Although previous RNA sequencing methods have been widely used in orthopedic research and have provided ideas for therapeutic strategies,the specific mechanisms of some orthopedic disorders,including osteoarthritis,lu...Although previous RNA sequencing methods have been widely used in orthopedic research and have provided ideas for therapeutic strategies,the specific mechanisms of some orthopedic disorders,including osteoarthritis,lumbar disc herniation,rheumatoid arthritis,fractures,tendon injuries,spinal cord injury,heterotopic ossification,and osteosarcoma,require further elucidation.The emergence of the single-cell RNA sequencing(sc RNA-seq)technique has introduced a new era of research on these topics,as this method provides information regarding cellular heterogeneity,new cell subtypes,functions of novel subclusters,potential molecular mechanisms,cell-fate transitions,and cell-cell interactions that are involved in the development of orthopedic diseases.Here,we summarize the cell subpopulations,genes,and underlying mechanisms involved in the development of orthopedic diseases identified by sc RNA-seq,improving our understanding of the pathology of these diseases and providing new insights into therapeutic approaches.展开更多
Bone formation and deposition are initiated by sensory nerve infiltration in adaptive bone remodeling. Here, we focused on the role of Semaphorin 3A(Sema3A), expressed by sensory nerves, in mechanical loads-induced bo...Bone formation and deposition are initiated by sensory nerve infiltration in adaptive bone remodeling. Here, we focused on the role of Semaphorin 3A(Sema3A), expressed by sensory nerves, in mechanical loads-induced bone formation and nerve withdrawal using orthodontic tooth movement(OTM) model. Firstly, bone formation was activated after the 3rd day of OTM,coinciding with a decrease in sensory nerves and an increase in pain threshold. Sema3A, rather than nerve growth factor(NGF),highly expressed in both trigeminal ganglion and the axons of periodontal ligament following the 3rd day of OTM. Moreover, in vitro mechanical loads upregulated Sema3A in neurons instead of in human periodontal ligament cells(hPDLCs) within 24 hours.Furthermore, exogenous Sema3A restored the suppressed alveolar bone formation and the osteogenic differentiation of hPDLCs induced by mechanical overload. Mechanistically, Sema3A prevented overstretching of F-actin induced by mechanical overload through ROCK2 pathway, maintaining mitochondrial dynamics as mitochondrial fusion. Therefore, Sema3A exhibits dual therapeutic effects in mechanical loads-induced bone formation, both as a pain-sensitive analgesic and a positive regulator for bone formation.展开更多
Traumatic spinal cord injury is potentially catastrophic and can lead to permanent disability or even death.China has the largest population of patients with traumatic spinal cord injury.Previous studies of traumatic ...Traumatic spinal cord injury is potentially catastrophic and can lead to permanent disability or even death.China has the largest population of patients with traumatic spinal cord injury.Previous studies of traumatic spinal cord injury in China have mostly been regional in scope;national-level studies have been rare.To the best of our knowledge,no national-level study of treatment status and economic burden has been performed.This retrospective study aimed to examine the epidemiological and clinical features,treatment status,and economic burden of traumatic spinal cord injury in China at the national level.We included 13,465 traumatic spinal cord injury patients who were injured between January 2013 and December 2018 and treated in 30 hospitals in 11 provinces/municipalities representing all geographical divisions of China.Patient epidemiological and clinical features,treatment status,and total and daily costs were recorded.Trends in the percentage of traumatic spinal cord injuries among all hospitalized patients and among patients hospitalized in the orthopedic department and cost of care were assessed by annual percentage change using the Joinpoint Regression Program.The percentage of traumatic spinal cord injuries among all hospitalized patients and among patients hospitalized in the orthopedic department did not significantly change overall(annual percentage change,-0.5%and 2.1%,respectively).A total of 10,053(74.7%)patients underwent surgery.Only 2.8%of patients who underwent surgery did so within 24 hours of injury.A total of 2005(14.9%)patients were treated with high-dose(≥500 mg)methylprednisolone sodium succinate/methylprednisolone(MPSS/MP);615(4.6%)received it within 8 hours.The total cost for acute traumatic spinal cord injury decreased over the study period(-4.7%),while daily cost did not significantly change(1.0%increase).Our findings indicate that public health initiatives should aim at improving hospitals’ability to complete early surgery within 24 hours,which is associated with improved sensorimotor recovery,increasing the awareness rate of clinical guidelines related to high-dose MPSS/MP to reduce the use of the treatment with insufficient evidence.展开更多
Traditional orthopedic metal implants,such as titanium(Ti),Ti alloys,and cobalt-chromium(Co-Cr)alloys,cannot be degraded in vivo.Fracture patients is must always suffer a second operation to remove the implants.Moreov...Traditional orthopedic metal implants,such as titanium(Ti),Ti alloys,and cobalt-chromium(Co-Cr)alloys,cannot be degraded in vivo.Fracture patients is must always suffer a second operation to remove the implants.Moreover,stress shielding,or stress protection occurs when traditional orthopedic metal implants are applied in fractures surgery.The mechanical shunt produced by traditional orthopedic metal implants can cause bone loss over time,resulting in decreased bone strength and delayed fracture healing.Biodegradable metals that‘biocorrode’are currently attracting significant interest in the orthopedics field due to their suitability as temporary implants.As one of the biodegradable metals,magnesium(Mg)and Mg alloys have gained interest in the field of medicine due to their low density,excellent biocompatibility,high bioresorbability,and proper mechanical properties.Additionally,Mg ions released from the metal implants can promote osteogenesis and angiogenesis during the degradation process in vivo,which is substantially better for orthopedic fixation than other bioinert metal materials.Therefore,this review focuses on the properties,fabrication,biological functions,and surface modification of Mg-based alloys as novel bioabsorbable biomaterials for orthopedic applications.展开更多
After spinal cord injury,the concentrations of total and hyperphosphorylated tau in cerebrospinal fluid increase,and levels of both correlate with injury severity.Tau inhibition is considered effective therapy for man...After spinal cord injury,the concentrations of total and hyperphosphorylated tau in cerebrospinal fluid increase,and levels of both correlate with injury severity.Tau inhibition is considered effective therapy for many central nervous system diseases,including traumatic brain injury and Alzheimer's disease.However,whether it can play a role in the treatment of spinal cord injury remains unclear.In this study,the therapeutic effects of tau inhibition were investigated in a rat model of transection spinal cord injury by injecting the rats with a lentivirus encoding tau siRNA that inhibits tau expression.We found that tau inhibition after spinal cord injury down-regulated the levels of inflammatory mediators,including tumor necrosis factor-α,interleukin-6 and interleukin-1β.It also led to a shift of activated microglial polarization from the M1 pro-inflammatory phenotype to the M2 anti-inflammatory phenotype,and reduced the amount of reactive oxygen species in the acute phase.Furthermore,the survival of residual neural cells around the injury epicenter,and neuronal and axonal regeneration were also markedly enhanced,which promoted locomotor recovery in the model rats.Collectively,our findings support the conclusion that tau inhibition can attenuate neuroinflammation,alleviate oxidative stress,protect residual cells,facilitate neurogenesis,and improve the functional recovery after spinal cord injury,and thus suggest that tau could be a good molecular target for spinal cord injury therapy.展开更多
