Animal models of tendon calcification:Past,present,and future

Tendon calcification is a common clinical condition that frequently occurs as a complication after tendon injury and surgery,or as an expression of fibrodysplasia ossificans progressiva.This condition can be referred to by various names in clinical practice and literature,including tendon ossification,tendon mineralization,heterotopic ossification,and calcific tendonitis.The exact pathogenesis of tendon calcification remains uncertain,but current mainstream research suggests that calcification is mostly cell mediated.To further elucidate the pathogenesis of tendon calcification and to better simulate the overall process,selecting appropriate experimental animal models is important.Numerous animal models have been utilized in various clinical studies,each with its own set of advantages and limitations.In this review,we have discussed the advancements made in research on animal models of tendon calcification,with a focus on the selection of experimental animals,the sites of injury in these models,and the methods employed for modeling.

Risk of metabolic abnormalities in osteoarthritis:a new perspective to understand its pathological mechanisms

Although aging has traditionally been viewed as the most important risk factor for osteoarthritis(OA),an increasing amount of epidemiological evidence has highlighted the association between metabolic abnormalities and OA,particularly in younger individuals.Metabolic abnormalities,such as obesity and typeⅡdiabetes,are strongly linked to OA,and they affect both weightbearing and non-weight-bearing joints,thus suggesting that the pathogenesis of OA is more complicated than the mechanical stress induced by overweight.This review aims to explore the recent advances in research on the relationship between metabolic abnormalities and OA risk,including the impact of abnormal glucose and lipid metabolism,the potential pathogenesis and targeted therapeutic strategies.

Abnormal subchondral bone remodeling and its association with articular cartilage degradation in knees of type 2 diabetes patients

Type 2 diabetes （T2D） is associated with systemic abnormal bone remodeling and bone loss. Meanwhile, abnormal subchondral bone remodeling induces cartilage degradation, resulting in osteoarthritis （OA）. Accordingly, we investigated alterations in subchondral bone remodeling, microstructure and strength in knees from T2D patients and their association with cartilage degradation. Tibial plateaus were collected from knee OA patients undergoing total knee arthroplasty and divided into non-diabetic （n---70） and diabetes （n = 51） groups. Tibial plateaus were also collected from cadaver donors （n = 20） and used as controls. Subchondral bone microstructure was assessed using micro-computed tomography. Bone strength was evaluated by micro-finite-element analysis. Cartilage degradation was estimated using histology. The expression of tartrate-resistant acidic phosphatase （TRAP）, osterix, and osteocalcin were calculated using immunohistochemistry. Osteoarthritis Research Society International （OARSI） scores of lateral tibial plateau did not differ between non-diabetic and diabetes groups, while higher OARSI scores on medial side were detected in diabetes group. Lower bone volume fraction and trabecular number and higher structure model index were found on both sides in diabetes group. These microstructural alterations translated into lower elastic modulus in diabetes group. Moreover, diabetes group had a larger number of TRAP~ osteoclasts and lower number of Osterix~ osteoprogenitors and Osteocalcin~ osteoblasts. T2D knees are characterized by abnormal subchondral bone remodeling and microstructural and mechanical impairments, which were associated with exacerbated cartilage degradation. In regions with intact cartilage the underlying bone still had abnormal remodeling in diabetes group, suggesting that abnormal bone remodeling may contribute to the early pathogenesis of T2D-associated knee OA.

Trim21 depletion alleviates bone loss in osteoporosis via activation of YAP1/β-catenin signaling

