BACKGROUND:Upper lumbar spinal stenosis is a multifactorial degenerative disorder of the spine.For narrowing of the spinal canal in the upper lumbar region(L1-L4),surgical decision-making is particularly complex.Existing minimally invasive surgeries each have their own advantages and limitations.Currently,there are few reports on biomechanical comparison and finite element analysis of different surgical methods for the treatment of high lumbar spinal stenosis.OBJECTIVE:To analyze the biomechanical impact of endoscopic unilateral laminotomy for bilateral decompression,transforaminal endoscopic lumbar decompression,and cross-overtop decompression in the treatment of upper lumbar spinal stenosis using endoscopy,and to verify the reliability and effectiveness of these three surgical techniques in treating upper lumbar spinal stenosis,providing a biomechanical basis for clinical decision-making.METHODS:The CT images of the lumbar spine of a healthy volunteer were selected,and the finite element model M0 of the normal lumbar L1-L5 segments was established using Mimics,Geomagic,Solid works,and Ansys software.The L2-L3 segment,representing upper lumbar characteristics,was chosen.Based on this model,the surgical models for endoscopic unilateral laminotomy for bilateral decompression(M1),transforaminal endoscopic lumbar decompression(M2),and cross-overtop decompression(M3)were established.Using software,the changes in the range of motion of the entire lumbar segment and the maximum Von Mises stress of the intervertebral discs were simulated and evaluated for each group of models under six loading conditions:flexion,extension,left lateral bending,right lateral bending,left rotation,and right rotation.RESULTS AND CONCLUSION:(1)Compared with model MO,the range of motion in M1,M2,and M3 increased under all six conditions,with M1 showing a greater increase.(2)M1 and M2 demonstrated significant increases in range of motion under forward bending,extension,and right rotation,while the increase under other conditions remained below 7％.(3)Compared with model M3,model M1 exhibited slightly increased overall joint range of motion during extension and left bending,while no significant changes were observed in other aspects,and the L1-L5 lumbar segments did not reach an unstable state.(4)In model M1,the maximum Von Mises stress of the intervertebral discs increased most significantly under flexion and extension loading conditions.However,under left lateral bending,right lateral bending,left rotation,and right rotation loading conditions,the increase did not exceed 5％.(5)These findings suggest that due to the sagittal anatomical characteristics of the facet joints,the unilateral laminotomy for bilateral decompression technique,while decompressing,involves resection of more facet joints,which impacts overall segmental stability.The transforaminal endoscopic lumbar decompression technique is suitable for patients with foraminal stenosis but cannot achieve complete decompression for those with severe ventral central stenosis.The Cross-Overtop technique effectively enlarges the volume of the central canal and lateral recess,optimizing decompression,and shows unique advantages in treating upper lumbar spinal stenosis.

BACKGROUND:Upper lumbar spinal stenosis is a multifactorial degenerative disorder of the spine.For narrowing of the spinal canal in the upper lumbar region(L1-L4),surgical decision-making is particularly complex.Existing minimally invasive surgeries each have their own advantages and limitations.Currently,there are few reports on biomechanical comparison and finite element analysis of different surgical methods for the treatment of high lumbar spinal stenosis.OBJECTIVE:To analyze the biomechanical impact of endoscopic unilateral laminotomy for bilateral decompression,transforaminal endoscopic lumbar decompression,and cross-overtop decompression in the treatment of upper lumbar spinal stenosis using endoscopy,and to verify the reliability and effectiveness of these three surgical techniques in treating upper lumbar spinal stenosis,providing a biomechanical basis for clinical decision-making.METHODS:The CT images of the lumbar spine of a healthy volunteer were selected,and the finite element model M0 of the normal lumbar L1-L5 segments was established using Mimics,Geomagic,Solid works,and Ansys software.The L2-L3 segment,representing upper lumbar characteristics,was chosen.Based on this model,the surgical models for endoscopic unilateral laminotomy for bilateral decompression(M1),transforaminal endoscopic lumbar decompression(M2),and cross-overtop decompression(M3)were established.Using software,the changes in the range of motion of the entire lumbar segment and the maximum Von Mises stress of the intervertebral discs were simulated and evaluated for each group of models under six loading conditions:flexion,extension,left lateral bending,right lateral bending,left rotation,and right rotation.RESULTS AND CONCLUSION:(1)Compared with model MO,the range of motion in M1,M2,and M3 increased under all six conditions,with M1 showing a greater increase.(2)M1 and M2 demonstrated significant increases in range of motion under forward bending,extension,and right rotation,while the increase under other conditions remained below 7％.(3)Compared with model M3,model M1 exhibited slightly increased overall joint range of motion during extension and left bending,while no significant changes were observed in other aspects,and the L1-L5 lumbar segments did not reach an unstable state.(4)In model M1,the maximum Von Mises stress of the intervertebral discs increased most significantly under flexion and extension loading conditions.However,under left lateral bending,right lateral bending,left rotation,and right rotation loading conditions,the increase did not exceed 5％.(5)These findings suggest that due to the sagittal anatomical characteristics of the facet joints,the unilateral laminotomy for bilateral decompression technique,while decompressing,involves resection of more facet joints,which impacts overall segmental stability.The transforaminal endoscopic lumbar decompression technique is suitable for patients with foraminal stenosis but cannot achieve complete decompression for those with severe ventral central stenosis.The Cross-Overtop technique effectively enlarges the volume of the central canal and lateral recess,optimizing decompression,and shows unique advantages in treating upper lumbar spinal stenosis.