Experimental studies have shown that exercise and human adipose-derived stem cells(ADSCs)play positive roles in spinal cord injury(SCI).However,whether ADSCs and/or exercise have a positive effect on SCI-induced neuro...Experimental studies have shown that exercise and human adipose-derived stem cells(ADSCs)play positive roles in spinal cord injury(SCI).However,whether ADSCs and/or exercise have a positive effect on SCI-induced neuropathic pain is still unclear.Thus,there is a need to explore the effects of exercise combined with administration of ADSCs on neuropathic pain after SCI.In this study,a thoracic 11(T11)SCI contusion model was established in adult C57BL/6 mice.Exercise was initiated from 7 days post-injury and continued to 28 days post-injury,and approximately 1×105 ADSCs were transplanted into the T11 spinal cord lesion site immediately after SCI.Motor function and neuropathic pain-related behaviors were assessed weekly using the Basso Mouse Scale,von Frey filament test,Hargreaves method,and cold plate test.Histological studies(Eriochrome cyanine staining and immunohistochemistry)were performed at the end of the experiment(28 days post-injury).Exercise combined with administration of ADSCs partially improved early motor function(7,14,and 21 days postinjury),mechanical allodynia,mechanical hypoalgesia,thermal hyperalgesia,and thermal hypoalgesia.Administration of ADSCs reduced white and gray matter loss at the lesion site.In addition,fewer microglia and astrocytes(as identified by expression of ionized calcium-binding adapter molecule 1 and glial fibrillary acidic protein,respectively)were present in the lumbar dorsal horn in the SCI+ADSCs and SCI+exercise+ADSCs groups compared with the sham group.Our findings suggest that exercise combined with administration of ADSCs is beneficial for the early recovery of motor function and could partially ameliorate SCIinduced neuropathic pain.展开更多
Regeneration and reconstruction of bone tissue is always a challenge for clinicians due to the uncertainty of bone repair materials in terms of long-term and efficient effects on osteoblasts.Here,we propose a novel st...Regeneration and reconstruction of bone tissue is always a challenge for clinicians due to the uncertainty of bone repair materials in terms of long-term and efficient effects on osteoblasts.Here,we propose a novel strategy combining benidipine,an antihypertensive drug and nanoparticles to synergistically promote the healing of bone defects.Loose and porous benidipine-loaded magnesium silicate nanoparticles were prepared and validated for their biosafety.The nanoparticles were efficiently taken up by preosteoblasts and uniformly distributed around the nucleus.After internalization into cells,the nanosystem is degraded by lysosomes,and the effect of promoting osteogenic differentiation is reflected by the continuous release of benidipine,silicon and magnesium ions.Our results clearly evaluated that the nanoflower-like magnesium silicate delivering benidipine tends to be more appropriate for the bone regeneration in preosteoblasts,indicating that it might be a potential approach in guiding bone repair in clinical applications.展开更多
Recurrence is the key factor affecting the prognosis of osteosarcoma.Currently,there is a lack of clinically useful tools to predict osteosarcoma recurrence.The application of pathological images for artificial intell...Recurrence is the key factor affecting the prognosis of osteosarcoma.Currently,there is a lack of clinically useful tools to predict osteosarcoma recurrence.The application of pathological images for artificial intelligence‐assisted accurate prediction of tumour out-comes is increasing.Thus,the present study constructed a quantitative histological image classifier with tumour nuclear features to predict osteosarcoma outcomes using haema-toxylin and eosin(H&E)‐stained whole‐slide images(WSIs)from 150 osteosarcoma patients.We first segmented eight distinct tissues in osteosarcoma H&E‐stained WSIs,with an average accuracy of 90.63%on the testing set.The tumour areas were auto-matically and accurately acquired,facilitating the tumour cell nuclear feature extraction process.Based on six selected tumour nuclear features,we developed an osteosarcoma histological image classifier(OSHIC)to predict the recurrence and survival of osteo-sarcoma following standard treatment.The quantitative OSHIC derived from tumour nuclear features independently predicted the recurrence and survival of osteosarcoma patients,thereby contributing to precision oncology.Moreover,we developed a fully automated workflow to extract quantitative image features,evaluate the diagnostic values of feature sets and build classifiers to predict osteosarcoma outcomes.Thus,the present study provides a novel tool for predicting osteosarcoma outcomes,which has a broad application prospect in clinical practice.展开更多
Previous studies of animal models of chronic mechanical compression of the spinal cord have mainly focused on cervical and thoracic lesions, but few studies have investigated thoracolumbar injury. The specific pathoph...Previous studies of animal models of chronic mechanical compression of the spinal cord have mainly focused on cervical and thoracic lesions, but few studies have investigated thoracolumbar injury. The specific pathophysiological mechanism of chronic thoracolumbar cord injury has not yet been elucidated. The purpose of this study was to improve animal models of chronic thoracolumbar cord compression using the progressive screw. A custom-designed flat plastic screw was implanted in the spinal cord between thoracic vertebrae 12 and lumbar 1 of rats. The screw was tightened one complete turn(0.5 mm) every 7 days for 4 weeks to create different levels of chronic spinal cord compression. Following insertion of the screw, there was a significant decline in motor function of the hind limbs, and severe stenosis of micro-computed tomography parameters in the spinal cord. Cortical somatosensory evoked potential amplitudes were reduced remarkably, and latencies were prolonged at 30 minutes after surgery. The loss of motor neurons in the gray matter was marked. Demyelination and cavitation were observed in the white matter. An appropriate rat model of chronic thoracolumbar cord compression was successfully created using the progressive screw compression method, which simulated spinal cord compression injury.展开更多
Osteoarthritis(OA)is a prevalent degenerative joint disease characterized by cartilage loss and accounts for a major source of pain and disability worldwide.However,effective strategies for cartilage repair are lackin...Osteoarthritis(OA)is a prevalent degenerative joint disease characterized by cartilage loss and accounts for a major source of pain and disability worldwide.However,effective strategies for cartilage repair are lacking,and patients with advanced OA usually need joint replacement.Better comprehending OA pathogenesis may lead to transformative therapeutics.Recently studies have reported that exosomes act as a new means of cell-to-cell communication by delivering multiple bioactive molecules to create a particular microenvironment that tunes cartilage behavior.Specifically,exosome cargos,such as noncoding RNAs(ncRNAs)and proteins,play a crucial role in OA progression by regulating the proliferation,apoptosis,autophagy,and inflammatory response of joint cells,rendering them promising candidates for OA monitoring and treatment.This review systematically summarizes the current insight regarding the biogenesis and function of exosomes and their potential as therapeutic tools targeting cell-to-cell communication in OA,suggesting new realms to improve OA management.展开更多
AIM To determine social, logistical and demographic factors that influence time to discharge in a short stay pathway(SSP) by following total knee arthroplasty(TKA). METHODS The study included primary TKA's perform...AIM To determine social, logistical and demographic factors that influence time to discharge in a short stay pathway(SSP) by following total knee arthroplasty(TKA). METHODS The study included primary TKA's performed in a highvolume arthroplasty center from January 2016 through December 2016. Potential variables associated with increased hospital length of stay(LOS) were obtained from patient medical records. These included age, gender, race, zip code, body mass index(BMI), number of pre-operative medications used, number of narcotic medications used, number of patient reported allergies(PRA), simultaneous bilateral surgery, tobacco use, marital status, living arrangements, distance traveled for surgery, employment history, surgical day of the week, procedure end time and whether the surgery was performed during a major holiday week. Multivariate step-wise regression determined the impact of social, logistical and demographic factors on LOS. RESULTS Eight hundred and six consecutive primary SSP TKA's were included in this study. Patients were discharged at a median of 49 h(post-operative day two). The following factors increased LOS: Simultaneous bilateral TKA [46.1 h longer(P < 0.001)], female gender [4.3 h longer(P = 0.012)], age [3.5 h longer per ten-year increase in age(P < 0.001)], patient-reported allergies [1.1 h longer per allergy reported(P = 0.005)], later procedure endtimes [0.8 h longer per hour increase in end-time(P = 0.004)] and Black or African American patients [6.1 h longer(P = 0.047)]. Decreased LOS was found in married patients [4.8 h shorter(P = 0.011)] and TKA's performed during holiday weeks [9.4 h shorter(P = 0.011)]. Non-significant factors included: BMI, median income, patient's living arrangement, smoking status, number of medications taken, use of pre-operative pain medications, distance traveled to hospital, and the day of surgery. CONCLUSION The cost of TKA is dependent upon LOS, which is affected by multiple factors. The clinical care team should acknowledge socio-demographic factors to optimize LOS.展开更多
