Abstract:BACKGROUND:Neural stem cells located in the ventricular zone and subventricular zone are crucial for cortical neurodevelopment and the treatment of neurodegenerative diseases.However,their precise regulatory mechanisms remain incompletely understood.miRNA-9 is one of the most abundantly expressed miRNAs in the vertebrate embryonic and adult brain,playing diverse roles during development.Yet,the function of miRNA-9 in neural stem cell differentiation remains unclear. OBJECTIVE:To investigate the role of miRNA-9 in regulating the differentiation of neural stem cells in the ventricular zone and subventricular zone. METHODS:Neural stem cells were isolated from the ventricular zone and subventricular zone of embryonic day 14.5 ICR mice and cultured in proliferation medium for 3-4 days to form neurospheres.The stemness of these cells was confirmed by Pax6/Nestin immunofluorescence staining.The expression profile of miRNA-9 was assessed using qRT-PCR in forebrain tissues at different developmental stages(embryonic days 12.5,14.5,16.5,18.5,postnatal days 0,and 7)as well as in in vitro cultured neural stem cells at embryonic day 14.5.Neural stem cells were transfected with either a miRNA-9 inhibitor or mimic using a transfection reagent.After 24 hours of transfection,cells were induced to differentiate for 3-4 days(for neurons)or 6-8 days(for glial cells).The differentiation ratios of neuronal and glial lineages were quantified via immunofluorescence staining for Tuj1(a neuronal marker),myelin basic protein(an oligodendrocyte marker),and glial fibrillary acidic protein(an astrocyte marker). RESULTS AND CONCLUSION:qRT-PCR results revealed that miRNA-9 was highly expressed during early embryonic stages(embryonic days 12.5-14.5),with its expression gradually decreasing as development progressed(embryonic day 16.5 to postnatal day 7).The expression level of miRNA-9 in neural stem cells at embryonic day 14.5 was approximately 90%of the expression level of the internal reference RNU6B.Functional experiments demonstrated that compared with the control group,the proportion of Tuj1-positive neurons and myelin basic protein-positive oligodendrocytes decreased in the miRNA-9 inhibition group,while the proportion of glial fibrillary acidic protein-positive astrocytes increased.Conversely,the proportion of Tuj1-positive neurons and myelin basic protein-positive oligodendrocytes increased in the miRNA-9 overexpression group,while the proportion of glial fibrillary acidic protein-positive astrocytes decreased.All differences were significant(P<0.001).Results indicate that miRNA-9 plays a bidirectional regulatory role in neural stem cell differentiation:(1)It participates in the temporal regulation of neurogenesis through a developmental-stage-specific expression pattern(high expression early,downregulation later);(2)It maintains a balance in tri-lineage differentiation by promoting neural stem cell differentiation into neurons and oligodendrocytes while inhibiting astrocyte formation.

Abstract:BACKGROUND:Elderly patients with intertrochanteric fractures often have multiple medical comorbidities and significant osteoporosis,posing considerable challenges for treatment.Proximal femoral nail anti-rotation and InterTAN are both commonly used intramedullary fixation systems.However,there remains insufficient evidence regarding the optimal selection of fixation systems for patients with different medical conditions and fracture types. OBJECTIVE:To compare the clinical outcomes and complication differences between integrated compression screw and lag screw intertrochanteric nail(InterTAN)and proximal femoral nail anti-rotation in the treatment of elderly patients with intertrochanteric fractures. METHODS:A prospective randomized controlled trial was conducted.A total of 118 elderly patients with intertrochanteric fractures who met the inclusion criteria were enrolled.Patients were randomly divided into groups.The proximal femoral nail anti-rotation group(59 cases)underwent internal fixation with proximal femoral nail anti-rotation,and the InterTAN group(59 cases)underwent internal fixation with InterTAN.Perioperative parameters,including operation time,intraoperative blood loss,fluoroscopy frequency,and hospital stay,were recorded.Follow-up assessments were conducted at 1,3,6,and 12 months postoperatively.The fracture healing rate,internal fixation stability,and complications were evaluated using Harris hip scores and imaging examinations. RESULTS AND CONCLUSION:(1)Operation time,intraoperative blood loss,and fluoroscopy frequency in the proximal femoral nail anti-rotation group were significantly lower than those in the InterTAN group(P<0.001).No significant difference was found in hospital stay(P>0.05).(2)The fracture healing rates were similar between the two groups at 12-month follow-up(P>0.05).At 12 months,the incidence of instability was significantly lower in the InterTAN group(P<0.05).Harris scores in terms of pain,function,and joint mobility in the InterTAN group were significantly superior to those in the proximal femoral nail anti-rotation group(P<0.05).There was no significant difference in overall complication rates between the two groups(P>0.05).(3)These results indicate that proximal femoral nail anti-rotation has certain advantages in reducing perioperative trauma,whereas InterTAN demonstrates greater potential value in terms of fixation stability and functional recovery at the 1-year follow-up.Clinical selection of internal fixation systems should be based comprehensively on the patient's condition and fracture type.

Abstract:BACKGROUND:The oblique pulling manipulation has good therapeutic effects on cervical spondylosis,but its biomechanical mechanism of action on intervertebral discs with different degrees of degeneration is not clear. OBJECTIVE:To explore the biomechanical mechanism of the oblique pulling manipulation on the discs with different degrees of degeneration through three-dimensional finite element model. METHODS:The motion capture system was used to measure the kinematic parameters of the key steps during the oblique pulling manipulation,and a three-dimensional finite element model of the whole cervical spine of the C5/6 mildly,moderately,and severely degenerated intervertebral discs was established.The kinematic parameters were converted into moments and loaded onto the whole cervical spine of the mildly,moderately,and severely degenerated intervertebral discs in a step-by-step manner,so as to obtain the biomechanical parameters of the stress-strain of each structure during the simulated oblique pulling manipulation. RESULTS AND CONCLUSION:(1)In the simulation of the oblique pulling manipulation to the right side,with the increase of disc degeneration,the Von-Mise stress of the annulus fibrosus gradually increased,and the stress was concentrated on the right outer side of the annulus fibrosus.The stress of the nucleus pulposus decreased and the stress was concentrated at the junction of the nucleus pulposus and the annulus fibrosus.The overall displacement of the intervertebral disc decreased;the stress of the left facet joints decreased;the Von-Mise stress of the spinal cord increased,and the stress of the spinal cord was concentrated in the upper cervical spine.(2)In the simulation of the oblique pulling manipulation to the right side,with the increase of disc degeneration,the overall strain of the C5/6 segment disc,the pressure inside the nucleus pulposus,and the stress of the left nerve root decreased;the disc shear force increased;the relative distance between the left nerve root and the disc increased,and the relative distance between the right nerve root and the disc did not change significantly.(3)These results indicate that the cervical oblique-pulling manipulation improves biomechanical imbalances in mild-to-moderately degenerated intervertebral discs by modulating facet joint stress and increasing the distance between nerve roots and intervertebral discs.However,its application in severely degenerated discs requires caution due to a sharp rise in annulus fibrosus stress and potential spinal cord compression risks.

