODS A randomized,multicenter study was conducted between June 2017 and November 2022 in 10 hospitals in Zhejiang,China.Overall,302 patients diagnosed with KOA(Kellgren-Lawrence grades 2-3)were randomized to the MFAT group(n=151,were administered MFAT following arthroscopic surgery),or the control group(n=151,were administered hyaluronic acid following arthroscopic surgery).The study outcomes were changes in the Western Ontario and McMaster Universities Osteoarthritis Index(WOMAC)score,the visual analog scale(VAS)score,the Lequesne index score,the Whole-Organ Magnetic Resonance Imaging Score(WORMS),and safety over a 24-mo period from baseline.RESULTS The changes in the WOMAC score(including the three subscale scores),VAS pain score,and Lequesne index score at the 24-mo mark were significantly different in the MFAT and control groups,as well as when comparing values at the posttreatment visit and those at baseline(P<0.001).The MFAT group consistently demonstrated significant decreases in the WOMAC pain scores and VAS scores at all follow-ups compared to the control group(P<0.05).Furthermore,the WOMAC stiffness score,WOMAC function score,and Lequesne index score differed significantly between the groups at 12 and 24 mo(P<0.05).However,no signicant between-group differences were observed in the WORMS at 24 mo(P=0.367).No serious adverse events occurred in both groups.CONCLUSION The MFAT injection combined with arthroscopic surgery treatment group showed better mid-term clinical outcomes compared to the control group,suggesting its efficacy as a therapeutic approach for patients with KOA.

Clinical value of ankle flexion and extension exercises combined with a psychological intervention in knee osteoarthritis

BACKGROUND Considering the limited effectiveness of clinical interventions for knee osteoarthritis(KOA),it is necessary to continue to explore appropriate and effective treatment strategies to improve the condition of KOA patients.AIM To clarify the influence of ankle flexion and extension exercises combined with a psychological intervention on the psychological status and activities of daily living(ADLs)of patients with KOA.METHODS The research participants were 116 KOA patients admitted to The First Affiliated Hospital of Guizhou University of Traditional Chinese Medicine between May 2019 and May 2022,including 54 patients receiving routine treatment,care and psychological intervention(control group)and 62 patients additionally treated with ankle flexion and extension exercises(research group).The two groups were comparatively analyzed in terms of psychological status(Self-rating Anxiety/Depression Scale,SDS/SAS),ADLs,knee joint function(Lysholm Knee Scoring Scale),pain(Visual Analog Scale,VAS),fatigue(Multidimensional Fatigue Inventory,MFI),and quality of life(QoL;Short-Form 36 Item Health Survey,SF-36).RESULTS After evaluation,it was found that the postinterventional SDS,SAS,VAS,and MFI scores in the research group were significantly reduced compared with the baseline(before the intervention)values and those of the control group,while the postinterventional Lysholm,ADL and SF-36 scores were markedly elevated.CONCLUSION Therefore,ankle flexion and extension exercises are highly effective in easing negative psychological status,enhancing ADLs,daily living ability,knee joint function and QoL,and relieving pain and fatigue in KOA patients,thus warranting clinical promotion.

There is more to the knee joint than just the quadriceps:A systematic review with meta-analysis and evidence gap map of hamstring strength,flexibility,and morphology in individuals with gradual-onset knee disorders