Antarctic krill is a potentially nutritious food source for humans, but fluorine(F) toxicity is a matter of concern. To evaluate the toxicity of F in Antarctic krill, 30 Wistar rats were divided into three groups with...Antarctic krill is a potentially nutritious food source for humans, but fluorine(F) toxicity is a matter of concern. To evaluate the toxicity of F in Antarctic krill, 30 Wistar rats were divided into three groups with different dietary regimens: a control group, a krill treatment group(150 mg·kg-1 F), and a sodium fluoride(NaF) treatment group(150 mg·kg-1 F). After three months, F concentrations in feces, plasma, and bone were determined, and the degree of dental and skeletal fluorosis was assessed. The F concentrations in plasma and bone from the krill treatment group were 0.167 0±0.020 4 mg.L-1 and 2 709.8±301.9 mg·kg-1, respectively, compared with 0.043 8±0.005 5 mg·L-1 and 442.4±60.7 mg·kg-1, respectively, in samples from the control group. Concentrations of F in plasma and bone in the krill treatment group were higher than in the control group, but lower than in the NaF treatment group. The degree of dental fluorosis in the krill treatment group was moderate, compared with severe in the NaF treatment group and normal in the control group. The degree of skeletal fluorosis did not change significantly in any group. These results showed that the toxicity of F in Antarctic krill was lower than for an equivalent concentration of F in NaF, but it was toxic for rats consuming krill in large quantities. To conclude, we discuss possible reasons for the reduced toxicity of F in Antarctic krill. The present study provides a direct toxicological reference for the consideration of Antarctic krill for human consumption.展开更多
The LIM domain-containing proteins Pinch1/2 regulate integrin activation and cell–extracellular matrix interaction and adhesion.Here,we report that deleting Pinch1 in limb mesenchymal stem cells(MSCs)and Pinch2 globa...The LIM domain-containing proteins Pinch1/2 regulate integrin activation and cell–extracellular matrix interaction and adhesion.Here,we report that deleting Pinch1 in limb mesenchymal stem cells(MSCs)and Pinch2 globally(double knockout;dKO)in mice causes severe chondrodysplasia,while single mutant mice do not display marked defects.Pinch deletion decreases chondrocyte proliferation,accelerates cell differentiation and disrupts column formation.Pinch loss drastically reduces Smad2/3 protein expression in proliferative zone(PZ)chondrocytes and increases Runx2 and Col10a1 expression in both PZ and hypertrophic zone(HZ)chondrocytes.Pinch loss increases sclerostin and Rankl expression in HZ chondrocytes,reduces bone formation,and increases bone resorption,leading to low bone mass.In vitro studies revealed that Pinch1 and Smad2/3 colocalize in the nuclei of chondrocytes.Through its C-terminal region,Pinch1 interacts with Smad2/3 proteins.Pinch loss increases Smad2/3 ubiquitination and degradation in primary bone marrow stromal cells(BMSCs).Pinch loss reduces TGF-β-induced Smad2/3 phosphorylation and nuclear localization in primary BMSCs.Interestingly,compared to those from single mutant mice,BMSCs from dKO mice express dramatically lower protein levels ofβ-catenin and Yap1/Taz and display reduced osteogenic but increased adipogenic differentiation capacity.Finally,ablating Pinch1 in chondrocytes and Pinch2 globally causes severe osteopenia with subtle limb shortening.Collectively,our findings demonstrate critical roles for Pinch1/2 and a functional redundancy of both factors in the control of chondrogenesis and bone mass through distinct mechanisms.展开更多
BACKGROUND Whether it’s better to adopt unilateral pedicle screw(UPS)fixation or to use bilateral pedicle screw(BPS)one for lumbar degenerative diseases is still controversially undetermined.AIM To make a comparison ...BACKGROUND Whether it’s better to adopt unilateral pedicle screw(UPS)fixation or to use bilateral pedicle screw(BPS)one for lumbar degenerative diseases is still controversially undetermined.AIM To make a comparison between UPS and BPS fixation as to how they work efficaciously and safely in patients suffering from lumbar degenerative diseases.METHODS We have searched a lot in the databases through 2020 with index terms such as“unilateral pedicle screw fixation”and“bilateral pedicle screw fixation.”Only randomized controlled trials and some prospective cohort studies could be found,yielding 15 studies.The intervention was unilateral pedicle screw fixation;Primarily We’ve got outcomes of complications and fusion rates.Secondarily,we’ve achieved outcomes regarding total blood loss,operative time,as well as length of stay.Softwares were installed and utilized for subgroup analysis,analyzing forest plots,sensitivity,heterogeneity,forest plots,publication bias,and risk of bias.RESULTS Fifteen previous cases of study including 992 participants have been involved in our meta-analysis.UPS had slightly lower effects on fusion rate[relative risk(RR)=0.949,95%CI:0.910 to 0.990,P=0.015],which contributed mostly to this metaanalysis,and similar complication rates(RR=1.140,95%CI:0.792 to 1.640,P=0.481),Δvisual analog scale[standard mean difference(SMD)=0.178,95%CI:-0.021 to 0.378,P=0.080],andΔOswestry disability index(SMD=-0.254,95%CI:-0.820 to 0.329,P=0.402).In contrast,an obvious difference has been observed inΔJapanese Orthopedic Association(JOA)score(SMD=0.305,95%CI:0.046 to 0.563,P=0.021),total blood loss(SMD=-1.586,95%CI:-2.182 to-0.990,P=0.000),operation time(SMD=-2.831,95%CI:-3.753 to-1.909,P=0.000),and length of hospital stay(SMD=-0.614,95%CI:-1.050 to-0.179,P=0.006).CONCLUSION Bilateral fixation is more effective than unilateral fixation regarding fusion rate after lumbar interbody fusion.However,JOA,operation time,total blood loss,as well as length of stay were improved for unilateral fixation.展开更多
BACKGROUND Postoperative chylothorax is usually regarded as a complication associated with cardiothoracic surgery;however,it is one of the rare complications in orthopedic surgery.This case report describes a female p...BACKGROUND Postoperative chylothorax is usually regarded as a complication associated with cardiothoracic surgery;however,it is one of the rare complications in orthopedic surgery.This case report describes a female patient who developed chylothorax after a successful L4-S1 transforaminal lumbar interbody fusion surgery.The etiology,diagnosis,and treatment were analyzed and discussed.CASE SUMMARY A 50-year-old woman was admitted with repeated back and leg pain.She was diagnosed with L4 degenerative spondylolisthesis,L4/L5 and L5/S1 intervertebral disc herniation and L5 instability,and underwent successful posterior L4-S1 instrumentation and fusion surgery.Unfortunately,thoracic effusion was identified 2 d after operation.The thoracic effusion was finally confirmed to be chylous based on twice positive chyle qualitative tests.The patient was discharged after 12-d persisting drainage,3-d total parenteral nutrition and fasting,and other supportive treatments.No recurring symptoms were observed within 12 mo follow-up.CONCLUSION Differential diagnosis is crucial for unusual thoracic effusion.Comprehensive diagnosis and treatment of chylothorax are necessary.Thorough intraoperative protection to relieve high thoracic pressure caused by the prone position is important.展开更多
BACKGROUND Missed or delayed diagnosis of cervical spine instability after acute trauma can have catastrophic consequences for the patient,resulting in severe neurological impairment.Currently,however,there is no cons...BACKGROUND Missed or delayed diagnosis of cervical spine instability after acute trauma can have catastrophic consequences for the patient,resulting in severe neurological impairment.Currently,however,there is no consensus on the optimal strategy for diagnosing occult cervical spine instability.Thus,we present a case of occult cervical spine instability and provide a clinical algorithm to aid physicians in diagnosing occult instability of the cervical spine.CASE SUMMARY A 57-year-old man presented with cervical spine pain and inability to stand following a serious fall from a height of 2 m.No obvious vertebral fracture or dislocation was found at the time on standard lateral X-ray,computed tomography,and magnetic resonance imaging(MRI).Subsequently,the initial surgical plan was unilateral open-door laminoplasty(C3-7)with alternative levels of centerpiece mini-plate fixation(C3,5,and 7).However,the intraoperative C-arm fluoroscopic X-rays revealed significantly increased intervertebral space at C5-6,indicating instability at this level that was previously unrecognized on preoperative imaging.We finally performed lateral mass fixation and fusion at the C5-6 level.Looking back at the preoperative images,we found that the preoperative T2 MRI showed non-obvious high signal intensity at the C5-6 intervertebral disc and posterior interspinous ligament.CONCLUSION MRI of cervical spine trauma patients should be carefully reviewed to detect disco-ligamentous injury,which will lead to further cervical spine instability.In patients with highly suspected cervical spine instability indicated on MRI,lateral X-ray under traction or after anesthesia and muscle relaxation needs to be performed to avoid missed diagnoses of occult cervical instability.展开更多