Abstract:BACKGROUND:The elastic modulus of β-tricalcium phosphate bioceramic rods is close to that of normal bone tissue,and it exhibits excellent biocompatibility and mechanical properties.It can be used as a supporting material inside the femoral head after core decompression.However,there are few biomechanical studies on osteonecrosis of the femoral head and the changes in stress and displacement of the femoral head after ceramic rod implantation. OBJECTIVE:To explore the biomechanical effects of core decompression with ceramic rod implantation in the treatment of osteonecrosis of the femoral head during the peri-collapse stage. METHODS:A total of 21 hips were selected from 19 patients with osteonecrosis of the femoral head implanted with ceramic rods at the peri-collapse stage.Preoperative and postoperative imaging data were obtained,and relevant CT images were loaded in Mimics 21.0 software to construct a three-dimensional model of the femoral head.A global model of the proximal femur that includes cortical and cancellous bone,as well as a model of the proximal cancellous bone of the femur were created.The preoperative MRI image data of the patients were imported,and the necrotic lesion model was made by using the graphic matching technology,which was saved in.stl format.They were transferred to Geomagic 2012 software for smooth and precise surfacing processing.The ceramic rod was designed and modeled in SolidWorks 2021 software,and the relevant models were imported for assembly and Boolean operation.After ensuring that the interference check was correct,the stress and displacement of the weight-bearing area and necrotic area of the femoral head during the one-legged standing and walking post-pedal stages were calculated and observed by the ANSYS 2021 software. RESULTS AND CONCLUSION:(1)The area of maximum stress on the femoral head was located above the anterolateral aspect of the necrotic part,and the stress values of the postoperative weight-bearing area and necrotic area were significantly lower than those before operation when standing on one foot(P<0.05).The risk of femoral head collapse was lower than that before operation(P<0.05).(2)In the postoperative pedaling stage,with the increase of the load,the stress values and collapse risk of the postoperative weight-bearing area and necrosis area increased,but they were still lower than those before the operation(P<0.05).(3)Medullary core decompression combined with ceramic rod implantation can help to reduce the load on the weight-bearing area of the femoral head surface,so that the stress in the weight-bearing area can be effectively dispersed,and the load part is transferred to the direction of the femoral moment,which can improve the local stress concentration state and effectively support the femoral head to prevent further collapse.

Abstract:BACKGROUND:Current studies suggest that acetabular coverage may be a risk factor for idiopathic osteonecrosis of the femoral head;however,there is a lack of comparative studies on acetabular coverage among different subtypes of osteonecrosis of the femoral head. OBJECTIVE:To investigate the association between acetabular coverage and the onset of idiopathic osteonecrosis of the femoral head. METHODS:Fifty-four patients(87 hips)with idiopathic osteonecrosis of the femoral head who were admitted to the Wangjing Hospital of the China Academy of Chinese Medical Sciences between January 2018 and June 2024 and a matched group of 162 patients(261 hips)were enrolled,including patients with steroid-induced osteonecrosis of the femoral head,alcohol-induced osteonecrosis of the femoral head,and patients without obvious hip joint disease.Four acetabular morphological parameters were measured on anteroposterior pelvic radiographs using standardized imaging methods:center-edge angle,Sharp angle,acetabular depth ratio,and acetabular head index. RESULTS AND CONCLUSION:(1)The central-edge angle in the idiopathic osteonecrosis of the femoral head group was significantly smaller than that in the matched group[(27.4±4.5)° vs.(32.4±5.7)°],and the Sharp angle in the idiopathic osteonecrosis of the femoral head group was significantly larger than that in the matched group[(40.2±3.5)° vs.(38.7±2.9)°].The acetabular depth ratio(276.4±33.3 vs.319.3±31.6)and acetabular head index(82.4±5.1 vs.85.4±4.2)in the idiopathic osteonecrosis of the femoral head group were significantly smaller than those in the matched group(all P<0.001).(2)Compared with the steroid-induced osteonecrosis of the femoral head subgroup,the idiopathic osteonecrosis of the femoral head group had a smaller central-edge angle[(27.4±4.5)° vs.(33.0±5.2)°]and a larger Sharp angle[(40.2±3.5)° vs.(38.7±3.1)°],lower acetabular depth ratio and acetabular head index(all P<0.05).(3)Compared with the alcoholic osteonecrosis of the femoral head subgroup,the idiopathic osteonecrosis of the femoral head subgroup also showed a smaller center-edge angle[(27.4±4.5)° vs.(32.7±5.4)°],a larger Sharp angle[(40.2±3.5)° vs.(38.7±3.0)°],and a lower acetabular depth ratio and acetabular head index(all P<0.05).These results suggest that patients with idiopathic osteonecrosis of the femoral head have characteristic acetabular undercoverage,manifested by a reduced center-edge angle,increased Sharp angle,decreased acetabular depth ratio,and acetabular head index.This anatomical feature may serve as a potential risk factor for idiopathic osteonecrosis of the femoral head and aid in differentiating it from other subtypes of osteonecrosis of the femoral head.It is recommended to focus on acetabular morphology in clinical evaluations to optimize early screening and individualized intervention strategies.

