Invasive inflammation and excessive scar formation are the main reasons for the difficulty in repairing nervous tissue after spinal cord injury.Microglia and astrocytes play key roles in the spinal cord injury micro-e...Invasive inflammation and excessive scar formation are the main reasons for the difficulty in repairing nervous tissue after spinal cord injury.Microglia and astrocytes play key roles in the spinal cord injury micro-environment and share a close interaction.However,the mechanisms involved remain unclear.In this study,we found that after spinal cord injury,resting microglia(M0)were polarized into pro-inflammatory phenotypes(MG1 and MG3),while resting astrocytes were polarized into reactive and scar-forming phenotypes.The expression of growth arrest-specific 6(Gas6)and its receptor Axl were significantly down-regulated in microglia and astrocytes after spinal cord injury.In vitro experiments showed that Gas6 had negative effects on the polarization of reactive astrocytes and pro-inflammatory microglia,and even inhibited the cross-regulation between them.We further demonstrated that Gas6 can inhibit the polarization of reactive astrocytes by suppressing the activation of the Yes-associated protein signaling pathway.This,in turn,inhibited the polarization of pro-inflammatory microglia by suppressing the activation of the nuclear factor-κB/p65 and Janus kinase/signal transducer and activator of transcription signaling pathways.In vivo experiments showed that Gas6 inhibited the polarization of pro-inflammatory microglia and reactive astrocytes in the injured spinal cord,thereby promoting tissue repair and motor function recovery.Overall,Gas6 may play a role in the treatment of spinal cord injury.It can inhibit the inflammatory pathway of microglia and polarization of astrocytes,attenuate the interaction between microglia and astrocytes in the inflammatory microenvironment,and thereby alleviate local inflammation and reduce scar formation in the spinal cord.展开更多
Purpose:This study aimed to assess the influence of older vs.younger age and previous anterior cruciate ligament(ACL)injury on resting serum cartilage oligomeric matrix protein(sCOMP(t_(pre)))concentration,on immediat...Purpose:This study aimed to assess the influence of older vs.younger age and previous anterior cruciate ligament(ACL)injury on resting serum cartilage oligomeric matrix protein(sCOMP(t_(pre)))concentration,on immediate load-induced sCOMP kinetics after a 30-min treadmill walking stress(ΔsCOMP(t_(post))),and on the dose-response relationship between ambulatory load magnitude andΔsCOMP(t_(post)).Methods:A total of 85 participants were recruited in 4 groups(20-30 years:24 healthy,23 ACL-injured;40-60 years:23 healthy,15 ACL-injured).Blood samples were collected immediately before and after a walking stress at 80%,100%,or 120%bodyweight(BW)on 3 test days and analyzed for sCOMP concentration.Linear models were used to estimate the effect of age,knee status(unilateral ACL injury,2-10 years prior),and sex on sCOMP(t_(pre)),ΔsCOMP(t_(post)),and the dose-re sponse between ambulatory load magnitude andΔsCOMP(t_(post)).Results:We found that sCOMP(t_(pre))was 21%higher in older than younger participants(p<0.001)but did not differ between ACL-injured and healthy participants(p=0.632).Also,ΔsCOMP(t_(post))was 19%lower in older than younger participants(p=0.030)and increased with body mass index(p<0.001),sCOMP(t_(pre))(p=0.008),and with 120%BW(p<0.001),independent of age,ACL injury,or sex.Conclusion:Age but not prior ACL injury influences resting sCOMP and load-induced sCOMP.The dose-response relationship between ambulatory load magnitude and load-induced sCOMP changes is not affected by age,ACL injury,or sex.A better understanding of systemic sCOMP and the role of its mechanoresponse for the understanding of osteoarthritis pathophysiology and monitoring intervention efficacy may require knowledge of individual cartilage composition and tissue-level loading parameters.展开更多
Magnetostrictive Fe-Ga alloys have captivated substantial focus in biomedical applications because of their exceptional transition efficiency and favorable cytocompatibility.Nevertheless,Fe-Ga alloys always exhibit fr...Magnetostrictive Fe-Ga alloys have captivated substantial focus in biomedical applications because of their exceptional transition efficiency and favorable cytocompatibility.Nevertheless,Fe-Ga alloys always exhibit frustrating magnetostriction coefficients when presented in bulk dimensions.It is well-established that the magnetostrictive performance of Fe-Ga alloys is intimately linked to their phase and crystal structures.In this study,various concentrations of boron(B)were doped into Fe_(81)Ga_(19) alloys via the laser-beam powder bed fusion(LPBF)technique to tailor the crystal and phase structures,thereby improving the magnetostrictive performance.The results revealed the capacity for quick solidification of the LPBF process in expediting the solid solution of B element,which increased both lattice distortion and dislocations within the Fe-Ga matrix.These factors contributed to an elevation in the density of the modified-D0_(3) phase structure.Moreover,the prepared Fe-Ga-B alloys also exhibited a(001)preferred grain orientation caused by the high thermal gradients during the LPBF process.As a result,a maximum magnetostriction coefficient of 105 ppm was achieved in the(Fe_(81)Ga_(19))_(98.5)B_(1.5) alloy.In alternating magnetic fields,all the LPBF-prepared alloys showed good dynamic magnetostriction response without visible hysteresis,while the(Fe_(81)Ga_(19))_(98.5)B_(1.5) alloy presented a notable enhancement of~30%in magnetostriction coefficient when compared with the Fe_(81)Ga_(19) alloy.Moreover.the(Fe_(81)Ga_(19))_(98.5)B_(1.5) alloy exhibited favorable biocompatibility and osteogenesis,as confirmed by increased alkaline phosphatase(ALP)activity and the formation of mineralized nodules.These findings suggest that the B-doped Fe-Ga alloys combined with the LPBF technique hold promise for the development of bulk magnetostrictive alloys that are applicable for bone repair applications.展开更多
BACKGROUND Uniportal full-endoscopy(UFE)technique has been continuously developed and applied for treating lumbar spinal stenosis.However,achieving effective decompression outcome of using the UFE technique remains te...BACKGROUND Uniportal full-endoscopy(UFE)technique has been continuously developed and applied for treating lumbar spinal stenosis.However,achieving effective decompression outcome of using the UFE technique remains technically demanding and uncertain.Previously,we have proposed the biportal full-endoscopy(BFE)technique to integrate the respective advantages of both UFE and unilateral biportal endoscopy technique.There is limited published data on the comparison of clinical outcomes between biportal and UFE techniques in lumbar spinal stenosis with bilateral symptoms.AIM To contrast the clinical outcomes between biportal and UFE techniques for treating lumbar spinal stenosis with bilateral symptoms.METHODS This study retrospectively examined 100 patients diagnosed with lumbar spinal stenosis and bilateral symptoms.Among them,52 cases were part of group A(BFE technique group),and 48 cases belonged to group B(UFE technique group).The visual analogue scale(VAS),Oswestry Disability Index(ODI),and modified Macnab criteria were used to evaluate the clinical outcomes.RESULTS Group A had significantly shorter operation time than group B.Both groups experienced substantial relief in lower back and lower extremity pain on the severe side at postoperative 3 days,3 months,and 12 months.Group A had notably lower VAS scores for mild side lower extremity pain at postoperative 3 months and 12 months compared to group B.Group A's ODI scores were significantly lower at postoperative 3 months and 12 months,whereas group B's scores did not significantly differ from preoperative values.Group A's ODI scores were significantly lower than group B's at postoperative 3 months and 12 months.Group A had a significantly higher excellent and good response rate(94.23%)compared to group B(81.25%)at postoperative 12 months based on the modified Macnab scale outcomes.CONCLUSION The BFE technique offers multiple benefits,including reduced trauma and quicker recovery as a minimally invasive surgery,and enhanced decompression efficiency over the UFE technique when treating lumbar spinal stenosis with bilateral symptoms.展开更多
