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:Age-related degeneration is closely associated with bone metabolic imbalance.In the jaw,this manifests as alveolar bone resorption,tooth loosening,and even loss.Impaired osteogenic differentiation potential of senescent jaw bone marrow mesenchymal stem cells is a critical factor hindering jaw bone regeneration.Quercetin,a natural flavonoid compound,exhibits antioxidant,anti-inflammatory,and cell differentiation-regulating properties,yet effect and mechanism of quercetin in osteogenic differentiation of senescent jaw bone marrow mesenchymal stem cells remain unclear. OBJECTIVE:To investigate the effects of quercetin on the proliferation,migration,osteogenic differentiation,and senescence of aged jaw bone marrow mesenchymal stem cells. METHODS:Jaw bone marrow mesenchymal stem cells were isolated from the mandibles of 10 8-week-old SD rats and cultured using a combination of bone marrow flushing and bone slice digestion.Jaw bone marrow mesenchymal stem cells were subcultured to the third and seventh passages,serving as the young and senescent cell groups,respectively.Quercetin was then added to the senescent cell group.The CCK-8 assay was used to assess the effects of 0.01,0.1,1,10,and 100 μmol/L quercetin solutions on the proliferation of senescent jaw bone marrow mesenchymal stem cells to identify the optimal quercetin concentration.Cell migration ability was assessed by cell scratch test.RT-qPCR and western blot assay were used to examine the expression of senescence markers.β-Galactosidase staining was used to assess the proportion of cells expressing these markers.Seven days after osteogenic induction,the expression of osteogenic-related markers was assessed by RT-qPCR and western blot assay.Alkaline phosphatase staining was performed on day 14 of osteogenic induction.Alizarin red staining was performed on day 21 of osteogenic induction.Western blot assay was used to assess the expression of phosphorylated protein kinase B,protein kinase B,phosphorylated mammalian target of rapamycin,and mammalian target of rapamycin. RESULTS AND CONCLUSION:(1)Compared with the young cell group,the proliferation ability of the senescent cell group was decreased.Compared with the senescent cell group,1 μmol/L quercetin significantly promoted the proliferation of senescent jaw bone marrow mesenchymal stem cells(P<0.01).(2)Compared with the senescent cell group,the migration ability of senescent jaw bone marrow mesenchymal stem cells was improved;the proportion of β-galactosidase-positive cells was significantly decreased,and the expression of senescence-related P16,P53,and P21 mRNA and protein was decreased in the quercetin group(P<0.05).(3)After osteogenic induction,compared with the senescent cell group,the calcium nodule formation ability,alkaline phosphatase staining area,and the mRNA and protein expressions of alkaline phosphatase,osteopontin,and Runt-related transcription factor 2 were increased in the quercetin group(P<0.05).(4)Compared with the senescent cell group,the phosphorylation levels of protein kinase B and mammalian target of rapamycin were significantly decreased in the quercetin group(P<0.05).These results suggest that quercetin inhibits multiple-passage senescence of jaw bone marrow mesenchymal stem cells and promotes osteogenic differentiation by regulating the protein kinase B/mammalian target of rapamycin signaling pathway.