Abstract:BACKGROUND:The T cell immunosuppressive activity of mesenchymal stromal cells offers new hope for the treatment of autoimmune diseases.Amimatoside injection,a drug of human umbilical cord mesenchymal stromal cells,has been approved for the treatment of acute graft-versus-host disease(GVHD)primarily affecting the digestive tract,after steroid therapy failure,in patients aged 14 years and older.Therefore,further exploration of the T cell immunosuppressive potential of mesenchymal stromal cells could lay the foundation for the treatment of autoimmune diseases. OBJECTIVE:To investigate the impact of programmed cell death ligand 1 gene overexpression on the inhibition of CD4+T cell proliferation by human umbilical cord mesenchymal stromal cells. METHODS:(1)Human umbilical cord mesenchymal stromal cells were cultured in vitro to passages 0,1,2,and 3,and the percentage of programmed death ligand 1-positive cells was detected by flow cytometry.(2)Human umbilical cord mesenchymal stromal cells were divided into an experimental group and a negative control group.The experimental group was modified with lentivirus-mediated programmed death ligand 1 gene,while the negative control group was transfected with blank plasmid vector lentivirus.The transfection efficiency was detected by flow cytometry,real-time fluorescence quantitative PCR,and western blot assay.(3)CD4+T cells were enriched with magnetic beads from the peripheral blood of healthy subjects.T cells were labeled with carboxyfluorescein diacetate succinimidyl ester and co-cultured with human umbilical cord mesenchymal stromal cells from the experimental and negative control groups at a ratio of 5:1.The proportion of CD4+T cells attenuated by carboxyfluorescein diacetate succinimidyl ester was measured by flow cytometry.(4)RNA sequencing was performed on human umbilical cord mesenchymal stromal cells from the experimental and negative control groups.Single-cell RNA sequencing was also performed on human umbilical cord mesenchymal stromal cells from the experimental group.Subpopulations were then grouped according to function.Bioinformatics analysis methods were used to depict heat maps of marker genes,enriched signaling pathways,and gene regulatory networks for each subpopulation. RESULTS AND CONCLUSION:(1)With the increase in passage number,the percentage of programmed death ligand 1-positive cells in human umbilical cord mesenchymal stromal cells gradually decreased.(2)Human umbilical cord mesenchymal stromal cells stably overexpressing programmed death ligand 1 were successfully constructed,and the expression of programmed death ligand 1 in the experimental group was significantly increased.(3)Transcriptome sequencing data suggested that human umbilical cord mesenchymal stromal cells overexpressing programmed death ligand 1 could promote the upregulation of genes related to immune effector regulatory pathways.(4)Co-culture of CD4+T cells with human umbilical cord mesenchymal stromal cells showed a significant downregulation of the proportion of CD4+T cells in the experimental group.(5)Based on single-cell RNA sequencing results,human umbilical cord mesenchymal stromal cells overexpressing programmed death ligand 1 could be divided into three functional subpopulations,which were heterogeneous.The expression level of programmed death ligand 1 gene was higher in subpopulation 1,and the significantly high expression of histone methyltransferase SETDB1 may be closely related to the enhanced immunosuppressive function of T cells.These results demonstrate that overexpression of the programmed death ligand 1 gene significantly enhances the T cell immunosuppressive capacity of human umbilical cord mesenchymal stromal cells.Single-cell RNA sequencing allows for the effective stratification of human umbilical cord mesenchymal stromal cells based on their functional properties,providing theoretical support for improving the clinical efficacy of human umbilical cord mesenchymal stromal cell therapy.

Abstract:BACKGROUND:Collagen triple helix repeat-containing protein 1 is a positive regulator of bone formation.However,its role and underlying mechanisms in periodontal ligament stem cells remain unclear. OBJECTIVE:To investigate the effects of collagen triple helix repeat-containing protein 1 on the proliferation and osteogenic differentiation of periodontal ligament stem cells and its mechanism of action. METHODS:Human periodontal ligament stem cells were isolated and cultured in vitro,and the cells were transfected with a overexpressed collagen triple helix repeat-containing protein 1 lentiviral vector.The effect of overexpression of collagen triple helix repeat-containing protein 1 on the proliferation activity of periodontal ligament stem cells was determined by CCK-8 assay and flow cytometry.The effect of overexpression of collagen triple helix repeat-containing protein 1 on the osteogenic differentiation of periodontal ligament stem cells was determined by alkaline phosphatase activity and Alizarin red staining.Western blot assay was used to determine the expression of extracellular regulated protein kinase 1/2 and phosphorylated extracellular regulated protein kinase 1/2 after overexpression of collagen triple helix repeat-containing protein 1.Western blot assay and qRT-PCR were used to determine the effect of overexpression of collagen triple helix repeat-containing protein 1 on the expression of osteogenic differentiation-related factors Runt-related transcription factor 2,osteocalcin,and Osterix in periodontal ligament stem cells after blocking the extracellular regulated protein kinase 1/2 signaling pathway. RESULTS AND CONCLUSION:(1)CCK-8 assay and flow cytometry results showed that overexpression of collagen triple helix repeat-containing protein 1 promoted the proliferation of periodontal ligament stem cells.(2)Alkaline phosphatase activity and Alizarin red staining showed that overexpression of collagen triple helix repeat-containing protein 1 promoted the osteogenic differentiation of periodontal ligament stem cells.(3)Western blot assay results showed that overexpression of collagen triple helix repeat-containing protein 1 activated the extracellular regulated protein kinase 1/2 signaling pathway.(4)Western blot assay and qRT-PCR results showed that overexpression of collagen triple helix repeat-containing protein 1 promoted the expression of Runt-related transcription factor 2,osteocalcin,and Osterix protein and mRNA.When the extracellular regulated protein kinase signaling pathway-specific inhibitor PD98059 was used to inhibit signaling pathway activation,the upregulation of osteogenic-related factors was suppressed to a certain extent.These results suggest that overexpression of collagen triple helix repeat-containing protein 1 can promote the proliferation and osteogenic differentiation of periodontal ligament stem cells,and its osteogenic differentiation-promoting effect may be related to the activation of the extracellular regulated protein kinase 1/2 signaling pathway.