This letter focuses on a recently published article that provided an exceptional description of the effect of epigenetic modifications on gene expression patterns related to skeletal system remodeling.Specifically,it ...This letter focuses on a recently published article that provided an exceptional description of the effect of epigenetic modifications on gene expression patterns related to skeletal system remodeling.Specifically,it discusses a novel modality of epigenetic regulation,the long noncoding RNAs(lncRNAs),and provides evidence of their involvement in mesenchymal stromal/stem cells osteo-/adipogenic differentiation balance.Despite focus on lncRNAs,there is an emerging cross talk between lncRNAs and miRNAs interaction as a novel mechanism in the regulation of the function of the musculoskeletal system,by controlling bone homeostasis and bone regeneration,as well as the osteogenic differentiation of stem cells.Thus,we touched on some examples to demonstrate this interaction.In addition,we believe there is still much to discover from the effects of lncRNAs on progenitor and non-progenitor cell differentiation.We incorporated data from other published articles to review lncRNAs in normal progenitor cell osteogenic differentiation,determined lncRNAs involved in osteoarthritis pathogenesis in progenitor cells,and provided a review of lncRNAs in non-progenitor cells that are differentially regulated in osteoarthritis.In conclusion,we really enjoyed reading this article and with this information we hope to further our understanding of lncRNAs and mesenchymal stromal/stem cells regulation.展开更多
Platelet-derived growth factor-BB(PDGF-BB)/platelet-derived growth factor receptor-β(PDGFR-β)pathway is conventionally considered as an important pathway to promote osteogenesis;however,recent study suggested its ro...Platelet-derived growth factor-BB(PDGF-BB)/platelet-derived growth factor receptor-β(PDGFR-β)pathway is conventionally considered as an important pathway to promote osteogenesis;however,recent study suggested its role during osteogenesis to be controversial.Regarding the differential functions of this pathway during 3 stages of bone healing,we hypothesized that temporal inhibition of PDGF-BB/PDGFR-βpathway could shift the proliferation/differentiation balance of skeletal stem and progenitor cells,toward osteogenic lineage,which leads to improved bone regeneration.We first validated that inhibition of PDGFR-βat late stage of osteogenic induction effectively enhanced differentiation toward osteoblasts.This effect was also replicated invivo by showing accelerated bone formation when block PDGFR-βpathway at late stage of critical bone defect healing mediated using biomaterials.Further,we found that such PDGFR-βinhibitor-initiated bone healing was also effective in the absence of scaffold implantation when administrated intraperitoneally.Mechanistically,timely inhibition of PDGFR-βblocked extracellular regulated protein kinase 1/2 pathway,which shift proliferation/differentiation balance of skeletal stem and progenitor cell to osteogenic lineage by upregulating osteogenesis-related products of Smad to induce osteogenesis.This study offered updated understanding of the use of PDGFR-βpathway and provides new insight routes of action and novel therapeutic methods in the field of bone repair.展开更多
Bacteria-associated infection represents one of the major threats for orthopedic implants failure during their life cycles.However,ordinary antimicrobial treatments usually failed to combat multiple waves of infection...Bacteria-associated infection represents one of the major threats for orthopedic implants failure during their life cycles.However,ordinary antimicrobial treatments usually failed to combat multiple waves of infections during arthroplasty and prosthesis revisions etc.As these incidents could easily introduce new microbial pathogens in/onto the implants.Herein,we demonstrate that an antimicrobial trilogy strategy incorporating a sophisticated multilayered coating system leveraging multiple ion exchange mechanisms and fine nanotopography tuning,could effectively eradicate bacterial infection at various stages of implantation.Early stage bacteriostatic effect was realized via nano-topological structure of top mineral coating.Antibacterial effect at intermediate stage was mediated by sustained release of zinc ions from doped CaP coating.Strong antibacterial potency was validated at 4 weeks post implantation via an implanted model in vivo.Finally,the underlying zinc titanate fiber network enabled a long-term contact and release effect of residual zinc,which maintained a strong antibacterial ability against both Staphylococcus aureus and Escherichia coli even after the removal of top layer coating.Moreover,sustained release of Sr2+and Zn2+during CaP coating degradation substantially promoted implant osseointegration even under an infectious environment by showing more peri-implant new bone formation and substantially improved bone-implant bonding strength.展开更多
The custom-tailored medicine requires a developmental strategy that integrates excellent osteogene-sis with mechanical stability to enhance the reconstruction of the critical-size bone defect(CSBD)and the healing proc...The custom-tailored medicine requires a developmental strategy that integrates excellent osteogene-sis with mechanical stability to enhance the reconstruction of the critical-size bone defect(CSBD)and the healing process in weight-bearing bone.We prepared three-dimensional(3D)printed biphasic cal-cium phosphate(BCP)scaffolds composited with nano-graphene oxide(GO).The biological effects of the GO/BCP composite scaffolds could induce the differentiation of rat bone marrow stem cells(BM-SCs)and the migration of human umbilical vein endothelial cells(HUVECs)for bone repair.The proper ratio of GO in the composite scaffold regulated the composites’surface roughness and hydrophilicity to a suitable range for the adhesion and proliferation of BMSCs and HUVECs.Besides,the GO/BCP composite scaffold increased osteogenesis and angiogenesis by activating BMP-2,RUNX-2,Smad1/4,and VEGF.The customized intramedullary nail combined with GO/BCP scaffold was applied to repair CSBD(2.0 cm in length)in a beagle femur model.This fixation strategy was confirmed by finite element analysis.In vivo,the results indicated that the custom-made internal fixation provided sufficient stability in the early stage,ensuring bone healing in a considerable mechanical environment.At 9 months postoperatively,longitudi-nal bony union and blood vessels in osteon were observed in the CSBD area with partial degradation in the 0.3%GO/BCP group.In the three-point bending test,the ultimate load of 0.3%GO/BCP group reached over 50%of the normal femur at 9 months after repair.These results showed a promising application of osteogenic GO/BCP scaffold and custom-made intramedullary nails in repairing CSBD of the beagle femur.This effective strategy could provide an option to treat the clinical CSBD in weight-bearing bones.展开更多
文摘Although previous RNA sequencing methods have been widely used in orthopedic research and have provided ideas for therapeutic strategies,the specific mechanisms of some orthopedic disorders,including osteoarthritis,lumbar disc herniation,rheumatoid arthritis,fractures,tendon injuries,spinal cord injury,heterotopic ossification,and osteosarcoma,require further elucidation.The emergence of the single-cell RNA sequencing(sc RNA-seq)technique has introduced a new era of research on these topics,as this method provides information regarding cellular heterogeneity,new cell subtypes,functions of novel subclusters,potential molecular mechanisms,cell-fate transitions,and cell-cell interactions that are involved in the development of orthopedic diseases.Here,we summarize the cell subpopulations,genes,and underlying mechanisms involved in the development of orthopedic diseases identified by sc RNA-seq,improving our understanding of the pathology of these diseases and providing new insights into therapeutic approaches.