Abstract:BACKGROUND:Studies showed that multiple myeloma microenvironment has the function of inducing mesenchymal stem cells to become senescent phenotype,while the effect of senescent bone marrow mesenchymal stem cells on multiple myeloma cells is rarely reported. OBJECTIVE:To investigate the effect of senescent bone marrow mesenchymal stem cells on the proliferation of multiple myeloma cells through paracrine galectin-3. METHODS:Bone marrow blood was collected from healthy donors,and bone marrow mesenchymal stem cells were extracted by Ficoll density gradient centrifugation and adherent purification.The third-generation bone marrow mesenchymal stem cells were taken and induced with 200 µmol/L hydrogen peroxide solution for 2 hours.After the treatment was completed,they were replaced with L-DMEM complete medium for 24 hours of culture to construct the senescent bone marrow mesenchymal stem cell model.β-Galactosylase staining and senescence gene P21 were used for identification.Meanwhile,the expression of galectin-3 in aging bone marrow mesenchymal stem cells was detected by RT-qPCR.The supernatant of senescent bone marrow mesenchymal stem cells was collected and the conditioned medium of senescent bone marrow mesenchymal stem cells was prepared by centrifugal concentration.After culturing the multiple myeloma cell line U266 for 24 hours with it,the proliferation of U266 cells was detected by CCK-8 assay.The apoptosis of U266 cells was detected by flow cytometry.The expression levels of BCL-2 protein and mRNA in U266 cells were detected by RT-qPCR and western blot assay.Bone marrow blood was collected from patients with multiple myeloma and healthy individuals.The level of galectin-3 was detected by ELISA. RESULTS AND CONCLUSION:(1)After hydrogen peroxide induction,the number of cells positive for β-galactosidase staining increased significantly,and P21 and galectin-3 mRNA expression levels were upregulated(P<0.01).(2)Compared with the control group,24 hours of culture of U266 cells with conditioned medium from senescent bone marrow mesenchymal stem cells increased the level of cell proliferation(P<0.05),decreased the apoptosis rate(P<0.05),and rose the expression levels of BCL-2 protein and mRNA(P<0.05).(3)Galectin-3 levels in the bone marrow of patients with multiple myeloma were significantly higher than those in healthy controls(P<0.05).These results suggest that senescent bone marrow mesenchymal stem cells may promote the proliferation of multiple myeloma cells by paracrine galectin-3,which in turn upregulates BCL-2 expression.

Abstract:BACKGROUND:Breast cancer organoids,as a novel in vitro model,can not only simulate the biological characteristics of breast cancer but also to some extent reproduce the impact of the tumor microenvironment on the tumor,facilitating research on breast cancer and further promoting precision medicine. OBJECTIVE:To review the application status of breast cancer organoids in the field of therapeutic drugs,including chemotherapy,targeted therapy,and immunotherapy,over the past few years,and to discuss the existing limitations in order to further promote their application in breast cancer treatment. METHODS:The first author conducted a search in the China National Knowledge Infrastructure(CNKI)and PubMed databases in June 2025,with the publication time of the literature ranging from January 2010 to June 2025.The Chinese and English search terms included"organoid,breast organoid,breast cancer organoid,breast cancer experimental model,precision medicine,targeted therapy,chemotherapy,immunotherapy,drug sensitivity."A total of 58 articles were included in the review. RESULTS AND CONCLUSION:(1)Compared with traditional breast cancer cell experiments that lack validation of tissue structure,cell-to-cell interactions,and in vivo microenvironments,breast cancer organoids,with their diverse origins from primary tumor cells and continuous innovation in culture systems,can simulate cell-to-cell interactions and reproduce the biological characteristics of breast cancer and its tumor microenvironment.This makes breast cancer organoids one of the most promising tools in the field of breast cancer research and provides greater potential for improving treatment resistance in clinical breast cancer patients through drug sensitivity screening.(2)The application of drug sensitivity trial results from breast cancer organoids in clinical practice has yielded promising outcomes.By conducting drug sensitivity tests with common chemotherapeutic agents,targeted drugs,and immunotherapeutic agents in breast cancer organoids,the mechanisms of drug action against tumors and the synergistic effects of multiple drugs are validated.This approach helps avoid the use of primarily resistant and highly toxic treatment drugs in patients,enabling the formulation of personalized treatment plans and evidence-based precision medical strategies.(3)Breast cancer organoids still face limitations in practical applications,such as low success rates in model construction,difficulties in model growth,and the lack of angiogenesis processes.To overcome these limitations,it is necessary to increase the amount of source tissue,improve culture systems,and innovate culture techniques.These improvements will facilitate comprehensive therapeutic drug selection through breast cancer organoids and assist in the development of personalized precision medicine.

