Practice of Infection Prevention and Control Strategies in Risk Departments during the COVID-19 Epidemic

Objective: To explore the practice and application of infection prevention and control strategies in risk departments during the COVID-19 epidemic, and to formulate the infection prevention and control measures to provide advice and guidance in risk departments. Methods: According to the latest plan of diagnosis and treatment, prevention and control issued by the National Health Commission, expert advice and consensus, combined with the actual situation in our hospital, a series of infection prevention and control measures of COVID-19 in risk department was formulated. Results: During the epidemic period, the prevention and control measures of nine risk departments including emergency operation, anesthesiology, endoscopy center, blood purification center, otolaryngology, stomatology, medical imaging department, medical cosmetology department and pulmonary function room were established from six aspects, including pre-examination and screening, medical technology control, personnel management, personal protection, environmental disinfection, medical waste disposal, etc. Conclusion: During the epidemic period, the infection prevention and control strategy of risk departments is one of the key links to control the spread of the epidemic, and risk departments must pay attention to and strictly implement various infection prevention and control measures.

Influence of layer thickness on formation quality,microstructure,mechanical properties,and corrosion resistance of WE43 magnesium alloy fabricated by laser powder bed fusion

Laser powder bed fusion(L-PBF)of Mg alloys has provided tremendous opportunities for customized production of aeronautical and medical parts.Layer thickness(LT)is of great significance to the L-PBF process but has not been studied for Mg alloys.In this study,WE43 Mg alloy bulk cubes,porous scaffolds,and thin walls with layer thicknesses of 10,20,30,and 40μm were fabricated.The required laser energy input increased with increasing layer thickness and was different for the bulk cubes and porous scaffolds.Porosity tended to occur at the connection joints in porous scaffolds for LT40 and could be eliminated by reducing the laser energy input.For thin wall parts,a large overhang angle or a small wall thickness resulted in porosity when a large layer thicknesses was used,and the porosity disappeared by reducing the layer thickness or laser energy input.A deeper keyhole penetration was found in all occasions with porosity,explaining the influence of layer thickness,geometrical structure,and laser energy input on the porosity.All the samples achieved a high fusion quality with a relative density of over 99.5%using the optimized laser energy input.The increased layer thickness resulted to more precipitation phases,finer grain sizes and decreased grain texture.With the similar high fusion quality,the tensile strength and elongation of bulk samples were significantly improved from 257 MPa and 1.41%with the 10μm layer to 287 MPa and 15.12%with the 40μm layer,in accordance with the microstructural change.The effect of layer thickness on the compressive properties of porous scaffolds was limited.However,the corrosion rate of bulk samples accelerated with increasing the layer thickness,mainly attributed to the increased number of precipitation phases.

Which approach of total hip arthroplasty is the best efficacy and least complication?

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.

Epidemiology of shoulder dislocations presenting to United States emergency departments:An updated ten-year study

BACKGROUND Glenohumeral dislocation is a common injury that may predispose patients to chronic pain and instability.However,there is a paucity of current data available regarding the epidemiological trends of this injury.AIM To provide an updated,comparative assessment of the epidemiology of shoulder dislocations presenting to emergency departments in the United States.We also sought to analyze patient demographic risk factors and consumer products associated with dislocation events.METHODS Data were obtained from the national electronic injury surveillance system database for glenohumeral dislocations between 2012 and 2021.Incidence,age,sex,and injury characteristics were analyzed using weighted population statistics as well as incidence rates and 95%confidence intervals(CI).RESULTS In total,an estimated 773039 shoulder dislocations(CI:640598-905481)presented to emergency rooms across the United States during the study period.The annual incidence rate was 23.96 per 100000 persons and the average patient age at the time of injury was 37.1 years.Significantly more male patients sustained dislocations than female patients(537189,69.5%,vs 235834,30.5%,P<0.001).With regard to associated consumer products,sports and recreation equipment were involved in the highest proportion of incidents(44.31%),followed by home structures and construction materials(21.22%),and home furnishings,fixtures,and accessories(21.21%).Regarding product sub-groups,stairs,ramps,landings,floors was cited in the greatest number of cases(131745).CONCLUSION The national annual incidence rate of glenohumeral dislocations throughout the study period was approximately 23.92 per 100000 persons.Male adolescents sustained the highest proportion of dislocations,with a peak incidence in age group 15-20 years,predominantly secondary to participation in sporting and recreational activities.Conversely,women experienced a relatively consistent incidence of dislocation throughout their lifespan.After age 63,the incidence rate of dislocations in females was found to surpass that observed in males.