Background:Impairments in hamstring strength,flexibility,and morphology have been associated with altered knee biomechanics,pain,and function.Determining the presence of these impairments in individuals with gradual-onset knee disorders is important and may indicate targets for assessment and rehabilitation.This systematic review aimed to synthesize the literature to determine the presence of impairments in hamstring strength,flexibility,and morphology in individuals with gradual-onset knee disorders.Methods:Five databases(MEDLINE,Embase,CINAHL,SPORTDiscus,and Web of Science)were searched from inception to September 2022.Only studies comparing hamstring outcomes(e.g.,strength,flexibility,and/or morphology)between individuals with gradual-onset knee disorders and their unaffected limbs or pain-free controls were included.Meta-analyses for each knee disorder were performed.Outcome-level certainty was assessed using the Grading of Recommendations Assessment,Development,and Evaluation,and evidence gap maps were created.Results:Seventy-nine studies across 4 different gradual-onset knee disorders(i.e.,knee osteoarthritis(OA),patellofemoral pain(PFP),chondromalacia patellae,and patellar tendinopathy)were included.Individuals with knee OA presented with reduced hamstring strength compared to pain-free controls during isometric(standard mean difference(SMD)=-0.76,95%confidence interval(95%CI):-1.32 to-0.21)and concentric contractions(SMD=-0.97,95%CI:-1.49 to-0.45).Individuals with PFP presented with reduced hamstring strength compared to painfree controls during isometric(SMD=-0.48,95%CI:-0.82 to-0.14),concentric(SMD=-1.07,95%CI:-2.08 to-0.06),and eccentric contractions(SMD=-0.59,95%CI:-0.97 to-0.21).No differences were observed in individuals with patellar tendinopathy.Individuals with PFP presented with reduced hamstring flexibility when compared to pain-free controls(SMD=-0.76,95%CI:-1.15 to-0.36).Evidence gap maps identified insufficient evidence for chondromalacia patellae and hamstring morphology across all gradual-onset knee disorders.Conclusion:Our findings suggest that assessing and targeting impairments in hamstring strength and flexibility during rehabilitation may be recommended for individuals with knee OA or PFP.

膝三针温针灸配合微波照射治疗KOA的疗效及对微循环、血管炎症的影响

目的探讨膝三针温针灸配合微波照射治疗膝关节骨性关节炎(KOA)的疗效及对微循环、血管炎症的影响。方法将2021年1月至2022年3月该院收治的104例KOA患者按随机数字表法分为观察组和对照组,每组52例。对照组采用微波照射治疗,观察组在其基础上联合膝三针温针灸治疗。比较两组治疗疗效、膝关节功能[采用Lysholm-Ⅱ量表(Lysholm得分)进行评估]、不良反应,治疗前后血清骨代谢[Ⅰ型胶原C-末端肽(CTX-Ⅰ)、软骨寡聚基质蛋白(COMP)、基质金属蛋白酶-3(MMP-3)]、炎症指标[白细胞介素-7R(IL-7R)、白细胞介素-1β(IL-1β)、Toll样受体4(TLR4)、核因子-κB p65(NF-κB p65)]以及患侧腿股内侧肌微循环指标[血细胞浓度(CMBC)、微血管血流灌注量(MBP)、血细胞平均运动速度(AVBC)增加率]变化。结果观察组治疗总有效率为86.54%,高于对照组的69.23%(P<0.05)。重复测量方差分析结果显示,两组Lysholm得分存在时间效应、组间效应及交互效应(P<0.001),故进一步做单独效应分析。单因素重复测量方差分析结果显示,观察组与对照组不同时间点Lysholm得分比较,差异均有统计学意义(F=178.205、150.612,P<0.001)。两组Lysholm得分均表现为治疗前<治疗后2周<治疗后4周<治疗后6周,且任意两个时间比较,差异均有统计学意义(P<0.05)。多变量方差分析结果显示,观察组治疗后2周、4周、6周Lysholm得分均高于对照组(F=10.500、13.252、18.120,P<0.001)。治疗后,两组血清COMP、MMP-3及CTX-Ⅰ水平均较治疗前降低(P<0.05);且治疗后观察组血清COMP、MMP-3及CTX-Ⅰ水平低于对照组(P<0.05)。治疗后,两组血清TLR4、NF-κB p65、IL-1β水平均较治疗前降低(P<0.05),IL-7R水平较治疗前升高(P<0.05);且治疗后观察组血清TLR4、NF-κB p65、IL-1β水平低于对照组(P<0.05),IL-7R水平高于对照组(P<0.05)。治疗后,两组MBP、CMBC增加率均较治疗前升高(P<0.05),AVBC增加率与治疗前比较,差异无统计学意义(P>0.05);治疗后,观察组MBP、CMBC增加率大于对照组(P<0.05),两组AVBC增加率比较,差异无统计学意义(P>0.05)。观察组、对照组不良反应总发生率分别为23.08%、19.23%,差异无统计学意义(P>0.05)。结论膝三针温针灸配合微波照射治疗可以显著提高KOA的疗效,改善患者膝关节功能和骨代谢状况,促进局部微循环,改善血管炎症。