BACKGROUND Degenerative disc disease(DDD)is characterized by the loss of nucleus pulposus cells(NPCs).Inducing differentiation of bone marrow mesenchymal stem cells(MSCs)into NPCs has emerged as a novel therapeutic st...BACKGROUND Degenerative disc disease(DDD)is characterized by the loss of nucleus pulposus cells(NPCs).Inducing differentiation of bone marrow mesenchymal stem cells(MSCs)into NPCs has emerged as a novel therapeutic strategy for DDD.However,the efficiency of MSC differentiation and the underlying mechanisms remain to be fully elucidated.AIM To investigate the role and mechanism of miR-365 in promoting the differentiation of MSCs into NPCs for DDD treatment.METHODS In vitro,the effects of miR-365 on MSC proliferation,apoptosis,and differentiation were assessed by cell counting kit-8 assay,flow cytometry,and quantitative realtime polymerase chain reaction(qRT-PCR).In vivo,the expression levels of miR-365,HIF-1α,Sox9,Kdm6a,and HOXA9 in the spinal cord of rats with spinal cord injury were determined by qRT-PCR and Western blot.RESULTS In vitro,miR-365 significantly promoted MSC proliferation and inhibited MSC apoptosis.The expression levels of glycosaminoglycans,proteoglycan,and type 2 collagen were significantly increased with miR-365 ectopic expression.In vivo,the expression levels of miR-365,HIF-1α,Sox9,and Kdm6a were significantly increased,whereas HOXA9 was remarkably decreased.Mechanically,miR-365 inhibited HOXA9 expression by directly binding to its 3’untranslated region.HOXA9 could inhibit HIF-1αexpression by binding to the Hif-1αpromoter,thereby affecting the expression levels of Sox9 and Kdm6a.Moreover,HOXA9 knockdown significantly reversed the differentiation of MSCs into NPCs induced by miR-365.CONCLUSION miR-365 promotes HOXA9-mediated differentiation of MSCs into NPCs by interacting with HIF-1αand may serve as a potential target for DDD treatment.展开更多
Objective To explore the causality between reproductive traits and risk of psoriasis by using a large Mendelian randomization(MR)study.Methods A two-sample MR study was performed using summarized statistics from the g...Objective To explore the causality between reproductive traits and risk of psoriasis by using a large Mendelian randomization(MR)study.Methods A two-sample MR study was performed using summarized statistics from the genome-wide association studies(GWAS)conducted in reproductive traits,as well as GWAS data on overall psoriasis,psoriatic arthritis(PsA),and psoriasis vulgaris(PV).Besides univariable MR(UVMR),multivariable MR and two-step MR was used to calculate the independent effects and quantify the proportion mediated by education or body mass index(BMI).Results Genetically predicted early age at first sexual intercourse(AFS)led to an increased risk of overall psoriasis[odds ratio(OR)UVMR:0.54];36.13%of this effect was mediated through BMI and 47.79%through educational attainment.The direct negative casual association between age at first birth(AFB)-PsA was dominant(ORUVMR:0.76),with 49.61%proportion of the mediation due to BMI.The mediating effect was found for BMI on the AFS-PV relationship,which accounted for 26.27%of the proportion.AFS was inversely associated with the risk of overall psoriasis and PV,with considerable mediation by BMI and educational attainment.Conclusion Early AFB may cause a higher risk of PsA,while the AFS-PsA association was fully mediated by BMI.展开更多
Dyslipidemia,a complex disorder characterized by systemic lipid profile abnormalities,affects more than half of adults globally and constitutes a major modifiable risk factor for atherosclerotic cardiovascular disease...Dyslipidemia,a complex disorder characterized by systemic lipid profile abnormalities,affects more than half of adults globally and constitutes a major modifiable risk factor for atherosclerotic cardiovascular disease.Mounting evidence has established the gut microbiota(GM)as a pivotal metabolic modulator that is correlated with atherogenic lipid profiles through dietary biotransformation,immunometabolic regulation,and bioactive metabolite signaling.However,the host-microbe interactions that drive dyslipidemia pathogenesis involve complex gene-environment crosstalk spanning epigenetic modifications to circadian entrainment.Mechanistically,GM perturbations disrupt lipid homeostasis via lipopolysaccharide-triggered hepatic very low-density lipoprotein overproduction,short-chain fatty acid-G protein-coupled receptor 43/41-mediated adipocyte lipolysis,bile acid-farnesoid X receptor/Takeda G proteincoupled receptor 5 axis dysfunction altering cholesterol flux,microbialβ-oxidation intermediates impairing mitochondrial energetics,and host-microbiota noncoding RNA crosstalk regulating lipogenic genes.This comprehensive review systematically examines three critical dimensions,including bidirectional GMlipid axis interactions,molecular cascades bridging microbial ecology to metabolic dysfunction,and translational applications of GM modulation through precision probiotics,structure-specific prebiotics,and a metabolically optimized fecal microbiota transplantation protocol.Notwithstanding these advances,critical gaps persist in establishing causal microbial taxa-pathway relationships and optimal intervention timing.Future directions require longitudinal multi-omic studies,gnotobiotic models for mechanistic validation,and machine learning-driven personalized microbiota profiling.This synthesis provides a framework for developing microbiotacentric strategies targeting dyslipidemia pathophysiology,with implications for precision dyslipidemia management and next-generation cardiovascular disease prevention.展开更多
Objective:To observe and study the actual effects of percutaneous pedicle screw minimally invasive surgery in the treatment of spinal fractures and its impact on spinal function.Methods:This study included 48 patients...Objective:To observe and study the actual effects of percutaneous pedicle screw minimally invasive surgery in the treatment of spinal fractures and its impact on spinal function.Methods:This study included 48 patients with spinal fractures admitted between May 2023 and May 2024.The patients were divided into a control group and an experimental group based on treatment differences,with 24 patients in each group.The control group underwent open internal fixation surgery,while the experimental group received percutaneous pedicle screw minimally invasive surgery.Clinical index improvements,cervical dysfunction index,Japanese Orthopaedic Association scores,and pain level improvements were compared between the two groups.Results:The intraoperative blood loss,incision length,operation time,and hospitalization duration in the experimental group were(88.63±18.85),(6.32±1.05),(73.42±4.05),and(12.58±2.56),respectively,compared to(279.95±17.32),(12.89±1.36),(89.93±4.79),and(22.41±2.87)in the control group.Significant differences were observed between the groups,with the experimental group showing superior improvements across all metrics(P<0.05).Conclusion:Percutaneous pedicle screw minimally invasive surgery shows more significant effects in treating spinal fractures,particularly in improving cervical and lumbar spine function,enhancing treatment efficacy and safety,reducing pain levels,and shortening recovery time.Clinical application and promotion are recommended.展开更多
Pelvic fractures are rare but severe injuries that severely affect patients’quality of life.Treatment of these fractures often involves invasive approaches with high risk of injuries to nervous structures,particularl...Pelvic fractures are rare but severe injuries that severely affect patients’quality of life.Treatment of these fractures often involves invasive approaches with high risk of injuries to nervous structures,particularly lumbosacral plexus.The introduction of minimally invasive surgical approaches,such as the lateral rectus approach,not only contributes to preserving lumbar plexus integrity in operated patients but also positively impacts their psychological well-being.Patients treated by surgical reduction of pelvic fractures with lumbosacral plexus injury often experience states of anxiety and depression.The lateral rectus approach is associated with lower levels of anxiety and depression compared to more invasive surgical techniques used for similar fractures.展开更多