Despite the diverse roles of tripartite motif(Trim)-containing proteins in the regulation of autophagy,the innate immune response,and cell differentiation,their roles in skeletal diseases are largely unknown.We recently demonstrated that Trim21 plays a crucial role in regulating osteoblast(OB)differentiation in osteosarcoma.However,how Trim21 contributes to skeletal degenerative disorders,including osteoporosis,remains unknown.First,human and mouse bone specimens were evaluated,and the results showed that Trim21 expression was significantly elevated in bone tissues obtained from osteoporosis patients.Next,we found that global knockout of the Trim21 gene(KO,Trim2^(1-/-))resulted in higher bone mass compared to that of the control littermates.We further demonstrated that loss of Trim21 promoted bone formation by enhancing the osteogenic differentiation of bone marrow mesenchymal stem cells(BMSCs)and elevating the activity of OBs;moreover,Trim21 depletion suppressed osteoclast(OC)formation of RAW264.7 cells.In addition,the differentiation of OCs from bone marrow-derived macrophages(BMMs)isolated from Trim21^(-/-)and Ctsk-cre;Trim21^(f/f)mice was largely compromised compared to that of the littermate control mice.Mechanistically,YAP1/β-catenin signaling was identified and demonstrated to be required for the Trim21-mediated osteogenic differentiation of BMSCs.More importantly,the loss of Trim21 prevented ovariectomy(OVX)-and lipopolysaccharide(LPS)-induced bone loss in vivo by orchestrating the coupling of OBs and OCs through YAP1 signaling.Our current study demonstrated that Trim21 is crucial for regulating OB-mediated bone formation and OC-mediated bone resorption,thereby providing a basis for exploring Trim21 as a novel dual-targeting approach for treating osteoporosis and pathological bone loss.

SWIR FluorescenceImaging In Vivo Monitoring and Evaluating Implanted M2 Macrophages in Skeletal Muscle Regeneration

Skeletal muscle has a robust regeneration ability that is impaired by severe injury,disease,and aging.resulting in a decline in skeletal muscle function.Therefore,improving skeletal muscle regeneration is a key challenge in treating skeletal muscle-related disorders.Owing to their significant role in tissue regeneration,implantation of M2 macrophages(M2MФ)has great potential for improving skeletal muscle regeneration.Here,we present a short-wave infrared(SWIR)fluorescence imaging technique to obtain more in vivo information for an in-depth evaluation of the skeletal muscle regeneration effect after M2MФtransplantation.SWIR fluorescence imaging was employed to track implanted M2MФin the injured skeletal muscle of mouse models.It is found that the implanted M2MФaccumulated at the injury site for two weeks.Then,SWIR fluorescence imaging of blood vessels showed that M2MФimplantation could improve the relative perfusion ratio on day 5(1.09±0.09 vs 0.85±0.05;p=0.01)and day 9(1.38±0.16 vs 0.95±0.03;p=0.01)post-injury,as well as augment the degree of skeletal muscle regencration on day 13 post-injury.Finally,multiple linear regression analyses determined that post-injury time and relative perfusion ratio could be used as predictive indicators to evaluate skeletal muscle regeneration.These results provide more in vivo details about M2MФin skeletal muscle regeneration and confirm that M2MФcould promote angiogenesis and improve the degree of skeletal muscle repair,which will guide the research and development of M2MФimplantation to improve skeletal muscle regeneration.

Long-term assessment of collagenase treatment for Dupuytren’s contracture:A 10-year follow-up study

BACKGROUND Enzymatic fasciotomy with collagenase clostridium histolyticum(CCH)has revolutionized the treatment for Dupuytren’s contracture(DC).Despite its benefits,the long-term outcomes remain unclear.This study presented a comprehensive 10-year follow-up assessment of the enduring effects of CCH on patients with DC.AIM To compare the short-term(12 wk)and long-term(10 years)outcomes on CCH treatment in patients with DC.METHODS A cohort of 45 patients was treated with CCH at the metacarpophalangeal(MCP)joint and the proximal interphalangeal(PIP)joint and underwent systematic reevaluation.The study adhered to multicenter trial protocols,and assessments were conducted at 12 wk,7 years,and 10 years post-surgery.RESULTS Thirty-seven patients completed the 10-year follow-up.At 10 years,patients treated at the PIP joint exhibited a 100%recurrence.However,patients treated at the MCP joint only showed a 50%recurrence.Patient satisfaction varied,with a lower satisfaction reported in PIP joint cases.Recurrence exceeding 20 degrees on the total passive extension deficit was observed,indicating a challenge for sustained efficacy.Significant differences were noted between outcomes at the 7-year and 10-year intervals.CONCLUSION CCH demonstrated sustained efficacy when applied to the MCP joint.However,caution is warranted for CCH treatment at the PIP joint due to a high level of recurrence and low patient satisfaction.Re-intervention is needed within a decade of treatment.