桂枝调节RIPK1/RIPK3信号通路干预KOA小鼠软骨坏死性凋亡

目的 基于RIPK1/RIPK3信号通路探讨桂枝治疗膝骨关节炎(knee osteoarthritis, KOA)小鼠软骨细胞坏死性凋亡的作用机制。方法 选取48只雄性C57小鼠,随机分为空白组、造模组、Nec-1组[5 mg/(kg·d),腹腔注射给药]、桂枝低剂量组[0.43 g/(kg·d),灌胃给药]、桂枝中剂量组[0.65 g/(kg·d),灌胃给药]、桂枝高剂量组[2.6 g/(kg·d),灌胃给药]。除空白组外均采用内侧半月板失稳法构建KOA小鼠模型,经药物干预28 d后,取小鼠血清及软骨组织,采用HE染色及番红O-固绿染色观察小鼠膝关节组织病理形态;免疫荧光分析小鼠软骨RIPK3表现情况;使用qRT-PCR及Western Blot检测RIPK1、RIPK3、p-RIPK1、p-RIPK3等相关mRNA及蛋白表达;使用ELISA检测TNF-α、IL-1β、IL-6含量。结果 与正常组相比,造模组小鼠关节软骨边缘严重破坏,RIPK1、RIPK3、p-RIPK1、p-RIPK3的mRNA及蛋白表达明显升高(P<0.05),TNF-α、IL-1β、IL-6含量明显升高(P<0.05);桂枝低剂量、中剂量、高剂量组及Nec-1组软骨结构趋于正常,RIPK1、RIPK3、p-RIPK1、p-RIPK3的mRNA及蛋白表达明显降低(P<0.05),IL-1β、IL-6、TNF-α含量明显降低(P<0.05)。结论 桂枝可以通过调节RIPK1/RIPK3信号通路,抑制膝关节软骨细胞坏死性凋亡,从而改善小鼠膝关节炎症环境,延缓KOA病理进程。

Effects of acupotomy on the activity of osteoclasts and osteoblasts in the subchondral bone of rabbits with early and mid-stage knee osteoarthritis models

Objective:To investigate whether acupotomy could inhibit subchondral bone remodeling in knee osteoarthritis(KOA)rabbits by regulating the activity of osteoblasts and osteoclasts.Methods:KOA rabbits were prepared by immobilization for 6 and 9 weeks by Videman method.Nine groups of rabbits(control,6 weeks and 9 weeks model,6 weeks and 9 weeks acupotomy,6 weeks and 9 weeks electroacupuncture,and 6 weeks and 9 weeks drug groups)received acupotomy,electroacupuncture and risedronate sodium intervention,respectively,for 3 weeks.Results:Acupotomy can inhibit the activity of osteoclasts and osteoblasts in subchondral bone by reducing the proteins expression of cathepsin K(CK)and tartrate-resistant acid phosphatase(TRAP)and decreasing the proteins expression of osteocalcin(OCN)and alkaline phosphatase(ALP),to intercept the abnormal bone resorption and bone formation of subchondral bone in 6-week and 9-week immobilization-induced KOA rabbits.Conclusion:These findings indicated that acupotomy may be more advantageous than risedronate sodium intervention in modulating subchondral bone remodeling in KOA rabbits,especially in 9-week immobilization-induced KOA rabbits.