Abstract:BACKGROUND:Clinically,the unique anatomical characteristics and internal trabecular distribution of the scaphoid bone often result in poor fracture treatment outcomes,often leading to nonunion and avascular necrosis of the fracture,which in turn causes wrist arthritis and functional loss. OBJECTIVE:To analyze the internal microstructural characteristics of scaphoid bone specimens using Micro CT technology and measure the microstructural parameters of trabeculae in each region to identify regional differences in scaphoid trabeculae and provide a scientific basis for the prevention,treatment,and fracture mechanism research of scaphoid fractures. METHODS:Bilateral scaphoid bones from five adult cadaveric specimens(10 cases)were scanned with Micro CT.Trabeculae within three regions of interest(tuberosity,waist,and body)were selected and reconstructed to examine the microscopic morphology of the scaphoid bone in detail.The differences in trabecular microstructural parameters were measured and compared within each region. RESULTS AND CONCLUSION:(1)Micro CT images showed that the cortical bone on the surface of the scaphoid bone was relatively thin,while the interior was filled with complex trabecular microstructures.The lamellar trabeculae near the cortical bone were relatively dense,extending into rod-shaped trabeculae inward.Observations from sagittal,coronal,and transverse planes showed that the trabeculae were sparsely distributed in the waist,while they were densely distributed in the body and tuberosity.(2)The bone volume,bone surface,bone surface/total volume,trabecular separation,trabecular number,connectivity,connection density,fractal dimension,bone mineral density,and bone mineral content of the scaphoid bone were significantly different between the left and right sides(P<0.05).There were no significant differences in the trabecular microstructural parameters of the waist and body between the left and right sides(P>0.05).(3)The bone volume,bone volume fraction,bone surface,bone surface/total tissue volume,bone surface/total bone volume,bone mineral density,and bone mineral content of the scaphoid bone were significantly different between the body and the tuberosity,as well as the waist(P<0.05);the trabecular thickness of the scaphoid bone was significantly different between the body and the tuberosity,as well as the waist(P<0.05);the trabecular separation and fractal dimension of the scaphoid bone were significantly different between the body and the tuberosity,as well as the waist,and between the tuberosity and the waist(P<0.05).The trabecular number,connectivity,and connection density of the scaphoid bone were significantly different between the waist and the tuberosity,as well as the body(P<0.05).There were no significant differences in the tissue volume and anisotropy of the scaphoid bone between the body,tuberosity,and waist(P>0.05).(4)The results showed that there were regional differences in the values of trabecular microstructural parameters of the scaphoid bone.The lumbar region had lower bone density and strength and was the most prone to fracture.This finding provides a theoretical basis for understanding the mechanism of scaphoid fracture from the perspective of trabecular microstructure.Furthermore,the trabecular structural characteristics of different parts of the scaphoid bone revealed in this study also provide a theoretical basis for the design of targeted internal fixation devices.

Abstract:BACKGROUND:Currently,most studies on rigid post-traumatic thoracolumbar kyphosis focus on overall sagittal balance and surgical intervention,while the effect of the disease duration on the change of lumbar compensatory curvature and degeneration is still unclear. OBJECTIVE:To explore the effect of the disease duration on lumbar degeneration and the potential mechanism of rigid post-traumatic thoracolumbar kyphosis in patients with rigid post-traumatic thoracolumbar kyphosis,and provide a basis for optimizing treatment strategies. METHODS:Clinical and imaging data from 79 rigid post-traumatic thoracolumbar kyphosis patients were retrospectively analyzed.The patients were divided into two groups according to the disease duration:Patients with a disease duration of≤5 years were categorized as group A(n=40),and those with>5 years as group B(n=39).X-ray images were used to measure the local kyphosis angle of the injured vertebra,the height of the posterior walls of the injured vertebra and adjacent vertebrae,lumbar lordosis,the intervertebral space angle for each lumbar segment,and sacral slope.The Weishaupt-CT classification system was employed to assess lumbar facet joint degeneration.Pfirrmann-MRI grading system was applied to evaluate disc degeneration.The visual analog scale for back pain,Oswestry Disability Index,SRS-22 and American Spinal Injury Association spinal injury grading were compared between the groups.The impact of disease duration on clinical symptoms and imaging characteristics of patients with rigid post-traumatic thoracolumbar kyphosis was analyzed. RESULTS AND CONCLUSION:(1)There were no significant differences in age,gender,visual analog scale scores,fracture location,fracture type,or American Spinal Injury Association grading between the two groups(P>0.05).Group A had a significantly higher SRS-22 score than group B(P<0.05);Group B had a significantly higher Oswestry Disability Index score than group A(P<0.05).(2)Group B had a substantially greater kyphosis angle of the injured vertebra,lumbar lordosis,and L4/5 intervertebral space angle than group A(P<0.05).(3)There were no significant differences between groups A and B in the L1/2,L2/3,L3/4,or L5/S1 intervertebral space angles or sacral slope(P>0.05).(4)Group B showed significantly greater facet joint degeneration at the L3/4,L4/5,and L5/S1 segments and significantly greater disc degeneration at the L2/3,L3/4,L4/5,and L5/S1 segments compared with group A(both P<0.05).(5)Pearson correlation analysis indicated a positive correlation between disease duration and both the local kyphosis angle of the injured vertebra and lumbar lordosis in group B(r=0.335,0.418,P<0.05).(6)Over time,rigid post-traumatic thoracolumbar kyphosis patients experience increased lumbar lordosis and accelerated lumbar degeneration,with the L4/5 segment playing a primary role in compensatory lumbar curvature.Surgical correction should focus on adjusting the lower lumbar curvature.

Abstract:BACKGROUND:The dynamic interplay between the inflammatory microenvironment and oligodendrocytes following neural injury constitutes a central pathological feature in neurodegenerative and demyelinating diseases.Stem cell-derived exosomes,leveraging their inherent low immunogenicity,efficient barrier-penetrating capacity,and targeted delivery of diverse pro-repair factors,play a pivotal role in modulating oligodendrocyte differentiation and the inflammatory microenvironment,thereby facilitating neural repair and regeneration. OBJECTIVE:To investigate the mechanisms by which stem cell-derived exosomes regulate the inflammatory microenvironment to enhance oligodendrocyte survival,differentiation,and myelin repair.It seeks to establish a novel"cell-free therapy"paradigm,utilizing exosome-mediated multi-component synergy(miRNAs,proteins,and metabolites)and microenvironmental adaptation for treating neurological disorders. METHODS:Literature searches were conducted in the China National Knowledge Infrastructure,PubMed,and WanFang databases,covering publications from 2010 to 2025.Chinese search terms included"exosomes,stem cells,engineered,diagnosis,inflammatory microenvironment,oligodendrocytes,signaling pathways,"while English terms comprised"stem cell-derived exosomes,oligodendrocytes,inflammatory microenvironment,signaling pathway,regulatory mechanisms."Irrelevant studies were excluded,and 65 articles meeting inclusion criteria were systematically reviewed according to the inclusion and exclusion criteria. RESULTS AND CONCLUSION:(1)The biological characteristics of exosomes and their roles in the central nervous system were summarized,followed by an in-depth analysis of the inflammatory microenvironment's impact on oligodendrocytes and exosome-mediated regulatory mechanisms,including miRNA-modulated signaling pathways,anti-inflammatory factor secretion,and immune cell function regulation.(2)The regulatory mechanisms of the inflammatory microenvironment on oligodendrocyte behavior and their implications in disease pathogenesis were elucidated.(3)An engineered exosome delivery system incorporating targeted peptide modification and functional molecule loading was proposed,combined with traditional Chinese medicine-derived bioactive components to construct an innovative cell-free therapeutic strategy.(4)At the molecular level,the intricate crosstalk between exosome functional networks and myelin homeostasis was elucidated,providing a novel therapeutic direction for exosome-based targeted delivery systems in treating demyelinating neurological disorders.