Mitochondrial dysfunction and programmed cell death in osteosarcoma

Osteosarcoma is the most prevalent primarymalignant bone tumor,primarily affecting adolescents aged 15–25 years.It is characterized by a high recurrence rate,poor prognosis,and lack of important biomarkers.Significant mitochondrial dysfunction in osteosarcoma cells has been widely reported by recent studies.Dysfunctional mitochondria occupy an important position in cellularmetabolic reprogramming,immune microenvironment regulation,and programmed cell death.Therefore,targeting mitochondrial dysfunction may represent a new mechanism to overcome therapeutic barriers in the treatment of osteosarcoma and provides crucial target molecules for further development of targeted therapies and immunotherapies.The present article summarizes the recent reports of mitochondrial dysfunction in osteosarcoma and links it to various programmed cell death mechanisms,aiming to provide the basis for further clinical practice.

An adaptive biodegradable zinc alloy with bidirectional regulation of bone homeostasis for treating fractures and aged bone defects

Healing of fractures or bone defects is significantly hindered by overactivated osteoclasts and inhibited osteogenesis in patients with abnormal bone metabolism.Current clinical approaches using titanium alloys or stainless steel provide mechanical support but have no biological effects on bone regeneration.Therefore,designing and fabricating degradable metal materials with sufficient mechanical strength and bidirectional regulation of both osteoblasts and osteoclasts is a substantial challenge.Here,this study first reported an adaptive biodegradable Zn-0.8 Mg alloy with bidirectional regulation of bone homeostasis,which promotes osteogenic differentiation by activating the Pi3k/Akt pathway and inhibits osteoclast differentiation by inhibiting the GRB2/ERK pathway.The anti-osteolytic ability of the Zn-0.8 Mg alloy was verified in a mouse calvarial osteolysis model and its suitability for internal fracture fixation with high-strength screws was confirmed in the rabbit femoral condyle fracture model.Furthermore,in an aged postmenopausal rat femoral condyle defect model,3D printed Zn-0.8 Mg scaffolds promoted excellent bone regeneration through adaptive structures with good mechanical properties and bidirectionally regulated bone metabolism,enabling personalized bone defect repair.These findings demonstrate the substantial potential of the Zn-0.8 Mg alloy for treating fractures or bone defects in patients with aberrant bone metabolism.

Effect of low intensity pulsed ultrasound on expression of TIMP-2 in serum and expression of mmp-13 in articular cartilage of rabbits with knee osteoarthritis

Objective:To study the effect of low intensity pulsed ultrasound(LIPUS) on the expression of tissue inhibitor of metalloproteinase-2(TIMP-2) in the serum and expression of matrix metallopeptidase 13(MMP-13) in the articular cartilage cells of rabbits with knee osteoarthritis(OA).Methods:Inner patellar ligament defect method was used to establish the model of knee OA.Four weeks after the modeling,the arterial blood was drawn from the ear of each rabbit,while ELISA was employed to detect the expression of TIMP-2 in the serum.The chondrocytes were separated from animals in each group and then cultured in vitro.All rabbits were divided into control group,OA model group and OA + LIPUS group.Cells in the control and OA groups were not treated,while cells in the OA+ LIPUS group were treated with LIPUS(40 mW/cnr.1 time/day).Cells were collected 7 d later and the RNA and total protein were extracted respectively.Real-time PCR and Western blotting were employed to analyze the expression of MMP-13 in chondrocytes at the mRNA and protein level,respectively.Results:The success rate of establishment of OA model was 83%.The results of ELISA showed that the content of TIMP-2 in the serum of animals with OA was 22.3%,lower than the one in the control group(P<0.05).Compared with the normal control group,the expression of TIMP-2in the OA model group was significantly increased,while the expression of MMP-13 was significantly increased(P<0.05).After the stimulation of LIPUS,the expression of TIMP-2 and MMP-13 was close to the one in the normal control group.Conclusions:The inner patellar ligament defect method is a mature method to establish the rabbit OA model,with high success rate.The expression of serum TIMP-2 in the OA model group is significantly decreased.LIPUS can up-regulate TIMP-2 and down-regulate MMP-13.

