BACKGROUND For patients with acute paraplegia caused by spinal giant cell tumor(GCT)who require emergency decompressive surgery,there is still a lack of relevant reports on surgical options.This study is the first to ...BACKGROUND For patients with acute paraplegia caused by spinal giant cell tumor(GCT)who require emergency decompressive surgery,there is still a lack of relevant reports on surgical options.This study is the first to present the case of an acute paraplegic patient with a thoracic spinal GCT who underwent an emergency total en bloc spondylectomy(TES).Despite tumor recurrence,three-level TES was repeated after denosumab therapy.CASE SUMMARY A 27-year-old female patient who underwent single-level TES in an emergency presented with sudden severe back pain and acute paraplegia due to a thoracic spinal tumor.After emergency TES,the patient's spinal cord function recovered,and permanent paralysis was avoided.The postoperative histopathological examination revealed that the excised neoplasm was a rare GCT.Unfortunately,the tumor recurred 9 months after the first surgery.After 12 months of denosumab therapy,the tumor size was reduced,and tumor calcification.To prevent recurrent tumor progression and provide a possible cure,a three-level TES was performed again.The patient returned to an active lifestyle 1 month after the second surgery,and no recurrence of GCT was found at the last follow-up.CONCLUSION This patient with acute paraplegia underwent TES twice,including once in an emergency,and achieved good therapeutic results.TES in emergency surgery is feasible and safe when conditions permit;however,it may increase the risk of tumor recurrence.展开更多
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...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.展开更多
Objective:Smart insufflation(SI)techniques relying on valve and membrane-free insufflation are increasing in usage.Although considerable literature exists demonstrating the benefits of SI on procedural ease and patien...Objective:Smart insufflation(SI)techniques relying on valve and membrane-free insufflation are increasing in usage.Although considerable literature exists demonstrating the benefits of SI on procedural ease and patient outcomes,there remains a paucity describing the financial impact of these devices.The purpose of this study was to determine the financial and efficiency impact of these devices on the operating room and inpatient wards of a hospital.Methods:A discrete event simulation model representing a typical mid-sized North American hospital comparing SI to traditional insufflation(TI)was generated.The National Surgical Quality Improvement database from 2015 to 2019 was used to populate the model with data supplemented from the literature.Outcomes included length of stay(LOS),duration of surgery(DOS),annual procedure volume,profit,return on investment(ROI),and gross profit margin(GPM).From the literature review,DOS savings were 10e32 minutes/case,while LOS savings were 0e3 days/case.Results:Implementation of an SI led to an increase in annual throughput of 42e346(4.4%e36.6%)cases for all procedures and 38 to 297(4.3%e33.3%)cases for complex procedures.LOS was found to be decreased by 175e614(18.3%e64.2%)days for all procedures and 231 to 614(35.6%e77.9%)cases for complex procedures with the implementation of an SI.Together,this resulted in an increase in net profit of$104,685 per annum.The ROI of SI over the TI device was>1000%,and the GPM for the TI was 90.0%,while the GPM for the SI was 71.7%.Conclusion:Despite the initial financial investment being greater,the implementation of SI offsets these expenses and yields significant financial benefits.Our study demonstrates the financial benefits of SI over TI and illustrates how granular operational and financial analyses of technologies are essential to aid in sound healthcare procurement decision making.展开更多
BACKGROUND It has been said that the number of orthopaedic claims has increased in the last few years. Investigation through the most prevalent cause would help to prevent further cases.AIM To review the cases of medi...BACKGROUND It has been said that the number of orthopaedic claims has increased in the last few years. Investigation through the most prevalent cause would help to prevent further cases.AIM To review the cases of medical complaints in orthopedic patients who had been involved in a traumatic accident.METHODS A retrospective multi-center review of trauma orthopaedic-related malpractice lawsuits from 2010 to 2021 was conducted utilizing the regional medicolegal database. Defendant and plaintiff characteristics along with fracture location, allegations, and litigation outcomes were investigated.RESULTS A total of 228 claims referred to trauma-related conditions with a mean age of 31.29 ± 12.56 were enrolled. The most common injuries were at hand, thigh, elbow, and forearm, respectively.Likewise, the most common alleged complication was related to malunion or nonunion. In 47% of the cases, the main problem that led to the complaint was the inappropriate or insufficient explanation to the patient, and in 53%, there was a problem in the surgery. Eventually, 76% of the complaints resulted in a defense verdict, and 24% resulted in a plaintiff verdict.CONCLUSION Surgical treatment of hand injuries and surgery in non-educational hospitals received the most complaints. The majority of litigation outcomes were caused by a physician’s failure to fully explain and educate the traumatic orthopedic patients and technological errors.展开更多
BACKGROUND Septic arthritis of the knee in children is a challenging problem.Surgical debridement is an established treatment,but there is a paucity of literature on long-term prognosis.AIM To determine the rates and ...BACKGROUND Septic arthritis of the knee in children is a challenging problem.Surgical debridement is an established treatment,but there is a paucity of literature on long-term prognosis.AIM To determine the rates and factors associated with return to surgery(RTS)and readmission after index surgical debridement for septic arthritis of the knee in children.METHODS This is a retrospective cohort study that utilizes data from the Healthcare Cost and Utilization Project(HCUP).We included patients between ages 0 to 18 years that underwent surgical debridement for septic arthritis of the knee between 2005 and 2017.Demographic data included age,gender,race,hospital type and insurance type.Clinical data including index admission length of stay(LOS)and Charlson Comorbidity Index(CCI)were available from the HCUP database.Descriptive statistics were used to summarize the data and univariate and multivariate analyses were performed.RESULTS Nine-hundred