OBJECTIVE: To compare the biomechanical properties of personalized Y-shaped plates with horizontal plates, vertical plates, and traditional Y-shaped plates in the treatment of distal humeral intra-articular fractures through finite element analysis, and to evaluate their potential for clinical application. METHODS: The study selected a 38-year-old male volunteer and obtained a three-dimensional model of the humerus by scanning his upper limbs using a 64-slice spiral CT. Four types of fracture-internal fixation models were constructed using Mimics 19.0, Geomagic Wrap 2017, Creo 6.0, and other software: horizontal plates, vertical plates, traditional Y-shaped plate, and personalized Y-shaped plate. The models were then meshed using Hypermesh 14.0 software, and material properties and boundary conditions were defined in Abaqus 6.14 software. AnyBody 7.3 software was used to simulate elbow flexion and extension movements, calculate muscle strength, joint forces, and load torques, and compare the peak stress and maximum displacement of the four fixation methods at different motion angles (10°, 30°, 50°, 70°, 90°, 110°, 130°, 150°) during elbow flexion and extension. RESULTS: Under dynamic loading during elbow flexion and extension, the personalized Y-shaped plate exhibits significant biomechanical advantages. During elbow flexion, the peak internal fixation stress of the personalized Y-shaped plate was (28.8±0.9) MPa, which was significantly lower than that of the horizontal plates, vertical plates, and traditional Y-shaped plate ( P<0.05). During elbow extension, the peak internal fixation stress of the personalized Y-shaped plate was (18.1±1.6) MPa, which was lower than those of the other three models, with significant differences when compared with horizontal plates and vertical plates ( P<0.05). Regarding the peak humeral stress, the personalized Y-shaped plate model showed mean values of (10.9±0.8) and (13.1±1.4) MPa during elbow flexion and extension, respectively, which were significantly lower than those of the other three models ( P<0.05). Displacement analysis showed that the maximum displacement of the humerus with the personalized Y-shaped plate during elbow flexion was (2.03±0.08) mm, slightly higher than that of the horizontal plates, but significantly lower than that of the vertical plates, showing significant differences ( P<0.05). During elbow extension, the maximum displacement of the humerus with the personalized Y-shaped plate was (1.93±0.13) mm, which was lower than that of the other three models, with significant differences when compared with vertical plates and traditional Y-shaped plates ( P<0.05). Stress contour analysis showed that the stress of the personalized Y-shaped plate was primarily concentrated at the bifurcation of the Y-shaped structure. Displacement contour analysis showed that the personalized Y-shaped plate effectively controlled the displacement of the distal humerus during both flexion and extension, demonstrating excellent stability. CONCLUSION The personalized Y-shaped plate demonstrates excellent biomechanical performance in the treatment of distal humeral intra-articular fractures, with lower stress and displacement, providing more stable fixation effects.
Humans ; Male ; Adult ; Healthy Volunteers ; Finite Element Analysis ; Tomography, Spiral Computed ; Models, Anatomic ; Biomechanical Phenomena ; Humeral Fractures, Distal/surgery* ; Fracture Fixation, Internal/instrumentation* ; Bone Plates ; Computer Simulation ; Precision Medicine/methods* ; Elbow Joint/surgery* ; Elbow/surgery* ; Humerus/surgery* ; Torque ; Stress, Mechanical ; Intra-Articular Fractures/surgery* ; Prosthesis Design/methods* ; Imaging, Three-Dimensional ; Range of Motion, Articular

BACKGROUND:Adult stem cell therapy is one of the research hotspots in the field of peripheral nerve injury repair and regeneration.With excellent properties of mesenchymal stem cells such as high acquisition rate,wide source,and rapid proliferation,mesoderm have been regarded as the ideal source of adult stem cells,while ectoderm-derived adult stem cells,especially neural crest stem cells,have certain neurogenic properties and attract more and more attention from researchers. OBJECTIVE:To mainly review the role and mechanism of multifunctional adult stem cells from ectoderm and mesoderm in peripheral nerve injury repair and regeneration,so as to explore the research progress and application prospect of adult stem cells from different sources and discuss the potential application value of adult stem cell therapy and the problems to be solved in connection with clinical studies. METHODS:The first author searched the relevant articles published from December 2001 to February 2024 in PubMed and SinoMed by computer in February 2024.The Chinese and English search terms were"ectodermal stem cells,mesenchymal stem cells,peripheral nerve injury,repair,regeneration."Finally,69 articles were included and analyzed. RESULTS AND CONCLUSION:(1)Ectodermal adult stem cells have excellent differentiation and regeneration potential,especially epidermal neural crest stems cells,olfactory stem cells,and dental ectomesenchymal stem cells,which have certain neurogenic properties and can express neural specific markers in vitro.However,relevant clinical research needs to be accumulated.