Fibrotic remodeling of nucleus pulposus(NP)leads to structural and mechanical anomalies of intervertebral discs that prone to degeneration,leading to low back pain incidence and disability.Emergence of fibroblastic ce...Fibrotic remodeling of nucleus pulposus(NP)leads to structural and mechanical anomalies of intervertebral discs that prone to degeneration,leading to low back pain incidence and disability.Emergence of fibroblastic cells in disc degeneration has been reported,yet their nature and origin remain elusive.In this study,we performed an integrative analysis of multiple single-cell RNA sequencing datasets to interrogate the cellular heterogeneity and fibroblast-like entities in degenerative human NP specimens.We found that disc degeneration severity is associated with an enrichment of fibrocyte phenotype,characterized by CD45 and collagen I dual positivity,and expression of myofibroblast markerα-smooth muscle actin.Refined clustering and classification distinguished the fibrocyte-like populations as subtypes in the NP cells-and immunocytes-clusters,expressing disc degeneration markers HTRA1 and ANGPTL4 and genes related to response to TGF-β.In injury-induced mouse disc degeneration model,fibrocytes were found recruited into the NP undergoing fibrosis and adopted a myofibroblast phenotype.Depleting the fibrocytes in CD11b-DTR mice in which myeloid-derived lineages were ablated by diphtheria toxin could markedly attenuate fibrous modeling and myofibroblast formation in the NP of the degenerative discs,and prevent disc height loss and histomorphological abnormalities.Marker analysis supports that disc degeneration progression is dependent on a function of CD45^(+)COL1A1^(+)andαSMA^(+)cells.Our findings reveal that myeloid-derived fibrocytes play a pivotal role in NP fibrosis and may therefore be a target for modifying disc degeneration and promoting its repair.展开更多
Aging is a pivotal risk factor for intervertebral disc degeneration(IVDD)and chronic low back pain(LBP).The restoration of aging nucleus pulposus cells(NPCs)to a youthful epigenetic state is crucial for IVDD treatment...Aging is a pivotal risk factor for intervertebral disc degeneration(IVDD)and chronic low back pain(LBP).The restoration of aging nucleus pulposus cells(NPCs)to a youthful epigenetic state is crucial for IVDD treatment,but remains a formidable challenge.Here,we proposed a strategy to partially reprogram and reinstate youthful epigenetics of senescent NPCs by delivering a plasmid carrier that expressed pluripotency-associated genes(Oct4,Klf4 and Sox2)in Cavin2-modified exosomes(OKS@M-Exo)for treatment of IVDD and alleviating LBP.The functional OKS@M-Exo efficaciously alleviated senescence markers(p16^(INK4a),p21^(CIP1)and p53),reduced DNA damage and H4K20me3 expression,as well as restored proliferation ability and metabolic balance in senescent NPCs,as validated through in vitro experiments.In a rat model of IVDD,OKS@M-Exo maintained intervertebral disc height,nucleus pulposus hydration and tissue structure,effectively ameliorated IVDD via decreasing the senescence markers.Additionally,OKS@MExo reduced nociceptive behavior and downregulated nociception markers,indicating its efficiency in alleviating LBP.The transcriptome sequencing analysis also demonstrated that OKS@M-Exo could decrease the expression of age-related pathways and restore cell proliferation.Collectively,reprogramming by the OKS@M-Exo to restore youthful epigenetics of senescent NPCs may hold promise as a therapeutic platform to treat IVDD.展开更多
Unlike mammals,zebrafish possess a remarkable ability to regenerate their spinal cord after injury,making them an ideal vertebrate model for studying regeneration.While previous research has identified key cell types ...Unlike mammals,zebrafish possess a remarkable ability to regenerate their spinal cord after injury,making them an ideal vertebrate model for studying regeneration.While previous research has identified key cell types involved in this process,the underlying molecular and cellular mechanisms remain largely unexplored.In this study,we used single-cell RNA sequencing to profile distinct cell populations at different stages of spinal cord injury in zebrafish.Our analysis revealed that multiple subpopulations of neurons showed persistent activation of genes associated with axonal regeneration post injury,while molecular signals promoting growth cone collapse were inhibited.Radial glial cells exhibited significant proliferation and differentiation potential post injury,indicating their intrinsic roles in promoting neurogenesis and axonal regeneration,respectively.Additionally,we found that inflammatory factors rapidly decreased in the early stages following spinal cord injury,creating a microenvironment permissive for tissue repair and regeneration.Furthermore,oligodendrocytes lost maturity markers while exhibiting increased proliferation following injury.These findings demonstrated that the rapid and orderly regulation of inflammation,as well as the efficient proliferation and redifferentiation of new neurons and glial cells,enabled zebrafish to reconstruct the spinal cord.This research provides new insights into the cellular transitions and molecular programs that drive spinal cord regeneration,offering promising avenues for future research and therapeutic strategies.展开更多
Bone resorption by osteoclasts is a critical step in bone remodeling,a process important for maintaining bone homeostasis and repairing injured bone.We previously identified a bone marrow mesenchymal subpopulation,mar...Bone resorption by osteoclasts is a critical step in bone remodeling,a process important for maintaining bone homeostasis and repairing injured bone.We previously identified a bone marrow mesenchymal subpopulation,marrow adipogenic lineage precursors(MALPs),and showed that its production of RANKL stimulates bone resorption in young mice using Adipoq-Cre.To exclude developmental defects and to investigate the role of MALPs-derived RANKL in adult bone,we generated inducible reporter mice(Adipoq-CreER Tomato)and RANKL deficient mice(Adipoq-CreER RANKLflox/flox,iCKO).Single cell-RNA sequencing data analysis and lineage tracing revealed that Adipoq+cells contain not only MALPs but also some mesenchymal progenitors capable of osteogenic differentiation.In situ hybridization showed that RANKL mRNA is only detected in MALPs,but not in osteogenic cells.RANKL deficiency in MALPs induced at 3 months of age rapidly increased trabecular bone mass in long bones as well as vertebrae due to diminished bone resorption but had no effect on the cortical bone.Ovariectomy(OVX)induced trabecular bone loss at both sites.RANKL depletion either before OVX or at 6 weeks post OVX protected and restored trabecular bone mass.Furthermore,bone healing after drill-hole injury was delayed in iCKO mice.Together,our findings demonstrate that MALPs play a dominant role in controlling trabecular bone resorption and that RANKL from MALPs is essential for trabecular bone turnover in adult bone homeostasis,postmenopausal bone loss,and injury repair.展开更多
BACKGROUND Gestational diabetes mellitus(GDM)has recently been associated with abnormal profiles of inflammatory cells and cytokines,though the findings remain incon-sistent and unclear.AIM To elucidate the peripheral...BACKGROUND Gestational diabetes mellitus(GDM)has recently been associated with abnormal profiles of inflammatory cells and cytokines,though the findings remain incon-sistent and unclear.AIM To elucidate the peripheral immune status in GDM.METHODS We systematically screened databases including Web of Science,PubMed,and EMBASE for eligible studies.Original articles reporting different immune cell levels in GDM compared to normal glucose-tolerance pregnant women were included to extract usable data.The pooled mean difference(MD)with 95%confidence interval(CI)was analyzed as the outcome measure.The Newcastle-Ottawa scale was employed to assess study quality.RESULTS A total of 19 studies involving various immune cell subgroups were included in our analysis.Specifically,total CD4+T cells(WMD=3.08;95%CI:0.81-5.35)were significantly increased in GDM groups.In contrast,total lymphocytes(SMD=0.05;95%CI:-0.16 to 0.26),CD3+T cells(SMD=-0.34;95%CI:-1.01 to 0.32),CD8+T cells(SMD=0.21;95%CI:-0.31 to 0.73),and natural killer T(NKT)Cells(SMD=0.83;95%CI:-1.10 to 2.75)showed no significant changes in GDM.Activation markers(HLA-DR+or CD69+)on CD4+T cells(WMD=0.20;95%CI:0.06-0.34)were increased in GDM patients.Treg cells,a classical subgroup of CD4+T cells,showed a decreasing trend in GDM compared to controls(SMD=-0.83;95%CI:-1.31 to-0.34).These results indicate an abnormal immune status in the peripheral profiles of GDM.CONCLUSION GDM may not only be a dysglycemia-related condition but also an immune disorder characterized by abnormal peripheral immune profiles,including higher levels of CD4+T cells and a reduced population of Treg cells.Tr-eating immune dysregulation could be a new direction for GDM management,although further research is needed to understand the precise mechanisms of immune overactivation in GDM.展开更多