电针对KOA大鼠关节软骨及软骨下骨降解相关蛋白表达的影响

目的:探讨电针对KOA大鼠关节软骨及软骨下骨降解相关蛋白表达的影响。方法:16只24月龄SD雄性大鼠随机分为老年组和电针组各8只,另8只6月龄SD雄性大鼠为青年组。电针组接受电针治疗(穴位:双侧“太溪”“足三里”“阳陵泉”“血海”;电针参数:疏密波,密波15Hz,疏波3Hz,电流1mA,每天1次,每次30min,每周5天,连续干预8周),其余两组不做处理。干预8周后取材,ELISA法检测血清Ⅱ型胶原C端肽(CTX-Ⅱ)含量;显微CT检测左侧胫骨软骨下骨微结构;番红-固绿染色在光镜下观察左胫骨平台软骨组织形态结构,改良Mankin’s评分评估关节软骨退变程度;RT-qPCR、Western blot检测aggrecanase-2、SIRT1 mRNA及蛋白表达水平。结果:(1)与青年组大鼠相比,老年组CTX-Ⅱ含量增高(P<0.05);番红-固绿染色显示老年组软骨表面结构破坏严重,出现裂层,软骨与软骨下骨分界不清,形态结构异常,染色不均;改良Mankin’s评分增加(P<0.05);骨密度、骨体积分数、骨小梁数量减少(P<0.05),骨小梁间距增大(P<0.05);aggrecanase-2 mRNA及蛋白表达升高(P<0.05),SIRT1 mRNA及蛋白表达降低(P<0.05)。(2)与老年组大鼠相比,电针组大鼠的CTX-Ⅱ含量降低(P<0.05);番红-固绿染色显示软骨表面平整,未见明显裂层,染色较均匀;改良Mankin’s评分降低(P<0.05);骨密度增加(P<0.05),骨小梁间距减少(P<0.05),骨体积分数、骨小梁数量有增加的趋势(P>0.05),aggrecanase-2 mRNA及蛋白表达降低(P<0.05),SIRT1 mRNA及蛋白表达升高(P<0.05)。结论:电针可通过促进SIRT1的表达,抑制关节软骨降解,改善软骨下骨骨微结构,从而保护关节软骨。

Detection Algorithm of Knee Osteoarthritis Based on Magnetic Resonance Images

Knee osteoarthritis(OA)is a common disease that impairs knee function and causes pain.Currently,studies on the detection of knee OA mainly focus on X-ray images,but X-ray images are insensitive to the changes in knee OA in the early stage.Since magnetic resonance(MR)imaging can observe the early features of knee OA,the knee OA detection algorithm based on MR image is innovatively proposed to judge whether knee OA is suffered.Firstly,the knee MR images are preprocessed before training,including a region of interest clipping,slice selection,and data augmentation.Then the data set was divided by patient-level and the knee OA was classified by the deep transfer learning method based on the DenseNet201 model.The method divides the training process into two stages.The first stage freezes all the base layers and only trains the weights of the embedding neural networks.The second stage unfreezes part of the base layers and trains the unfrozen base layers and the weights of the embedding neural network.In this step,we design a block-by-block fine-tuning strategy for training based on the dense blocks,which improves detection accuracy.We have conducted training experiments with different depth modules,and the experimental results show that gradually adding more dense blocks in the fine-tuning can make the model obtain better detection performance than only training the embedded neural network layer.We achieve an accuracy of 0.921,a sensitivity of 0.960,a precision of 0.885,a specificity of 0.891,an F1-Score of 0.912,and an MCC of 0.836.The comparative experimental results on the OAI-ZIB dataset show that the proposed method outperforms the other detection methods with the accuracy of 92.1%.

Randomized, Double-Blind, Double-Masked, Parallel Group Clinical Study to Compare the Effectiveness of Diclofenac Potassium 150 mg, LP OD, vs Diclofenac Potassium 50 mg, TID, Three Times a Day, in Knee Osteoarthritis

Background: Osteoarthritis is a chronic disease associated with pain, inflammation, stiffness and synovial effusion, with progressive functional limitation, compromising quality of life. It progressively leads to loss or decrease in joint function. Pharmacological and non-pharmacological therapy seeks symptomatic management, complicated by a lack of adherence. After acetaminophen, non-steroidal anti-inflammatory drugs such as diclofenac are the most widely used medications. Objectives: The primary objective compared the analgesic effect of diclofenac 150 mg once daily vs. 50 mg three times daily in patients with knee osteoarthritis. The secondary objective assessed changes in quality of life. Method: One group received diclofenac 150 mg OD with placebo TTD. Another group received placebo OD and 50 mg active diclofenac (reference) TTD, both for 30 days. The evaluation of pain was carried out by a visual analog scale (VAS), at the beginning, 2, 3, 4, 15 and 30 days, quality of life (the WOMAC scale) and adverse effects, at 15 and 30 days. Results: Pain decreased significantly on days 15 and 30, compared to day 0, in both groups, without differences between groups. The total results in the WOMAC scale showed a very marked improvement at 15 and 30 days, without differences between groups. The most frequent adverse effects were constipation 6% in the reference group, and gastric discomfort 30.3% in the reference group vs 28.1%, in the Test group. Conclusions: Prolonged-release diclofenac 150 mg OD is as effective as diclofenac 50 mg TID for the treatment of patients with knee osteoarthritis.