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:The local immune microenvironment plays an important regulatory role in the process of bone formation,and the immune system is intricately linked to the skeletal system.OBJECTIVE:To systematically review the promotion of bone regeneration from three aspects:immune cell regulation of microenvironment,regulation of immune response by small extracellular vesicles,and induction of immune response by bone biomaterials,and to elucidate the immune regulatory mechanisms involved in bone regeneration.METHODS:Relevant literature was retrieved from PubMed,CNKI,WanFang Database,and VIP Database,using the search terms of"osteoimmunology,immune microenvironment,small extracellular vesicles,bone regeneration,bone tissue repair,biomaterials,and tissue engineering"in English and Chinese.Repeat and irrelevant literature was screened and removed,and 92 articles that met the criteria were selected for intensive reading and review.RESULTS AND CONCLUSION:Multiple immune cells and bone cells are in the same microenvironment,and immune cells can regulate the differentiation and activity of bone cells,collectively forming an immune microenvironment that affects bone regeneration.Neutrophils can significantly reduce local inflammatory responses in the early stages of bone injury,creating a favorable microenvironment for bone regeneration.M1 macrophages can clear foreign bodies and reduce early inflammatory responses,while M2 macrophages can promote the expression of osteogenic markers and factors,playing an important role in the repair process of bone injury.B cells and T cells can directly or indirectly affect the generation and activity of osteoblasts and osteoclasts,regulate bone metabolism,and promote bone regeneration.Extracellular vesicles of small cells regulate the local immune microenvironment through paracrine secretion,promoting bone formation and angiogenesis at the site of bone injury.The metal ions,surface hydrophilicity,porosity,pore size,surface morphology,and surface roughness on the surface of biomaterials can directly regulate local immune responses,and have anti-inflammatory,angiogenic,and osteogenic effects,thereby accelerating bone regeneration.

OBJECTIVE:Postoperative recurrence is a common complication of percutaneous endoscopic lumbar discectomy for lumbar disc herniation,which can significantly increase the risk of reoperation.A well-performing risk prediction model can help identify high-risk groups early and prevent postoperative recurrence.This study systematically evaluated the risk prediction model for postoperative recurrence after percutaneous endoscopic lumbar discectomy to provide a reference for surgical decision-making.METHODS:The PubMed,Embase,Web of Science,CNKI,WanFang Data,VIP,and CBM were electronically searched to collect studies on the recurrence risk prediction models after percutaneous endoscopic lumbar discectomy from inception to July 1,2024.Two reviewers independently screened the literature and extracted data.The models' risk of bias,applicability,and report quality were assessed using prediction model risk of bias assessment tool(PROBAST)and Transparent Reporting of a Multivariable Prediction Model for Individual Prognosis or Diagnosis(TRIPOD)tools,respectively.Meta-analysis of postoperative recurrence rate of percutaneous endoscopic lumbar discectomy and related predictors was performed using Revman 5.4 software.RESULTS:(1)A total of 15 studies were included,all of which were retrospective studies,including 24 models for predicting the risk of recurrence after percutaneous endoscopic lumbar discectomy.(2)The PROBAST evaluation results indicated that all 15 studies exhibited a high risk of bias.Regarding applicability,two studies demonstrated a low risk,while 13 presented a high risk.(3)Regarding the TRIPOD reporting quality,the overall quality across the 15 studies was low.The primary reasons for this low compliance included the failure to report blinding,a lack of explanation for the sample size calculation method,lack of detailed description of missing data processing methods,and lack of information such as introduction to the model used.(4)Furthermore,the area under the receiver operating characteristic curve for the model ranged from 0.684 to 0.972,with the number of potential predictor variables varying from 15 to 28.(5)The results of meta-analysis showed that the postoperative recurrence rate of lumbar disc herniation patients treated with percutaneous endoscopic lumbar discectomy was 12％(95％CI=9.0％-15.0％),Modic changes(OR=6.72,95％CI=3.90-11.59),body mass index(OR=1.28,95％CI=1.10-1.49),work intensity(OR=3.22,95％CI=1.85-5.59),age(OR=2.28,95％CI=1.50-3.48),and smoking history(OR=2.65,95％CI=1.75-4.00)were independent influencing factors for postoperative recurrence of percutaneous endoscopic lumbar discectomy(all P＜0.05).CONCLUSION:The overall predictive performance of the recurrence risk prediction models after percutaneous endoscopic lumbar discectomy is satisfactory;however,the model exhibits a high overall risk of bias and applicability,coupled with low reporting quality.Additionally,there is a lack of prospective research and external validation.Future,risk prediction models should consider factors such as Modic changes,body mass index,work intensity,age,and smoking history as potential predictors.