Intervertebral disc degeneration is a degenerative disease where inflammation and immune responses play significant roles.Macrophages,as key immune cells,critically regulate inflammation through polarization into diff...Intervertebral disc degeneration is a degenerative disease where inflammation and immune responses play significant roles.Macrophages,as key immune cells,critically regulate inflammation through polarization into different phenotypes.In recent years,the role of macrophages in inflammation-related degenerative diseases,such as intervertebral disc degeneration,has been increasingly recognized.Macrophages construct the inflammatory microenvironment of the intervertebral disc and are involved in regulating intervertebral disc cell activities,extracellular matrix metabolism,intervertebral disc vascularization,and innervation,profoundly influencing the progression of disc degeneration.To gain a deeper understanding of the inflammatory microenvironment of intervertebral disc degeneration,this review will summarize the role of macrophages in the pathological process of intervertebral disc degeneration,analyze the regulatory mechanisms involving macrophages,and review therapeutic strategies targeting macrophage modulation for the treatment of intervertebral disc degeneration.These insights will be valuable for the treatment and research directions of intervertebral disc degeneration.展开更多
Spinal fusion is a commonly used technique to treat acute and chronic spinal diseases by fusion of the adjacent vertebrae, aiming at achieving stability and eliminating the mobility of the objective segment. While bon...Spinal fusion is a commonly used technique to treat acute and chronic spinal diseases by fusion of the adjacent vertebrae, aiming at achieving stability and eliminating the mobility of the objective segment. While bone autografts and allografts have been conventionally used for spinal fusion, limitations persist in achieving optimization of both good osteoinductive capacity and mechanical stability. In this study, additively manufactured Zn-Li scaffolds were developed and evaluated for their potential in spinal fusion. First, three scaffold structures (BCC, Diamond, and Gyroid) were designed and verified in vitro. Due to the smooth transition surfaces and uniform degradation behavior, the Gyroid Zn-Li scaffold demonstrated mechanical integrity during degradation and enhanced cellular proliferation compared to the other two scaffolds. Subsequently, Zn-Li scaffolds (Gyroid) were selected for posterolateral lumbar fusion (L4/L5) in rabbits. Following 12 weeks of implantation, the Zn-Li scaffolds demonstrated a moderate biodegradation rate and satisfactory biocompatibility. Compared to bone allografts, the Zn-Li scaffolds significantly improved osseointegration adjacent to the transverse processes, which led to enhanced segmental stability of the fused vertebrae post posterolateral lumbar fusion. Overall, the results show that the biodegradable Zn-Li scaffold holds substantial potential as the next-generation graft for spinal fusion.展开更多
Bone morphogenetic proteins are osteoinductive factors which have gained popularity in orthopaedicsurgery and especially in spine surgery. The use of recombinant human bone morphogenetic protein-2 has been officially ...Bone morphogenetic proteins are osteoinductive factors which have gained popularity in orthopaedicsurgery and especially in spine surgery. The use of recombinant human bone morphogenetic protein-2 has been officially approved by the United States Food and Drug Administration only for single level anterior lumbar interbody fusion, nevertheless it is widely used by many surgeons with off-label indications. Despite advantages in bone formation, its use still remains a controversial issue and several complications have been described by authors who oppose their wide use.展开更多
BACKGROUND Few reports have described lumbar foraminal stenosis-induced radiculopathy after treatment by full-endoscopic spine surgery(FESS)combined with percutaneous vertebroplasty(PVP)in patients with vertebral comp...BACKGROUND Few reports have described lumbar foraminal stenosis-induced radiculopathy after treatment by full-endoscopic spine surgery(FESS)combined with percutaneous vertebroplasty(PVP)in patients with vertebral compression fractures.We herein report such a case,including the patient’s treatment process and doctor’s surgical experience.CASE SUMMARY A 79-year-old man presented with symptoms of radiculopathy after sustaining L4 vertebral compression fractures.Imaging and physical examination revealed L4 vertebral compression fractures combined with L3/4 Lumbar foraminal stenosis(LFS).The patient’s symptoms were low back pain with pain in the lateral left leg.Although many reports have described radiculopathy induced by osteoporotic vertebral compression fractures,the use of FESS combined with PVP has rarely been reported.This case report indicates that the combination of FESS and PVP is a safe and effective approach for the treatment of LFS-induced radiculopathy after vertebral compression fractures.This minimally invasive technique has great potential to replace traditional lumbar fixation and decompression surgery.Thus,we suggest the continued accumulation of similar cases to discuss the wider application of FESS.CONCLUSION For patients with osteoporotic vertebral compression fracture(OVCF)and LFS,PVP and FESS can be used to restore the vertebral height and reduce the pressure around the intervertebral foramen.Additionally,the combination of FESS and PVP can treat the pain or numbness of the low back and lower limbs and allow for recovery in a short time with excellent postoperative effects.In general,FESS is a good treatment for radiculopathy caused by foraminal stenosis after OVCF.展开更多
Across many of the surgical specialties,the use of minimally invasive techniques that utilize indirect visualization has been increasingly replacing traditional techniques which utilize direct visualization.Arthroscop...Across many of the surgical specialties,the use of minimally invasive techniques that utilize indirect visualization has been increasingly replacing traditional techniques which utilize direct visualization.Arthroscopic surgery of the appendicular skeleton has evolved dramatically and become an integral part of musculoskeletal surgery over the last several decades,allowing surgeons to achieve similar or better outcomes,while reducing cost and recovery time.However,to date,the axial skeleton,with its close proximity to critical neural and vascular structures,has not adopted endoscopic techniques at as rapid of a rate.Over the past decade,increased patient demand for less invasive spine surgery combined with surgeon desire to meet these demands has driven significant evolution and innovation in endoscopic spine surgery.In addition,there has been an enormous advancement in technologies that assist in navigation and automation that help surgeons circumvent limitations of direct visualization inherent to less invasive techniques.There are currently a multitude of endoscopic techniques and approaches that can be utilized in the treatment of spine disorders,many of which are evolving rapidly.Here we present a review of the field of endoscopic spine surgery,including the background,techniques,applications,current trends,and future directions,to help providers gain a better understanding of this growing modality in spine surgery.展开更多