基金supported in part by National Natural Science Foundation of China(32271364 & 31971240)Interdisciplinary innovation project from West China Hospital of Stomatology, Sichuan University(RD-03-202305)。
文摘Bone formation and deposition are initiated by sensory nerve infiltration in adaptive bone remodeling. Here, we focused on the role of Semaphorin 3A(Sema3A), expressed by sensory nerves, in mechanical loads-induced bone formation and nerve withdrawal using orthodontic tooth movement(OTM) model. Firstly, bone formation was activated after the 3rd day of OTM,coinciding with a decrease in sensory nerves and an increase in pain threshold. Sema3A, rather than nerve growth factor(NGF),highly expressed in both trigeminal ganglion and the axons of periodontal ligament following the 3rd day of OTM. Moreover, in vitro mechanical loads upregulated Sema3A in neurons instead of in human periodontal ligament cells(hPDLCs) within 24 hours.Furthermore, exogenous Sema3A restored the suppressed alveolar bone formation and the osteogenic differentiation of hPDLCs induced by mechanical overload. Mechanistically, Sema3A prevented overstretching of F-actin induced by mechanical overload through ROCK2 pathway, maintaining mitochondrial dynamics as mitochondrial fusion. Therefore, Sema3A exhibits dual therapeutic effects in mechanical loads-induced bone formation, both as a pain-sensitive analgesic and a positive regulator for bone formation.
基金supported by the National Key Research and Development Project,No.2019YFA0112100(to SF).
文摘Traumatic spinal cord injury is potentially catastrophic and can lead to permanent disability or even death.China has the largest population of patients with traumatic spinal cord injury.Previous studies of traumatic spinal cord injury in China have mostly been regional in scope;national-level studies have been rare.To the best of our knowledge,no national-level study of treatment status and economic burden has been performed.This retrospective study aimed to examine the epidemiological and clinical features,treatment status,and economic burden of traumatic spinal cord injury in China at the national level.We included 13,465 traumatic spinal cord injury patients who were injured between January 2013 and December 2018 and treated in 30 hospitals in 11 provinces/municipalities representing all geographical divisions of China.Patient epidemiological and clinical features,treatment status,and total and daily costs were recorded.Trends in the percentage of traumatic spinal cord injuries among all hospitalized patients and among patients hospitalized in the orthopedic department and cost of care were assessed by annual percentage change using the Joinpoint Regression Program.The percentage of traumatic spinal cord injuries among all hospitalized patients and among patients hospitalized in the orthopedic department did not significantly change overall(annual percentage change,-0.5%and 2.1%,respectively).A total of 10,053(74.7%)patients underwent surgery.Only 2.8%of patients who underwent surgery did so within 24 hours of injury.A total of 2005(14.9%)patients were treated with high-dose(≥500 mg)methylprednisolone sodium succinate/methylprednisolone(MPSS/MP);615(4.6%)received it within 8 hours.The total cost for acute traumatic spinal cord injury decreased over the study period(-4.7%),while daily cost did not significantly change(1.0%increase).Our findings indicate that public health initiatives should aim at improving hospitals’ability to complete early surgery within 24 hours,which is associated with improved sensorimotor recovery,increasing the awareness rate of clinical guidelines related to high-dose MPSS/MP to reduce the use of the treatment with insufficient evidence.
基金supported by the National Natural Science Foundation of China(31870961,81501879)the Sino-German Center for Research Promotion(GZ1219)+1 种基金the International Cooperation Project of the Science and Technology Department of Sichuan Province(Grant No.2015HH0049,No.2017SZ0127,No.2020YFS0140)the National Clinical Research Center for Geriatrics,West China Hospital,Sichuan University(Z2018A11)。
文摘Traditional orthopedic metal implants,such as titanium(Ti),Ti alloys,and cobalt-chromium(Co-Cr)alloys,cannot be degraded in vivo.Fracture patients is must always suffer a second operation to remove the implants.Moreover,stress shielding,or stress protection occurs when traditional orthopedic metal implants are applied in fractures surgery.The mechanical shunt produced by traditional orthopedic metal implants can cause bone loss over time,resulting in decreased bone strength and delayed fracture healing.Biodegradable metals that‘biocorrode’are currently attracting significant interest in the orthopedics field due to their suitability as temporary implants.As one of the biodegradable metals,magnesium(Mg)and Mg alloys have gained interest in the field of medicine due to their low density,excellent biocompatibility,high bioresorbability,and proper mechanical properties.Additionally,Mg ions released from the metal implants can promote osteogenesis and angiogenesis during the degradation process in vivo,which is substantially better for orthopedic fixation than other bioinert metal materials.Therefore,this review focuses on the properties,fabrication,biological functions,and surface modification of Mg-based alloys as novel bioabsorbable biomaterials for orthopedic applications.
基金supported by the National Natural Science Foundation of China,No.81801907(to NNC)Shenzhen Commitiee of Science and Technology,No.JCYJ20180307145215811(to NNC)+1 种基金Sun Yat-sen University Youth Teacher Training Project,No.19ykpy11(to NNC)Sanming Project of Medicine in Shenzhen,No.SZSM201911002(to SYL)。
文摘After spinal cord injury,the concentrations of total and hyperphosphorylated tau in cerebrospinal fluid increase,and levels of both correlate with injury severity.Tau inhibition is considered effective therapy for many central nervous system diseases,including traumatic brain injury and Alzheimer's disease.However,whether it can play a role in the treatment of spinal cord injury remains unclear.In this study,the therapeutic effects of tau inhibition were investigated in a rat model of transection spinal cord injury by injecting the rats with a lentivirus encoding tau siRNA that inhibits tau expression.We found that tau inhibition after spinal cord injury down-regulated the levels of inflammatory mediators,including tumor necrosis factor-α,interleukin-6 and interleukin-1β.It also led to a shift of activated microglial polarization from the M1 pro-inflammatory phenotype to the M2 anti-inflammatory phenotype,and reduced the amount of reactive oxygen species in the acute phase.Furthermore,the survival of residual neural cells around the injury epicenter,and neuronal and axonal regeneration were also markedly enhanced,which promoted locomotor recovery in the model rats.Collectively,our findings support the conclusion that tau inhibition can attenuate neuroinflammation,alleviate oxidative stress,protect residual cells,facilitate neurogenesis,and improve the functional recovery after spinal cord injury,and thus suggest that tau could be a good molecular target for spinal cord injury therapy.
基金supported in part by the National Natural Science Foundation of China,Nos.81971151(to YW),82201360(to XC),82102583(to LW),and 82202739(to GPM)China Postdoctoral Science Foundation,Nos.YJ20210208 and 2022M713592+2 种基金Guangdong Basic and Applied Basic Research Foundation,China,No.2021A1515110188(to XC)the Natural Science Foundation of Guangdong Province,China,No.2020A1515010306(to LW)the Science and Technology Program of Guangzhou,China,No.202102020040(to LW)。
文摘Experimental studies have shown that exercise and human adipose-derived stem cells(ADSCs)play positive roles in spinal cord injury(SCI).However,whether ADSCs and/or exercise have a positive effect on SCI-induced neuropathic pain is still unclear.Thus,there is a need to explore the effects of exercise combined with administration of ADSCs on neuropathic pain after SCI.In this study,a thoracic 11(T11)SCI contusion model was established in adult C57BL/6 mice.Exercise was initiated from 7 days post-injury and continued to 28 days post-injury,and approximately 1×105 ADSCs were transplanted into the T11 spinal cord lesion site immediately after SCI.Motor function and neuropathic pain-related behaviors were assessed weekly using the Basso Mouse Scale,von Frey filament test,Hargreaves method,and cold plate test.Histological studies(Eriochrome cyanine staining and immunohistochemistry)were performed at the end of the experiment(28 days post-injury).Exercise combined with administration of ADSCs partially improved early motor function(7,14,and 21 days postinjury),mechanical allodynia,mechanical hypoalgesia,thermal hyperalgesia,and thermal hypoalgesia.Administration of ADSCs reduced white and gray matter loss at the lesion site.In addition,fewer microglia and astrocytes(as identified by expression of ionized calcium-binding adapter molecule 1 and glial fibrillary acidic protein,respectively)were present in the lumbar dorsal horn in the SCI+ADSCs and SCI+exercise+ADSCs groups compared with the sham group.Our findings suggest that exercise combined with administration of ADSCs is beneficial for the early recovery of motor function and could partially ameliorate SCIinduced neuropathic pain.