Abstract:BACKGROUND:Our group developed a rat lumbar spine model inducing L6-S1 segmental degeneration by prolonged fixation in an abnormal forward-bending posture through a specific device.However,biomechanical evaluation of this model remains lacking. OBJECTIVE:To evaluate the biomechanical properties of L6-S1 motion segment in rats with abnormal forward bending posture through X-ray verification and finite element analysis. METHODS:This study utilized a previously established SD rat model of abnormal forward-flexed posture.Lateral X-ray images of three healthy female SD rats were taken in both restrained(unanesthetized)and relaxed(anesthetized)states to measure the L6-S1 disc angle and analyze its changes under different postures.Micro-CT data from one healthy female SD rat were used to reconstruct a 3D L6-S1 model with Mimics,Geomagic Wrap,and SolidWorks.The model was then meshed,assigned material properties,and subjected to forward flexion loading simulation in ANSYS Workbench to calculate stress distribution in L6-S1 disc structures. RESULTS AND CONCLUSION:(1)The mean L6-S1 intervertebral disc angle was(12.16±0.57)° in the relaxed posture and(1.26±0.26)° in the restrained posture.(2)Under a 10° forward-flexed posture,the maximum von-Mises stress in the superior endplate,inferior endplate,annulus fibrosus,and nucleus pulposus of the L6-S1 intervertebral disc was 10.398,19.928,6.819,and 0.104 MPa,respectively.The maximum von-Mises stress in the superior and inferior endplates was significantly higher than in the annulus fibrosus and nucleus pulposus.(3)These findings suggest that in the 10° flexion modeling posture of the L6-S1 intervertebral disc,the reduction of the L6-S1 intervertebral disc angle leads to significant changes in disc morphology and load distribution.The constructed finite element model successfully simulated the biomechanical environment of the L6-S1 intervertebral disc under abnormal forward-flexed posture in rats.The superior and inferior endplates bear higher equivalent stress in this posture,making them the structures most likely to undergo early degenerative changes.

Abstract:BACKGROUND:Effective analgesia after total knee arthroplasty is crucial for rehabilitation,with adductor canal block being a commonly used method.Traditional single-injection local anesthetics provides limited analgesic duration,and continuous catheter infusion exhibits complexity and high cost. OBJECTIVE:To compare the efficacy and safety of a single injection of liposomal bupivacaine versus continuous catheter infusion of ropivacaine hydrochloride for adductor canal block analgesia after total knee arthroplasty. METHODS:Eighty patients undergoing primary unilateral total knee arthroplasty at Gaoyou People's Hospital from March 2024 to February 2025 were randomly assigned to two groups:the liposomal bupivacaine group and the continuous infusion group.The liposomal bupivacaine group received a single adductor canal block injection of 133 mg(10 mL)liposomal bupivacaine mixed with 5 mL of 0.75%ropivacaine hydrochloride postoperatively.The continuous infusion group received an adductor canal block catheter placed near the saphenous nerve,connected to an analgesic pump delivering 0.25%ropivacaine hydrochloride(loading dose:10 mL;infusion rate:6 mL/h).Analgesic efficacy was assessed by comparing pain scores at various time points postoperatively,postoperative analgesia-free duration,morphine rescue consumption,and postoperative walking distance in both groups.Safety was evaluated by monitoring complications.Additionally,procedural time,cost,patient satisfaction,and hospital stay were compared between the two groups. RESULTS AND CONCLUSION:(1)Pain scores at rest and during movement showed no significant differences between liposomal bupivacaine group and continuous infusion group at 6,12,24,48,and 72 hours postoperatively(P>0.05).The postoperative analgesia-free duration was 19 hours in the liposomal bupivacaine group and 22 hours in the continuous infusion group(P>0.05).(2)Within 72 hours postoperatively,the liposomal bupivacaine group required an average of 78.6 morphine rescue treatments,while the continuous infusion group required 80.5,without significant differences(P>0.05).(3)Procedural time was significantly shorter in the liposomal bupivacaine group(6.1±1.4 min)than in the continuous infusion group(20.3±1.2 min,P<0.05).(4)No differences were observed in patient satisfaction,hospital stay,or walking ability(P>0.05).(5)One case of quadriceps paralysis occurred in the continuous infusion group at 6 hours postoperatively but resolved spontaneously without further complications.Each patient in the liposomal bupivacaine group saved 132 RMB in analgesia-related costs.(6)It is concluded that within 72 hours after total knee arthroplasty,single-injection liposomal bupivacaine provided comparable analgesia to continuous ropivacaine infusion in terms of pain scores,postoperative analgesia-free duration,and morphine rescue requirements.Hospital stay,patient satisfaction,and functional recovery were similar.However,single-injection liposomal bupivacaine adductor canal block is more convenient,saves time,and reduces costs.