Triptolide Inhibits Expression of Inflammatory Cytokines and Proliferation of Fibroblast-like Synoviocytes Induced by IL-6/sIL-6R-Mediated JAK2/STAT3 Signaling Pathway

Triptolide,a component of the Chinese herb Tripterygium wilfordii Hook F,has been proved to be effective in the treatment of rheumatoid arthritis(RA).However,its underlying mechanisms on RA have not yet been well established.We observed the inhibitory effect of triptolide on the expression of inflammatory cytokines and proliferation of fibroblast-like synoviocytes(FLS)induced by the complex of interleukin-6(IL-6)and the soluble form of the IL-6 receptor(sIL-6R).Furthermore,to clarify the underlying mechanisms,we treated FLS with the Janus-activated kinase 2(JAK2)inhibitor/signal transducer and activator of transcription 3(STAT3)activation blocker AZD1480.In this study,immunohistochemical staining was used to identify vimentin(+)and CD68(−)in FLS.The FLS proliferation was measured by cell proliferation assay,and the cell cycles were analyzed by flow cytometry.Furthermore,ELISA was used to detect the expression of the inflammatory factors in culture solution.The expression levels of p-JAK2,JAK2,p-STAT3 and STAT3 were investigated through Western blotting analysis.The results showed that IL-6/sIL-6R significantly increased the cell proliferation and expression of inflammatory cytokines,including IL-6,interleukin-1β(IL-1β)and vascular endothelial growth factor(VEGF).Triptolide or AZD1480 inhibited the cell proliferation and inflammatory cytokine expression in IL-6/sIL-6R-stimulated FLS by suppressing JAK2/STAT3.The study suggested that the physiological effects of triptolide on RA were due to its contribution to the inhibition of the inflammatory cytokine expression and FLS proliferation by suppressing the JAK2/STAT3 signaling pathway.It may provide an innovative insight into the effect of triptolide in preventing RA pathogenesis.

Challenges and Solutions for the Additive Manufacturing of H) Biodegradable Magnesium Implants

Due to their capability of fabricating geometrically complex structures,additive manufacturing(AM)techniques have provided unprecedented opportunities to produce biodegradable metallic implants—especially using Mg alloys,which exhibit appropriate mechanical properties and outstanding biocompatibility.However,many challenges hinder the fabrication of AM-processed biodegradable Mg-based implants,such as the difficulty of Mg powder preparation,powder splash,and crack formation during the AM process.In the present work,the challenges of AM-processed Mg components are analyzed and solutions to these challenges are proposed.A novel Mg-based alloy(Mg-Nd-Zn-Zr alloy,JDBM)powder with a smooth surface and good roundness was first synthesized successfully,and the AM parameters for Mg-based alloys were optimized.Based on the optimized parameters,porous JDBM scaffolds with three different architectures(biomimetic,diamond,and gyroid)were then fabricated by selective laser melting(SLM),and their mechanical properties and degradation behavior were evaluated.Finally,the gyroid scaffolds with the best performance were selected for dicalcium phosphate dihydrate(DCPD)coating treatment,which greatly suppressed the degradation rate and increased the cytocompatibility,indicating a promising prospect for clinical application as bone tissue engineering scaffolds.

Autophagy-related long non-coding RNA prognostic model predicts prognosis and survival of melanoma patients