基金supported by the National Natural Science Foundation of China(Nos.8212200044,82071085,31872752,and 81600909)the Zhejiang Provincial Natu-ral Science Foundation of China(Nos.LR21H140001,LY22H140002,and LQ22C100003)+1 种基金the National Key Research and Development Pro-gram of China(No.2018YFA0703000)the Medical Technology and Education of Zhejiang Province of China(No.2018KY501).
文摘Regeneration and reconstruction of bone tissue is always a challenge for clinicians due to the uncertainty of bone repair materials in terms of long-term and efficient effects on osteoblasts.Here,we propose a novel strategy combining benidipine,an antihypertensive drug and nanoparticles to synergistically promote the healing of bone defects.Loose and porous benidipine-loaded magnesium silicate nanoparticles were prepared and validated for their biosafety.The nanoparticles were efficiently taken up by preosteoblasts and uniformly distributed around the nucleus.After internalization into cells,the nanosystem is degraded by lysosomes,and the effect of promoting osteogenic differentiation is reflected by the continuous release of benidipine,silicon and magnesium ions.Our results clearly evaluated that the nanoflower-like magnesium silicate delivering benidipine tends to be more appropriate for the bone regeneration in preosteoblasts,indicating that it might be a potential approach in guiding bone repair in clinical applications.
基金supported by the China Postdoctoral Science Foundation(2021M692792)National Natural Science Foun-dation of China(82103499,81872173,82072959,U1809205,61771249,91959207,81871352)+2 种基金Natural Science Foundation of Jiangsu Province of China(BK20181411)Natural Science Foundation of Zhejiang Province(LD21H160002)Med-ical and Health Science and Technology Plan of Department of Health of Zhejiang Province(WKJ‐ZJ‐1821).
文摘Recurrence is the key factor affecting the prognosis of osteosarcoma.Currently,there is a lack of clinically useful tools to predict osteosarcoma recurrence.The application of pathological images for artificial intelligence‐assisted accurate prediction of tumour out-comes is increasing.Thus,the present study constructed a quantitative histological image classifier with tumour nuclear features to predict osteosarcoma outcomes using haema-toxylin and eosin(H&E)‐stained whole‐slide images(WSIs)from 150 osteosarcoma patients.We first segmented eight distinct tissues in osteosarcoma H&E‐stained WSIs,with an average accuracy of 90.63%on the testing set.The tumour areas were auto-matically and accurately acquired,facilitating the tumour cell nuclear feature extraction process.Based on six selected tumour nuclear features,we developed an osteosarcoma histological image classifier(OSHIC)to predict the recurrence and survival of osteo-sarcoma following standard treatment.The quantitative OSHIC derived from tumour nuclear features independently predicted the recurrence and survival of osteosarcoma patients,thereby contributing to precision oncology.Moreover,we developed a fully automated workflow to extract quantitative image features,evaluate the diagnostic values of feature sets and build classifiers to predict osteosarcoma outcomes.Thus,the present study provides a novel tool for predicting osteosarcoma outcomes,which has a broad application prospect in clinical practice.
基金supported by the Military Medical Research Foundation of China,No.06MA283
文摘Previous studies of animal models of chronic mechanical compression of the spinal cord have mainly focused on cervical and thoracic lesions, but few studies have investigated thoracolumbar injury. The specific pathophysiological mechanism of chronic thoracolumbar cord injury has not yet been elucidated. The purpose of this study was to improve animal models of chronic thoracolumbar cord compression using the progressive screw. A custom-designed flat plastic screw was implanted in the spinal cord between thoracic vertebrae 12 and lumbar 1 of rats. The screw was tightened one complete turn(0.5 mm) every 7 days for 4 weeks to create different levels of chronic spinal cord compression. Following insertion of the screw, there was a significant decline in motor function of the hind limbs, and severe stenosis of micro-computed tomography parameters in the spinal cord. Cortical somatosensory evoked potential amplitudes were reduced remarkably, and latencies were prolonged at 30 minutes after surgery. The loss of motor neurons in the gray matter was marked. Demyelination and cavitation were observed in the white matter. An appropriate rat model of chronic thoracolumbar cord compression was successfully created using the progressive screw compression method, which simulated spinal cord compression injury.
基金funded by the National Natural Science Foundation of China(No.81974347)the Science and Technology Program of Sichuan Province(No.2021YJ0444)+1 种基金China Postdoctoral Science Foundation(No.2021M702351)Post-Doctor Research Project,West China Hospital,Sichuan University(No.2020HXBH081)。
文摘Osteoarthritis(OA)is a prevalent degenerative joint disease characterized by cartilage loss and accounts for a major source of pain and disability worldwide.However,effective strategies for cartilage repair are lacking,and patients with advanced OA usually need joint replacement.Better comprehending OA pathogenesis may lead to transformative therapeutics.Recently studies have reported that exosomes act as a new means of cell-to-cell communication by delivering multiple bioactive molecules to create a particular microenvironment that tunes cartilage behavior.Specifically,exosome cargos,such as noncoding RNAs(ncRNAs)and proteins,play a crucial role in OA progression by regulating the proliferation,apoptosis,autophagy,and inflammatory response of joint cells,rendering them promising candidates for OA monitoring and treatment.This review systematically summarizes the current insight regarding the biogenesis and function of exosomes and their potential as therapeutic tools targeting cell-to-cell communication in OA,suggesting new realms to improve OA management.
文摘AIM To determine social, logistical and demographic factors that influence time to discharge in a short stay pathway(SSP) by following total knee arthroplasty(TKA). METHODS The study included primary TKA's performed in a highvolume arthroplasty center from January 2016 through December 2016. Potential variables associated with increased hospital length of stay(LOS) were obtained from patient medical records. These included age, gender, race, zip code, body mass index(BMI), number of pre-operative medications used, number of narcotic medications used, number of patient reported allergies(PRA), simultaneous bilateral surgery, tobacco use, marital status, living arrangements, distance traveled for surgery, employment history, surgical day of the week, procedure end time and whether the surgery was performed during a major holiday week. Multivariate step-wise regression determined the impact of social, logistical and demographic factors on LOS. RESULTS Eight hundred and six consecutive primary SSP TKA's were included in this study. Patients were discharged at a median of 49 h(post-operative day two). The following factors increased LOS: Simultaneous bilateral TKA [46.1 h longer(P < 0.001)], female gender [4.3 h longer(P = 0.012)], age [3.5 h longer per ten-year increase in age(P < 0.001)], patient-reported allergies [1.1 h longer per allergy reported(P = 0.005)], later procedure endtimes [0.8 h longer per hour increase in end-time(P = 0.004)] and Black or African American patients [6.1 h longer(P = 0.047)]. Decreased LOS was found in married patients [4.8 h shorter(P = 0.011)] and TKA's performed during holiday weeks [9.4 h shorter(P = 0.011)]. Non-significant factors included: BMI, median income, patient's living arrangement, smoking status, number of medications taken, use of pre-operative pain medications, distance traveled to hospital, and the day of surgery. CONCLUSION The cost of TKA is dependent upon LOS, which is affected by multiple factors. The clinical care team should acknowledge socio-demographic factors to optimize LOS.