Abstract:BACKGROUND:Myelination deficits are a core feature of white matter injury in preterm infants.In recent years,human umbilical cord mesenchymal stem cells have been applied in various animal models of brain injury,demonstrating the capacity to promote myelin repair.Elucidating the regulatory mechanisms by which human umbilical cord mesenchymal stem cells enhance neural myelination will contribute to optimizing therapeutic strategies and facilitating clinical translation. OBJECTIVE:To clarify the reparative effect of human umbilical cord mesenchymal stem cells on myelination disorders caused by maturation arrest of the oligodendrocyte lineage in neonatal rats with white matter injury. METHODS:Seventy-two two-day-old Sprague-Dawley rats were randomly divided into a sham-operated group,a white matter injury group,and a human umbilical cord mesenchymal stem cell transplantation group,with twenty-four rats in each group.A neonatal rat white matter injury model was established by a combination of low-dose lipopolysaccharide and hypoxia-ischemia.Fourteen days after modeling,hematoxylin-eosin staining was used to observe pathological changes in white matter.Immunohistochemistry,western blotting,and real-time quantitative polymerase chain reaction were used to detect the positive expression,protein expression,and mRNA expression levels of oligodendrocyte transcription factor 2,glial antigen 2,and myelin basic protein.Twenty-eight days after modeling,Luxol fast blue staining was performed to observe myelin formation,and the Morris water maze test was used to evaluate spatial learning and memory ability. RESULTS AND CONCLUSION:(1)Fourteen days after modeling,hematoxylin-eosin staining showed that a large number of cells in the white matter injury group were degenerated and necrotic,and the arrangement of nerve fibers was disordered;while the cell morphology in the human umbilical cord mesenchymal stem cell transplantation group was close to normal,and the nerve fibers were arranged more neatly.(2)On day 14 after modeling,there was no statistically significant difference in the positive expression,protein,and mRNA levels of oligodendrocyte transcription factor 2 among the groups(P>0.05).Compared with the sham-operated group,the positive expression,protein,and mRNA levels of glial antigen 2 in the white matter injury group were upregulated(P<0.05),while the positive expression,protein,and mRNA levels of myelin basic protein were downregulated(P<0.05).Compared with the white matter injury group,the positive expression,protein,and mRNA levels of glial antigen 2 in the human umbilical cord mesenchymal stem cell transplantation group were downregulated(P<0.05),while the positive expression,protein,and mRNA levels of myelin basic protein were upregulated(P<0.05).(3)On day 28 after modeling,Luxol fast blue staining results showed that compared with the sham-operated group,the white matter injury group had decreased myelin expression(P<0.05).Compared with the white matter injury group,the human umbilical cord mesenchymal stem cell transplantation group had increased myelin expression(P<0.05).(4)On day 28 after modeling,Morris water maze results showed that compared with the sham-operated group,the white matter injury group had prolonged escape latency and decreased platform crossing times(P<0.05).Compared with the white matter injury group,the human umbilical cord mesenchymal stem cell transplantation group had shortened escape latency and increased platform crossing times(P<0.05).There was no statistical difference in average swimming distance between the groups(P>0.05).These results suggest that human umbilical cord mesenchymal stem cells can promote the maturation of oligodendrocytes in neonatal rats with white matter injury,repair myelination disorders,and improve cognitive function.

Abstract:BACKGROUND:Pulmonary fibrosis is a chronic progressive lung disease characterized by abnormal deposition of extracellular matrix,with current therapeutic options remaining limited.Extracellular vesicles derived from mesenchymal stem cells,with their lipid membrane structure,can cross the internal barriers in the body and directly deliver various anti-fibrotic,immunomodulatory factors(such as growth factors,immunomodulatory cytokines,and chemokines),lipids and nucleic acids(mRNAs and miRNAs)and other bioactive substances to target cells in the lungs. OBJECTIVE:To systematically review the core mechanisms of mesenchymal stem cell extracellular vesicles in the treatment of pulmonary fibrosis,summarize and elaborate on how extracellular vesicles directly deliver the bioactive substances they carry to different target cells in the lungs,demonstrating their unique advantages in regulating the pulmonary fibrosis microenvironment,providing a theoretical basis for the future use of mesenchymal stem cell extracellular vesicles in the treatment of pulmonary fibrosis diseases. METHODS:China National Knowledge Infrastructure,PubMed,clinicaltrials.gov,and the Chinese Clinical Trial Registry were searched.English search terms were"mesenchymal stem cells,extracellular vesicles,pulmonary fibrosis,alveolar epithelium,microvascular endothelium,macrophages,neutrophils."A total of 56 articles were finally included for the summary. RESULTS AND CONCLUSION:In alveolar epithelial cells,the process of epithelial-mesenchymal transition is inhibited by regulating signaling pathways such as protein kinase B/glycogen synthase kinase 3β and transforming growth factor β/Smad.The pro-fibrotic signaling network can be blocked by specific miRNAs(such as miR-466f-3p and let-7).In fibroblasts and endothelial cells,miR-21-5p and miR-218/miR-214-3p are used to intervene in the activation of fibroblasts and endothelial-mesenchymal transition,respectively.From a macroscopic perspective,monocytes are reprogrammed,macrophage polarization is regulated,dendritic cell maturation is inhibited,and the Th17/Treg response is balanced,reshaping the immune microenvironment.Furthermore,mesenchymal stem cell extracellular vesicles modified through engineering approaches(targeted peptide modification and drug co-loading)can also enhance the precise targeting of multiple cell subtypes in the lesion area.However,vesicle heterogeneity,large-scale preparation standards,and in vivo dynamic tracing techniques remain key bottlenecks for clinical translation.Future research should integrate single-cell sequencing and spatial multi-omics technologies to deeply explore the underlying mechanisms of mesenchymal stem cell-derived extracellular vesicles in regulating cellular networks and develop novel clinical treatment strategies for pulmonary fibrosis targeting cells.