BACKGROUND The anatomical features of the atlantoaxial spine increase the difficulty of complete and safe removal of atlantoaxial intradural extramedullary(IDEM)tumors.Studies concerning surgical interventions via a p...BACKGROUND The anatomical features of the atlantoaxial spine increase the difficulty of complete and safe removal of atlantoaxial intradural extramedullary(IDEM)tumors.Studies concerning surgical interventions via a posterior approach are limited.AIM To investigate the safety and efficacy of atlantoaxial IDEM tumor resection using a one-stage posterior approach.METHODS We retrospectively analyzed clinical databases for one-stage atlantoaxial IDEM tumor resection via a posterior approach between January 2008 and January 2018.The analyzed data included tumor position,histopathological type,pre-and postoperative Japanese Orthopedic Association(JOA)scores and Nurick grades,postoperative complication and recurrence status.RESULTS A total of 13 patients who underwent C1-C2 Laminectomy and/or unilateral facetectomy via the posterior approach were enrolled in the study.In all cases reviewed,total tumor resection and concomitant C1-C2 fusion were achieved.The average follow-up was 35.3±6.9 mo(range,26-49 mo).A statistically significant difference was noted between the preoperative JOA score(11.2±1.1)and the score at the last final follow-up(15.6±1.0)(P<0.05).A statistically significant difference was noted between the preoperative Nurick grade(2.3±0.9)and that at the last follow-up(1.2±0.4)(P<0.05).However,no statistically significant difference was noted between the preoperative and last follow-up C1-2 Cobb angle and C2-7 Cobb angle(P>0.05).No mortalities,severe complications or tumor recurrence were observed during the follow-up period.CONCLUSION Total resection of atlantoaxial IDEM tumors is feasible and effective via a posterior approach.Surgical reconstruction should be considered to avoid iatrogenic kyphosis and improve spinal stability and overall clinical outcomes.展开更多
基金supported by the National Natural Science Foundation of China, Nos.81971151 (to YW), 82102528 (to XL), 82102583 (to LW)the Natural Science Foundation of Guangdong Province, China, Nos.2020A1515010265 (to YW), 2020A1515110679 (to XL), and 2021A1515010358 (to XL)
文摘Invasive inflammation and excessive scar formation are the main reasons for the difficulty in repairing nervous tissue after spinal cord injury.Microglia and astrocytes play key roles in the spinal cord injury micro-environment and share a close interaction.However,the mechanisms involved remain unclear.In this study,we found that after spinal cord injury,resting microglia(M0)were polarized into pro-inflammatory phenotypes(MG1 and MG3),while resting astrocytes were polarized into reactive and scar-forming phenotypes.The expression of growth arrest-specific 6(Gas6)and its receptor Axl were significantly down-regulated in microglia and astrocytes after spinal cord injury.In vitro experiments showed that Gas6 had negative effects on the polarization of reactive astrocytes and pro-inflammatory microglia,and even inhibited the cross-regulation between them.We further demonstrated that Gas6 can inhibit the polarization of reactive astrocytes by suppressing the activation of the Yes-associated protein signaling pathway.This,in turn,inhibited the polarization of pro-inflammatory microglia by suppressing the activation of the nuclear factor-κB/p65 and Janus kinase/signal transducer and activator of transcription signaling pathways.In vivo experiments showed that Gas6 inhibited the polarization of pro-inflammatory microglia and reactive astrocytes in the injured spinal cord,thereby promoting tissue repair and motor function recovery.Overall,Gas6 may play a role in the treatment of spinal cord injury.It can inhibit the inflammatory pathway of microglia and polarization of astrocytes,attenuate the interaction between microglia and astrocytes in the inflammatory microenvironment,and thereby alleviate local inflammation and reduce scar formation in the spinal cord.
基金funded by the Swiss National Science Foundation(#184912,in 2019)funding from the German Research Foundation(SFB 1483,in 2021).
文摘Purpose:This study aimed to assess the influence of older vs.younger age and previous anterior cruciate ligament(ACL)injury on resting serum cartilage oligomeric matrix protein(sCOMP(t_(pre)))concentration,on immediate load-induced sCOMP kinetics after a 30-min treadmill walking stress(ΔsCOMP(t_(post))),and on the dose-response relationship between ambulatory load magnitude andΔsCOMP(t_(post)).Methods:A total of 85 participants were recruited in 4 groups(20-30 years:24 healthy,23 ACL-injured;40-60 years:23 healthy,15 ACL-injured).Blood samples were collected immediately before and after a walking stress at 80%,100%,or 120%bodyweight(BW)on 3 test days and analyzed for sCOMP concentration.Linear models were used to estimate the effect of age,knee status(unilateral ACL injury,2-10 years prior),and sex on sCOMP(t_(pre)),ΔsCOMP(t_(post)),and the dose-re sponse between ambulatory load magnitude andΔsCOMP(t_(post)).Results:We found that sCOMP(t_(pre))was 21%higher in older than younger participants(p<0.001)but did not differ between ACL-injured and healthy participants(p=0.632).Also,ΔsCOMP(t_(post))was 19%lower in older than younger participants(p=0.030)and increased with body mass index(p<0.001),sCOMP(t_(pre))(p=0.008),and with 120%BW(p<0.001),independent of age,ACL injury,or sex.Conclusion:Age but not prior ACL injury influences resting sCOMP and load-induced sCOMP.The dose-response relationship between ambulatory load magnitude and load-induced sCOMP changes is not affected by age,ACL injury,or sex.A better understanding of systemic sCOMP and the role of its mechanoresponse for the understanding of osteoarthritis pathophysiology and monitoring intervention efficacy may require knowledge of individual cartilage composition and tissue-level loading parameters.
基金supported by the National Natural Science Foundation of China(Nos.52275395,51935014,and 82072084)the Science and Technology Innovation Program of Hunan Province(No.2023RC3046)+4 种基金the Young Elite Scientists Sponsorship Program byCAST(No.2020QNRC002)the NationalKeyResearchand Development Program of China(No.2023YFB4605800)the Central South University Innovation-Driven Research Programme(No.2023CXQD023)the Jiangxi Provincial Natural Science Foundation of China(No.20224ACB204013)the Project of State Key Laboratory of Precision Manufacturing for Extreme Service Performance,Central South University.
文摘Magnetostrictive Fe-Ga alloys have captivated substantial focus in biomedical applications because of their exceptional transition efficiency and favorable cytocompatibility.Nevertheless,Fe-Ga alloys always exhibit frustrating magnetostriction coefficients when presented in bulk dimensions.It is well-established that the magnetostrictive performance of Fe-Ga alloys is intimately linked to their phase and crystal structures.In this study,various concentrations of boron(B)were doped into Fe_(81)Ga_(19) alloys via the laser-beam powder bed fusion(LPBF)technique to tailor the crystal and phase structures,thereby improving the magnetostrictive performance.The results revealed the capacity for quick solidification of the LPBF process in expediting the solid solution of B element,which increased both lattice distortion and dislocations within the Fe-Ga matrix.These factors contributed to an elevation in the density of the modified-D0_(3) phase structure.Moreover,the prepared Fe-Ga-B alloys also exhibited a(001)preferred grain orientation caused by the high thermal gradients during the LPBF process.As a result,a maximum magnetostriction coefficient of 105 ppm was achieved in the(Fe_(81)Ga_(19))_(98.5)B_(1.5) alloy.In alternating magnetic fields,all the LPBF-prepared alloys showed good dynamic magnetostriction response without visible hysteresis,while the(Fe_(81)Ga_(19))_(98.5)B_(1.5) alloy presented a notable enhancement of~30%in magnetostriction coefficient when compared with the Fe_(81)Ga_(19) alloy.Moreover.the(Fe_(81)Ga_(19))_(98.5)B_(1.5) alloy exhibited favorable biocompatibility and osteogenesis,as confirmed by increased alkaline phosphatase(ALP)activity and the formation of mineralized nodules.These findings suggest that the B-doped Fe-Ga alloys combined with the LPBF technique hold promise for the development of bulk magnetostrictive alloys that are applicable for bone repair applications.
基金Supported by National Natural Science Foundation of China,No.82202694Clinical Research Innovation Plan of Shanghai General Hospital,No.CTCCR-2021C10.