基金the financial support of the Open Research Fund from the Key Laboratory for Polar Science,State Oceanic Administration,P.R.China(Grant no.KP201106)the Research Industry Joint Innovation Project of Jiangsu(Grant no.BY2011186)
文摘Antarctic krill is a potentially nutritious food source for humans, but fluorine(F) toxicity is a matter of concern. To evaluate the toxicity of F in Antarctic krill, 30 Wistar rats were divided into three groups with different dietary regimens: a control group, a krill treatment group(150 mg·kg-1 F), and a sodium fluoride(NaF) treatment group(150 mg·kg-1 F). After three months, F concentrations in feces, plasma, and bone were determined, and the degree of dental and skeletal fluorosis was assessed. The F concentrations in plasma and bone from the krill treatment group were 0.167 0±0.020 4 mg.L-1 and 2 709.8±301.9 mg·kg-1, respectively, compared with 0.043 8±0.005 5 mg·L-1 and 442.4±60.7 mg·kg-1, respectively, in samples from the control group. Concentrations of F in plasma and bone in the krill treatment group were higher than in the control group, but lower than in the NaF treatment group. The degree of dental fluorosis in the krill treatment group was moderate, compared with severe in the NaF treatment group and normal in the control group. The degree of skeletal fluorosis did not change significantly in any group. These results showed that the toxicity of F in Antarctic krill was lower than for an equivalent concentration of F in NaF, but it was toxic for rats consuming krill in large quantities. To conclude, we discuss possible reasons for the reduced toxicity of F in Antarctic krill. The present study provides a direct toxicological reference for the consideration of Antarctic krill for human consumption.
基金the National Key Research and Development Program of China Grant(2019YFA0906004,2019YFA0906001)the National Natural Science Foundation of China(81991513,82022047,81630066,81870532,and 81972100)+1 种基金the Guangdong Provincial Science and Technology Innovation Council(2017B030301018)Science and Technology Innovation Commission of Shenzhen Municipal Government(JCYJ20180302174117738,JCYJ20180302174246105,KQJSCX20180319114434843,and JSGG20180503182321166).
文摘The LIM domain-containing proteins Pinch1/2 regulate integrin activation and cell–extracellular matrix interaction and adhesion.Here,we report that deleting Pinch1 in limb mesenchymal stem cells(MSCs)and Pinch2 globally(double knockout;dKO)in mice causes severe chondrodysplasia,while single mutant mice do not display marked defects.Pinch deletion decreases chondrocyte proliferation,accelerates cell differentiation and disrupts column formation.Pinch loss drastically reduces Smad2/3 protein expression in proliferative zone(PZ)chondrocytes and increases Runx2 and Col10a1 expression in both PZ and hypertrophic zone(HZ)chondrocytes.Pinch loss increases sclerostin and Rankl expression in HZ chondrocytes,reduces bone formation,and increases bone resorption,leading to low bone mass.In vitro studies revealed that Pinch1 and Smad2/3 colocalize in the nuclei of chondrocytes.Through its C-terminal region,Pinch1 interacts with Smad2/3 proteins.Pinch loss increases Smad2/3 ubiquitination and degradation in primary bone marrow stromal cells(BMSCs).Pinch loss reduces TGF-β-induced Smad2/3 phosphorylation and nuclear localization in primary BMSCs.Interestingly,compared to those from single mutant mice,BMSCs from dKO mice express dramatically lower protein levels ofβ-catenin and Yap1/Taz and display reduced osteogenic but increased adipogenic differentiation capacity.Finally,ablating Pinch1 in chondrocytes and Pinch2 globally causes severe osteopenia with subtle limb shortening.Collectively,our findings demonstrate critical roles for Pinch1/2 and a functional redundancy of both factors in the control of chondrogenesis and bone mass through distinct mechanisms.
基金Supported by the Health Science and Technology of Tianjin Municipality,No.RC20204Tianjin Institute of Orthopedics,No.2019TJGYSKY03the National Natural Science Foundation of China,No.818717771177226。
文摘BACKGROUND Whether it’s better to adopt unilateral pedicle screw(UPS)fixation or to use bilateral pedicle screw(BPS)one for lumbar degenerative diseases is still controversially undetermined.AIM To make a comparison between UPS and BPS fixation as to how they work efficaciously and safely in patients suffering from lumbar degenerative diseases.METHODS We have searched a lot in the databases through 2020 with index terms such as“unilateral pedicle screw fixation”and“bilateral pedicle screw fixation.”Only randomized controlled trials and some prospective cohort studies could be found,yielding 15 studies.The intervention was unilateral pedicle screw fixation;Primarily We’ve got outcomes of complications and fusion rates.Secondarily,we’ve achieved outcomes regarding total blood loss,operative time,as well as length of stay.Softwares were installed and utilized for subgroup analysis,analyzing forest plots,sensitivity,heterogeneity,forest plots,publication bias,and risk of bias.RESULTS Fifteen previous cases of study including 992 participants have been involved in our meta-analysis.UPS had slightly lower effects on fusion rate[relative risk(RR)=0.949,95%CI:0.910 to 0.990,P=0.015],which contributed mostly to this metaanalysis,and similar complication rates(RR=1.140,95%CI:0.792 to 1.640,P=0.481),Δvisual analog scale[standard mean difference(SMD)=0.178,95%CI:-0.021 to 0.378,P=0.080],andΔOswestry disability index(SMD=-0.254,95%CI:-0.820 to 0.329,P=0.402).In contrast,an obvious difference has been observed inΔJapanese Orthopedic Association(JOA)score(SMD=0.305,95%CI:0.046 to 0.563,P=0.021),total blood loss(SMD=-1.586,95%CI:-2.182 to-0.990,P=0.000),operation time(SMD=-2.831,95%CI:-3.753 to-1.909,P=0.000),and length of hospital stay(SMD=-0.614,95%CI:-1.050 to-0.179,P=0.006).CONCLUSION Bilateral fixation is more effective than unilateral fixation regarding fusion rate after lumbar interbody fusion.However,JOA,operation time,total blood loss,as well as length of stay were improved for unilateral fixation.
基金Supported by National Natural Science Foundation of China,No.81874027.
文摘BACKGROUND Postoperative chylothorax is usually regarded as a complication associated with cardiothoracic surgery;however,it is one of the rare complications in orthopedic surgery.This case report describes a female patient who developed chylothorax after a successful L4-S1 transforaminal lumbar interbody fusion surgery.The etiology,diagnosis,and treatment were analyzed and discussed.CASE SUMMARY A 50-year-old woman was admitted with repeated back and leg pain.She was diagnosed with L4 degenerative spondylolisthesis,L4/L5 and L5/S1 intervertebral disc herniation and L5 instability,and underwent successful posterior L4-S1 instrumentation and fusion surgery.Unfortunately,thoracic effusion was identified 2 d after operation.The thoracic effusion was finally confirmed to be chylous based on twice positive chyle qualitative tests.The patient was discharged after 12-d persisting drainage,3-d total parenteral nutrition and fasting,and other supportive treatments.No recurring symptoms were observed within 12 mo follow-up.CONCLUSION Differential diagnosis is crucial for unusual thoracic effusion.Comprehensive diagnosis and treatment of chylothorax are necessary.Thorough intraoperative protection to relieve high thoracic pressure caused by the prone position is important.
基金Supported by grants from China Postdoctoral Science Foundation General Program No.2019M653417Sichuan Science and Technology Program,No.2020YJ0025,No.2017SZ0046,and No.2017SZDZX0021+1 种基金Post-Doctor Research Project,Sichuan University,No.2019SCU12043and International Postdoctoral Exchange Fellowship Program,No.PC2019060.