(2)There are many types of adult stem cells derived from mesoderm,which are easy to obtain and purify.Among them,the efficacy and safety of bone marrow mesenchymal stem cells and umbilical cord mesenchymal stem cells in the repair of peripheral nerve injury are supported by clinical trials;that is,they can improve sensory and motor nerve conduction and there are no complications and obvious adverse reactions in follow-up.The acquisition of bone marrow mesenchymal stem cells needs invasive surgery and requires the patient to match the donor bone marrow type,which limit the application to some extent.Although umbilical cord mesenchymal stem cells do not require invasive harvesting,their isolation is difficult and phenotypically unstable.(3)Adult stem cells derived from endoderm often fail to grow in vitro,so the possibility of clinical application is low.(4)In conclusion,bone marrow mesenchymal stem cells are still the first choice for adult stem cell therapy in the treatment of peripheral nerve injury,which is suitable for cases without surgical contraindications and meeting the matching requirements,followed by umbilical cord mesenchymal stem cells supplemented by improved isolation methods and advanced phenotypic stability strategies.(5)Dental ectomesenchymal stem cells and adipose-derived mesenchymal stem cells have high application potential and need to be further tested in clinical trials.Other adult stem cells derived from ectodermal and mesodermal layers have significant advantages in animal and cell experimental studies due to their excellent properties.

AIM:To elucidate the mechanism by which Polygonatum sibiricum polysaccharides(PSP)miti-gate high-sugar diet-induced neuroinflammation through the gut microbiota-serum metabolome axis.METHODS:Fifty male ICR mice were divided into 5 groups:control group,model group,low-dose(250 mg/kg)PSP group,high-dose(500 mg/kg)PSP group,and donepezil hydrochloride(3 mg/kg)group.The neuroinflammation model was established through administration of high-sugar chow and 10%sucrose water for 12 weeks.Cognitive function assessment was per-formed utilizing the Morris water maze.Hippocampal histopathology was examined by hematoxylin-eosin(HE)staining,activated microglia were assessed via immunofluorescence,and neuronal apoptosis was evaluated by TUNEL assay.Serum and hippocampal levels of interleukin-6(IL-6),IL-1β,tumor necrosis factor-α(TNF-α)and nitric oxide(NO)were quantified using ELISA and Western blot.Gut microbiota diversity and serum untargeted metabolomics analyses were car-ried out employing 16S rRNA sequencing and LC-MS/GC-MS,respectively.Differential metabolites were screened,and key metabolic pathways were enriched using MetaboAnalyst 6.0.Spearman correlation analysis established relationships between gut microbiota,metabolites,and inflammatory factors.RESULTS:Model mice demonstrated increased escape latency(P<0.05 or P<0.01)and decreased platform crossings(P<0.01)compared with controls,which were reversed by PSP treatment(P<0.05 or P<0.01).Treatment with PSP substantially reduced IL-6,IL-1β,TNF-α and NO levels in se-rum and hippocampus(P<0.05 or P<0.01),diminished inflammatory infiltration,inhibited microglial activation,and re-duced neuronal damage.Gut microbiota analysis demonstrated that PSP increased Lactobacillus and Bacteroides abun-dance while reducing Alistipes(P<0.05).Metabolomics identified 15 differential metabolites(including betaine,kyotor-phin and ε-caprolactam)and highlighted the significance of alanine,aspartate and glutamate metabolism pathways.Spear-man analysis revealed that abundance of Alistipes and Bacteroides were positively correlated with IL-1β(P<0.05),while abundance of Lactobacillus was negatively correlated with inflammatory factors(P<0.05 or P<0.01).Key metabolites(be-taine,kyotorphin,ε-caprolactam,trans-cinnamate,cis-zeatin and galactitol)showed strong associations with inflamma-tion factors(P<0.05 or P<0.01).CONCLUSION:Treatment with PSP attenuates neuroinflammation through modula-tion of gut microbiota(Lactobacillus,Bacteroides and Alistipes),regulation of metabolites(betaine,kyotorphin and so on),and targeting amino acid metabolism pathways.