thirty-two cases of pediatric septic knee were included.This cohort was 62.3%male,with mean age of 9.0(±6.1)years.Approximately 46%of patients were white and approximately half had Medicaid insurance.Thirty-six patients(3.6%)required RTS at a minimum of 2 year after index surgery,and 172 patients(18.5%)were readmitted at any point.The mean readmission LOS was 11.6(±11.3)d.Higher CCI was associated with RTS(P=0.041).There were no significant associations in age,gender,race,insurance type,or type of hospital to which patients presented.Multivariate analysis showed that both increased CCI(P=0.008)and shorter LOS(P=0.019)were predictive of RTS.CONCLUSION Septic arthritis of the knee is an important condition in children.The CCI was associated with RTS at a minimum of 2 years after index procedure.No association was found with age,gender,race,insurance type,or hospital type.Shorter LOS and CCI were associated with RTS in multivariate analysis.Overall,risk of subsequent surgery and readmission after pediatric septic knee arthritis is low,and CCI and shorter LOS are predictive of RTS.展开更多
Mechanically aligned total knee arthroplasty (TKA) for valgus knee is considered a “challenging surgery.” Recently, the kinematic alignment (KA) method has gained attention. This study aimed to present objective cli...Mechanically aligned total knee arthroplasty (TKA) for valgus knee is considered a “challenging surgery.” Recently, the kinematic alignment (KA) method has gained attention. This study aimed to present objective clinical data, such as intraoperative balance assessment and radiographic evaluation of postoperative lower extremity alignment after TKA using the KA method for valgus deformity. Twenty-one TKA knees (mean age, 74 years;2 males, 19 females) with KA for severe valgus deformity (hip-knee-ankle-angle ≥ 10°) performed at our department in the past 3 years were included in this study. Intraoperative gap and balance measurements and postoperative radiographic evaluation were performed. A total arc of range of motion was achieved up to 98% of preoperative values at 3 weeks postoperatively. Intraoperative gap and balance were stable throughout the entire range of motion. In addition, there were no statistically significant differences in either balance or gap values at each flexion angle. KA TKA is a “simple surgery” rather than a “challenging surgery” because additional soft tissue procedures are not required, operative time is short, intraoperative and postoperative balance is very stable, and a good alignment is achieved. This procedure may relieve surgeons of the stress of TKA for valgus deformities.展开更多
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...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.展开更多
Disc degeneration primarily contributes to chronic low back and neck pain.Consequently,there is an urgent need to understand the spectrum of disc degeneration phenotypes such as fibrosis,ectopic calcification,herniati...Disc degeneration primarily contributes to chronic low back and neck pain.Consequently,there is an urgent need to understand the spectrum of disc degeneration phenotypes such as fibrosis,ectopic calcification,herniation,or mixed phenotypes.Amongst these phenotypes,disc calcification is the least studied.Ectopic calcification,by definition,is the pathological mineralization of soft tissues,widely studied in the context of conditions that afflict vasculature,skin,and cartilage.Clinically,disc calcification is associated with poor surgical outcomes and back pain refractory to conservative treatment.It is frequently seen as a consequence of disc aging and progressive degeneration but exhibits unique molecular and morphological characteristics:hypertrophic chondrocyte-like cell differentiation;TNAP,ENPP1,and ANK upregulation;cell death;altered Pi and PPi homeostasis;and local inflammation.Recent studies in mouse models have provided a better understanding of the mechanisms underlying this phenotype.It is essential to recognize that the presentation and nature of mineralization differ between AF,NP,and EP compartments.Moreover,the combination of anatomic location,genetics,and environmental stressors,such as aging or trauma,govern the predisposition to calcification.Lastly,the systemic regulation of calcium and Pi metabolism is less important than the local activity of PPi modulated by the ANK-ENPP1 axis,along with disc cell death and differentiation status.While there is limited understanding of this phenotype,understanding the molecular pathways governing local intervertebral disc calcification may lead to developing disease-modifying drugs and better clinical management of degeneration-related pathologies.展开更多
BACKGROUND Total knee arthroplasty(TKA)is a mature procedure recommended for correcting knee osteoarthritis deformity,relieving pain,and restoring normal biomechanics.Although TKA is a successful and cost-effective pr...BACKGROUND Total knee arthroplasty(TKA)is a mature procedure recommended for correcting knee osteoarthritis deformity,relieving pain,and restoring normal biomechanics.Although TKA is a successful and cost-effective procedure,patient dissatisfaction is as high as 50%.Knee pain after TKA is a significant cause of patient dissatisfaction;the most common location for residual pain is the anterior region.Between 4%and 40%of patients have anterior knee pain(AKP).AIM To investigate the effect of various TKA procedures on postoperative AKP.METHODS We searched PubMed,EMBASE,and Cochrane from January 2000 to September 2022.Randomized controlled trials with one intervention in the experimental group and no corresponding intervention(or other interventions)in the control group were collected.Two researchers independently read the title and abstract of the studies,preliminarily screened the articles,and read the full text in detail according to the selection criteria.Conflicts were resolved by consultation with a third researcher.And relevant data from the included studies were extracted and analyzed using Review Manager 5.4 software.RESULTS There were 25 randomized controlled trials;13 were comparative studies with or without patellar resurfacing.The meta-analysis showed no significant difference between the experimental and control groups(P=0.61).Six studies were comparative studies of circumpatellar denervation vs non-denervation,divided into three subgroups for meta-analysis.The two-subgroup meta-analysis showed no significant difference between the experimental and the control groups(P=0.31,P=0.50).One subgroup meta-analysis showed a significant difference between the experimental and control groups(P=0.001).Two studies compared fixed-bearing TKA and mobile-bearing TKA;the results meta-analysis showed no significant difference between the experimental and control groups(P=0.630).Two studies compared lateral retinacular release vs non-release;the meta-analysis showed a significant difference between the experimental and control groups(P=0.002);two other studies compared other factors.CONCLUSION Patellar resurfacing,mobile-bearing TKA,and fixed-bearing TKA do not reduce the incidence of AKP.Lateral retinacular release can reduce AKP;however,whether circumpatellar denervation can reduce AKP is controversial.展开更多