文摘BACKGROUND Missed or delayed diagnosis of cervical spine instability after acute trauma can have catastrophic consequences for the patient,resulting in severe neurological impairment.Currently,however,there is no consensus on the optimal strategy for diagnosing occult cervical spine instability.Thus,we present a case of occult cervical spine instability and provide a clinical algorithm to aid physicians in diagnosing occult instability of the cervical spine.CASE SUMMARY A 57-year-old man presented with cervical spine pain and inability to stand following a serious fall from a height of 2 m.No obvious vertebral fracture or dislocation was found at the time on standard lateral X-ray,computed tomography,and magnetic resonance imaging(MRI).Subsequently,the initial surgical plan was unilateral open-door laminoplasty(C3-7)with alternative levels of centerpiece mini-plate fixation(C3,5,and 7).However,the intraoperative C-arm fluoroscopic X-rays revealed significantly increased intervertebral space at C5-6,indicating instability at this level that was previously unrecognized on preoperative imaging.We finally performed lateral mass fixation and fusion at the C5-6 level.Looking back at the preoperative images,we found that the preoperative T2 MRI showed non-obvious high signal intensity at the C5-6 intervertebral disc and posterior interspinous ligament.CONCLUSION MRI of cervical spine trauma patients should be carefully reviewed to detect disco-ligamentous injury,which will lead to further cervical spine instability.In patients with highly suspected cervical spine instability indicated on MRI,lateral X-ray under traction or after anesthesia and muscle relaxation needs to be performed to avoid missed diagnoses of occult cervical instability.
文摘This letter focuses on a recently published article that provided an exceptional description of the effect of epigenetic modifications on gene expression patterns related to skeletal system remodeling.Specifically,it discusses a novel modality of epigenetic regulation,the long noncoding RNAs(lncRNAs),and provides evidence of their involvement in mesenchymal stromal/stem cells osteo-/adipogenic differentiation balance.Despite focus on lncRNAs,there is an emerging cross talk between lncRNAs and miRNAs interaction as a novel mechanism in the regulation of the function of the musculoskeletal system,by controlling bone homeostasis and bone regeneration,as well as the osteogenic differentiation of stem cells.Thus,we touched on some examples to demonstrate this interaction.In addition,we believe there is still much to discover from the effects of lncRNAs on progenitor and non-progenitor cell differentiation.We incorporated data from other published articles to review lncRNAs in normal progenitor cell osteogenic differentiation,determined lncRNAs involved in osteoarthritis pathogenesis in progenitor cells,and provided a review of lncRNAs in non-progenitor cells that are differentially regulated in osteoarthritis.In conclusion,we really enjoyed reading this article and with this information we hope to further our understanding of lncRNAs and mesenchymal stromal/stem cells regulation.
基金supported by the National Key Research and Development Projects(2018YFC1105400)the National Natural Science Foundation of China(81872173,82072959,and 31870959)+1 种基金the Zhejiang Provincial Natural Science Foundation(GF22H068757)the Zhejiang Undergraduate Talent Project(2021R401214).
文摘Platelet-derived growth factor-BB(PDGF-BB)/platelet-derived growth factor receptor-β(PDGFR-β)pathway is conventionally considered as an important pathway to promote osteogenesis;however,recent study suggested its role during osteogenesis to be controversial.Regarding the differential functions of this pathway during 3 stages of bone healing,we hypothesized that temporal inhibition of PDGF-BB/PDGFR-βpathway could shift the proliferation/differentiation balance of skeletal stem and progenitor cells,toward osteogenic lineage,which leads to improved bone regeneration.We first validated that inhibition of PDGFR-βat late stage of osteogenic induction effectively enhanced differentiation toward osteoblasts.This effect was also replicated invivo by showing accelerated bone formation when block PDGFR-βpathway at late stage of critical bone defect healing mediated using biomaterials.Further,we found that such PDGFR-βinhibitor-initiated bone healing was also effective in the absence of scaffold implantation when administrated intraperitoneally.Mechanistically,timely inhibition of PDGFR-βblocked extracellular regulated protein kinase 1/2 pathway,which shift proliferation/differentiation balance of skeletal stem and progenitor cell to osteogenic lineage by upregulating osteogenesis-related products of Smad to induce osteogenesis.This study offered updated understanding of the use of PDGFR-βpathway and provides new insight routes of action and novel therapeutic methods in the field of bone repair.
基金This work was financially supported by the National Key Research and Development Program of China(Grant No.2018YFC1105401,2018YFC1105404)National Natural Science Foundation of China(81702118,31870959)2018 Zhejiang University Academic Award for Outstanding Doctoral Candidates and Medical and Health Science and Technology Plan of Department of Health of Zhejiang Province(WKJ-ZJ-1821).
文摘Bacteria-associated infection represents one of the major threats for orthopedic implants failure during their life cycles.However,ordinary antimicrobial treatments usually failed to combat multiple waves of infections during arthroplasty and prosthesis revisions etc.As these incidents could easily introduce new microbial pathogens in/onto the implants.Herein,we demonstrate that an antimicrobial trilogy strategy incorporating a sophisticated multilayered coating system leveraging multiple ion exchange mechanisms and fine nanotopography tuning,could effectively eradicate bacterial infection at various stages of implantation.Early stage bacteriostatic effect was realized via nano-topological structure of top mineral coating.Antibacterial effect at intermediate stage was mediated by sustained release of zinc ions from doped CaP coating.Strong antibacterial potency was validated at 4 weeks post implantation via an implanted model in vivo.Finally,the underlying zinc titanate fiber network enabled a long-term contact and release effect of residual zinc,which maintained a strong antibacterial ability against both Staphylococcus aureus and Escherichia coli even after the removal of top layer coating.Moreover,sustained release of Sr2+and Zn2+during CaP coating degradation substantially promoted implant osseointegration even under an infectious environment by showing more peri-implant new bone formation and substantially improved bone-implant bonding strength.
基金This work was financially supported,in part,by the Sci-ence and Technology Research Program of Sichuan Province(No.2020YFS0036,Dr.Tu)the 1·3·5 project for disciplines of excel-lence,West China Hospital,Sichuan University(No.ZYJC18036,Dr.Tu).
文摘The custom-tailored medicine requires a developmental strategy that integrates excellent osteogene-sis with mechanical stability to enhance the reconstruction of the critical-size bone defect(CSBD)and the healing process in weight-bearing bone.We prepared three-dimensional(3D)printed biphasic cal-cium phosphate(BCP)scaffolds composited with nano-graphene oxide(GO).The biological effects of the GO/BCP composite scaffolds could induce the differentiation of rat bone marrow stem cells(BM-SCs)and the migration of human umbilical vein endothelial cells(HUVECs)for bone repair.The proper ratio of GO in the composite scaffold regulated the composites’surface roughness and hydrophilicity to a suitable range for the adhesion and proliferation of BMSCs and HUVECs.Besides,the GO/BCP composite scaffold increased osteogenesis and angiogenesis by activating BMP-2,RUNX-2,Smad1/4,and VEGF.The customized intramedullary nail combined with GO/BCP scaffold was applied to repair CSBD(2.0 cm in length)in a beagle femur model.This fixation strategy was confirmed by finite element analysis.In vivo,the results indicated that the custom-made internal fixation provided sufficient stability in the early stage,ensuring bone healing in a considerable mechanical environment.At 9 months postoperatively,longitudi-nal bony union and blood vessels in osteon were observed in the CSBD area with partial degradation in the 0.3%GO/BCP group.In the three-point bending test,the ultimate load of 0.3%GO/BCP group reached over 50%of the normal femur at 9 months after repair.These results showed a promising application of osteogenic GO/BCP scaffold and custom-made intramedullary nails in repairing CSBD of the beagle femur.This effective strategy could provide an option to treat the clinical CSBD in weight-bearing bones.