Improving corrosion resistance of additively manufactured WE43 magnesium alloy by high temperature oxidation for biodegradable applications

Laser powder bed fusion(L-PBF)has been employed to additively manufacture WE43 magnesium(Mg)alloy biodegradable implants,but WE43 L-PBF samples exhibit excessively rapid corrosion.In this work,dense WE43 L-PBF samples were built with the relativity density reaching 99.9%.High temperature oxidation was performed on the L-PBF samples in circulating air via various heating temperatures and holding durations.The oxidation and diffusion at the elevated temperature generated a gradient structure composed of an oxide layer at the surface,a transition layer in the middle and the matrix.The oxide layer consisted of rare earth(RE)oxides,and became dense and thick with increasing the holding duration.The matrix was composed ofα-Mg,RE oxides and Mg_(24)RE_(5) precipitates.The precipitates almost disappeared in the transition layer.Enhanced passivation effect was observed in the samples treated by a suitable high temperature oxidation.The original L-PBF samples lost 40%weight after 3-day immersion in Hank’s solution,and broke into fragments after 7-day immersion.The casted and solution treated samples lost roughly half of the weight after 28-day immersion.The high temperature oxidation samples,which were heated at 525℃ for 8 h,kept the structural integrity,and lost only 6.88%weight after 28-day immersion.The substantially improved corrosion resistance was contributed to the gradient structure at the surface.On one hand,the outmost dense layer of RE oxides isolated the corrosive medium;on the other hand,the transition layer considerably inhibited the corrosion owing to the lack of precipitates.Overall,high temperature oxidation provides an efficient,economic and safe approach to inhibit the corrosion of WE43 L-PBF samples,and has promising prospects for future clinical applications.

Tenosynovitis of hand: Causes and complications

Tenosynovitis represents a common clinical condition characterized by inflam-mation of the synovium that encases the tendon sheath.Although tenosynovities may be noted in any tendon in the body,extremities such as hand,and foot remain the sites of high predilection to acquire this condition.The predominant cause of this predilection rests in the intricate tendon arrangements in these extremities that permit fine motor actions.This editorial explores the common causes and the complications associated with this condition to improve the understanding of the readers of this common condition encountered in our everyday clinical practice.

Multi-omics analysis of human tendon adhesion reveals that ACKR1-regulated macrophage migration is involved in regeneration

Tendon adhesion is a common complication after tendon injury with the development of accumulated fibrotic tissues without effective anti-fibrotic therapies,resulting in severe disability.Macrophages are widely recognized as a fibrotic trigger during peritendinous adhesion formation.However,different clusters of macrophages have various functions and receive multiple regulation,which are both still unknown.In our current study,multi-omics analysis including single-cell RNA sequencing and proteomics was performed on both human and mouse tendon adhesion tissue at different stages after tendon injury.The transcriptomes of over 74000 human single cells were profiled.As results,we found that SPP1^(+)macrophages,RGCC^(+)endothelial cells,ACKR1^(+)endothelial cells and ADAM12^(+)fibroblasts participated in tendon adhesion formation.Interestingly,despite specific fibrotic clusters in tendon adhesion,FOLR2^(+)macrophages were identified as an antifibrotic cluster by in vitro experiments using human cells.Furthermore,ACKR1 was verified to regulate FOLR2^(+)macrophages migration at the injured peritendinous site by transplantation of bone marrow from Lysm-Cre;R26R^(tdTomato) mice to lethally irradiated Ackr1^(-/-)mice(Ackr1^(-/-)chimeras;deficient in ACKR1)and control mice(WT chimeras).Compared with WT chimeras,the decline of FOLR2^(+)macrophages was also observed,indicating that ACKR1 was specifically involved in FOLR2^(+)macrophages migration.Taken together,our study not only characterized the fibrosis microenvironment landscape of tendon adhesion by multi-omics analysis,but also uncovered a novel antifibrotic cluster of macrophages and their origin.These results provide potential therapeutic targets against human tendon adhesion.