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 pat...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.展开更多
BACKGROUND Total hip arthroplasty is as an effective intervention to relieve pain and improve hip function.Approaches of the hip have been exhaustively explored about pros and cons.The efficacy and the complications o...BACKGROUND Total hip arthroplasty is as an effective intervention to relieve pain and improve hip function.Approaches of the hip have been exhaustively explored about pros and cons.The efficacy and the complications of hip approaches remains inconclusive.This study conducted an umbrella review to systematically appraise previous meta-analysis(MAs)including conventional posterior approach(PA),and minimally invasive surgeries as the lateral approach(LA),direct anterior approach(DAA),2-incisions method,mini-lateral approach and the newest technique direct superior approach(DSA)or supercapsular percutaneouslyassisted total hip(SuperPath).AIM To compare the efficacy and complications of hip approaches that have been published in all MAs and randomized controlled trials(RCTs).METHODS MAs were identified from MEDLINE and Scopus from inception until 2023.RCTs were then updated from the latest MA to September 2023.This study included studies which compared hip approaches and reported at least one outcome such as Harris Hip Score(HHS),dislocation,intra-operative fracture,wound compliData were independently selected,extracted and assessed by two reviewers.Network MA and cluster rank and surface under the cumulative ranking curve(SUCRA)were estimated for treatment efficacy and safety.RESULTS Finally,twenty-eight MAs(40 RCTs),and 13 RCTs were retrieved.In total 47 RCTs were included for reanalysis.The results of corrected covered area showed high degree(13.80%).Among 47 RCTs,most of the studies were low risk of bias in part of random process and outcome reporting,while other domains were medium to high risk of bias.DAA significantly provided higher HHS at three months than PA[pooled unstandardized mean difference(USMD):3.49,95%confidence interval(CI):0.98,6.00 with SUCRA:85.9],followed by DSA/SuperPath(USMD:1.57,95%CI:-1.55,4.69 with SUCRA:57.6).All approaches had indifferent dislocation and intraoperative fracture rates.SUCRA comparing early functional outcome and composite complications(dislocation,intra-operative fracture,wound complication,and nerve injury)found DAA was the best approach followed by DSA/SuperPath.CONCLUSION DSA/SuperPath had better earlier functional outcome than PA,but still could not overcome the result of DAA.This technique might be the other preferred option with acceptable complications.展开更多
The integrated repair of bone and cartilage boasts advantages for osteochondral restoration such as a long-term repair effect and less deterioration compared to repairing cartilage alone.Constructing multifactorial,sp...The integrated repair of bone and cartilage boasts advantages for osteochondral restoration such as a long-term repair effect and less deterioration compared to repairing cartilage alone.Constructing multifactorial,spatially oriented scaffolds to stimulate osteochondral regeneration,has immense significance.Herein,targeted drugs,namely kartogenin@polydopamine(KGN@PDA)nanoparticles for cartilage repair and miRNA@calcium phosphate(miRNA@CaP)NPs for bone regeneration,were in situ deposited on a patterned supramolecular-assembled 2-ureido-4[lH]-pyrimidinone(UPy)modified gelation hydrogel film,facilitated by the dynamic and responsive coordination and complexation of metal ions and their ligands.This hydrogel film can be rolled into a cylindrical plug,mimicking the Haversian canal structure of natural bone.The resultant hydrogel demonstrates stable mechanical properties,a self-healing ability,a high capability for reactive oxygen species capture,and controlled release of KGN and miR-26a.In vitro,KGN@PDA and miRNA@CaP promote chondrogenic and osteogenic differentiation of mesenchymal stem cells via the JNK/RUNX1 and GSK-3β/β-catenin pathways,respectively.In vivo,the osteochondral plug exhibits optimal subchondral bone and cartilage regeneration,evidenced by a significant increase in glycosaminoglycan and collagen accumulation in specific zones,along with the successful integration of neocartilage with subchondral bone.This biomaterial delivery approach represents a significant toward improved osteochondral repair.展开更多
Osteoarthritis(OA)is a common degenerative disease worldwide and new therapeutics that target inflammation and the crosstalk between immunocytes and chondrocytes are being developed to prevent and treat OA.These attem...Osteoarthritis(OA)is a common degenerative disease worldwide and new therapeutics that target inflammation and the crosstalk between immunocytes and chondrocytes are being developed to prevent and treat OA.These attempts involve repolarizing pro-inflammatory M1 macrophages into the anti-inflammatory M2 phenotype in synovium.In this study,we found that phosphoglycerate mutase 5(PGAM5)significantly increased in macrophages in OA synovium compared to controls based on histology of human samples and single-cell RNA sequencing results of mice models.To address the role of PGAM5 in macrophages in OA,we found conditional knockout of PGAM5 in macrophages greatly alleviated OA symptoms and promoted anabolic metabolism of chondrocytes in vitro and in vivo.Mechanistically,we found that PGAM5 enhanced M1 polarization via AKT-mTOR/p38/ERK pathways,whereas inhibited M2 polarization via STAT6-PPARγpathway in murine bone marrow-derived macrophages.Furthermore,we found that PGAM5 directly dephosphorylated Dishevelled Segment Polarity Protein 2(DVL2)which resulted in the inhibition ofβ-catenin and repolarization of M2 macrophages into M1 macrophages.Conditional knockout of both PGAM5 andβ-catenin in macrophages significantly exacerbated osteoarthritis compared to PGAM5-deficient mice.Motivated by these findings,we successfully designed mannose modified fluoropolymers combined with siPGAM5 to inhibit PGAM5 specifically in synovial macrophages via intra-articular injection,which possessed desired targeting abilities of synovial macrophages and greatly attenuated murine osteoarthritis.Collectively,these findings defined a key role for PGAM5 in orchestrating macrophage polarization and provides insights into novel macrophage-targeted strategy for treating OA.展开更多
