1.Cerium dioxide nanoparticles regulate expression of inflammatory factors in M1 macrophages and affect fibroblast co-culture system
Peisen XIE ; Zhenpeng GUAN ; Xianjie WEI ; Keshi ZHANG ; Qingyuan KANG ; Wentao XIAO ; Xiaoshuai GUO
Chinese Journal of Tissue Engineering Research 2026;30(2):375-383
BACKGROUND:Macrophage polarization plays a key role in chronic inflammatory joint diseases such as rheumatoid arthritis.Cerium dioxide(CeO2)nanoparticles have a wide range of biomedical applications such as modulating the local inflammatory microenvironment of tissues.OBJECTIVE:To investigate the role of CeO2 nanoparticles on macrophage polarization and inflammatory factor expression,as well as inflammatory modulation in a co-culture system of macrophages and fibroblasts.METHODS:(1)CeO2 nanoparticles were dispersed and observed morphologically by transmission electron microscopy.(2)Human leukemia monocytes(THP-1)were induced to differentiate and establish the M1 macrophage pro-inflammatory cell model of rheumatoid arthritis.The cells were divided into M0 group(undifferentiated macrophages),M1 group(successful macrophage modeling),CeO2 nanoparticle treatment group(M1 group with CeO2 nanoparticle treatment),and dexamethasone control group(M1 group with dexamethasone treatment)and incubated for 48 hours.The effects of CeO2 nanoparticles on the expression of inflammatory factors(endogenous nitric oxide synthase,CD86,CD80)in M1 macrophages and M1 macrophage phenotype(CD80,CD206)were detected by RT-qPCR,western blot assay,and flow cytometry.(3)A co-culture system of macrophages and fibroblasts was established,and CeO2 nanoparticles acted on the upper macrophages.The regulation of CeO2 nanoparticles on the expression of inflammatory factors(interleukin-6,tumor necrosis factor-α,cyclooxygenase-2,and endogenous nitric oxide synthase)of fibroblasts in the co-culture system was observed at the mRNA and protein levels.RESULTS AND CONCLUSION:(1)Transmission electron microscopy showed that the diameter of CeO2 nanoparticles was(19.5±2.0)nm.(2)Compared with the M0 group,the mRNA of endogenous nitric oxide synthase and CD86,and the protein expression of endogenous nitric oxide synthase and CD80 in the M1 group were upregulated.Compared with the M1 group,the mRNA expression of endogenous nitric oxide synthase and CD86,and the protein expression of endogenous nitric oxide synthase and CD80 in the CeO2 nanoparticle treatment group were downregulated.Flow cytometry showed that 20 nm CeO2 nanoparticles downregulated the number of M1 macrophages.(3)Compared with the M1 group,20 nm CeO2 nanoparticles downregulated the mRNA and protein expression of inflammatory factors(tumor necrosis factor α,interleukin 6,cyclooxygenase 2,and endogenous nitric oxide synthase)in the co-culture system HFL1 cells.(4)The results showed that 20 nm CeO2 nanoparticles can alleviate inflammation in the co-culture system by inhibiting the expression of pro-inflammatory factors in M1 macrophages,providing a new idea for the treatment of inflammatory diseases such as rheumatoid arthritis.
2.Mitogen-activated protein kinase signaling pathway regulates the development of osteoarthritis:guiding targeted therapy with traditional Chinese medicine
Hao LI ; Hongcheng TAO ; Ping ZENG ; Jinfu LIU ; Qiang DING ; Chicheng NIU ; Kai HUANG ; Hongyu KANG
Chinese Journal of Tissue Engineering Research 2026;30(6):1476-1485
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.
3.Relationship between Alzheimer's disease and sarcopenia and body mass index:analysis of GWAS datasets for European populations
Qiwang HE ; Bo CHEN ; Fuchao LIANG ; Zewei KANG ; Yuan ZHOU ; Anxu JI ; Xialin TANG
Chinese Journal of Tissue Engineering Research 2026;30(4):1036-1046
BACKGROUND:Alzheimer's disease has been associated with sarcopenia,but a causal relationship has not been established.Exploring the causal relationship between the two most common disability-burdening diseases in the aging population-Alzheimer's disease and sarcopenia-and their potential mediating factors holds certain implications for further alleviating the healthcare costs and socioeconomic burden for older adults in China.OBJECTIVE:To explore the potential causal relationship between Alzheimer's disease and sarcopenia in the general population using a Mendelian randomization study and to explore the role of body mass index in this context.METHODS:Two-sample Mendelian randomization analysis based on published genome-wide association studies(GWAS)were used to infer causality,and univariate Mendelian randomization and mediation analyses were used in the study design.Through the Integrative Epidemiology Unit(IEU)database,ieu-b-2 was selected as the Alzheimer's disease dataset(sample size:63 926),ieu-b-4816 as the body mass index dataset(99 998),ebi-a-GCST90000027 as the appendicular lean mass dataset(244 730),ukb-b-7478 as the left hand grip strength dataset(461 026),ukb-b-10215 as the right hand grip strength dataset(461 089)and ukb-b-4711 as the walking pace dataset(459 915).Inverse-variance weighting was used as the primary analysis method,and the results were validated by pleiotropy and heterogeneity analysis.The Steiger Directionality Test was performed to validate the reasonableness of the causal direction.RESULTS AND CONCLUSION:(1)The Mendelian randomization analyses provided evidence that Alzheimer's disease predicted the risk of appendicular lean mass[odds ratio(OR)=1.009;95%confidence interval(Cl),1.001-1.017;P=0.023),and walking pace(OR=1.010;95%Cl,1.003-1.017;P=0.008).No correlation with hand grip strength was observed.