Sorafenib inhibits ossification of the posterior longitudinal ligament by blocking LOXL2-mediated vascularization

Ossification of the Posterior Longitudinal Ligament(OPLL)is a degenerative hyperostosis disease characterized by the transformation of the soft and elastic vertebral ligament into bone,resulting in limited spinal mobility and nerve compression.Employing both bulk and single-cell RNA sequencing,we elucidate the molecular characteristics,cellular components,and their evolution during the OPLL process at a single-cell resolution,and validate these findings in clinical samples.This study also uncovers the capability of ligament stem cells to exhibit endothelial cell-like phenotypes in vitro and in vivo.Notably,our study identifies LOXL2 as a key regulator in this process.Through gain-and loss-of-function studies,we elucidate the role of LOXL2 in the endothelial-like differentiation of ligament cells.It acts via the HIF1A pathway,promoting the secretion of downstream VEGFA and PDGF-BB.This function is not related to the enzymatic activity of LOXL2.Furthermore,we identify sorafenib,a broad-spectrum tyrosine kinase inhibitor,as an effective suppressor of LOXL2-mediated vascular morphogenesis.By disrupting the coupling between vascularization and osteogenesis,sorafenib demonstrates significant inhibition of OPLL progression in both BMP-induced and enpp1 deficiency-induced animal models while having no discernible effect on normal bone mass.These findings underscore the potential of sorafenib as a therapeutic intervention for OPLL.

Does progress in microfracture techniques necessarily translate into clinical effectiveness?

BACKGROUND Multitudinous advancements have been made to the traditional microfracture(MFx)technique,which have involved delivery of various acellular 2nd generation MFx and cellular MFx-III components to the area of cartilage defect.The relative benefits and pitfalls of these diverse modifications of MFx technique are still not widely understood.AIM To comparatively analyze the functional,radiological,and histological outcomes,and complications of various generations of MFx available for the treatment of cartilage defects.METHODS A systematic review was performed using PubMed,EMBASE,Web of Science,Cochrane,and Scopus.Patients of any age and sex with cartilage defects undergoing any form of MFx were considered for analysis.We included only randomized controlled trials(RCTs)reporting functional,radiological,histological outcomes or complications of various generations of MFx for the management of cartilage defects.Network meta-analysis(NMA)was conducted in Stata and Cochrane’s Confidence in NMA approach was utilized for appraisal of evidence.RESULTS Forty-four RCTs were included in the analysis with patients of mean age of 39.40(±9.46)years.Upon comparing the results of the other generations with MFX-I as a constant comparator,we noted a trend towards better pain control and functional outcome(KOOS,IKDC,and Cincinnati scores)at the end of 1-,2-,and 5-year time points with MFx-III,although the differences were not statistically significant(P>0.05).We also noted statistically significant Magnetic resonance observation of cartilage repair tissue score in the higher generations of microfracture(weighted mean difference:17.44,95%confidence interval:0.72,34.16,P=0.025;without significant heterogeneity)at 1 year.However,the difference was not maintained at 2 years.There was a trend towards better defect filling on MRI with the second and third generation MFx,although the difference was not statistically significant(P>0.05).CONCLUSION The higher generations of traditional MFx technique utilizing acellular and cellular components to augment its potential in the management of cartilage defects has shown only marginal improvement in the clinical and radiological outcomes.

Effect of weight-adjusted antimicrobial antibiotic prophylaxis on postoperative dosage and surgical site infection incidence in total joint arthroplasty

Surgical site infections(SSI)following total joint arthroplasty pose a significant concern for both providers and patients across the globe.Currently,administration of antimicrobial antibiotic prophylaxis is used throughout the world to reduce the incidence of SSI.However,the correct dosage and frequency of administration remains debatable.In this editorial,we emphasized the determination of the effect of administration of weight-adjusted antimicrobial antibiotic prophylaxis regime on the incidence of SSI and postoperative dosage reduction compared to the conventionally used regime during total joint arthroplasty.The results demonstrated similar efficacy between both regimes with respect to the incidence of SSI.In addition,weight-adjustment led to reduced postoperative dosage and has the potential to reduce chances of achieving lower therapeutic concentration,drug resistance,drug toxicity,and costs.

Research progresses of artificial intelligence in MRI of lumbar degenerative diseases

The incidence of lumbar degenerative diseases is increasing year by year,and MRI is often used in clinical diagnosis.In recent years,artificial intelligence(AI)has rapidly developed in medical field and can be used for image segmentation and auxiliary diagnosis of lumbar degenerative diseases.The research progresses of AI in MRI of lumbar degenerative diseases were reviewed in this article.