Background: The growth and use of Artificial Intelligence (AI) in the medical field is rapidly rising. AI is exhibiting a practical tool in the healthcare industry in patient care. The objective of this current review...Background: The growth and use of Artificial Intelligence (AI) in the medical field is rapidly rising. AI is exhibiting a practical tool in the healthcare industry in patient care. The objective of this current review is to assess and analyze the use of AI and its use in orthopedic practice, as well as its applications, limitations, and pitfalls. Methods: A review of all relevant databases such as EMBASE, Cochrane Database of Systematic Reviews, MEDLINE, Science Citation Index, Scopus, and Web of Science with keywords of AI, orthopedic surgery, applications, and drawbacks. All related articles on AI and orthopaedic practice were reviewed. A total of 3210 articles were included in the review. Results: The data from 351 studies were analyzed where in orthopedic surgery. AI is being used for diagnostic procedures, radiological diagnosis, models of clinical care, and utilization of hospital and bed resources. AI has also taken a chunk of share in assisted robotic orthopaedic surgery. Conclusions: AI has now become part of the orthopedic practice and will further increase its stake in the healthcare industry. Nonetheless, clinicians should remain aware of AI’s serious limitations and pitfalls and consider the drawbacks and errors in its use.展开更多
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 poo...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.展开更多
Interfering with the ferroptosis pathway is a new strategy for the treatment of spinal cord injury.Fibroblast growth factor 21 can inhibit ferro ptosis and promote neurofunctional recovery,while heme oxygenase-1 is a ...Interfering with the ferroptosis pathway is a new strategy for the treatment of spinal cord injury.Fibroblast growth factor 21 can inhibit ferro ptosis and promote neurofunctional recovery,while heme oxygenase-1 is a regulator of iron and reactive oxygen species homeostasis.The relationship between heme oxygenase-1and ferroptosis remains controve rsial.In this study,we used a spinal co rd injury rat model to show that the levels of fibroblast growth factor 21 in spinal co rd tissue decreased after spinal cord injury.In addition,there was a significant aggravation of ferroptosis and a rapid increase in heme oxygenase-1 expression after spinal cord injury.Furthe r,heme oxygenase-1 aggravated fe rroptosis after spinal cord injury,while fibroblast growth factor 21 inhibited fe rroptosis by downregulating heme oxygenase-1.Thus,the activation of fibroblast growth factor 21 may provide a potential treatment for spinal co rd injury.These findings could provide a new potential mechanistic explanation for fibroblast growth factor 21 in the treatment of spinal cord injury.展开更多
Background:Arthrofibrosis is a joint disorder characterized by excessive scar formation in the joint tissues.Vitamin E is an antioxidant with potential anti-fibroblastic effect.The aim of this study was to establish a...Background:Arthrofibrosis is a joint disorder characterized by excessive scar formation in the joint tissues.Vitamin E is an antioxidant with potential anti-fibroblastic effect.The aim of this study was to establish an arthrofibrosis rat model after joint replacement and assess the effects of vitamin E supplementation on joint fibrosis.Methods:We simulated knee replacement in 16 male Sprague–Dawley rats.We immobilized the surgical leg with a suture in full flexion.The control groups were killed at 2 and 12 weeks(n=5 per group),and the test group was supplemented daily with vitamin E(0.2 mg/mL)in their drinking water for 12 weeks(n=6).We performed histological staining to investigate the presence and severity of arthrofibrosis.Immunofluorescent staining andα2-macroglobulin(α2M)enzyme-linked immunosorbent assay(ELISA)were used to assess local and systemic inflammation.Static weight bearing(total internal reflection)and range of motion(ROM)were collected for functional assessment.Results:The ROM and weight-bearing symmetry decreased after the procedure and recovered slowly with still significant deficit at the end of the study for both groups.Histological analysis confirmed fibrosis in both lateral and posterior periarticular tissue.Vitamin E supplementation showed a moderate anti-inflammatory effect on the local and systemic levels.The vitamin E group exhibited significant improvement in ROM and weight-bearing symmetry at day 84 compared to the control group.Conclusions:This model is viable for simulating arthrofibrosis after joint replacement.Vitamin E may benefit postsurgical arthrofibrosis,and further studies are needed for dosing requirements.展开更多
With its main features of cartilage degeneration, subchondral bone sclerosis and osteophyte formation, osteoarthritisrepresents a multifactorial disease with no effective treatment options. As biomechanical shift in t...With its main features of cartilage degeneration, subchondral bone sclerosis and osteophyte formation, osteoarthritisrepresents a multifactorial disease with no effective treatment options. As biomechanical shift in thetrabecular network may be a driver for further cartilage degeneration, bone enhancement could possibly delayOA progression. Magnesium is known to be osteoconductive and already showed positive effects in OA models.We aimed to use magnesium cylinders to enhance subchondral bone quality, condition of cartilage and painsensation compared to sole drilling in vivo. After eight weeks of implantation in rabbits, significant increase insubchondral bone volume and trabecular thickness with constant bone mineral density was found indicatingfavored biomechanics. As representative for pain, a higher number of CD271+ vessels were present in controlsamples without magnesium. However, this result could not be confirmed by sensitive, objective lamenessevaluation using a pressure sensing mat and no positive effect could be shown on either cartilage degenerationevaluated by OARSI score nor the presence of regenerative cells in CD271-stained samples. The presented resultsshow a relevant impact of implanted magnesium on key structures in OA pain with missing clinical relevanceregarding pain. Further studies with shifted focus should examine additional structures as joint capsule orosteophytes.展开更多
基金Supported by The Shanghai Municipal Health Commission Clinical Research Project,No.202140140.