Objective:To analyze the changes in the phylogenetic and antigenic characteristics of the hemagglutinin (HA) gene of influenza virus A(H3N2) [A(H3N2)] during the 2022-2024 influenza seasons in Beijing.Methods:The data of influenza-like cases and A(H3N2) strains from 17 network laboratories and their corresponding sentinel hospitals were collected during the 2022-2024 influenza seasons. The HA genes were amplified and sequenced after extracting nucleic acids of the chosen virus strains. BioEdit, the nucleotide and amino acid sequence identity were conducted, and the maximum likelihood method in MEGA 5.0 software was used to construct the phylogenetic tree of HA genes. Web Logo displayed the amino acid mutation, and the N-glycosylation sites of HA online were analyzed using the NetNGlyc1.0 Server online. The Datamonkey platform was utilized to analyze the positive selection pressure sites of the HA protein.Results:The 2022-2024 influenza season includes 2022-2023 and 2023-2024. During the influenza seasons of 2022-2024, the positive rates of A(H3N2) nucleic acid were 10.35% (2 127/20 543) and 10.47% (4 386/41 876), respectively. In the 2022-2023 influenza season, there were two peaks in the A(H3N2). The comparison of HA genes between all A(H3N2) strains studied with the 2022-2024 vaccine strain (A/Darwin/9/2021) revealed that all of the strains studied have the two amino acid mutations involving 186 and 225 receptor binding sites. There were 31 amino acid substitutions in the 2022-2023 influenza season, of which 18 variant sites involved antigenic determinants. There were 35 amino acid mutations during the 2023-2024 influenza season, of which 14 were related to antigenic determinants. There were changes in the genetic evolutionary subclades of A(H3N2) strains in two influenza seasons: from 2022 to 2023, three evolutionary subclades were co-prevalent together, with the 3C.2a1b.2a.2a.3a.1 accounting for 76.67% (23/30), the 3C.2a1b.2a.1a accounting for 20.00% (6/30), the 3C.2a1b.2a.2a.1 accounting for 3.33% (1/30); from 2023 to 2024, two subclades were prevalent, with 3C.2a1b.2a.2a.3a.1 accounting for 95.12% (39/41) and 3C.2a1b.2a.2a.1 accounting for 4.88% (2/41). The glycosylation site changes of the HA protein of A(H3N2) have been enhanced from 2023 to 2024. The 145 amino acid position of the HA protein of the A(H3N2) was the positive selection site for stress selection site analysis.Conclusions:The evolutionary subclades of the HA gene of A(H3N2) in Beijing showed changes from 2022 to 2024, and the glycosylation site polymorphism of the HA protein of A(H3N2) significantly increased from 2023 to 2024. Continuous monitoring of HA mutations in the A(H3N2) is crucial, providing a basis for developing influenza prevention and control strategies, as well as new strategic support for screening influenza vaccine components, vaccine design, and discovery of drug targets.