Abstract:BACKGROUND:Cell transplantation is one of the effective approaches for repairing spinal cord injury.Our research team previously found that transplanted cerebrospinal fluid-contacting neurons can survive and promote motor function recovery in mice with spinal cord injury.However,whether these transplanted cerebrospinal fluid-contacting neurons differentiate into functional neurons and thereby facilitate motor function recovery remains unclear. OBJECTIVE:To investigate whether transplanted cerebrospinal fluid-contacting neurons differentiate into functional neurons in vivo and contribute to motor function recovery after spinal cord injury. METHODS:Primary cells containing cerebrospinal fluid-contacting neurons were isolated from the cervical spinal cord of C57BL/6 mice within 24 hours after birth and cultured in adherent conditions.The cells were transduced with a lentivirus carrying a multimodal imaging fusion gene and selected with puromycin to purify cerebrospinal fluid-contacting neurons.Differentiation was induced using serum-containing medium.Immunofluorescence staining was performed to detect the expression of neuronal marker NeuN and motor neuron marker ChAT after differentiation.Thirty C57BL/6 mice were randomly divided into three groups.The T10 segment spinal cord injury model was established in the transplantation group and PBS group by clamping method,and the sham operation group only opened the lamina.One week after spinal cord injury,the transplantation group received cell transplantation,and the PBS group was injected with an equivalent volume of PBS.At weeks 1,4,and 8 post-transplantation,spinal cord tissues were collected for immunofluorescence to assess ChAT expression.At week 8,the expression of synaptic marker SYN,inhibitory neurotransmitter marker GAD65/67,and excitatory neurotransmitter marker vGLUT1 was further evaluated.Hematoxylin and eosin staining was used to observe spinal cord morphology.Motor function recovery was assessed using Basso Mouse Scale scoring and footprint analysis. RESULTS AND CONCLUSION:(1)Cerebrospinal fluid-contacting neurons exhibited neural stem cell characteristics in vitro and could differentiate into motor neurons.(2)Transplanted cerebrospinal fluid-contacting neurons survived long-term and differentiated into motor neurons in vivo.(3)The proportion of cerebrospinal fluid-contacting neurons differentiating into motor neurons reached the highest level at 8 weeks post-transplantation(P<0.000 1).(4)At 8 weeks post-transplantation,cerebrospinal fluid-contacting neurons co-expressed SYN,GAD65/67,and vGLUT1,indicating synaptic formation between transplanted cerebrospinal fluid-contacting neurons and host neurons.(5)The Basso Mouse Scale scores of the PBS group remained significantly lower than those of the transplantation group(P<0.001).Transplanted mice exhibited more coordinated gait patterns with only minor toe dragging,whereas PBS-treated mice displayed severe hindlimb dragging.(6)Hematoxylin and eosin staining revealed large cavitation areas in the injury site of PBS-treated mice,whereas the cavitation area was significantly reduced in the transplantation group.These findings confirm that transplanted cerebrospinal fluid-contacting neurons can differentiate into motor neurons both in vitro and in vivo,establish synaptic connections,and ultimately improve motor function in spinal cord injury mice.

Abstract:BACKGROUND:Recently,percutaneous minimally invasive pedicle screw fixation systems have become a popular treatment option for thoracolumbar fractures due to ongoing innovation in orthopedic internal fixation devices.Currently,while many studies compare the effectiveness of open pedicle screw fixation through or across the fractured vertebra,fewer studies compare these two methods when using navigation-assisted percutaneous minimally invasive techniques. OBJECTIVE:To compare the clinical efficacy of percutaneous minimally invasive pedicle screw fixation in the treatment of thoracolumbar fracture through and across the injured vertebra. METHODS:A retrospective analysis was performed on 67 patients with single level thoracolumbar fracture without spinal cord nerve injury who were treated in the Department of Spine Surgery,Affiliated Hospital of Yan'an University from October 2021 to June 2023.All of them were treated with percutaneous pedicle screw fixation with the assistance of computer navigation,and were followed up to 6 months after surgery.The injured vertebrae were divided into transinjured vertebrae group(n=35)and cross-injured vertebrae group(n=32)according to whether or not the injured vertebrae were nailed.The general data,perioperative data,anterior vertebral height ratio,Cobb angle,visual analog scale score and Oswestry disability index of injured vertebra were compared before and after treatment between the two groups.Clinical efficacy of minimally invasive percutaneous transvertebral fixation and transvertebral fixation in thoracolumbar fracture patients without spinal cord nerve injury was compared. RESULTS AND CONCLUSION:(1)There was no significant difference in preoperative general data between the two groups(P>0.05),indicating comparability.(2)Intra-group comparison:anterior vertebral height ratio,Cobb angle,visual analog scale score and Oswestry disability index score of the injured vertebra were significantly improved 7 days and 6 months after surgery in both groups(P<0.05).(3)Comparison between groups:The operative time,intraoperative blood loss,incision length,and intraoperative fluoroscopy times in the transinjured vertebrae group were significantly lower than those in the cross-injured vertebrae group,respectively;the differences were statistically significant(P<0.05).However,there was no significant difference in hospitalization days between the two groups(P>0.05).There was no significant difference in anterior vertebral height ratio,Cobb angle,visual analog scale score and Oswestry disability index score between the two groups at 7 days and 6 months after surgery(P>0.05).(4)It is suggested that for patients with single level thoracolumbar fracture without spinal cord nerve injury,minimally invasive percutaneous pedicle screws across injured vertebrae have the advantages of shorter intraoperative time,less bleeding,smaller surgical incision,and low number of fluoroscopies than transinjured vertebrae.In short-and medium-term follow-up,both percutaneous minimally invasive transvertebral fixation and transvertebral fixation can effectively restore and maintain the height of the injured vertebra,correct kyphotic deformity,restore spinal stability and reduce pain,and obtain excellent clinical results.Less invasive transvertebral percutaneous fixation is recommended for patients with thoracolumbar fracture of AO type A with normal body mass index and no spinal nerve injury or posterior ligament complex injury.

Abstract:BACKGROUND:Surgical decision-making for posterior cruciate ligament avulsion fractures is highly dependent on imaging evaluation.Traditional methods rely on subjective interpretation of CT images,which suffer from limitations such as difficulties in quantifying three-dimensional spatial displacement parameters and insufficient precision in assessing rotational angles.Given the advancements in artificial intelligence(AI)technology,there is a need to develop automated,intelligent image recognition software based on AI algorithms. OBJECTIVE:To investigate the intelligent diagnostic capabilities of AI algorithms for posterior cruciate ligament tibial avulsion fractures in 3D CT images and their effectiveness in accurately assessing 3D parameters of fracture fragments. METHODS:Knee CT data from 24 patients with posterior cruciate ligament tibial avulsion fractures who were treated at the Wangjing Hospital of the China Academy of Chinese Medical Sciences between December 1,2022,and August 30,2024,were retrospectively collected.Three-dimensional reconstruction,intelligent fracture point recognition,and simulated reduction were performed using self-developed AI image recognition software.Translational and rotational parameters of the fracture fragments along the X,Y,and Z axes were obtained.The results were compared with those obtained using picture archiving and communication system(PACS system).The consistency of the two methods was assessed using the rank sum test,Bland-Altman analysis,and linear regression model.The coefficient of variation was calculated to assess software stability. RESULTS AND CONCLUSION:(1)No statistically significant differences were observed in fracture fragment displacement(translation/rotation along X/Y/Z axes)between AI and traditional methods(P>0.05).(2)Bland-Altman analysis indicated good consistency between the two methods,with no significant differences(P>0.05).(3)The R² values of the linear regression models for X,Y,and Z axis displacement and angle fitting were all>0.99.(4)The coefficient of variation of the AI software for three repeated fracture point identifications showed that the coefficient of variation was<20%for 21 imaging samples for total fracture identification and<20%for 18 imaging samples for articular surface fracture identification.(5)This indicates that the AI image recognition software can accurately quantify the three-dimensional parameters of posterior cruciate ligament avulsion fracture fragments.Its measurement results are consistent with those of traditional methods and are highly stable.It can assist physicians in determining the degree of displacement and provide accurate data support for preoperative planning.This software has promising application prospects in the treatment of avulsion fractures.Future studies should expand the sample size and validate its impact on surgical outcomes.