BACKGROUND:Osteoarthritis is pathologically characterized by progressive degeneration of the articular cartilage and abnormal deformation of the subchondral bone.In recent years,with the deepening of medical research,it has been found that the mitogen-activated protein kinases(MAPK)signaling pathway has a regulatory role in inflammatory cell infiltration,inflammatory factor release,and chondrocyte proliferation,which is particularly important for the treatment of osteoarthritis.OBJECTIVE:To briefly review the main research progress in the mechanism of MAPK signaling pathway regulating osteoarthritis in recent years,aiming to provide new ideas for the treatment of osteoarthritis.METHODS:CNKI,WanFang and PubMed databases were searched for relevant literature using the search terms of"mitogen-activated protein kinases,osteoarthritis,extracellular signal-regulated MAP kinases,p38 mitogen-activated protein kinases,JNK mitogen-activated protein kinase"in Chinese and English.Relevant literature published from January 2019 to November 2024 was searched,and 108 articles were finally included for summary analysis.RESULTS AND CONCLUSION:(1)Various stimuli inside and outside the cells activate the MAPK signaling pathway,regulate gene transcription and protein synthesis,and promote the release of inflammatory factors,such as tumor necrosis factor-α,interleukin-1β,and interleukin-6.The release of these inflammatory factors aggravates the progression of osteoarthritis.(2)The active ingredients of traditional Chinese medicine,mainly saponins and flavonoids,as well as Chinese herbal formulas and preparations with the main effects of activating blood circulation and removing blood stasis,tonifying the liver and kidney,can play a therapeutic role in osteoarthritis by inhibiting the MAPK signaling pathway,regulating the release of matrix metalloproteinases,balancing the homeostatic state of osteogenesis and osteoblastogenesis,attenuating the synovial inflammation,decreasing the release of inflammatory factors and inflammatory vesicles,decreasing cellular pyroptosis,promoting autophagy,and ameliorating oxidative stress.(3)Although traditional Chinese medicine has become popular in the treatment of osteoarthritis by virtue of its own advantages of multi-components,multi-targets,multi-pathways,and low side effects,the use of MAPK signaling pathway to guide the treatment of individual osteoarthritis is the difficulty of the technology,which needs to be continuously researched and explored.(4)Therefore,further development of relevant herbal inhibitors that can modulate the MAPK signaling pathway may be a potential drug strategy for the treatment of osteoarthritis in the future.

BACKGROUND:Osteoarthritis is pathologically characterized by progressive degeneration of the articular cartilage and abnormal deformation of the subchondral bone.In recent years,with the deepening of medical research,it has been found that the mitogen-activated protein kinases(MAPK)signaling pathway has a regulatory role in inflammatory cell infiltration,inflammatory factor release,and chondrocyte proliferation,which is particularly important for the treatment of osteoarthritis.OBJECTIVE:To briefly review the main research progress in the mechanism of MAPK signaling pathway regulating osteoarthritis in recent years,aiming to provide new ideas for the treatment of osteoarthritis.METHODS:CNKI,WanFang and PubMed databases were searched for relevant literature using the search terms of"mitogen-activated protein kinases,osteoarthritis,extracellular signal-regulated MAP kinases,p38 mitogen-activated protein kinases,JNK mitogen-activated protein kinase"in Chinese and English.Relevant literature published from January 2019 to November 2024 was searched,and 108 articles were finally included for summary analysis.RESULTS AND CONCLUSION:(1)Various stimuli inside and outside the cells activate the MAPK signaling pathway,regulate gene transcription and protein synthesis,and promote the release of inflammatory factors,such as tumor necrosis factor-α,interleukin-1β,and interleukin-6.The release of these inflammatory factors aggravates the progression of osteoarthritis.(2)The active ingredients of traditional Chinese medicine,mainly saponins and flavonoids,as well as Chinese herbal formulas and preparations with the main effects of activating blood circulation and removing blood stasis,tonifying the liver and kidney,can play a therapeutic role in osteoarthritis by inhibiting the MAPK signaling pathway,regulating the release of matrix metalloproteinases,balancing the homeostatic state of osteogenesis and osteoblastogenesis,attenuating the synovial inflammation,decreasing the release of inflammatory factors and inflammatory vesicles,decreasing cellular pyroptosis,promoting autophagy,and ameliorating oxidative stress.(3)Although traditional Chinese medicine has become popular in the treatment of osteoarthritis by virtue of its own advantages of multi-components,multi-targets,multi-pathways,and low side effects,the use of MAPK signaling pathway to guide the treatment of individual osteoarthritis is the difficulty of the technology,which needs to be continuously researched and explored.(4)Therefore,further development of relevant herbal inhibitors that can modulate the MAPK signaling pathway may be a potential drug strategy for the treatment of osteoarthritis in the future.