AIM:To elucidate the mechanism by which Polygonatum sibiricum polysaccharides(PSP)miti-gate high-sugar diet-induced neuroinflammation through the gut microbiota-serum metabolome axis.METHODS:Fifty male ICR mice were divided into 5 groups:control group,model group,low-dose(250 mg/kg)PSP group,high-dose(500 mg/kg)PSP group,and donepezil hydrochloride(3 mg/kg)group.The neuroinflammation model was established through administration of high-sugar chow and 10%sucrose water for 12 weeks.Cognitive function assessment was per-formed utilizing the Morris water maze.Hippocampal histopathology was examined by hematoxylin-eosin(HE)staining,activated microglia were assessed via immunofluorescence,and neuronal apoptosis was evaluated by TUNEL assay.Serum and hippocampal levels of interleukin-6(IL-6),IL-1β,tumor necrosis factor-α(TNF-α)and nitric oxide(NO)were quantified using ELISA and Western blot.Gut microbiota diversity and serum untargeted metabolomics analyses were car-ried out employing 16S rRNA sequencing and LC-MS/GC-MS,respectively.Differential metabolites were screened,and key metabolic pathways were enriched using MetaboAnalyst 6.0.Spearman correlation analysis established relationships between gut microbiota,metabolites,and inflammatory factors.RESULTS:Model mice demonstrated increased escape latency(P<0.05 or P<0.01)and decreased platform crossings(P<0.01)compared with controls,which were reversed by PSP treatment(P<0.05 or P<0.01).Treatment with PSP substantially reduced IL-6,IL-1β,TNF-α and NO levels in se-rum and hippocampus(P<0.05 or P<0.01),diminished inflammatory infiltration,inhibited microglial activation,and re-duced neuronal damage.Gut microbiota analysis demonstrated that PSP increased Lactobacillus and Bacteroides abun-dance while reducing Alistipes(P<0.05).Metabolomics identified 15 differential metabolites(including betaine,kyotor-phin and ε-caprolactam)and highlighted the significance of alanine,aspartate and glutamate metabolism pathways.Spear-man analysis revealed that abundance of Alistipes and Bacteroides were positively correlated with IL-1β(P<0.05),while abundance of Lactobacillus was negatively correlated with inflammatory factors(P<0.05 or P<0.01).Key metabolites(be-taine,kyotorphin,ε-caprolactam,trans-cinnamate,cis-zeatin and galactitol)showed strong associations with inflamma-tion factors(P<0.05 or P<0.01).CONCLUSION:Treatment with PSP attenuates neuroinflammation through modula-tion of gut microbiota(Lactobacillus,Bacteroides and Alistipes),regulation of metabolites(betaine,kyotorphin and so on),and targeting amino acid metabolism pathways.

Objective To investigate the effects of inclined axial compressive force and flexion moment on the anterior and posterior shear stiffness of the lumbosacral segment.Methods Six fresh-frozen human cadaveric L5-S1 segments were tested under intact and two progressively impaired structural conditions:intact,a 4-mm bilateral facet joint gap,and anterior discectomy with nucleus pulposus removal plus circumferential release of the inner annular fibers(disc injury).A 300 N axial compressive force was applied either vertically downward or with a 10° or 20° anterior inclination through the disc's shear center.Anterior(0 N to 250 N)and posterior(-50 N to 0 N)shear tests were conducted using a material testing machine.These tests were repeated under a 5 N-m flexion moment.The relative motion between L5 and Si was measured using a three-dimensional motion capture system.Results In the intact state,the inclination of the axial compressive force did not significantly alter anterior or posterior shear stiffness.However,the application of a flexion moment increased anterior shear stiffness by 49.3％.Progressive structural damage resulted in incremental increases in anteroposterior shear translation and corresponding reductions in stiffness.Notably,under combined loading with axial compression and flexion moment,anterior stiffness decreased from 939 N/mm(intact)to 224 N/mm(disc injury),while posterior stiffness decreased from 572 N/mm to 217 N/mm.Within the low-load range,no significant differences in shear stiffness were observed across any structural conditions,regardless of axial force inclination or combined with a flexion moment.Conclusions This study supports the clinical view that retro-inclination of the pelvis serves as a compensatory mechanism to enhance segmental shear stability.However,this compensatory capacity gradually diminishes and ultimately fails as spinal degeneration progresses.