Abstract:BACKGROUND:High tibial osteotomy is an effective treatment for certain patients with knee osteoarthritis;however,traditional T-shaped plates have multiple limitations. OBJECTIVE:To compare the biomechanical performance of titanium alloy porous blocks with that of conventional T-shaped plates and bone grafting schemes in high tibial osteotomy using finite element analysis. METHODS:A computer simulation experiment was conducted,performing three-dimensional finite element analysis on a 55-year-old male patient who underwent high tibial osteotomy.Three different implant geometries were constructed:a conventional T-shaped plate high tibial osteotomy model(Model A),a bone graft-augmented high tibial osteotomy model(Model B),and a titanium alloy porous block-augmented high tibial osteotomy model(Model C).These models were used to evaluate the effects of each implant on total displacement and stress distribution under two loading conditions:standing and initial rising from a seated position. RESULTS AND CONCLUSION:(1)Validation results confirmed that the finite element models were effective.(2)In terms of stability,Model C(titanium alloy porous block-augmented high tibial osteotomy)demonstrated the best reduction in total displacement,with maximum displacements under both standing and rising conditions significantly lower than those of the other two models.(3)Stress analysis revealed that Model C's T-shaped plate experienced the lowest stress values:(40.9±36.5)MPa(standing)and(66.1±44.7)MPa(rising),representing reductions of 91.2%and 92.9%,respectively,compared with Model A.Additionally,Model C exhibited significantly lower mean stress at the lateral hinge region than Models A and B,indicating a reduced risk of lateral hinge fracture.Stress distribution at the proximal osteotomy contact surface and hinge region showed that Model C provided more favorable stress stimulation,which may promote bone healing while lowering hinge fracture risk.(4)It is indicated that the titanium alloy porous block not only enhances initial stability at the osteotomy site but,by optimizing stress transmission pathways and offering a biocompatible environment,also addresses shortcomings in mechanical stability and biological integration found in existing plating techniques.These findings suggest promising clinical application potential.

Abstract:BACKGROUND:Current finite element models of the wrist joint predominantly focus on osseous and ligamentous structures,with insufficient incorporation of musculotendinous components,thereby limiting their fidelity and accuracy. OBJECTIVE:To establish a high-fidelity finite element model of the wrist joint,providing a reference for in-depth biomechanical investigations. METHODS:Upper limb CT and MRI data from a 33-year-old healthy male volunteer were imported into Mimics 20.0.Threshold-based selection,region growing,and image segmentation techniques were employed to reconstruct wrist-related bones and soft tissues(including muscles).The model underwent surface optimization,patch generation,and meshing in SolidWorks 2020 and HyperMesh 14.0.Material property assignment and ligament-cartilage contact interfaces were implemented in ABAQUS 6.13 to construct a three-dimensional finite element model of the wrist joint.Stress distribution across wrist structures under axial compression was analyzed. RESULTS AND CONCLUSION:(1)A three-dimensional finite element model encompassing the ulna,radius,distal humerus,carpal bones,metacarpals,pronator teres,pronator quadratus,supinator,lateral muscle group,volar muscle group,dorsal muscle group,interosseous membrane,major ligaments,and cartilage structures was successfully established,comprising 759 191 elements and 245 510 nodes.The stress distribution pattern at the radiocarpal joint under axial compressive loading on the metacarpals was computationally analyzed and compared with cadaveric studies reported in literature,thereby validating the authenticity and effectiveness of the current model.(2)This investigation employed CT and MRI data to simulate and reconstruct comprehensive wrist joint osseous and soft tissue structures through computational methodologies.The model precisely delineates starting point and ending point of the muscle and characterizes contact interactions between forearm musculature and skeletal elements during muscle pathway simulations,ultimately resulting in a more realistic finite element model of the wrist joint.

Abstract:BACKGROUND:Diabetes wound is one of the serious complications of diabetes patients,and its complex pathological mechanism and clinical treatment dilemma is still a major challenge.In recent years,exosomes have become a new focus in the field of diabetes wound research because they play a key role in intercellular communication,immune regulation,and tissue repair. OBJECTIVE:To investigate the research hotspots and evolutionary trends of exosomes in diabetic wound healing. METHODS:A systematic search was conducted in the Web of Science core collection to identify English literature focusing on exosomes in diabetic wound healing and published between the inception of the database and December 31,2024.The annual publication volume was analyzed to track changes over time.Visual analyses using VOSviewer and CiteSpace software were performed on the retrieved literature to examine key aspects such as authors,countries,institutions,journals,and keywords,providing insights into the current research landscape and evolving hot topics in exosomes for diabetic wound healing. RESULTS AND CONCLUSION:From 2014 to 2024,a total of 424 publications on exosome-promoted diabetic wound healing were produced,contributed by 2 883 authors from 46 countries and featured in 199 journals.In the realm of exosome-promoted diabetic wound healing research,China has emerged as the leading contributor,followed closely by the United States.The journals Journal of Nanobiotechnology and Advanced Healthcare Materials have published the highest number of papers and are recognized for their significant influence in the field.Notably,author Chen Zhenbing and Huazhong University of Science and Technology stand out as the most prolific author and institution,respectively.However,the researcher clusters have yet to attain a substantial scale,indicating that future efforts are necessary to enhance team collaboration.Global research focus is primarily concentrated on ten thematic groups,including adipose-derived stem cells,diabetic wounds,diabetic wound healing,wound healing,endoplasmic reticulum stress,microbubbles,collagen,proteomics,and diabetic foot infections.The research hotspots in this field are undergoing a transition from molecular mechanisms to systemic interventions.Future research trends will center on angiogenesis,macrophages,antimicrobial agents and hydrogels.It is essential to integrate multidisciplinary technologies on this basis to achieve more effective precision treatments and optimize management strategies for diabetic wounds.