文摘BACKGROUND For patients with acute paraplegia caused by spinal giant cell tumor(GCT)who require emergency decompressive surgery,there is still a lack of relevant reports on surgical options.This study is the first to present the case of an acute paraplegic patient with a thoracic spinal GCT who underwent an emergency total en bloc spondylectomy(TES).Despite tumor recurrence,three-level TES was repeated after denosumab therapy.CASE SUMMARY A 27-year-old female patient who underwent single-level TES in an emergency presented with sudden severe back pain and acute paraplegia due to a thoracic spinal tumor.After emergency TES,the patient's spinal cord function recovered,and permanent paralysis was avoided.The postoperative histopathological examination revealed that the excised neoplasm was a rare GCT.Unfortunately,the tumor recurred 9 months after the first surgery.After 12 months of denosumab therapy,the tumor size was reduced,and tumor calcification.To prevent recurrent tumor progression and provide a possible cure,a three-level TES was performed again.The patient returned to an active lifestyle 1 month after the second surgery,and no recurrence of GCT was found at the last follow-up.CONCLUSION This patient with acute paraplegia underwent TES twice,including once in an emergency,and achieved good therapeutic results.TES in emergency surgery is feasible and safe when conditions permit;however,it may increase the risk of tumor recurrence.
基金the National Natural Science Foundation of China,No.82274547the Major Program of the National Natural Science Foundation of Zhejiang Province,No.LD22C060002+1 种基金the State Administration of Traditional Chinese Medicine of Zhejiang Province,No.GZY-ZJ-KJ-23064the Zhejiang Provincial Research Foundation for Basic Public Welfare Research,No.LGF20H270005.
文摘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.
基金funding to conduct this study was provided by a research innovation grant provided by CONMED Corporation(#IRB 22-0113-C).
文摘Objective:Smart insufflation(SI)techniques relying on valve and membrane-free insufflation are increasing in usage.Although considerable literature exists demonstrating the benefits of SI on procedural ease and patient outcomes,there remains a paucity describing the financial impact of these devices.The purpose of this study was to determine the financial and efficiency impact of these devices on the operating room and inpatient wards of a hospital.Methods:A discrete event simulation model representing a typical mid-sized North American hospital comparing SI to traditional insufflation(TI)was generated.The National Surgical Quality Improvement database from 2015 to 2019 was used to populate the model with data supplemented from the literature.Outcomes included length of stay(LOS),duration of surgery(DOS),annual procedure volume,profit,return on investment(ROI),and gross profit margin(GPM).From the literature review,DOS savings were 10e32 minutes/case,while LOS savings were 0e3 days/case.Results:Implementation of an SI led to an increase in annual throughput of 42e346(4.4%e36.6%)cases for all procedures and 38 to 297(4.3%e33.3%)cases for complex procedures.LOS was found to be decreased by 175e614(18.3%e64.2%)days for all procedures and 231 to 614(35.6%e77.9%)cases for complex procedures with the implementation of an SI.Together,this resulted in an increase in net profit of$104,685 per annum.The ROI of SI over the TI device was>1000%,and the GPM for the TI was 90.0%,while the GPM for the SI was 71.7%.Conclusion:Despite the initial financial investment being greater,the implementation of SI offsets these expenses and yields significant financial benefits.Our study demonstrates the financial benefits of SI over TI and illustrates how granular operational and financial analyses of technologies are essential to aid in sound healthcare procurement decision making.
基金the Clinical Research Development Center of Taleghani and Imam Ali Hospital, University of Medical Sciences, Kermanshah, IranShohada Tajrish Clinical Research Development Center at Shahid Beheshti University of Medical Sciences in Tehran, Iran, for their support。
文摘BACKGROUND It has been said that the number of orthopaedic claims has increased in the last few years. Investigation through the most prevalent cause would help to prevent further cases.AIM To review the cases of medical complaints in orthopedic patients who had been involved in a traumatic accident.METHODS A retrospective multi-center review of trauma orthopaedic-related malpractice lawsuits from 2010 to 2021 was conducted utilizing the regional medicolegal database. Defendant and plaintiff characteristics along with fracture location, allegations, and litigation outcomes were investigated.RESULTS A total of 228 claims referred to trauma-related conditions with a mean age of 31.29 ± 12.56 were enrolled. The most common injuries were at hand, thigh, elbow, and forearm, respectively.Likewise, the most common alleged complication was related to malunion or nonunion. In 47% of the cases, the main problem that led to the complaint was the inappropriate or insufficient explanation to the patient, and in 53%, there was a problem in the surgery. Eventually, 76% of the complaints resulted in a defense verdict, and 24% resulted in a plaintiff verdict.CONCLUSION Surgical treatment of hand injuries and surgery in non-educational hospitals received the most complaints. The majority of litigation outcomes were caused by a physician’s failure to fully explain and educate the traumatic orthopedic patients and technological errors.