Abstract:BACKGROUND:Transforaminal lumbar interbody fusion is one of the main surgical methods for treating degenerative lumbar diseases such as lumbar disc herniation,lumbar spinal stenosis,and lumbar spondylolisthesis.Hidden blood loss refers to the concealed loss of blood volume in patients,which is often overlooked by people. OBJECTIVE:To evaluate the perioperative blood loss during transforaminal lumbar interbody fusion using a new method,calculate the hidden blood loss based on the new method,and analyze its risk factors. METHODS:The medical records of 93 patients with lumbar degenerative diseases(lumbar spinal stenosis,lumbar disc herniation,and lumbar spondylolisthesis)who were hospitalized in the Department of Spine Surgery of Second Affiliated Hospital of Soochow University from October 2023 to October 2024 were retrospectively analyzed.The general data of patients were collected,such as age,gender,height,body mass,body mass index,and whether they had hypertension and diabetes;surgical data,such as the number of surgical segments,operation time,and American Society of Anesthesiologists anesthesia grade;laboratory tests,such as prothrombin time,activated partial thromboplastin time,international normalized ratio,platelet count,fibrinogen,and D-dimer level.Pearson or Spearman correlation analysis was used to explore the correlation between patient characteristics and postoperative hidden blood loss,and multivariate linear regression analysis was utilized to determine the independent risk factors for postoperative hidden blood loss. RESULTS AND CONCLUSION:(1)The average hidden blood loss calculated by the new method for transforaminal lumbar interbody fusion was(284.24±352.76)mL,accounting for 58.6%of the total blood loss;while the average hidden blood loss calculated by the traditional surgical method was(165.77±339.89)mL,accounting for 34.15%of the total blood loss.The difference between the two was significant(P<0.05).(2)In the univariate analysis,hidden blood loss was significantly correlated with the number of segments(r=0.213,P=0.040)and operation time(r=0.210,P=0.043)and negatively correlated with platelet count(r=-0.324,P=0.018).(3)In the multivariate linear regression analysis,decreased platelet count was an independent risk factor for hidden blood loss(P=0.016).(4)It is concluded that the new method was more accurate in estimating hidden blood loss,and hidden blood loss was an important part of the total blood loss during the perioperative period.Increased number of segments,prolonged operation time,and decreased platelet count were risk factors for hidden blood loss in transforaminal lumbar interbody fusion,among which decreased platelet count was an independent risk factor.

Abstract:OBJECTIVE:To conduct a meta-analysis concerning the effects of human umbilical cord blood mesenchymal stem cells on pain and function in patients with knee osteoarthritis. METHODS:Using the Chinese search terms"human umbilical cord blood,mesenchymal stem cells,knee joint-related diseases"and the English search terms"human cord blood,mesenchymal stem cell,MSC,knee osteoarthritis,knee joint disease,knee joint disorders,knee OA,"we conducted searches in the CNKI,WanFang,VIP,PubMed,Elsevier,and Web of Science databases.The search timeframe spanned from the establishment of each database until June 13,2024.The quality of the included literature was assessed using the Cochrane Risk of Bias tool and the ROBINS-I tool.For meta-analysis,the Revman software was utilized,calculating mean differences for continuous variables and relative risks for dichotomous variables,along with 95%confidence intervals. RESULTS:Three randomized controlled trials and three case-control studies involving a total of 248 subjects were included,with the quality of the literature evaluated as moderate.The results of the meta-analysis showed that(1)visual analog scale score was significantly lower in the trial group than in the control group,with significant differences(χ2=44.98,P<0.001,I²=91%).(2)The Western Ontario and McMaster Universities Osteoarthritis Index score was significantly lower in the trial group than in the control group,with significant differences(χ2=16.84,P<0.001,I²=88%).(3)The Lysholm scoring system score was significantly higher in the trial group than in the control group,with significant differences(χ2=0.12,P=0.73,I²=0%).(4)The incidence of adverse reactions was significantly higher in the trial group than in the control group,with significant differences(χ2=4.99,P<0.001,I²=20%),with a pooled risk difference of 0.21,corresponding to a number needed to treat of 5. CONCLUSION:Human umbilical cord blood mesenchymal stem cells can relieve pain in patients with knee osteoarthritis,improve knee function,and achieve a good balance between safety and effectiveness.