文摘BACKGROUND Uniportal full-endoscopy(UFE)technique has been continuously developed and applied for treating lumbar spinal stenosis.However,achieving effective decompression outcome of using the UFE technique remains technically demanding and uncertain.Previously,we have proposed the biportal full-endoscopy(BFE)technique to integrate the respective advantages of both UFE and unilateral biportal endoscopy technique.There is limited published data on the comparison of clinical outcomes between biportal and UFE techniques in lumbar spinal stenosis with bilateral symptoms.AIM To contrast the clinical outcomes between biportal and UFE techniques for treating lumbar spinal stenosis with bilateral symptoms.METHODS This study retrospectively examined 100 patients diagnosed with lumbar spinal stenosis and bilateral symptoms.Among them,52 cases were part of group A(BFE technique group),and 48 cases belonged to group B(UFE technique group).The visual analogue scale(VAS),Oswestry Disability Index(ODI),and modified Macnab criteria were used to evaluate the clinical outcomes.RESULTS Group A had significantly shorter operation time than group B.Both groups experienced substantial relief in lower back and lower extremity pain on the severe side at postoperative 3 days,3 months,and 12 months.Group A had notably lower VAS scores for mild side lower extremity pain at postoperative 3 months and 12 months compared to group B.Group A's ODI scores were significantly lower at postoperative 3 months and 12 months,whereas group B's scores did not significantly differ from preoperative values.Group A's ODI scores were significantly lower than group B's at postoperative 3 months and 12 months.Group A had a significantly higher excellent and good response rate(94.23%)compared to group B(81.25%)at postoperative 12 months based on the modified Macnab scale outcomes.CONCLUSION The BFE technique offers multiple benefits,including reduced trauma and quicker recovery as a minimally invasive surgery,and enhanced decompression efficiency over the UFE technique when treating lumbar spinal stenosis with bilateral symptoms.
基金Supported by Academic Subject Boosting Plan in Shanghai Fourth People's Hospital Affiliated to Tongji University School of Medicine,No.SY-XKZT-2019-3002Academic Project from the Health Commission of Hongkou District,Shanghai,No.2202-25Clinical Key Specialty Construction Unit from The Health Commission of Hongkou District,Shanghai,No.HKLCZD2024B03.
文摘BACKGROUND Degenerative disc disease(DDD)is characterized by the loss of nucleus pulposus cells(NPCs).Inducing differentiation of bone marrow mesenchymal stem cells(MSCs)into NPCs has emerged as a novel therapeutic strategy for DDD.However,the efficiency of MSC differentiation and the underlying mechanisms remain to be fully elucidated.AIM To investigate the role and mechanism of miR-365 in promoting the differentiation of MSCs into NPCs for DDD treatment.METHODS In vitro,the effects of miR-365 on MSC proliferation,apoptosis,and differentiation were assessed by cell counting kit-8 assay,flow cytometry,and quantitative realtime polymerase chain reaction(qRT-PCR).In vivo,the expression levels of miR-365,HIF-1α,Sox9,Kdm6a,and HOXA9 in the spinal cord of rats with spinal cord injury were determined by qRT-PCR and Western blot.RESULTS In vitro,miR-365 significantly promoted MSC proliferation and inhibited MSC apoptosis.The expression levels of glycosaminoglycans,proteoglycan,and type 2 collagen were significantly increased with miR-365 ectopic expression.In vivo,the expression levels of miR-365,HIF-1α,Sox9,and Kdm6a were significantly increased,whereas HOXA9 was remarkably decreased.Mechanically,miR-365 inhibited HOXA9 expression by directly binding to its 3’untranslated region.HOXA9 could inhibit HIF-1αexpression by binding to the Hif-1αpromoter,thereby affecting the expression levels of Sox9 and Kdm6a.Moreover,HOXA9 knockdown significantly reversed the differentiation of MSCs into NPCs induced by miR-365.CONCLUSION miR-365 promotes HOXA9-mediated differentiation of MSCs into NPCs by interacting with HIF-1αand may serve as a potential target for DDD treatment.
基金supported by the National Key R&D Program of China(No,2019YFA0112100)the National Natural Science Foundation of China(No.81472073)the Fundamental Research Funds for the Central Universities of Central South University(Grant Number:2022ZZTS0824).
文摘Objective To explore the causality between reproductive traits and risk of psoriasis by using a large Mendelian randomization(MR)study.Methods A two-sample MR study was performed using summarized statistics from the genome-wide association studies(GWAS)conducted in reproductive traits,as well as GWAS data on overall psoriasis,psoriatic arthritis(PsA),and psoriasis vulgaris(PV).Besides univariable MR(UVMR),multivariable MR and two-step MR was used to calculate the independent effects and quantify the proportion mediated by education or body mass index(BMI).Results Genetically predicted early age at first sexual intercourse(AFS)led to an increased risk of overall psoriasis[odds ratio(OR)UVMR:0.54];36.13%of this effect was mediated through BMI and 47.79%through educational attainment.The direct negative casual association between age at first birth(AFB)-PsA was dominant(ORUVMR:0.76),with 49.61%proportion of the mediation due to BMI.The mediating effect was found for BMI on the AFS-PV relationship,which accounted for 26.27%of the proportion.AFS was inversely associated with the risk of overall psoriasis and PV,with considerable mediation by BMI and educational attainment.Conclusion Early AFB may cause a higher risk of PsA,while the AFS-PsA association was fully mediated by BMI.
文摘Objective:To observe and study the actual effects of percutaneous pedicle screw minimally invasive surgery in the treatment of spinal fractures and its impact on spinal function.Methods:This study included 48 patients with spinal fractures admitted between May 2023 and May 2024.The patients were divided into a control group and an experimental group based on treatment differences,with 24 patients in each group.The control group underwent open internal fixation surgery,while the experimental group received percutaneous pedicle screw minimally invasive surgery.Clinical index improvements,cervical dysfunction index,Japanese Orthopaedic Association scores,and pain level improvements were compared between the two groups.Results:The intraoperative blood loss,incision length,operation time,and hospitalization duration in the experimental group were(88.63±18.85),(6.32±1.05),(73.42±4.05),and(12.58±2.56),respectively,compared to(279.95±17.32),(12.89±1.36),(89.93±4.79),and(22.41±2.87)in the control group.Significant differences were observed between the groups,with the experimental group showing superior improvements across all metrics(P<0.05).Conclusion:Percutaneous pedicle screw minimally invasive surgery shows more significant effects in treating spinal fractures,particularly in improving cervical and lumbar spine function,enhancing treatment efficacy and safety,reducing pain levels,and shortening recovery time.Clinical application and promotion are recommended.
文摘Pelvic fractures are rare but severe injuries that severely affect patients’quality of life.Treatment of these fractures often involves invasive approaches with high risk of injuries to nervous structures,particularly lumbosacral plexus.The introduction of minimally invasive surgical approaches,such as the lateral rectus approach,not only contributes to preserving lumbar plexus integrity in operated patients but also positively impacts their psychological well-being.Patients treated by surgical reduction of pelvic fractures with lumbosacral plexus injury often experience states of anxiety and depression.The lateral rectus approach is associated with lower levels of anxiety and depression compared to more invasive surgical techniques used for similar fractures.
基金jointly General Research Fund(17121619)of the Research Grant Council of Hong KongGuangdong Basic and Applied Basic Research Foundation(2024A1515010104 and 2023A1515220095)Scientific Research Foundation of Peking University Shenzhen Hospital(KYQD202100X)。
文摘Fibrotic remodeling of nucleus pulposus(NP)leads to structural and mechanical anomalies of intervertebral discs that prone to degeneration,leading to low back pain incidence and disability.Emergence of fibroblastic cells in disc degeneration has been reported,yet their nature and origin remain elusive.In this study,we performed an integrative analysis of multiple single-cell RNA sequencing datasets to interrogate the cellular heterogeneity and fibroblast-like entities in degenerative human NP specimens.We found that disc degeneration severity is associated with an enrichment of fibrocyte phenotype,characterized by CD45 and collagen I dual positivity,and expression of myofibroblast markerα-smooth muscle actin.Refined clustering and classification distinguished the fibrocyte-like populations as subtypes in the NP cells-and immunocytes-clusters,expressing disc degeneration markers HTRA1 and ANGPTL4 and genes related to response to TGF-β.In injury-induced mouse disc degeneration model,fibrocytes were found recruited into the NP undergoing fibrosis and adopted a myofibroblast phenotype.Depleting the fibrocytes in CD11b-DTR mice in which myeloid-derived lineages were ablated by diphtheria toxin could markedly attenuate fibrous modeling and myofibroblast formation in the NP of the degenerative discs,and prevent disc height loss and histomorphological abnormalities.Marker analysis supports that disc degeneration progression is dependent on a function of CD45^(+)COL1A1^(+)andαSMA^(+)cells.Our findings reveal that myeloid-derived fibrocytes play a pivotal role in NP fibrosis and may therefore be a target for modifying disc degeneration and promoting its repair.