文摘BACKGROUND Septic arthritis of the knee in children is a challenging problem.Surgical debridement is an established treatment,but there is a paucity of literature on long-term prognosis.AIM To determine the rates and factors associated with return to surgery(RTS)and readmission after index surgical debridement for septic arthritis of the knee in children.METHODS This is a retrospective cohort study that utilizes data from the Healthcare Cost and Utilization Project(HCUP).We included patients between ages 0 to 18 years that underwent surgical debridement for septic arthritis of the knee between 2005 and 2017.Demographic data included age,gender,race,hospital type and insurance type.Clinical data including index admission length of stay(LOS)and Charlson Comorbidity Index(CCI)were available from the HCUP database.Descriptive statistics were used to summarize the data and univariate and multivariate analyses were performed.RESULTS Nine-hundred thirty-two cases of pediatric septic knee were included.This cohort was 62.3%male,with mean age of 9.0(±6.1)years.Approximately 46%of patients were white and approximately half had Medicaid insurance.Thirty-six patients(3.6%)required RTS at a minimum of 2 year after index surgery,and 172 patients(18.5%)were readmitted at any point.The mean readmission LOS was 11.6(±11.3)d.Higher CCI was associated with RTS(P=0.041).There were no significant associations in age,gender,race,insurance type,or type of hospital to which patients presented.Multivariate analysis showed that both increased CCI(P=0.008)and shorter LOS(P=0.019)were predictive of RTS.CONCLUSION Septic arthritis of the knee is an important condition in children.The CCI was associated with RTS at a minimum of 2 years after index procedure.No association was found with age,gender,race,insurance type,or hospital type.Shorter LOS and CCI were associated with RTS in multivariate analysis.Overall,risk of subsequent surgery and readmission after pediatric septic knee arthritis is low,and CCI and shorter LOS are predictive of RTS.
文摘Mechanically aligned total knee arthroplasty (TKA) for valgus knee is considered a “challenging surgery.” Recently, the kinematic alignment (KA) method has gained attention. This study aimed to present objective clinical data, such as intraoperative balance assessment and radiographic evaluation of postoperative lower extremity alignment after TKA using the KA method for valgus deformity. Twenty-one TKA knees (mean age, 74 years;2 males, 19 females) with KA for severe valgus deformity (hip-knee-ankle-angle ≥ 10°) performed at our department in the past 3 years were included in this study. Intraoperative gap and balance measurements and postoperative radiographic evaluation were performed. A total arc of range of motion was achieved up to 98% of preoperative values at 3 weeks postoperatively. Intraoperative gap and balance were stable throughout the entire range of motion. In addition, there were no statistically significant differences in either balance or gap values at each flexion angle. KA TKA is a “simple surgery” rather than a “challenging surgery” because additional soft tissue procedures are not required, operative time is short, intraoperative and postoperative balance is very stable, and a good alignment is achieved. This procedure may relieve surgeons of the stress of TKA for valgus deformities.
文摘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.
基金support by R01AR055655, R01AR074813, and R01AG073349 from the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) and the National Institute on Aging (NIA)supported by PXE International.
文摘Disc degeneration primarily contributes to chronic low back and neck pain.Consequently,there is an urgent need to understand the spectrum of disc degeneration phenotypes such as fibrosis,ectopic calcification,herniation,or mixed phenotypes.Amongst these phenotypes,disc calcification is the least studied.Ectopic calcification,by definition,is the pathological mineralization of soft tissues,widely studied in the context of conditions that afflict vasculature,skin,and cartilage.Clinically,disc calcification is associated with poor surgical outcomes and back pain refractory to conservative treatment.It is frequently seen as a consequence of disc aging and progressive degeneration but exhibits unique molecular and morphological characteristics:hypertrophic chondrocyte-like cell differentiation;TNAP,ENPP1,and ANK upregulation;cell death;altered Pi and PPi homeostasis;and local inflammation.Recent studies in mouse models have provided a better understanding of the mechanisms underlying this phenotype.It is essential to recognize that the presentation and nature of mineralization differ between AF,NP,and EP compartments.Moreover,the combination of anatomic location,genetics,and environmental stressors,such as aging or trauma,govern the predisposition to calcification.Lastly,the systemic regulation of calcium and Pi metabolism is less important than the local activity of PPi modulated by the ANK-ENPP1 axis,along with disc cell death and differentiation status.While there is limited understanding of this phenotype,understanding the molecular pathways governing local intervertebral disc calcification may lead to developing disease-modifying drugs and better clinical management of degeneration-related pathologies.
基金Supported by the Capital Fund Project for Clinical Diagnosis and Treatment Technology Research and Translational Application,No.Z201100005520091and Beijing Traditional Chinese Medicine Science and Technology Development Fund Project,No.JJ-2020-67.
文摘BACKGROUND Total knee arthroplasty(TKA)is a mature procedure recommended for correcting knee osteoarthritis deformity,relieving pain,and restoring normal biomechanics.Although TKA is a successful and cost-effective procedure,patient dissatisfaction is as high as 50%.Knee pain after TKA is a significant cause of patient dissatisfaction;the most common location for residual pain is the anterior region.Between 4%and 40%of patients have anterior knee pain(AKP).AIM To investigate the effect of various TKA procedures on postoperative AKP.METHODS We searched PubMed,EMBASE,and Cochrane from January 2000 to September 2022.Randomized controlled trials with one intervention in the experimental group and no corresponding intervention(or other interventions)in the control group were collected.Two researchers independently read the title and abstract of the studies,preliminarily screened the articles,and read the full text in detail according to the selection criteria.Conflicts were resolved by consultation with a third researcher.And relevant data from the included studies were extracted and analyzed using Review Manager 5.4 software.RESULTS There were 25 randomized controlled trials;13 were comparative studies with or without patellar resurfacing.The meta-analysis showed no significant difference between the experimental and control groups(P=0.61).Six studies were comparative studies of circumpatellar denervation vs non-denervation,divided into three subgroups for meta-analysis.The two-subgroup meta-analysis showed no significant difference between the experimental and the control groups(P=0.31,P=0.50).One subgroup meta-analysis showed a significant difference between the experimental and control groups(P=0.001).Two studies compared fixed-bearing TKA and mobile-bearing TKA;the results meta-analysis showed no significant difference between the experimental and control groups(P=0.630).Two studies compared lateral retinacular release vs non-release;the meta-analysis showed a significant difference between the experimental and control groups(P=0.002);two other studies compared other factors.CONCLUSION Patellar resurfacing,mobile-bearing TKA,and fixed-bearing TKA do not reduce the incidence of AKP.Lateral retinacular release can reduce AKP;however,whether circumpatellar denervation can reduce AKP is controversial.