Abstract:BACKGROUND:Rutin can effectively prevent osteoporosis,but its mechanism of action remains unclear. OBJECTIVE:To investigate the effect of rutin on osteogenesis of MC3T3-E1 cells under the action of neutrophil extracellular traps. METHODS:(1)Human myeloid leukemia dHL60 cells were stimulated with phorbol 12-myristate 13-acetate to induce neutrophil extracellular trap formation in vitro.dHL60 cells were divided into four groups and cultured.The control group received Hank's balanced salt solution,while the other three groups received 50 nmol/L phorbol esters.The latter two groups were then treated with either 250 μmol/L rutin or 250 μmol/L rutin and 5 U/mL DNase I.dHL60 cell apoptosis was assessed by flow cytometry,and the expression of marker genes and proteins associated with neutrophil extracellular trap formation was determined by RT-qPCR and western blot assay.(2)MC3T3-E1 cells were divided into six groups for culture:the control group was treated with Hank's balanced salt solution,and the other five groups were treated with 50 nmol/L phorbol esters;dHL60 cells and 50 nmol/L phorbol esters;100 μmol/L rutin;dHL60 cells,50 nmol/L phorbol esters,and 250 μmol/L rutin;and dHL60 cells,50 nmol/L phorbol esters,250 μmol/L rutin,and 5 U/mL DNase I.Flow cytometry was used to assess apoptosis in MC3T3-E1 cells treated with neutrophil extracellular traps.Alkaline phosphatase staining and Alizarin red staining were used to determine the osteogenic and mineralization abilities of MC3T3-E1 cells treated with neutrophil extracellular traps.RT-qPCR and western blot assay were used to examine the expression of osteogenesis-related genes and proteins in MC3T3-E1 cells treated with neutrophil extracellular traps. RESULTS AND CONCLUSION:(1)Compared with the blank control group,rutin significantly inhibited the mRNA and protein expressions of protein arginine deiminase 4,myeloperoxidase,and neutrophil elastase in dHL60 cells(P<0.000 1).Compared with the rutin group alone,the combined intervention of rutin and DNase I had a more significant downregulation effect on protein arginine deiminase 4,myeloperoxidase,and neutrophil elastase(P<0.05),indicating that rutin could significantly inhibit the formation of neutrophil extracellular traps.(2)After dHL60 cells induced neutrophil extracellular traps and then co-cultured with MC3T3-E1 cells,the mRNA and protein expressions of Runt-related transcription factor 2,β-catenin,and bone morphogenetic protein 2 in MC3T3-E1 cells were significantly downregulated(P<0.000 1),and the apoptosis rate was significantly increased(P<0.000 1),which indicate that neutrophil extracellular traps significantly inhibit the osteogenic capacity of MC3T3-E1 cells in vitro and promote their apoptosis.Rutin alone or combined with DNase I significantly improved the apoptosis and osteogenic capacity of MC3T3-E1 cells exposed to neutrophil extracellular traps,and the combined effect of rutin and DNase I was more pronounced than that of rutin alone,suggesting that rutin may inhibit the formation of neutrophil extracellular traps,thereby improving the osteogenic capacity of MC3T3-E1 cells.(3)Molecular docking and molecular dynamics simulations revealed that rutin binds well to the target proteins of protein arginine deiminase 4,myeloperoxidase,and neutrophil elastase,indicating that rutin can specifically inhibit the formation of neutrophil extracellular traps.