BACKGROUND:Exosomes derived from mesenchymal stem cells play pivotal roles in cell communication and epigenetic regulation due to their low immunogenicity and targeted delivery effects,and have been clinically applied in the treatment of various diseases.OBJECTIVE:To review the isolation,purification,identification methods,and application progress of mesenchymal stem cell-derived exosomes,and to facilitate the development of large-scale preparation techniques and clinical translation of mesenchymal stem cell-derived exosomes.METHODS:The Chinese search terms"exosome,mesenchymal stem cells,isolation,purification,characterization,clinical application"and the English search terms"exosome,extracellular vesicles,mesenchymal stem cells,isolation,characterization,application"were used to search the literature published before September 2024 in CNKI,PubMed,and Web of Science databases.Articles with poor relevance to the topic,outdated,or duplicated content were excluded,and finally,109 articles were included for review.RESULTS AND CONCLUSION:(1)This paper reviews recent methods for isolating and purifying exosomes,comparing the characteristics of ultracentrifugation,ultrafiltration,size-exclusion chromatography,polymer precipitation,immunoaffinity,microfluidic methods,and other novel approaches based on their underlying principles.(2)Methods for identifying exosomes can be categorized into physical and biochemical analyses,characterizing exosomes based on their shape,size,and characteristic proteins.(3)Mesenchymal stem cell-derived exosomes have broad applications in multiple fields such as medical aesthetics,wound repair,and cancer treatment,due to their immune-regulatory properties and ability to cross biological barriers.(4)The clinical translation of exosomes faces challenges due to their complex structure,lack of universal isolation techniques,and poor stability,making it difficult to achieve in a short period of time.

BACKGROUND:The previous study of the research group confirmed that Bushen Zhuangjin Decoction can regulate bone metabolism and play an anti-osteoporosis role,and nanocrystalline collagen-based bone can assist in the repair of limb bone defects.OBJECTIVE:To explore the repair effect of nanocrystalline collagen-based bone combined with Bushen Zhuangjin Decoction on osteoporotic bone defects.METHODS:Totally 84 female SD rats were randomly divided into a sham operation group(n=6,no modeling)and a bilateral ovariectomy group(n=78).After 12 weeks of bilateral ovariectomy,the sham operation group(n=6)and the bilateral ovariectomy group(n=6)were selected for osteoporosis modeling verification.The remaining 72 rats in the bilateral ovariectomy group were randomly divided into 6 intervention groups,with 12 rats in each group:groups A-E had femoral defect models(diameter 3.5 mm,depth 4 mm)established 12 weeks after bilateral ovariectomy.Group A was given double distilled water by gavage(once a day)after surgery;group B was given Bushen Zhuangjin Decoction by gavage(once a day)after surgery;group C had nanocrystalline collagen-based bone filled in the bone defect and then given double distilled water by gavage(once a day);group D had nanocrystalline collagen-based bone filled in the bone defect and then given alendronate sodium by gavage(once a week);group E had nanocrystalline collagen-based bone filled in the bone defect and then given Bushen Zhuangjin Decoction by gavage(once a day);group F had femoral defect models established at the same time after bilateral ovariectomy,and bone defect sites were filled with nanocrystalline collagen-based bone and then given Bushen Zhuangjin Decoction by gavage(once a day).All drugs were given continuously for 12 weeks.12 hours after the last administration,serum levels of type Ⅰ procollagen amino-terminal propeptide,type Ⅰ collagen cross-linked C-terminal peptide,and estradiol were detected;bone volume in the bone defect area was detected by Micro-CT.The expression of type Ⅰ collagen and vascular endothelial growth factor in the bone defect area was detected by immunohistochemical staining.RESULTS AND CONCLUSION:(1)Compared with group A,the serum level of type Ⅰ procollagen amino-terminal propeptide in groups D and E was decreased(P＜0.05).Compared with groups A and C,the serum estradiol level in groups D,E,and F was increased(P＜0.05).There was no significant difference in the bone volume in the defect area between groups A-F(P＞0.05).(2)Immunohistochemical staining showed that compared with group A,the expression of typeⅠ collagen and vascular endothelial growth factor in groups B,D,and E increased(P＜0.05).Compared with group C,the expression of type Ⅰ collagen in groups B,D,E,and F increased(P＜0.05),and the expression of vascular endothelial growth factor in groups D,E,and F increased(P＜0.05).(3)The results show that nanocrystalline collagen-based bone combined with Bushen Zhuangjin Decoction may have the potential to repair bone defects in ovariectomized osteoporotic rats.