文摘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.
文摘BACKGROUND Total hip arthroplasty is as an effective intervention to relieve pain and improve hip function.Approaches of the hip have been exhaustively explored about pros and cons.The efficacy and the complications of hip approaches remains inconclusive.This study conducted an umbrella review to systematically appraise previous meta-analysis(MAs)including conventional posterior approach(PA),and minimally invasive surgeries as the lateral approach(LA),direct anterior approach(DAA),2-incisions method,mini-lateral approach and the newest technique direct superior approach(DSA)or supercapsular percutaneouslyassisted total hip(SuperPath).AIM To compare the efficacy and complications of hip approaches that have been published in all MAs and randomized controlled trials(RCTs).METHODS MAs were identified from MEDLINE and Scopus from inception until 2023.RCTs were then updated from the latest MA to September 2023.This study included studies which compared hip approaches and reported at least one outcome such as Harris Hip Score(HHS),dislocation,intra-operative fracture,wound compliData were independently selected,extracted and assessed by two reviewers.Network MA and cluster rank and surface under the cumulative ranking curve(SUCRA)were estimated for treatment efficacy and safety.RESULTS Finally,twenty-eight MAs(40 RCTs),and 13 RCTs were retrieved.In total 47 RCTs were included for reanalysis.The results of corrected covered area showed high degree(13.80%).Among 47 RCTs,most of the studies were low risk of bias in part of random process and outcome reporting,while other domains were medium to high risk of bias.DAA significantly provided higher HHS at three months than PA[pooled unstandardized mean difference(USMD):3.49,95%confidence interval(CI):0.98,6.00 with SUCRA:85.9],followed by DSA/SuperPath(USMD:1.57,95%CI:-1.55,4.69 with SUCRA:57.6).All approaches had indifferent dislocation and intraoperative fracture rates.SUCRA comparing early functional outcome and composite complications(dislocation,intra-operative fracture,wound complication,and nerve injury)found DAA was the best approach followed by DSA/SuperPath.CONCLUSION DSA/SuperPath had better earlier functional outcome than PA,but still could not overcome the result of DAA.This technique might be the other preferred option with acceptable complications.
基金the Natural Science Foundation of China(Grant Nos.82072413,82101649)National Key Research and Development Program of China(Grant Nos.2021YFE0105400).
文摘The integrated repair of bone and cartilage boasts advantages for osteochondral restoration such as a long-term repair effect and less deterioration compared to repairing cartilage alone.Constructing multifactorial,spatially oriented scaffolds to stimulate osteochondral regeneration,has immense significance.Herein,targeted drugs,namely kartogenin@polydopamine(KGN@PDA)nanoparticles for cartilage repair and miRNA@calcium phosphate(miRNA@CaP)NPs for bone regeneration,were in situ deposited on a patterned supramolecular-assembled 2-ureido-4[lH]-pyrimidinone(UPy)modified gelation hydrogel film,facilitated by the dynamic and responsive coordination and complexation of metal ions and their ligands.This hydrogel film can be rolled into a cylindrical plug,mimicking the Haversian canal structure of natural bone.The resultant hydrogel demonstrates stable mechanical properties,a self-healing ability,a high capability for reactive oxygen species capture,and controlled release of KGN and miR-26a.In vitro,KGN@PDA and miRNA@CaP promote chondrogenic and osteogenic differentiation of mesenchymal stem cells via the JNK/RUNX1 and GSK-3β/β-catenin pathways,respectively.In vivo,the osteochondral plug exhibits optimal subchondral bone and cartilage regeneration,evidenced by a significant increase in glycosaminoglycan and collagen accumulation in specific zones,along with the successful integration of neocartilage with subchondral bone.This biomaterial delivery approach represents a significant toward improved osteochondral repair.
基金This work was supported by grants from National Natural Science Foundation of China(81830078,82071868,32370892)Science and Technology Commission of Shanghai Municipality(23141901200)+2 种基金Health Commission of Shanghai Municipality(2022JC029)Biomaterials and Regenerative Medicine Institute Cooperative Research Project,Shanghai Jiaotong University School of Medicine(2022LHA11)Shanghai Key Laboratory of Orthopedic Implant(No.KFKT202206).
文摘Osteoarthritis(OA)is a common degenerative disease worldwide and new therapeutics that target inflammation and the crosstalk between immunocytes and chondrocytes are being developed to prevent and treat OA.These attempts involve repolarizing pro-inflammatory M1 macrophages into the anti-inflammatory M2 phenotype in synovium.In this study,we found that phosphoglycerate mutase 5(PGAM5)significantly increased in macrophages in OA synovium compared to controls based on histology of human samples and single-cell RNA sequencing results of mice models.To address the role of PGAM5 in macrophages in OA,we found conditional knockout of PGAM5 in macrophages greatly alleviated OA symptoms and promoted anabolic metabolism of chondrocytes in vitro and in vivo.Mechanistically,we found that PGAM5 enhanced M1 polarization via AKT-mTOR/p38/ERK pathways,whereas inhibited M2 polarization via STAT6-PPARγpathway in murine bone marrow-derived macrophages.Furthermore,we found that PGAM5 directly dephosphorylated Dishevelled Segment Polarity Protein 2(DVL2)which resulted in the inhibition ofβ-catenin and repolarization of M2 macrophages into M1 macrophages.Conditional knockout of both PGAM5 andβ-catenin in macrophages significantly exacerbated osteoarthritis compared to PGAM5-deficient mice.Motivated by these findings,we successfully designed mannose modified fluoropolymers combined with siPGAM5 to inhibit PGAM5 specifically in synovial macrophages via intra-articular injection,which possessed desired targeting abilities of synovial macrophages and greatly attenuated murine osteoarthritis.Collectively,these findings defined a key role for PGAM5 in orchestrating macrophage polarization and provides insights into novel macrophage-targeted strategy for treating OA.