ObjectiveTo analyze the phylogroups of Klebsiella pneumoniae isolates from laboratory rats and mice housed at the Laboratory Animal Center Fudan University, optimize the identification method for Klebsiella pneumoniae, and perform virulence genes detection and antimicrobial susceptibility testing, thereby providing a practical basis for microbial detection strategies and prevention and control measures in laboratory animal facilities. MethodsBetween September 2023 and September 2025, ileocecal contents were collected from laboratory rats and mice purchased from laboratory animal suppliers, from which 11 strains of Klebsiella pneumoniae were isolated and cryopreserved. These strains were tested for β-lactamase genes using multiplex PCR for phylogrouping. Furthermore, representative strains from different phylogroups were selected for biochemical tests, mass spectrometry analysis, 16S rRNA gene and tyrB gene sequencing, as well as virulence genes detection and antimicrobial susceptibility testing. ResultsMultiplex PCR detection of β-lactamase genes revealed that among 11 strains, 4 were identified as Klebsiella pneumoniae (Kp1), 4 as Klebsiella quasipneumoniae (Kp2), and 3 as Klebsiella variicola (Kp3). Kp1-Kp3 could not be differentiated using biochemical tests, mass spectrometry analysis, or 16S rRNA gene sequencing, whereas multiplex PCR of β-lactamase genes and tyrB gene sequencing enabled phylogrouping of all three. There were differences in the detection rates of capsular genes (capsule associated gene G and magnesium transport system ATP-binding protein A) and siderophore genes (Klebsiella pneumoniae iron uptake system genes) among Kp1-Kp3; susceptibility to different antibiotics also varied considerably. ConclusionKlebsiella pneumoniae phylogroups isolated from commercially produced laboratory rats and mice are similar to those in human clinical samples and likewise include multiple phylogroups of the species complex. In this study, the identification methods of Kp1-Kp3 were optimized,furthermore selected virulence genes and antimicrobial resistance in Kp1-Kp3 were preliminarily investigated, which could provide precise reference for the treatment of infections caused by different phylogroups occurring in laboratory animal facilities.

ObjectiveTo investigate the mRNA expression profile and clinical significance of the RAB24 gene in hepatocellular carcinoma （HCC） based on multi-source database including The Cancer Genome Atlas （TCGA） and clinical cohort validation. MethodsData from TCGA （n=424） were utilized to evaluate the prognostic value of RAB24 expression via Kaplan-Meier analysis and Cox regression models. An independent clinical cohort comprising 90 HCC and 30 paracancerous tissues was established to validate protein expression and histopathological features through immunohistochemistry （IHC） and routine histological staining. The TIMER database was employed to analyze the association between RAB24 and the tumor microenvironment （TME）. Furthermore， integrated with LinkedOmics， GSEA and GSVA algorithms were used to quantitatively characterize the core molecular pathways regulated by RAB24. ResultsThe mRNA expression level of RAB24 in HCC was significantly higher than that in non-tumor liver tissues （P<0.05）. Kaplan-Meier analysis revealed that the overall survival （OS） of patients in the RAB24 low-expression group was significantly longer compared to the high-expression group （HR=1.570， Log-rank P=0.01）. Cox proportional hazards regression analysis demonstrated that RAB24 expression （HR=1.480， P=0.028）， T stage （HR=2.949， P<0.001）， M stage （HR=4.077， P=0.017）， and tumor residual status （HR=2.317， P<0.001） were independent prognostic factors for HCC. RAB24 expression was highly correlated with alpha-fetoprotein （AFP） levels and immune infiltration levels （P<0.01）， and showed a significant， low-level positive correlation with the TP53 gene （Rho=0.31， P<0.01）. Quantitative analysis of the RAB24 protein in clinical samples validated that RAB24 expression in HCC tissues was significantly elevated compared to non-tumor liver tissues （P<0.05）. TIMER analysis confirmed that RAB24 expression was highly associated with the infiltration of multiple immune cells （such as B cells and NK cells）， as well as stromal and tumor purity scores in tumor tissues （P<0.01）. GSEA/GSVA enrichment revealed that the P53， MYC， and mTORC1 signaling pathways were activated in the RAB24 high-expression group； correlation analysis confirmed that the RAB24 expression level exhibited a significant， low-level positive correlation with the ribosome pathway activity score （r=0.23， P<0.01）. ConclusionsThe RAB24 gene， as a poor prognostic factor for HCC patients， is a potential biomarker for HCC diagnosis， treatment and prognosis. The study is expected to lay a theoretical foundation for the precise diagnosis and treatment of clinical HCC.