Objective:To analyze the changes in the phylogenetic and antigenic characteristics of the hemagglutinin (HA) gene of influenza virus A(H3N2) [A(H3N2)] during the 2022-2024 influenza seasons in Beijing.Methods:The data of influenza-like cases and A(H3N2) strains from 17 network laboratories and their corresponding sentinel hospitals were collected during the 2022-2024 influenza seasons. The HA genes were amplified and sequenced after extracting nucleic acids of the chosen virus strains. BioEdit, the nucleotide and amino acid sequence identity were conducted, and the maximum likelihood method in MEGA 5.0 software was used to construct the phylogenetic tree of HA genes. Web Logo displayed the amino acid mutation, and the N-glycosylation sites of HA online were analyzed using the NetNGlyc1.0 Server online. The Datamonkey platform was utilized to analyze the positive selection pressure sites of the HA protein.Results:The 2022-2024 influenza season includes 2022-2023 and 2023-2024. During the influenza seasons of 2022-2024, the positive rates of A(H3N2) nucleic acid were 10.35% (2 127/20 543) and 10.47% (4 386/41 876), respectively. In the 2022-2023 influenza season, there were two peaks in the A(H3N2). The comparison of HA genes between all A(H3N2) strains studied with the 2022-2024 vaccine strain (A/Darwin/9/2021) revealed that all of the strains studied have the two amino acid mutations involving 186 and 225 receptor binding sites. There were 31 amino acid substitutions in the 2022-2023 influenza season, of which 18 variant sites involved antigenic determinants. There were 35 amino acid mutations during the 2023-2024 influenza season, of which 14 were related to antigenic determinants. There were changes in the genetic evolutionary subclades of A(H3N2) strains in two influenza seasons: from 2022 to 2023, three evolutionary subclades were co-prevalent together, with the 3C.2a1b.2a.2a.3a.1 accounting for 76.67% (23/30), the 3C.2a1b.2a.1a accounting for 20.00% (6/30), the 3C.2a1b.2a.2a.1 accounting for 3.33% (1/30); from 2023 to 2024, two subclades were prevalent, with 3C.2a1b.2a.2a.3a.1 accounting for 95.12% (39/41) and 3C.2a1b.2a.2a.1 accounting for 4.88% (2/41). The glycosylation site changes of the HA protein of A(H3N2) have been enhanced from 2023 to 2024. The 145 amino acid position of the HA protein of the A(H3N2) was the positive selection site for stress selection site analysis.Conclusions:The evolutionary subclades of the HA gene of A(H3N2) in Beijing showed changes from 2022 to 2024, and the glycosylation site polymorphism of the HA protein of A(H3N2) significantly increased from 2023 to 2024. Continuous monitoring of HA mutations in the A(H3N2) is crucial, providing a basis for developing influenza prevention and control strategies, as well as new strategic support for screening influenza vaccine components, vaccine design, and discovery of drug targets.

Objective To investigate the effects of inclined axial compressive force and flexion moment on the anterior and posterior shear stiffness of the lumbosacral segment.Methods Six fresh-frozen human cadaveric L5-S1 segments were tested under intact and two progressively impaired structural conditions:intact,a 4-mm bilateral facet joint gap,and anterior discectomy with nucleus pulposus removal plus circumferential release of the inner annular fibers(disc injury).A 300 N axial compressive force was applied either vertically downward or with a 10° or 20° anterior inclination through the disc's shear center.Anterior(0 N to 250 N)and posterior(-50 N to 0 N)shear tests were conducted using a material testing machine.These tests were repeated under a 5 N-m flexion moment.The relative motion between L5 and Si was measured using a three-dimensional motion capture system.Results In the intact state,the inclination of the axial compressive force did not significantly alter anterior or posterior shear stiffness.However,the application of a flexion moment increased anterior shear stiffness by 49.3％.Progressive structural damage resulted in incremental increases in anteroposterior shear translation and corresponding reductions in stiffness.Notably,under combined loading with axial compression and flexion moment,anterior stiffness decreased from 939 N/mm(intact)to 224 N/mm(disc injury),while posterior stiffness decreased from 572 N/mm to 217 N/mm.Within the low-load range,no significant differences in shear stiffness were observed across any structural conditions,regardless of axial force inclination or combined with a flexion moment.Conclusions This study supports the clinical view that retro-inclination of the pelvis serves as a compensatory mechanism to enhance segmental shear stability.However,this compensatory capacity gradually diminishes and ultimately fails as spinal degeneration progresses.