BACKGROUND Melanomas are malignant tumors that can occur in different body parts or tissues such as the skin,mucous membrane,uvea,and pia mater.Long non-coding RNAs(lncRNAs)are key factors in the occurrence and development of many malignant tumors,and are involved in the prognosis of some patients.AIM To identify autophagy-related lncRNAs in melanoma that are crucial for the diagnosis,treatment,and prognosis of melanoma patients.METHODS We retrieved transcriptome expression profiles and clinical information of 470 melanoma patients from The Cancer Genome Atlas(TCGA)database.Then,we identified autophagy-related genes in the Human Autophagy Database.Using R,coexpression analysis of lncRNAs and autophagy-related genes was conducted to obtain autophagy-related lncRNAs and their expression levels.We also performed univariate and multivariate Cox proportional risk analyses on the obtained datasets,to systematically evaluate the prognostic value of autophagyrelated lncRNAs in melanoma.Fifteen autophagy-related lncRNAs were identified and an autophagy-related prognostic signature for melanoma was established.The Kaplan-Meier and univariate and multivariate Cox regression analyses were used to calculate risk scores.Based on the risk scores,melanoma patients were randomly divided into high-and low-risk groups.Receiver operating characteristic curve analysis,dependent on time,was performed to assess the accuracy of the prognostic model.At the same time,we also downloaded the melanoma data sets GSE65904,GSE19234,and GSE78220 from the GENE EXPRESSION OMNIBUS database for model verification.Finally,we performed Gene Set Enrichment Analysis functional annotation,which showed that the low and the high-risk groups had different enriched pathways.RESULTS The co-expression network for autophagy-related genes was constructed using R,and 936 lncRNAs related to autophagy were identified.Then,52 autophagy-related lncRNAs were significantly associated with TCGA melanoma patients’survival by univariate Cox proportional risk analysis(P<0.01).Further,the 52 autophagy-related lncRNAs mentioned above were analyzed by multivariate Cox analysis with R.Fifteen lncRNAs were selected:LINC01943,AC090948.3,USP30-AS1,AC068282.1,AC004687.1,AL133371.2,AC242842.1,PCED1B-AS1,HLADQB1-AS1,AC011374.2,LINC00324,AC018553.1,LINC00520,DBH-AS1,and ITGB2-AS1.The P values in all survival analyses using these 15 lncRNAs were<0.05.These lncRNAs were used to build a risk model based on the risk score.Negative correlations were observed between risk scores and overall survival rate in melanoma patients over time.Additionally,the melanoma risk curve and scatter plot analyses showed that the death number increased along with the increase in the risk score.Overall,we identified and established a new prognostic risk model for melanoma using 15 autophagy-related lncRNAs.The risk model constructed with these lncRNAs can help and guide melanoma patient prognosis predictions and individualized treatments in the future.CONCLUSION Overall,the risk model developed based on the 15 autophagy-related lncRNAs can have important prognostic value and may provide autophagy-related clinical targets for melanoma treatment.

Effects of various antimicrobial agents on multi-directional differentiation potential of bone marrow-derived mesenchymal stem cells

Antimicrobial drugs of several classes play an important role in the treatment of bone and joint infections. In addition to fighting pathogenic microorganisms, the effects of drugs on local tissues and cells are also related to the course and prognosis of bone and joint infections. The multi-directional differentiation potential of bone marrow-derived mesenchymal stem cells (MSCs) is essential for tissue repair after local injury, which is directly related to the recovery of bone, cartilage, and medullary adipose tissue. Our previous studies and the literature indicate that certain antimicrobial agents can regulate the differentiation potential of bone marrow-derived MSCs. Here, in order to systematically analyze the effects of various antimicrobial drugs on local tissue regeneration, we comprehensively review the studies on the effects of these drugs on MSC differentiation, and classify them according to the three differentiation directions (osteogenesis, chondrogenesis, and adipogenesis). Our review demonstrates the specific effects of different antimicrobial agents on bone marrow-derived MSCs and the range of concentrations at which they work, and provides a basis for drug selection at different sites of infection.

CDK5 inhibition promotes osteoblastic differentiation of MSCs and blocks the migration of osteosarcoma MG-63 cells

CDK5 belongs to the cyclin-dependent kinase family.CDK5 is multifunctional and plays an important role in neural differentiation.However,the role of CDK5 in osteoblastic differentiation remains unclear.The present study investigated functions and molecular mechanism of CDK5 in osteoblastic differentiation.It was found that,CDK5 inhibition promoted the expression of Runx2,ALP,OCN and OPN of MSCs and the mineralization of MC-3T3E1 cells and MSCs.CDK5 inhibition enhanced the development of F-actin,nuclear localization ofβ-catenin and YAP,as well as the expression of RMRP RNA.When F-actin was suppressed by Blebbistatin,the nuclear localization of YAP andβ-catenin,and expression of RMRP RNA as well as Runx2 and ALP were decreased.These indicate Seliciclib promotes osteoblastic differentiation mainly by F-actin.Moreover,Seliciclib also suppressed the migration of MG-63,suggesting a potential application for Seliciclib in bone defect repair and inhibition of the migration of osteosarcoma cells after osteosarcoma surgical resection.