AIM To investigate the effects of Wenfei Jiangzhuo Formula on mitochondrial function of Aβ25-35-induced BV-2 cells.METHODS In the establishment of cell model of Alzheimer's disease(AD)using Aβ25-35 on the BV-2 cells,the optimal concentration and time point of Aβ25-35 intervention were determined;and the groups for the intervention of LFHP-1c group(inhibitor)or the serum containing Wenfei Jiangzhuo Formula were set up.The detection of the optimal intervention concentration and time point by CCK-8 assay;the observation of cell migration and apoptosis by Transwell assay and Hoechst 33342 staining;the detection of the positive expressions of PGAM5 and Drp1 by immunofluorescence;and the detection of cellular PGAM5,Drp1,OPA1,and Mfn1/2 mRNA and protein expressions by RT-qPCR and Western blot were conducted.RESULTS The best AD cell model was established by 48 h exposure to 5 μmol/L of Aβ25-35,and most active cell viability was achieved with the 48 h use of serum containing 20％Wenfei Jiangzhuo Formula.Compared with the control group,the model group displayed decreased number of cell migration,more bright blue positive apoptotic cells,increased number of PGAM5 and Drp1 positive cells and their mRNA and protein expressions(P＜0.05);and decreased mRNA and protein expressions of OPA1 and Mfn1/2(P＜0.05).Compared with the model group,the groups intervened with the medicines shared increased number of cell migration,less bright blue positive apoptotic cells,decreased number of PGAM5 and Drp1 positive cells and their mRNA and protein expressions(P＜0.05);and elevated OPA1 and Mfn1/2 mRNA and protein expressions(P＜0.05).CONCLUSION Wenfei Jiangzhuo Formula exerts cerebroprotective effects to improve cognition by reducing cell damage and improving the balance of mitochondrial homeostasis through PGAM5-Drp1 axis in AD model.

Objective To explore the mechanism of action of total flavonoids of Rhizoma drynariae(TFRD)in improving lipid metabolism disorders in rabbits with avascular necrosis of femoral head(SANFH)based on the peroxisome proliferator-activated receptor γ(PPARγ)/adenosine monophosphate-activated protein kinase(AMPK)pathway.Methods Sixty New Zealand rabbits were randomly divided into the control group(n=10)and the model group(n=50).The rabbit SANFH model was established by injecting Escherichia coli endotoxin and methylprednisolone.The control group was injected with the same amount of physiological saline.The SANFH model was randomly classified into five subgroups:the SANFH group,the TFRD-low group(30 mg/kg),the TFRD-medium group(60 mg/kg),the TFRD-high group(100 mg/kg)and the TFRD-high+inhibitor(TFRD 100 mg/kg+AMPK inhibiter 30 mg/kg)group,with 10 rabbits in each subgroup.After the intervention,venous blood sample was collected from the rabbit ear margin,and serum lipid levels[high-density lipoprotein cholesterol(HDL-C)and total cholesterol,triglycerides(TG)]were detected.Micro-CT was used to detect bone volume/total volume(BV/TV)(%)and trabecular quantity(Tb.N).Hematoxylin-eosin(HE)staining was used to observe histopathological changes of femur and calculate empty bone lacuna rate.TUNEL was used to detect apoptosis of femoral tissue.Real-time fluorescence quantitative reverse transcription polymerase chain reaction(qRT-PCR)was employed to analyze the expression of B-cell lymphoma/leukemia-2(Bcl-2)and Bcl-2-related X protein(Bax)mRNA.Western blot assay was used to detect the expression of tissue-related proteins(PPARγ and p-AMPK/AMPK).Results Compared with the control group,HDL-C,BV/TV,Tb.N,Bcl-2 mRNAs,PPARγ and p-AMPK/AMPK were decreased in the SANFH group,and cholesterol,TG,apoptosis rate,empty bone lacuna rate and Bax mRNA were increased(P＜0.05).Compared with the SANFH group,HDL-C,BV/TV,Tb.N,Bcl-2 mRNAs,PPARγ and p-AMPK/AMPK were increased in sequence in the TFRD-low group,the TFRD-medium group and the TFRD-high group,and cholesterol,TG,apoptosis rate,empty bone lacuna rate and Bax mRNA were decreased in turn(P＜0.05).Compared with the TFRD-high group,changes in the above indicators were reversed in the TFRD-high+inhibitor group(P＜0.05).Conclusion TFRD improves lipid metabolism disorder in SANFH rabbits by activating PPARγ/AMPK pathway.