BACKGROUND:Myocardial hypertrophy often leads to severe cardiovascular diseases and is difficult to diagnose due to its early stages being hard to detect.Circulating inflammatory proteins have been found to be significantly associated with cardiovascular diseases,yet the specific mechanisms linking them to myocardial hypertrophy remain unclear.OBJECTIVE:To investigate the relationship between circulating proteins and myocardial hypertrophy using multiple Mendelian randomization approaches.METHODS:Utilizing data from 91 circulating inflammatory proteins in the GWAS Catalog database and the latest myocardial hypertrophy data from the R11 FinnGen database,we employed bidirectional two-sample Mendelian randomization,multivariate Mendelian randomization,and Genome-Wide Association Studies co-localization to investigate the causal relationship between circulating inflammatory proteins and myocardial hypertrophy.The accuracy of the results was verified through sensitivity tests including MR-PRESSO,Cochran's Q test,MR-Egger intercept assessment,leave-one-out analysis,and funnel plot analysis.RESULTS AND CONCLUSION:In the results of two-sample Mendelian randomization,the primary method used for evaluation was the Inverse Variance Weighting(IVW)approach.It was found that the level of T-cell surface glycoprotein CD6 isoform(IVW:P=0.046,OR=0.74,95％Cl:0.66-1.00),level of slit chemokine(IVW:P=2.1×10-2,OR=0.74,95％CI:0.556-0.95),level of Delta and Notch-like epidermal growth factor-related receptor(IVW:P=3.7×10-4,OR=0.66,95％CI:0.49-0.87),level of interleukin-2(IVW:P=3.8×103,OR=0.667,95％CI:0.50-0.88),and sulfotransferase 1A1(IVW:P=1.42×102,OR=0.80,95％CI:0.67-0.96)had a unidirectional causal effect on cardiac hypertrophy.(2)Among the findings in multivariate Mendelian randomization,the levels of the CD6 isoform of T-cell surface glycoprotein(IVW:P=1.39×102,OR=0.81,95％CI:0.69-0.96)and the levels of Delta and Notch-like epidermal growth factor-related receptor(IVW:P=3.7×10-2,OR=0.73,95％CI:0.55-0.98)were positive,indicating that the results remained significant after excluding the effects of other circulating inflammatory proteins that had an impact on myocardial hypertrophy.(3)In colocalization,T-cell surface glycoprotein CD6 isoform levels had H3+H4=0.96,with the most significant single nucleotide polymorphism being rs59570070,suggesting an intrinsic link between T-cell surface glycoprotein CD6 isoform levels and myocardial hypertrophy.(4)Sensitivity results showed no abnormalities,indicating no heterogeneity or pleiotropic effects influencing the results.(5)These results verified that T cell surface glycoprotein CD6 isoforms,Slit chemokine,Delta and Notch-like epidermal growth factor-related receptors,interleukin-2,and sulfotransferase 1A1 had a unidirectional causal effect on myocardial hypertrophy.T cell surface glycoprotein CD6 isoforms and Delta and Notch-like epidermal growth factor-related receptors had the deepest impact,suggesting that there may be related pathways between T cell surface glycoprotein CD6 isoforms and myocardial hypertrophy.Mendelian randomization studies require large amounts of clinical data and therefore often use European samples from international databases for analysis.Since this analytical method has significant advantages in causal inference,precision medicine,and cross-population validation,its research results still hold great significance for the medical development in China.As Mendelian randomization research deepens,it also promotes the collection and analysis of clinical data in China to some extent.In the future,we can further analyze key protein mechanisms,combine multiomics and clinical validation,develop an inflammatory marker monitoring system and novel anti-inflammatory therapies,thereby promoting the prevention and control of cardiovascular diseases and the development of personalized medicine.