Dialectical study of disulfidptosis and clinical outcome in patients with colorectal cancer

Background:Colorectal cancer(CRC)is a leading cause of cancer mortality globally.This study aims to develop a prognostic model based on disulfidptosis-related genes to assess survival outcomes in CRC,highlighting the tumor microenvironment’s role.Methods:The thought of traditional Chinese medicine syndrome differentiation and treatment runs through the whole study.We analyzed CRC tissue data from The Cancer Genome Atlas and the Gene Expression Omnibus using single-sample gene set enrichment and weighted gene correlation network analyses to identify prognostic markers and evaluate immune infiltration.We also investigated predictive drug sensitivities.Results:We identified seven disulfidptosis-related markers–complement C1q A chain(C1QA),solute carrier family 11 member 1(SLC11A1),cluster of differentiation 36(CD36),cluster of differentiation 6(CD6),interleukin 1 receptor associated kinase 3(IRAK3),S100 calcium binding protein A8(S100A8),and CD8 subunit alpha(CD8A)–that significantly influence prognosis.Patients classified in the low-risk group demonstrated improved overall survival compared to those in the high-risk group across training(P=0.0026)and validation cohorts(P=0.032).Differential gene expression was significant in the high-risk group(P<0.001),and prevalent mutations included APC regulator of WNT signaling pathway(APC),tumor protein P53(TP53),Titin(TTN),and Kirsten rat sarcoma viral oncogene(KRAS).The risk score correlated linearly with tumor microenvironment attributes.The results of drug analysis showed that some traditional drugs may have anticancer effects through the vertical action of disulfidptosis.Conclusion:Our prognostic model,integrating seven disulfidptosis-related genes,categorizes CRC patients by survival probability and underscores these genes as potential biomarkers linked to the tumor microenvironment.These findings support their use in refining therapeutic strategies for CRC.

Clinical outcomes of triceps reflecting anconeus pedicle and olecranon osteotomy approach for distal humerus intercondylar fractures

BACKGROUND The preferred treatment for distal humeral intercondylar fractures is open reduction and internal fixation.While there is consensus about the posterior approach,several posterior approaches have been developed.It is debatable as to which approach is best.AIM To compare triceps reflecting anconeus pedicle(TRAP)and olecranon osteotomy approaches for internal fixation of distal humeral intercondylar fracture.METHODS In total,40 cases of Arbeitsgemeinschaft für Osteosynthesefragen/Association of the Study of Internal Fixation type C,closed,and Gustilo type I intercondylar humeral fractures were included.Patients ranged in age from 18 years to 70 years.The patients were randomized into two groups:TRAP group and olecranon osteotomy group,with 20 cases in each.All were followed up at 6 wk,3 months,6 months,and 12 months.Functional outcomes were measured in terms of flexion-extension arc,Disabilities of Arm,Shoulder and Hand score,and Mayo Elbow Performance Score.RESULTS The mean age was 43.2 years in the TRAP group and 37.5 years in the olecranon osteotomy group.The mean operative time and mean duration of hospital stay in the TRAP group were significantly higher than in the olecranon osteotomy group(119.5 vs 111.5 min and 9.85 vs 5.45 d,respectively).The mean arc of flexion-extension,Disabilities of Arm,Shoulder and Hand score,and Mayo Elbow Performance Score were comparable without any significant difference in the groups at the 12-month follow-up(107.0 vs 106.2,18.3 vs 15.7,and 84.2 vs 86.2,respectively).Ulnar paresthesia and superficial infections were comparable in both groups(2 cases vs 3 cases and 3 cases vs 2 cases,respectively).Hardware prominence was significantly higher in the olecranon osteotomy group,mostly due to tension band wiring.CONCLUSION Both approaches were equivalent,but there is a need for further study including higher numbers of subjects and longer study duration to prove the benefits of one approach over the other.