Abstract:BACKGROUND:Currently,the biomechanical differences between cervical rotation manipulation and cervical rotation-traction manipulation for the treatment of cervical radiculopathy have not been systematically elucidated. OBJECTIVE:To compare the biomechanical differences between cervical rotation manipulation and cervical rotation-traction manipulation in the treatment of cervical spondylotic radiculopathy caused by cervical disc herniation,and to provide a basis for the rational selection of manipulation in clinical practice. METHODS:A 27-year-old Asian male patient with cervical spondylotic radiculopathy caused by left posterior cervical disc herniation compressing the nerve root was recruited.The CT scan data of the skull and cervical spine were extracted to construct a finite element model of the skull and the whole cervical spine.After the model was verified,the key parameters of cervical rotation manipulation and cervical rotation-traction manipulation were loaded into the model,and the effects of these two manipulations on the stress of the intervertebral disc,facet joint,spinal cord and nerve root,disc displacement,as well as the volume of the cervical intervertebral foramen and other indexes were compared and analyzed. RESULTS AND CONCLUSION:(1)In terms of Von-Mise stress,the maximum stresses of cervical rotation manipulation on the annulus fibrosus of the intervertebral disc,nucleus pulposus and facet joint were 0.903,0.139,and 2.186 MPa,respectively,which were increased by 18%,13%,and 30%compared with those of cervical rotation-traction manipulation(0.765,0.123,and 1.682 MPa).The maximum stress of the spinal cord and nerve root was 2.547 Mpa,which was 7%lower than that of cervical rotation-traction manipulation(2.738 MPa).(2)In terms of displacement,the maximum forward displacement of the side with intervertebral disc herniation under cervical rotation manipulation was 1.067 mm,which was 11.1%more than that under cervical rotation-traction manipulation(0.960 mm).(3)In terms of the change in the volume of the intervertebral foramen,both manipulations led to an increase compared with before the manipulation.The volume increased by 15.5%under rotation manipulation and 19.8%under rotation-traction manipulation,and the latter had a more significant effect on expanding the volume of the intervertebral foramen.(4)It is concluded that cervical rotation manipulation has an advantage in promoting the forward displacement of the herniated intervertebral disc,but it generates higher stress on the intervertebral disc and facet joint,and is likely to cause intervertebral disc injury.Cervical rotation-traction manipulation makes the spinal cord and nerve root bear slightly higher stress,but it can more effectively expand the volume of the intervertebral foramen and reduce the risk of intervertebral disc structural injury.In clinical treatment,the advantages and disadvantages of these two manipulations should be carefully weighed according to the specific condition of the patient,and the application should be rationally selected.

Abstract:BACKGROUND:In recent years,microRNA(miRNA)has received extensive attention in the pathogenesis and diagnosis and treatment of cerebral small vessel disease,and is involved in the regulation of various pathological processes of cerebral small vessel disease. OBJECTIVE:To review the role of miRNA in the pathogenesis,diagnosis,and treatment of cerebral small vessel disease,and to provide effective therapeutic targets and new potential biomarkers for the early diagnosis of cerebral small vessel disease. METHODS:"microRNA,cerebral small vessel disease,blood-brain barrier,chronic cerebral hypoperfusion,inflammation,apoptosis,diagnosis,biomarkers"were used as English search terms for PubMed search."Exosomal miRNA,cerebral small vessel disease"were used as Chinese search terms for CNKI search.The search time limit was from inception to January 2025.Through the preliminary screening of reading titles and abstracts,the literature with poor relevance and duplicate content was excluded,and finally 72 articles were included for inductive discussion. RESULTS AND CONCLUSION:(1)Through the excavation and discussion of the biological functions and characteristics of exosomal miRNAs,it was confirmed that exosomal miRNAs are important related components in the occurrence and progression of cerebral small vessel disease diseases.(2)Exosomal miRNA participates in the regulation of various pathological processes of cerebral small vessel disease,and plays an important role in the pathological mechanism of cerebral small vessel disease by protecting the blood-brain barrier,improving chronic cerebral hypoperfusion,reducing inflammatory response,and inhibiting apoptosis.(3)Exosomal miRNA can effectively target different pathological links of cerebral small vessel disease by targeting multiple signaling pathways to intervene at different stages of pathological development.(4)The combination of multiple exosomal miRNAs can effectively improve the disease process of cerebral small vessel disease,and the regulatory effects of different miRNAs play different roles in each stage of the pathological mechanism,and the construction of miRNA action network is of great significance for regulating the development of cerebral small vessel disease.(5)Exosomal miRNAs are widely and stably present in various body fluids,and their specific and significant expression in urine,serum,blood and other body fluids of cerebral small vessel disease patients can be used as an effective basis for the diagnosis of cerebral small vessel disease patients.(6)At present,the main clinical treatment method is to inject miRNA mimics or antagonists to regulate the expression of downstream target genes,and how to exert the most effective therapeutic effect of miRNA still needs to be further studied.(7)As exosome contents,miRNA has great application prospects in the treatment of cerebral small vessel disease.In the future,its mechanism of action should be further explored to provide effective ideas and further optimize the clinical treatment of cerebral small vessel disease.