文摘Background: The growth and use of Artificial Intelligence (AI) in the medical field is rapidly rising. AI is exhibiting a practical tool in the healthcare industry in patient care. The objective of this current review is to assess and analyze the use of AI and its use in orthopedic practice, as well as its applications, limitations, and pitfalls. Methods: A review of all relevant databases such as EMBASE, Cochrane Database of Systematic Reviews, MEDLINE, Science Citation Index, Scopus, and Web of Science with keywords of AI, orthopedic surgery, applications, and drawbacks. All related articles on AI and orthopaedic practice were reviewed. A total of 3210 articles were included in the review. Results: The data from 351 studies were analyzed where in orthopedic surgery. AI is being used for diagnostic procedures, radiological diagnosis, models of clinical care, and utilization of hospital and bed resources. AI has also taken a chunk of share in assisted robotic orthopaedic surgery. Conclusions: AI has now become part of the orthopedic practice and will further increase its stake in the healthcare industry. Nonetheless, clinicians should remain aware of AI’s serious limitations and pitfalls and consider the drawbacks and errors in its use.
基金supported by the Cutting Edge Development Fund of Advanced Medical Research Institute(GYY2023QY01)the China Postdoctoral Science Foundation(certificate number:2023M732093)。
文摘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.
基金supported by grants from Jiangsu Commission of Health,No.Z2021086(to XL)Science and Technology Program of Suzhou,Nos.SYSD2020008(to XL),SKYD2022012(to XL)+1 种基金Suzhou Municipal Health Commission,No.KJXW2020058(to XL)Science and Technology Program of Zhangjiagang,No.ZKS2018(to XL)。
文摘Interfering with the ferroptosis pathway is a new strategy for the treatment of spinal cord injury.Fibroblast growth factor 21 can inhibit ferro ptosis and promote neurofunctional recovery,while heme oxygenase-1 is a regulator of iron and reactive oxygen species homeostasis.The relationship between heme oxygenase-1and ferroptosis remains controve rsial.In this study,we used a spinal co rd injury rat model to show that the levels of fibroblast growth factor 21 in spinal co rd tissue decreased after spinal cord injury.In addition,there was a significant aggravation of ferroptosis and a rapid increase in heme oxygenase-1 expression after spinal cord injury.Furthe r,heme oxygenase-1 aggravated fe rroptosis after spinal cord injury,while fibroblast growth factor 21 inhibited fe rroptosis by downregulating heme oxygenase-1.Thus,the activation of fibroblast growth factor 21 may provide a potential treatment for spinal co rd injury.These findings could provide a new potential mechanistic explanation for fibroblast growth factor 21 in the treatment of spinal cord injury.
基金supported in part by the Ruth Jackson Orthopedic Society and the Harris Orthopedic Laboratoryapproved by the Institutional Care and Use Committee of Massachusetts General Hospital(2020N000081)。
文摘Background:Arthrofibrosis is a joint disorder characterized by excessive scar formation in the joint tissues.Vitamin E is an antioxidant with potential anti-fibroblastic effect.The aim of this study was to establish an arthrofibrosis rat model after joint replacement and assess the effects of vitamin E supplementation on joint fibrosis.Methods:We simulated knee replacement in 16 male Sprague–Dawley rats.We immobilized the surgical leg with a suture in full flexion.The control groups were killed at 2 and 12 weeks(n=5 per group),and the test group was supplemented daily with vitamin E(0.2 mg/mL)in their drinking water for 12 weeks(n=6).We performed histological staining to investigate the presence and severity of arthrofibrosis.Immunofluorescent staining andα2-macroglobulin(α2M)enzyme-linked immunosorbent assay(ELISA)were used to assess local and systemic inflammation.Static weight bearing(total internal reflection)and range of motion(ROM)were collected for functional assessment.Results:The ROM and weight-bearing symmetry decreased after the procedure and recovered slowly with still significant deficit at the end of the study for both groups.Histological analysis confirmed fibrosis in both lateral and posterior periarticular tissue.Vitamin E supplementation showed a moderate anti-inflammatory effect on the local and systemic levels.The vitamin E group exhibited significant improvement in ROM and weight-bearing symmetry at day 84 compared to the control group.Conclusions:This model is viable for simulating arthrofibrosis after joint replacement.Vitamin E may benefit postsurgical arthrofibrosis,and further studies are needed for dosing requirements.
基金funded by the German Research Foundation(Deutsche Forschungsgesellschaft,DFG,grant numbers 404534760).
文摘With its main features of cartilage degeneration, subchondral bone sclerosis and osteophyte formation, osteoarthritisrepresents a multifactorial disease with no effective treatment options. As biomechanical shift in thetrabecular network may be a driver for further cartilage degeneration, bone enhancement could possibly delayOA progression. Magnesium is known to be osteoconductive and already showed positive effects in OA models.We aimed to use magnesium cylinders to enhance subchondral bone quality, condition of cartilage and painsensation compared to sole drilling in vivo. After eight weeks of implantation in rabbits, significant increase insubchondral bone volume and trabecular thickness with constant bone mineral density was found indicatingfavored biomechanics. As representative for pain, a higher number of CD271+ vessels were present in controlsamples without magnesium. However, this result could not be confirmed by sensitive, objective lamenessevaluation using a pressure sensing mat and no positive effect could be shown on either cartilage degenerationevaluated by OARSI score nor the presence of regenerative cells in CD271-stained samples. The presented resultsshow a relevant impact of implanted magnesium on key structures in OA pain with missing clinical relevanceregarding pain. Further studies with shifted focus should examine additional structures as joint capsule orosteophytes.