BACKGROUND:Neutrophil extracellular traps and activated platelets are involved in the invasion,metastasis,growth,and angiogenesis of lung cancer,and are closely related to the development and prognosis of lung cancer.OBJECTIVE:To review the mechanism of neutrophil extracellular traps and activated platelets in lung cancer and their application in diagnosis,prognosis,and treatment of lung cancer.METHODS:"Platelet activation,lung neoplasms,extracellular traps,treatment"for English search terms and"lung cancer,neutrophil-extracellular traps,platelet activation,P-selectin,treatment"for Chinese search terms were searched in PubMed and CNKI databases.After reading the title and abstract of the literature,according to the inclusion and exclusion criteria,63 articles with high relevance were finally included.RESULTS AND CONCLUSION:(1)Formation of neutrophil extracellular traps and platelet activation were induced by lung tumor.(2)Neutrophil extracellular traps and activated platelets jointly promote the proliferation,growth and metastasis of lung cancer.(3)Neutrophil extracellular traps can be used as a novel biomarker for the diagnosis,prognosis and progression of lung cancer.(4)Targeting neutrophil extracellular traps and activating platelets can be used as potential therapies for lung cancer.

BACKGROUND:Oral submucous fibrosis is a chronic progressive disease that is prone to malignant transformation.Traditional treatment methods are not ideal and have limitations.As an emerging discipline,tissue engineering has opened up a new path for the treatment of oral submucous fibrosis.OBJECTIVE:To review the latest progress in the pathogenesis and treatment of oral submucous fibrosis,and to summarize and analyze the role and research progress of mesenchymal stem cells,bioscaffold materials,and tissue-engineered oral mucosa in oral submucous fibrosis,thereby providing ideas for the research and clinical application of tissue engineering in the treatment of oral submucous fibrosis.METHODS:In October 2024,the first author used computers to search for relevant literature from January 1970 to October 2024 in PubMed and CNKI databases.The search terms were"oral submucous fibrosis,tissue engineering,mesenchymal stem cells,bioscaffold materials"in English and Chinese,respectively.A total of 166 articles were finally included for analysis.RESULTS AND CONCLUSION:(1)The pathogenesis of oral submucous fibrosis is complex,and many factors are closely related to oral submucous fibrosis,but ultimately they promote the development of oral submucous fibrosis by promoting collagen deposition and accelerating fibroblast proliferation.(2)Traditional treatment methods for oral submucous fibrosis have problems such as low patient compliance and unsatisfactory results,and new treatment strategies are urgently needed.(3)Mesenchymal stem cells regulate the pathological microenvironment,reduce inflammation and inhibit the process of fibrosis due to their immunomodulatory and antioxidant properties,providing a new idea for the treatment of oral submucous fibrosis.(4)Biomass materials,as drug and cell delivery carriers,regulate the pathological microenvironment and are used in various fibrotic diseases,providing a new solution for the treatment of oral submucous fibrosis.(5)Tissue-engineered oral mucosa can be used as an autologous mucosa substitute to promote tissue repair,and also provides a basis for the establishment of disease models.(6)Tissue engineering treatment strategy has great potential for achieving comprehensive treatment of oral submucous fibrosis,but its role in the treatment of oral submucous fibrosis has not yet been verified.It is of great significance to explore tissue engineering-based treatment strategies for oral submucous fibrosis in the future.

BACKGROUND:Spondylolisthesis is a common disease,and there is a lack of effective drugs to treat it.There is still a need to further define the pathogenesis and screen out more suitable therapeutic targets for spondylolisthesis.Mendelian randomization analysis can be used to explore the drugable genes associated with spondylolisthesis and provide valuable guidance for the development of more effective and targeted therapeutic drugs.OBJECTIVE:To explore potential therapeutic targets and effective drugs for spondylolisthesis by means of pharmaceutically available genome-wide Mendelian randomization analysis.METHODS:Using the Finnish database,eQTLGen consortium,drug signature database,drug-gene interaction database,protein-protein interaction database,organic small molecule biological activity database and protein structure database,which contains genome and health information of half a million Finns,data on druggable genes were subjected to two-sample Mendelian randomization analysis and co-localization analysis with data from genome-wide association studies of spondylolisthesis to identify genes highly associated with spondylolisthesis.In addition,GO and KEGG enrichment analysis,protein network construction,drug prediction and molecular docking were performed to provide valuable guidance for the development of more effective and targeted therapeutic agents.RESULTS AND CONCLUSION:In this study,we identified 34 potential drug target genes that were significantly associated with spondylolisthesis,particularly the gene APOBEC3G.This gene showed a significant association with spondylolisthesis outcomes through Mendelian analysis and co-localization analysis,suggesting that APOBEC3G may be a priority therapeutic target.As for other potential mechanisms and drugs,we still need to conduct more in-depth research to determine their roles.This study used a database from a European population,which can be used as a reference for the study of population genetics in China.

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.