Chondrosarcoma of the toe:A case report and literature review

BACKGROUND Chondrosarcoma of the foot is a rare malignant bone tumour,and it is even rarer when it originates in a toe bone.Surgical excision is the only effective treatment.The osteolytic destruction of the tumour severely affects limb function and carries the risk of distant metastasis.Most such tumours are removed surgically to minimize local recurrence and distant metastases,maximize limb function,and prolong the patient’s tumour-free survival time.The main objective of this article is to present the case of a chondrosarcoma that invaded the first phalanx of the left foot and formed a large phalangeal mass with osteolytic destruction of the distal bone.CASE SUMMARY A 74-year-old man suffered from swelling of his left toe for six months,with pain and swelling for two months.Computed tomography and magnetic resonance imaging showed that the tumour on the first phalanx of the left foot was approximately 54.9 mm×44.6 mm,surrounded by a significant soft tissue signal mass,with osteolytic destruction of the distal phalanx and a speckled bone-like highdensity shadow within it.CONCLUSION Chondrosarcoma occurring in a toe bone is extremely rare.In this case,extensive surgical resection of the large low-grade chondrosarcoma,which showed osteolytic destruction and invaded the distal metatarsal bone,was safe and effective.

Consensus statement on research and application of Chinese herbal medicine derived extracellular vesicles-like particles(2023 edition)

To promote the development of extracellular vesicles of herbal medicine especially the establishment of standardization,led by the National Expert Committee on Research and Application of Chinese Herbal Vesicles,research experts in the field of herbal medicine and extracellular vesicles were invited nationwide with the support of the Expert Committee on Research and Application of Chinese Herbal Vesicles,Professional Committee on Extracellular Vesicle Research and Application,Chinese Society of Research Hospitals and the Guangdong Engineering Research Center of Chinese Herbal Vesicles.Based on the collation of relevant literature,we have adopted the Delphi method,the consensus meeting method combined with the nominal group method to form a discussion draft of“Consensus statement on research and application of Chinese herbal medicine derived extracellular vesicles-like particles(2023)”.The first draft was discussed in online and offline meetings on October 12,14,November 2,2022 and April and May 2023 on the current status of research,nomenclature,isolation methods,quality standards and research applications of extracellular vesicles of Chinese herbal medicines,and 13 consensus opinions were finally formed.At the Third Academic Conference on Research and Application of Chinese Herbal Vesicles,held on May 26,2023,Kewei Zhao,convenor of the consensus,presented and read the consensus to the experts of the Expert Committee on Research and Application of Chinese Herbal Vesicles.The consensus highlights the characteristics and advantages of Chinese medicine,inherits the essence,and keeps the righteousness and innovation,aiming to provide a reference for colleagues engaged in research and application of Chinese herbal vesicles at home and abroad,decode the mystery behind Chinese herbal vesicles together,establish a safe,effective and controllable accurate Chinese herbal vesicle prevention and treatment system,and build a bridge for Chinese medicine to the world.

拥抱未来:将ChatGPT融入中国护理教育

探讨ChatGPT在快速发展的人工智能领域中所扮演的角色,特别是其在护理教育领域内的巨大潜力。学术界对ChatGPT的关注日益增长,其在促进互动学习和提供实时反馈方面取得显著进展,ChatGPT在护理学科包括多个临床教学及场景中的应用研究成果,展现了其在多学科教育和解决临床问题方面的巨大潜力。通过比较多个大型语言模型在中国护理执业资格考试中的表现,发现ChatGPT相较于其他模型显示出更高的正确率,为其在中国护理教育和临床场景中的应用提供了坚实的理论基础。为了在本土化护理教育中有效利用ChatGPT,并承担起相应的责任,相关教育机构需要建立一个针对性的、有效的监管框架。通过规范化的使用者培训和对现有教育评估方法的调整,旨在防止潜在的误用和滥用,充分挖掘ChatGPT作为中国护理教育中的创新辅助工具的潜能,以适应现代化教学方法的发展需求。

Hemiarthroplasty for irreparable distal radius fractures in the elderly:A comprehensive review