基金supported by the Ministry of Science and Technology of China(2020YFA0908900)National Natural Science Foundation of China(21935011 and 82072490)+1 种基金Shenzhen Science and Technology Innovation Commission(KQTD20200820113012029 and KJZD20230923114612025)Guangdong Provincial Key Laboratory of Advanced Biomaterials(2022B1212010003).
文摘Aging is a pivotal risk factor for intervertebral disc degeneration(IVDD)and chronic low back pain(LBP).The restoration of aging nucleus pulposus cells(NPCs)to a youthful epigenetic state is crucial for IVDD treatment,but remains a formidable challenge.Here,we proposed a strategy to partially reprogram and reinstate youthful epigenetics of senescent NPCs by delivering a plasmid carrier that expressed pluripotency-associated genes(Oct4,Klf4 and Sox2)in Cavin2-modified exosomes(OKS@M-Exo)for treatment of IVDD and alleviating LBP.The functional OKS@M-Exo efficaciously alleviated senescence markers(p16^(INK4a),p21^(CIP1)and p53),reduced DNA damage and H4K20me3 expression,as well as restored proliferation ability and metabolic balance in senescent NPCs,as validated through in vitro experiments.In a rat model of IVDD,OKS@M-Exo maintained intervertebral disc height,nucleus pulposus hydration and tissue structure,effectively ameliorated IVDD via decreasing the senescence markers.Additionally,OKS@MExo reduced nociceptive behavior and downregulated nociception markers,indicating its efficiency in alleviating LBP.The transcriptome sequencing analysis also demonstrated that OKS@M-Exo could decrease the expression of age-related pathways and restore cell proliferation.Collectively,reprogramming by the OKS@M-Exo to restore youthful epigenetics of senescent NPCs may hold promise as a therapeutic platform to treat IVDD.
基金supported by the Jiangsu Province Traditional Chinese Medicine Technology Development Plan Project,Nos.MS2023113(to JC),MS2022090Young and Middle-aged Academic Leaders of Jiangsu Qing-Lan Project(to GL).
文摘Unlike mammals,zebrafish possess a remarkable ability to regenerate their spinal cord after injury,making them an ideal vertebrate model for studying regeneration.While previous research has identified key cell types involved in this process,the underlying molecular and cellular mechanisms remain largely unexplored.In this study,we used single-cell RNA sequencing to profile distinct cell populations at different stages of spinal cord injury in zebrafish.Our analysis revealed that multiple subpopulations of neurons showed persistent activation of genes associated with axonal regeneration post injury,while molecular signals promoting growth cone collapse were inhibited.Radial glial cells exhibited significant proliferation and differentiation potential post injury,indicating their intrinsic roles in promoting neurogenesis and axonal regeneration,respectively.Additionally,we found that inflammatory factors rapidly decreased in the early stages following spinal cord injury,creating a microenvironment permissive for tissue repair and regeneration.Furthermore,oligodendrocytes lost maturity markers while exhibiting increased proliferation following injury.These findings demonstrated that the rapid and orderly regulation of inflammation,as well as the efficient proliferation and redifferentiation of new neurons and glial cells,enabled zebrafish to reconstruct the spinal cord.This research provides new insights into the cellular transitions and molecular programs that drive spinal cord regeneration,offering promising avenues for future research and therapeutic strategies.
基金supported by NIH grants NIH/NIA R01AG069401(to L.Q.)NIH/NHLBI U54HL165442(to K.T.)P30AR069619(to Penn Center for Musculoskeletal Disorders).
文摘Bone resorption by osteoclasts is a critical step in bone remodeling,a process important for maintaining bone homeostasis and repairing injured bone.We previously identified a bone marrow mesenchymal subpopulation,marrow adipogenic lineage precursors(MALPs),and showed that its production of RANKL stimulates bone resorption in young mice using Adipoq-Cre.To exclude developmental defects and to investigate the role of MALPs-derived RANKL in adult bone,we generated inducible reporter mice(Adipoq-CreER Tomato)and RANKL deficient mice(Adipoq-CreER RANKLflox/flox,iCKO).Single cell-RNA sequencing data analysis and lineage tracing revealed that Adipoq+cells contain not only MALPs but also some mesenchymal progenitors capable of osteogenic differentiation.In situ hybridization showed that RANKL mRNA is only detected in MALPs,but not in osteogenic cells.RANKL deficiency in MALPs induced at 3 months of age rapidly increased trabecular bone mass in long bones as well as vertebrae due to diminished bone resorption but had no effect on the cortical bone.Ovariectomy(OVX)induced trabecular bone loss at both sites.RANKL depletion either before OVX or at 6 weeks post OVX protected and restored trabecular bone mass.Furthermore,bone healing after drill-hole injury was delayed in iCKO mice.Together,our findings demonstrate that MALPs play a dominant role in controlling trabecular bone resorption and that RANKL from MALPs is essential for trabecular bone turnover in adult bone homeostasis,postmenopausal bone loss,and injury repair.
文摘BACKGROUND Gestational diabetes mellitus(GDM)has recently been associated with abnormal profiles of inflammatory cells and cytokines,though the findings remain incon-sistent and unclear.AIM To elucidate the peripheral immune status in GDM.METHODS We systematically screened databases including Web of Science,PubMed,and EMBASE for eligible studies.Original articles reporting different immune cell levels in GDM compared to normal glucose-tolerance pregnant women were included to extract usable data.The pooled mean difference(MD)with 95%confidence interval(CI)was analyzed as the outcome measure.The Newcastle-Ottawa scale was employed to assess study quality.RESULTS A total of 19 studies involving various immune cell subgroups were included in our analysis.Specifically,total CD4+T cells(WMD=3.08;95%CI:0.81-5.35)were significantly increased in GDM groups.In contrast,total lymphocytes(SMD=0.05;95%CI:-0.16 to 0.26),CD3+T cells(SMD=-0.34;95%CI:-1.01 to 0.32),CD8+T cells(SMD=0.21;95%CI:-0.31 to 0.73),and natural killer T(NKT)Cells(SMD=0.83;95%CI:-1.10 to 2.75)showed no significant changes in GDM.Activation markers(HLA-DR+or CD69+)on CD4+T cells(WMD=0.20;95%CI:0.06-0.34)were increased in GDM patients.Treg cells,a classical subgroup of CD4+T cells,showed a decreasing trend in GDM compared to controls(SMD=-0.83;95%CI:-1.31 to-0.34).These results indicate an abnormal immune status in the peripheral profiles of GDM.CONCLUSION GDM may not only be a dysglycemia-related condition but also an immune disorder characterized by abnormal peripheral immune profiles,including higher levels of CD4+T cells and a reduced population of Treg cells.Tr-eating immune dysregulation could be a new direction for GDM management,although further research is needed to understand the precise mechanisms of immune overactivation in GDM.