Meta-analysis of new intervention measures for preventing side effects of artificial joint replacement

BACKGROUND Intertrochanteric fracture of the femur occurs mostly among older people,and seriously affects daily life and quality of life.At present,physical intervention,drug treatment,routine intervention and rehabilitation training are widely used for prevention of side effects,but it is still inconclusive which intervention has the best effect.AIM To compare the effects of new intervention measures for preventing side effects of artificial joint replacement.METHODS We searched the Chinese and English literatures for comparative studies on the prevention of side effects of new interventions for artificial joint replacement from July 2013 to June 2023 in China HowNet,PubMed,Wanfang,Weipu and other databases.Study quality was evaluated by improved Jadad scoring standard,and the effects of different interventions on preventing different complications were analyzed by meta-analysis of evidence-based medicine with Review Manager 5.0 software.RESULTS Ten articles,including 869 cases,were finally included.The preventive effects of different interventions on the side effects of artificial joint replacement were studied,and valid data were extracted.There were two articles on the preventive effects of drug intervention,four on comparison of the preventive effects of combined and single interventions,and three on the preventive effects of physical intervention,rehabilitation training and routine intervention.Meta-analysis showed that the preventive effect of rivaroxaban was significantly better than low molecular weight heparin calcium[mean difference(MD)=-0.16,95%CI:-0.28 to-0.04,P<0.05].The effect of combined intervention was significantly better than that of single intervention(MD=-0.08,95%CI:-0.16 to-0.01,P<0.001).Physical intervention was significantly better than routine intervention and rehabilitation training(MD=0.26,95%CI:0.16–0.36,P<0.001).CONCLUSION Rivaroxaban combined with rehabilitation training is preferred for preventing deep vein thrombosis after artificial joint replacement.In the prevention of pulmonary embolism,rivaroxaban drug intervention is given priority.The effect of combined intervention is better than that of single intervention.

Commentary on“The deterministic condition for the ground reaction force acting point on the combined knee valgus and tibial internal rotation moments in the early phase of cutting maneuvers in female athletes”

1.Introduction For decades,substantial disagreement has persisted as to whether dynamic knee valgus is the cause of the majority of anterior cruciate ligament(ACL)injuries or rather the result of the ACL rupture.1 Consequently,great effort and expense has gone into capturing 3-dimensional kinetics and kinematics from live athletes to drive in vitro and in silico models of ACL injury in order to elucidate the actual mechanism of injury,as these factors have been demonstrated to be surrogates of intraarticular structural loading on the ACL.2,3 The elucidation of injury mechanisms for non-contact ACL injuries is of great medical value as such knowledge consequently permits quantified examination and validation of interventions and their respective effectiveness in both prevention and rehabilitation of these traumatic knee injuries.

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

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

Advancing orthopaedic trauma care through WhatsApp:An analysis of clinical and non-clinical applications,challenges,and future directions

The integration of WhatsApp,a widely-used instant messaging application(IMA),into the realm of orthopaedics and trauma surgery has emerged as a significant development in recent years.This paper explores the multifaceted role of WhatsApp in orthopaedics,focusing on its clinical and non-clinical applications,advantages,disadvantages,and future prospects.The study synthesizes findings from various research papers,emphasizing the growing reliance on mobile technology in healthcare.WhatsApp’s role in orthopaedics is notable for its ease of use,real-time communication,and accessibility.Clinically,it facilitates triage,teleconsultation,diagnosis,treatment,patient advice,and post-operative monitoring.Non-clinically,it supports telemedicine,teleradiology,virtual frac-ture clinics,research,and education in orthopaedic surgery.The application has proven beneficial in enhancing communication among healthcare teams,providing quick responses,and motivating junior physicians.Its use in educational settings has been shown to improve learner’s understanding and patient care.However,the use of WhatsApp in orthopaedics is not without challenges.Risks include the potential spread of misleading information,privacy concerns,and issues with image quality affecting diagnosis and treatment decisions.The paper acknowledges the importance of maintaining professional boundaries and the need for oversight measures to ensure content accuracy.Looking forward,the potential of WhatsApp and similar IMAs in orthopaedics lies in their ability to streamline data collection and retrieval,improve doctor-patient communication,and address challenges like bureaucratic red tape and limited resources.The paper suggests that future orthopaedic practice,particularly in emergency departments,will increasingly rely on such technologies for efficient patient management.This shift,however,must be approached with an understanding of the ethical,legal,and practical implications of integrating social media and mobile technology in healthcare.