BACKGROUND Elderly patients maintaining functional independence can now be candidates for primary wrist hemiarthroplasty to manage acute irreparable distal radius fractures(DRFs).However,further investigation with long-term follow-up is required to validate these initial findings.AIM To review the literature on the outcomes of distal radius hemiarthroplasty with available implants to assess its viability as a treatment option.METHODS A comprehensive review of the literature was conducted using electronic databases,including PubMed,Medline,and Scopus.The search terms employed were"distal radius fracture","hemiarthroplasty","wrist arthroplasty",and related terminology.The search was restricted to articles published in English from 1980 until June 2023.Inclusion criteria encompassed cases or case series of DRF treated with hemiarthroplasty,providing clinical or radiographic outcomes,and published in peer-reviewed journals.RESULTS A total of 2508 articles from PubMed and 883 from Scopus were identified initially.Following screening and removal of duplicates,13 articles met the inclusion criteria.These articles,predominantly clinical retrospective studies,provided insights into hemiarthroplasty outcomes,including functional improvements and complications.Hemiarthroplasty was a treatment option for complex DRF,particularly those cases with severe comminution,intraarticular involvement,or severe osteoporosis.Functional outcomes demonstrated improvements in pain relief,wrist mobility,and grip strength,with variability across studies.Complications included implant loosening,infection,nerve injury,and stiffness,with varying incidence rates influenced by surgical techniques and implant choice.Long-term outcomes were inadequately documented,warranting further research.CONCLUSION Hemiarthroplasty is a promising treatment for irreparable DRF in the elderly.Long-term outcomes and complications require further study.

Targeting ferroptosis suppresses osteocyte glucolipotoxicity and alleviates diabetic osteoporosis

Diabetic osteoporosis(DOP) is the leading complication continuously threatening the bone health of patients with diabetes. A key pathogenic factor in DOP is loss of osteocyte viability. However, the mechanism of osteocyte death remains unclear. Here, we identified ferroptosis, which is iron-dependent programmed cell death, as a critical mechanism of osteocyte death in murine models of DOP. The diabetic microenvironment significantly enhanced osteocyte ferroptosis in vitro, as shown by the substantial lipid peroxidation, iron overload, and aberrant activation of the ferroptosis pathway. RNA sequencing showed that heme oxygenase-1(HO-1) expression was notably upregulated in ferroptotic osteocytes. Further findings revealed that HO-1 was essential for osteocyte ferroptosis in DOP and that its promoter activity was controlled by the interaction between the upstream NRF2 and c-JUN transcription factors. Targeting ferroptosis or HO-1 efficiently rescued osteocyte death in DOP by disrupting the vicious cycle between lipid peroxidation and HO-1 activation, eventually ameliorating trabecular deterioration. Our study provides insight into DOP pathogenesis, and our results provide a mechanism-based strategy for clinical DOP treatment.

BMP-induced Atoh8 attenuates osteoclastogenesis by suppressing Runx2 transcriptional activity and reducing the Rankl/Opg expression ratio in osteoblasts

Adult bone structural integrity is maintained by remodeling via the coupling of osteoclastic bone resorption and osteoblastic bone formation.Osteocytes or osteoblasts express receptor activator of nuclear factor k-B ligand(Rankl)or osteoprotegerin(Opg)to promote or inhibit osteoclastogenesis,respectively.Bone morphogenetic protein(BMP)is a potent bone inducer,but its major role in adult bone is to induce osteocytes to upregulate sclerostin(Sost)and increase the Rankl/Opg expression ratio,resulting in promotion of osteoclastogenesis.However,the precise effect of BMP-target gene(s)in osteoblasts on the Rankl/Opg expression ratio remains unclear.In the present study,we identified atonal homolog 8(Atoh8),which is directly upregulated by the BMPSmadl axis in osteoblasts.In vivo,Atoh8 was detected in osteoblasts but not osteocytes in adult mice.Although global Atoh8-knockout mice showed only a mild phenotype in the neonate skeleton,the bone volume was decreased and osteoclasts were increased in the adult phase.Atoh8-null marrow stroma cells were more potent than wild-type cells in inducing osteoclastogenesis in marrow cells.Atoh8 loss in osteoblasts increased Runx2 expression and the Rankl/Opg expression ratio,while Runx2 knockdown normalized the Rankl/Opg expression ratio.Moreover,Atoh8 formed a protein complex with Runx2 to inhibit Runx2 transcriptional activity and decrease the Rankl/Opg expression ratio.These results suggest that bone remodeling is regulated elaborately by BMP signaling;while BMP primarily promotes bone resorption,it simultaneously induces Atoh8 to inhibit Runx2 and reduce the Rankl/Opg expression ratio in osteoblasts,suppressing osteoclastogenesis and preventing excessive BMP-mediated bone resorption.