Objective To investigate the role of the ROS/NLRP3/Caspase-1 pyroptosis signaling pathway in mediating the inflammatory response of nerve roots in a rabbit model of lumbar disc herniation(LDH)following acupotomy intervention.Methods Forty New Zealand white rabbits were randomly assigned to four groups:a blank control group(10 rabbits),a model control group(10 rabbits),an electroacupuncture intervention group(positive control group,10 rabbits),and an acupotomy intervention group(10 rabbits).The LDH nerve root inflammatory response model was established in the model control group,electroacupuncture intervention group,and acupotomy intervention group using the classical autologous nucleus pulposus transplantation method.Following successful model establishment,corresponding interventions were administered.Dorsal root ganglion tissues were then collected for analysis.Reactive oxygen species levels were assessed using fluorescent probe staining.The expression of NLRP3 inflammasome-related proteins(NLRP3,ASC,GSDMD-N,and Caspase-1)was evaluated by Western blot.Mitochondrial permeability transition pore opening was assessed via Calcein AM staining.Results The comparison of relative fluorescence intensity of reactive oxygen species in dorsal root ganglion tissue among the groups indicated that the model control group exhibited significantly higher levels compared to the blank control group(P＜0.05).Both the electroacupuncture intervention group and the acupotomy intervention group demon-strated significantly lower levels than the model control group(P＜0.05).Western blot analysis revealed that the expression levels of NLRP3,ASC,GSDMD-N,and Caspase-1 in the model control group were significantly elevated compared to those in the blank control group(P＜0.05).Both intervention groups showed markedly reduced expression of these proteins compared to the model control group(P＜0.05).Additionally,the assessment of mito-chondrial permeability transition pore activity based on relative fluorescence intensity showed a significant increase in the model control group compared to the blank control group(P＜0.05),with both intervention groups exhibiting significantly lower levels than the model control group(P＜0.05).Conclusions Acupotomy therapy modulates the ROS/NLRP3/Caspase-1 signaling pathway,thereby inhibiting pyroptosis and attenuating the inflammatory response in nerve roots.This elucidates the potential molecular mechanism underlying the therapeutic effects of acupotomy on LDH through the regulation of ROS/NLRP3/Caspase-1-mediated downstream signaling cascades.

BACKGROUND:3D printing technology can design and construct models,surgical guides and personalized implants or fixture according to the actual condition and treatment demand of patients,which has great application prospects in the repair of traumatic fractures.OBJECTIVE:To review the application of 3D printing technology in traumatic fractures.METHODS:Web of Science,PubMed and CNKI databases were searched for relevant literature on the application of 3D printing technology in the field of trauma orthopedics published from 2020 to 2024.Chinese and English search terms were"traumatic fracture,3D printing technology,digital model,surgical guide."Finally,60 articles were included for analysis.RESULTS AND CONCLUSION:(1)Traumatic fracture is a fracture phenomenon with interruption of bones continuity and destruction of integrity caused by various injurious factors.Improving reduction and healing effects with reliable schemes has become a hot issue that needs to be handled urgently in orthopedics related field.(2)3D printing technology is a three-dimensional entity technology to meet demands based on digital model data,in which adhesive forming materials(powdered metal or polymer),stereolithography,deposition modeling,and optical polymer spray are used,and it is widely used in the field of digital orthopedic biomedicine.(3)3D printing technology has played significant advantages in disease diagnosis,preoperative planning,reconstructing fracture 3D model,customizing orthopedic implants,customizing fixation braces and prosthetics,fabrication of surgical guide and repair of bone defects,which can design and construct models,surgical guides,and personalized implants or fixture according to the actual conditions and treatment demands of patients.It can provide new ideas for the treatment of traumatic fractures.