Age-related secretion of grancalcin by macrophages induces skeletal stem/progenitor cell senescence during fracture healing

Skeletal stem/progenitor cell(SSPC)senescence is a major cause of decreased bone regenerative potential with aging,but the causes of SSPC senescence remain unclear.In this study,we revealed that macrophages in calluses secrete prosenescent factors,including grancalcin(GCA),during aging,which triggers SSPC senescence and impairs fracture healing.Local injection of human rGCA in young mice induced SSPC senescence and delayed fracture repair.Genetic deletion of Gca in monocytes/macrophages was sufficient to rejuvenate fracture repair in aged mice and alleviate SSPC senescence.Mechanistically,GCA binds to the plexin-B2 receptor and activates Arg2-mediated mitochondrial dysfunction,resulting in cellular senescence.Depletion of Plxnb2 in SSPCs impaired fracture healing.Administration of GCA-neutralizing antibody enhanced fracture healing in aged mice.Thus,our study revealed that senescent macrophages within calluses secrete GCA to trigger SSPC secondary senescence,and GCA neutralization represents a promising therapy for nonunion or delayed union in elderly individuals.

Prospects and challenges for the application of tissue engineering technologies in the treatment of bone infections

Osteomyelitis is a devastating disease caused by microbial infection in deep bone tissue.Its high recurrence rate and impaired restoration of bone deficiencies are major challenges in treatment.Microbes have evolved numerous mechanisms to effectively evade host intrinsic and adaptive immune attacks to persistently localize in the host,such as drug-resistant bacteria,biofilms,persister cells,intracellular bacteria,and small colony variants(SCVs).Moreover,microbial-mediated dysregulation of the bone immune microenvironment impedes the bone regeneration process,leading to impaired bone defect repair.Despite advances in surgical strategies and drug applications for the treatment of bone infections within the last decade,challenges remain in clinical management.The development and application of tissue engineering materials have provided new strategies for the treatment of bone infections,but a comprehensive review of their research progress is lacking.This review discusses the critical pathogenic mechanisms of microbes in the skeletal system and their immunomodulatory effects on bone regeneration,and highlights the prospects and challenges for the application of tissue engineering technologies in the treatment of bone infections.It will inform the development and translation of antimicrobial and bone repair tissue engineering materials for the management of bone infections.

Regulation of specific abnormal calcium signals in the hippocampal CA1 and primary cortex M1 alleviates the progression of temporal lobe epilepsy

Temporal lobe epilepsy is a multifactorial neurological dysfunction syndrome that is refractory,resistant to antiepileptic drugs,and has a high recurrence rate.The pathogenesis of temporal lobe epilepsy is complex and is not fully understood.Intracellular calcium dynamics have been implicated in temporal lobe epilepsy.However,the effect of fluctuating calcium activity in CA1 pyramidal neurons on temporal lobe epilepsy is unknown,and no longitudinal studies have investigated calcium activity in pyramidal neurons in the hippocampal CA1 and primary motor cortex M1 of freely moving mice.In this study,we used a multichannel fiber photometry system to continuously record calcium signals in CA1 and M1 during the temporal lobe epilepsy process.We found that calcium signals varied according to the grade of temporal lobe epilepsy episodes.In particular,cortical spreading depression,which has recently been frequently used to represent the continuously and substantially increased calcium signals,was found to correspond to complex and severe behavioral characteristics of temporal lobe epilepsy ranging from gradeⅡto gradeⅤ.However,vigorous calcium oscillations and highly synchronized calcium signals in CA1 and M1 were strongly related to convulsive motor seizures.Chemogenetic inhibition of pyramidal neurons in CA1 significantly attenuated the amplitudes of the calcium signals corresponding to gradeⅠepisodes.In addition,the latency of cortical spreading depression was prolonged,and the above-mentioned abnormal calcium signals in CA1 and M1 were also significantly reduced.Intriguingly,it was possible to rescue the altered intracellular calcium dynamics.Via simultaneous analysis of calcium signals and epileptic behaviors,we found that the progression of temporal lobe epilepsy was alleviated when specific calcium signals were reduced,and that the end-point behaviors of temporal lobe epilepsy were improved.Our results indicate that the calcium dynamic between CA1 and M1 may reflect specific epileptic behaviors corresponding to different grades.Furthermore,the selective regulation of abnormal calcium signals in CA1 pyramidal neurons appears to effectively alleviate temporal lobe epilepsy,thereby providing a potential molecular mechanism for a new temporal lobe epilepsy diagnosis and treatment strategy.