Objective:To investigate the influencing factors of the outcome after endovascular therapy (EVT) in patients with large vessel occlusive stroke in anterior circulation.Methods:Patients with large vessel occlusive stroke in anterior circulation received EVT at the Qingpu Branch of Zhongshan Hospital Affiliated with Fudan University and the Fourth Affiliated Hospital of Nanjing Medical University from October 2022 to December 2023 were included retrospectively. The modified Rankin Scale was used for outcome evaluation at 90 days after onset, ≤2 points were defined as good outcome and >2 points were defined as poor outcome. Multivariate logistic regression analysis was used to identify independent influencing factors for poor outcome after EVT. Results:A total of 156 patients with large vessel occlusive stroke in anterior circulation received EVT were enrolled from two stroke centers, including 81 males (51.9%), aged 73.32±9.68 years. Sixty-nine patients (44.2%) had good outcome, 87 (55.8%) had poor outcome. Univariate analysis showed that there were significant differences in the onset-to-door time, door-to-puncture time, puncture-to-reperfusion time, baseline National Institutes of Health Stroke Scale (NIHSS) score, baseline Alberta Stroke Program Early CT Score (ASPECTS), core infarct volume, ischemic penumbra volume, modified Thrombolysis in Cerebral Infarction (mTICI), postprocedural intracranial hemorrhage, and symptomatic intracranial hemorrhage between the good outcome group and the poor outcome group (all P<0.05). Multivariate logistic regression analysis showed that the baseline NIHSS score (odds ratio [ OR] 1.107, 95% confidence interval [ CI] 1.010-1.213; P=0.029), door-to-puncture time ( OR 1.014, 95% CI 1.000-1.028; P=0.048), onset-to-door time ( OR 1.006, 95% CI 1.003-1.009; P<0.001), the core infarct volume ( OR 1.043, 95% CI 1.004-1.084; P=0.029), and mTICI <2b ( OR 10.117, 95% CI 1.896-53.983; P=0.007) were the independent risk factors for poor outcome, while baseline ASPECTS ( OR 0.976, 95% CI 0.961-0.991; P=0.002) and ischemic penumbra volume ( OR 0.359, 95% CI 0.203-0.634; P<0.001) were the independent protective factors for good outcome. Conclusion:For patients with large vessel occlusive stroke in anterior circulation, higher baseline NIHSS score, longer onset-to-door time and door-to-puncture time, larger core infarct volume, and mTICI <2b are associated with the poor outcome after EVT, while higher baseline ASPECTS and larger ischemic penumbra volume are associated with the good outcome.

BACKGROUND:Osteoporosis is a disease in which bone density and structure are destroyed and fractures are caused by increased bone fragility,leading to high clinical disability and mortality rates. OBJECTIVE:To review the research progress in the role of bone immunity in physiological and pathological processes related to bone metabolism,providing ideas for the research and clinical application of bone immunity in bone diseases. METHODS:The first author searched PubMed and CNKI databases in November 2022 for relevant literature using the keywords of"osteoimmunology,immuno-skeletal interface,bone metabolism,skeletal metabolism,lymphocyte,immune factor"in English and Chinese,respectively.The time range of retrieval was mainly from January 2010 to November 2022,and a small number of classical long-term literatures were included.After reading the topic and abstract for preliminary screening and excluding repetitive studies,low-quality journals and unrelated literature,81 documents were finally included for review. RESULTS AND CONCLUSION:Osteoimmunology refers to that bone and immune cells share the same microenvironment and interact with each other to jointly perform the"bone immune system,"which includes all cells in the bone marrow.Immuno-skeletal interface has protective effects on bone under physiological conditions,but it may lead to bone destruction under pathological conditions.Osteoprotegerin is mainly derived from B cells and can inhibit osteoclast metabolism.However,when the body is in an inflammatory state,T cells and B cells work together to promote bone resorption.In addition,interleukin-1,interleukin-6 and tumor necrosis factor-α regulate the expression of receptor activator of nuclear factor-κB ligand in vivo and affect bone metabolism.In most clinical diseases(such as rheumatoid arthritis,estrogen deficiency,HIV infection,and hyperparathyroidism),the immuno-skeletal interface interacts with the bone immune system,resulting in the regulation of bone metabolism.In terms of clinical prospect,the interaction between bone immunity and bone metabolism should be studied in order to propose new strategies for therapeutic intervention to reduce the risk of fracture.