基金National Natural Science Foundation of China(U24A20670,82372419,82072435)Tianjin Science and Technology Plan Project“Unveiling and Directing”Major Project(21ZXJBSY00130)Beijing-Tianjin-Hebei Basic Research Cooperation Project(J230020)。
文摘Intervertebral disc degeneration is a degenerative disease where inflammation and immune responses play significant roles.Macrophages,as key immune cells,critically regulate inflammation through polarization into different phenotypes.In recent years,the role of macrophages in inflammation-related degenerative diseases,such as intervertebral disc degeneration,has been increasingly recognized.Macrophages construct the inflammatory microenvironment of the intervertebral disc and are involved in regulating intervertebral disc cell activities,extracellular matrix metabolism,intervertebral disc vascularization,and innervation,profoundly influencing the progression of disc degeneration.To gain a deeper understanding of the inflammatory microenvironment of intervertebral disc degeneration,this review will summarize the role of macrophages in the pathological process of intervertebral disc degeneration,analyze the regulatory mechanisms involving macrophages,and review therapeutic strategies targeting macrophage modulation for the treatment of intervertebral disc degeneration.These insights will be valuable for the treatment and research directions of intervertebral disc degeneration.
基金supported by the National Natural Science Foundation of China(grant Nos.52301302,U22A20121,52175274,52111530042,and 5210010632)the China Postdoctoral Science Foundation(grant No.2023M732339)+1 种基金the Guangdong Basic and Applied Basic Research Foundation(Nos.2021A1515220086,2023A1515220095,and 2024A1515012042)the Beijing Natural Science Foundation(Grant No.L212014).
文摘Spinal fusion is a commonly used technique to treat acute and chronic spinal diseases by fusion of the adjacent vertebrae, aiming at achieving stability and eliminating the mobility of the objective segment. While bone autografts and allografts have been conventionally used for spinal fusion, limitations persist in achieving optimization of both good osteoinductive capacity and mechanical stability. In this study, additively manufactured Zn-Li scaffolds were developed and evaluated for their potential in spinal fusion. First, three scaffold structures (BCC, Diamond, and Gyroid) were designed and verified in vitro. Due to the smooth transition surfaces and uniform degradation behavior, the Gyroid Zn-Li scaffold demonstrated mechanical integrity during degradation and enhanced cellular proliferation compared to the other two scaffolds. Subsequently, Zn-Li scaffolds (Gyroid) were selected for posterolateral lumbar fusion (L4/L5) in rabbits. Following 12 weeks of implantation, the Zn-Li scaffolds demonstrated a moderate biodegradation rate and satisfactory biocompatibility. Compared to bone allografts, the Zn-Li scaffolds significantly improved osseointegration adjacent to the transverse processes, which led to enhanced segmental stability of the fused vertebrae post posterolateral lumbar fusion. Overall, the results show that the biodegradable Zn-Li scaffold holds substantial potential as the next-generation graft for spinal fusion.
文摘Bone morphogenetic proteins are osteoinductive factors which have gained popularity in orthopaedicsurgery and especially in spine surgery. The use of recombinant human bone morphogenetic protein-2 has been officially approved by the United States Food and Drug Administration only for single level anterior lumbar interbody fusion, nevertheless it is widely used by many surgeons with off-label indications. Despite advantages in bone formation, its use still remains a controversial issue and several complications have been described by authors who oppose their wide use.
基金Supported by National Natural Science Foundation of China,No.81972108.
文摘BACKGROUND Few reports have described lumbar foraminal stenosis-induced radiculopathy after treatment by full-endoscopic spine surgery(FESS)combined with percutaneous vertebroplasty(PVP)in patients with vertebral compression fractures.We herein report such a case,including the patient’s treatment process and doctor’s surgical experience.CASE SUMMARY A 79-year-old man presented with symptoms of radiculopathy after sustaining L4 vertebral compression fractures.Imaging and physical examination revealed L4 vertebral compression fractures combined with L3/4 Lumbar foraminal stenosis(LFS).The patient’s symptoms were low back pain with pain in the lateral left leg.Although many reports have described radiculopathy induced by osteoporotic vertebral compression fractures,the use of FESS combined with PVP has rarely been reported.This case report indicates that the combination of FESS and PVP is a safe and effective approach for the treatment of LFS-induced radiculopathy after vertebral compression fractures.This minimally invasive technique has great potential to replace traditional lumbar fixation and decompression surgery.Thus,we suggest the continued accumulation of similar cases to discuss the wider application of FESS.CONCLUSION For patients with osteoporotic vertebral compression fracture(OVCF)and LFS,PVP and FESS can be used to restore the vertebral height and reduce the pressure around the intervertebral foramen.Additionally,the combination of FESS and PVP can treat the pain or numbness of the low back and lower limbs and allow for recovery in a short time with excellent postoperative effects.In general,FESS is a good treatment for radiculopathy caused by foraminal stenosis after OVCF.
文摘Across many of the surgical specialties,the use of minimally invasive techniques that utilize indirect visualization has been increasingly replacing traditional techniques which utilize direct visualization.Arthroscopic surgery of the appendicular skeleton has evolved dramatically and become an integral part of musculoskeletal surgery over the last several decades,allowing surgeons to achieve similar or better outcomes,while reducing cost and recovery time.However,to date,the axial skeleton,with its close proximity to critical neural and vascular structures,has not adopted endoscopic techniques at as rapid of a rate.Over the past decade,increased patient demand for less invasive spine surgery combined with surgeon desire to meet these demands has driven significant evolution and innovation in endoscopic spine surgery.In addition,there has been an enormous advancement in technologies that assist in navigation and automation that help surgeons circumvent limitations of direct visualization inherent to less invasive techniques.There are currently a multitude of endoscopic techniques and approaches that can be utilized in the treatment of spine disorders,many of which are evolving rapidly.Here we present a review of the field of endoscopic spine surgery,including the background,techniques,applications,current trends,and future directions,to help providers gain a better understanding of this growing modality in spine surgery.
基金the National Natural Science Foundation of China,No.81860406Guangxi Natural Science Foundation,No.2018GXNSFAA281127Medical Excellence Award Funded by the Creative Research Development Grant from The First Affiliated Hospital of Guangxi Medical University.
文摘BACKGROUND The anatomical features of the atlantoaxial spine increase the difficulty of complete and safe removal of atlantoaxial intradural extramedullary(IDEM)tumors.Studies concerning surgical interventions via a posterior approach are limited.AIM To investigate the safety and efficacy of atlantoaxial IDEM tumor resection using a one-stage posterior approach.METHODS We retrospectively analyzed clinical databases for one-stage atlantoaxial IDEM tumor resection via a posterior approach between January 2008 and January 2018.The analyzed data included tumor position,histopathological type,pre-and postoperative Japanese Orthopedic Association(JOA)scores and Nurick grades,postoperative complication and recurrence status.RESULTS A total of 13 patients who underwent C1-C2 Laminectomy and/or unilateral facetectomy via the posterior approach were enrolled in the study.In all cases reviewed,total tumor resection and concomitant C1-C2 fusion were achieved.The average follow-up was 35.3±6.9 mo(range,26-49 mo).A statistically significant difference was noted between the preoperative JOA score(11.2±1.1)and the score at the last final follow-up(15.6±1.0)(P<0.05).A statistically significant difference was noted between the preoperative Nurick grade(2.3±0.9)and that at the last follow-up(1.2±0.4)(P<0.05).However,no statistically significant difference was noted between the preoperative and last follow-up C1-2 Cobb angle and C2-7 Cobb angle(P>0.05).No mortalities,severe complications or tumor recurrence were observed during the follow-up period.CONCLUSION Total resection of atlantoaxial IDEM tumors is feasible and effective via a posterior approach.Surgical reconstruction should be considered to avoid iatrogenic kyphosis and improve spinal stability and overall clinical outcomes.