Abstract:BACKGROUND:Platelets,crucial blood components,are commonly discarded along with white blood cells in traditional blood processing and become medical waste.Optimizing whole blood separation processes to prepare platelet lysate products and exploring their applications in tissue engineering and regenerative medicine are of great value. OBJECTIVE:To optimize blood separation for therapeutic-grade platelet lysate production and explore the protective impact of platelet lysate on myocardial hypoxia injury. METHODS:Twenty-one platelets were isolated from whole blood using a closed blood bag and tubing system,followed by the preparation of twenty-one platelet lysates through the freeze-thaw method.The concentrations of platelet-derived growth factors(platelet-derived growth factor AA,platelet-derived growth factor BB,and platelet-derived growth factor AB),vascular endothelial growth factor,epidermal growth factor,insulin-like growth factor,fibroblast growth factor,and transforming growth factor-β1 in the platelet lysate were quantified using an enzyme-linked immunosorbent assay kit.Detection ranges for these factors were determined.Bacterial and mycoplasma contamination were observed using the colony culture method and a Mycoplasma PCR detection kit,respectively.A hypoxic cardiomyocyte model was established to evaluate the protective effects of platelet lysate on hypoxia-stressed cardiomyocytes. RESULTS AND CONCLUSION:(1)The concentration ranges of major growth factors and cytokines in platelet lysates were as follows:platelet-derived growth factor AA:12.86-24.17 μg/L,platelet-derived growth factor BB:0.25-0.32 μg/L,platelet-derived growth factor AB:85.09-114.91 μg/L,vascular endothelial growth factor:10.57-58.37 μg/L,epidermal growth factor:0.43-0.69 μg/L,insulin-like growth factor 1:106-204.9 μg/L,fibroblast growth factor:0.03-0.06 μg/L,transforming growth factor β1:124.17-192.38 μg/L.(2)Colony culture and mycoplasma detection yielded negative results.(3)The efficiency of cardiomyocyte proliferation was highest with a low concentration(1%)of platelet lysate in culture.A 1%concentration of platelet lysate effectively stimulated cardiomyocytes to produce high levels of superoxide dismutase and glutathione peroxidase,providing protective effects for cardiomyocytes.This study established a method for preparing therapeutic-grade platelet lysate by optimizing the whole blood separation process,thereby improving the utilization of blood resources.Platelet lysate,rich in essential growth factors,significantly promotes the repair of hypoxic injuries in cardiomyocytes.

Abstract:BACKGROUND:The principal compressive and tensile trabecular bones in the proximal femur are essential structures responsible for transmitting forces through the hip joint.Given their complex and heterogeneous composition,exploring their microstructural variations will help improve our understanding of principal stress trabeculae. OBJECTIVE:To extract trabecular microstructural information from various regions of femoral head specimens and study their morphometric patterns,elucidate the microstructural variations of principal stress trabeculae,and provide a theoretical basis for the design of future bionic hip prostheses. METHODS:Totally 11 fresh femoral heads were obtained from patients with femoral neck fractures.They were scanned by Micro-CT and reconstructed by image analysis software(InveonTM Acquisition Workplace).The principal compressive and tensile trabecular bones were segmented into five regions respectively.After selecting the volumes of interest for each region,morphometric analyses were subsequently performed on bone volume fraction,bone surface area fraction,trabecular thickness,trabecular number,trabecular spacing,trabecular pattern factor,and grayscale value. RESULTS AND CONCLUSION:(1)Among the principal compressive trabeculae,Region 5 exhibited the highest bone volume fraction,trabecular thickness,and grayscale value,followed by Region 4 and 1,with statistically significant differences between Region 5 and 1(all P<0.05).Moving from Region 3 to Region 2,1,and Regions 4,5,there was a decreasing trend in bone surface area fraction and trabecular number,accompanied by an increasing trend in trabecular thickness.(2)Among the principal tensile trabeculae,Region 3 displayed the highest values for bone volume fraction,trabecular thickness,trabecular number,and grayscale value,while Region 2 showed opposite trends,with statistically significant differences between the two regions,(excluding grayscale value;all P<0.001).(3)This study proposes a reliable method for extracting the volume of interest of principal stress trabeculae and introduces the novel concept that principal compressive trabeculae represent a functionally graded porous structure.These findings contribute new insights into the anatomical microstructure of principal compressive trabeculae and are expected to guide the future design of bionic hip prostheses.