(2)Alzheimer's disease was negatively correlated with body mass index(OR=0.893;95%Cl,0.811-0.984;P=0.022);body mass index was positively correlated with appendicular lean mass(OR=1.084;95%Cl,1.031-1.141;P=0.002)and negatively correlated with walking pace(OR=0.975;95%Cl,0.969-0.980;P<0.001).(3)Mediation analyses showed that the causal relationship between Alzheimer's disease and appendicular lean mass and walking pace was partially mediated by body mass index,with the proportion of mediations being 50.25%and 32.11%,respectively.(4)The results of this study suggest that based on large-scale population studies,genetic prediction of Alzheimer's disease is a potential risk factor for sarcopenia,in which body mass index plays an important mediating role.This suggests that in clinical practice,attention should be paid to the muscle condition of patients with Alzheimer's disease,and weight management should be implemented,as maintaining a body mass index within the normal high range may have a preventive effect on the occurrence of sarcopenia in patients with Alzheimer's disease.However,further research is needed to verify the applicability of this conclusion to other ethnic groups.This study utilized an international public database for analysis,providing a reference for research on the correlation between Alzheimer's disease and sarcopenia in the Chinese population.It also highlights the significant mediating role of body mass index,offering insights for further prevention and treatment of sarcopenia among Chinese individuals.
4.Finite element analysis of implants with different crown-to-implant ratios under different bone conditions
Zirui KANG ; Yang WU ; Hailong SONG ; Qiaoyun YANG ; Lixiang ZANG ; Dongliang XU
Chinese Journal of Tissue Engineering Research 2026;30(2):319-328
BACKGROUND:Clinical studies suggest that both bone quality and excessive crown-to-implant ratio are factors that affect the success rate of implant surgery,but there is no consensus on how large the crown-to-implant ratio under each bone quality will affect the prognosis of implant repair.OBJECTIVE:To analyze the stress and strain of bone tissue around implant restorations with different crown-to-implant ratios under different bone types after stress loading using three-dimensional finite element method.Combined with the Frost bone mechanics regulation system theory,the physiological limits of bone strain were observed for each bone type within a certain range of crown to implant ratios.METHODS:Cone beam CT data were selected from a patient to establish solid bone block models with four different bone types(class Ⅰ bone:cortical bone thickness 3 mm+dense cancellous bone,class Ⅱ bone:cortical bone thickness 2 mm+relatively dense cancellous bone,class Ⅲ bone:cortical bone thickness 1 mm+relatively low-density cancellous bone,class Ⅳ bone:cortical bone thickness 1 mm+low-density cancellous bone).Implant restorations with five different crown-to-implant ratios(1,1.5,2,2.5,and 3)were created on each bone block model,for a total of 20 models.Vertical and oblique forces were applied to the dental crown to observe the von Mises stress values,strains,and displacement of the cortical and cancellous bones,as well as the degree of implant displacement.RESULTS AND CONCLUSION:(1)In the class Ⅰ bone model,when the crown-to-implant ratio reached 3 under oblique loading,the cortical bone strain exceeded the physiological limit.In the class Ⅱ bone model,under oblique loading,when the crown-to-implant ratio reached 2.5,the cortical bone strain exceeded the physiological limit.In the class Ⅲ bone model,under oblique loading,cortical bone exceeded the physiological limit when the crown-to-implant ratio reached 2.5,while cancellous bone reached the critical physiological limit at 1.In the class Ⅳ bone model,under oblique loading,when the crown-to-implant ratio reached 1.5,2,2.5,and 3,the cortical bone strain exceeded the physiological limit.In the class Ⅳ bone model,all five crown-to-implant ratios of cancellous bone exceeded physiological limits.(2)Under vertical load,the cancellous bone strain exceeded the physiological limit when the crown-root ratio reached 1,2,2.5,and 3 in the class Ⅲ bone model,and when the cancellous bone strain of the five crown-root ratios in the class Ⅳ bone model exceeded the physiological limit.(3)Under oblique or vertical load,the implant displacement of the 20 groups of models did not exceed 100 μm.(4)From the perspective of biomechanics,when patients with insufficient bone height choose implant restoration,the crown-root ratio that class Ⅰ bone can tolerate is up to 2.5 times,the crown-root ratio that class Ⅱ bone can tolerate is up to 2 times,and the crown-root ratio that class Ⅲ and class Ⅳ bones can tolerate is up to 1 times due to excessive strain of cancellous bone;but the crown-root ratio that cortical bone in class Ⅲ bone can tolerate is up to 2 times.Whether class Ⅲ bone can tolerate implant restoration with a high crown-root ratio and whether cancellous bone can tolerate higher strains needs further study.
5.Development of a dual-track predictive model for active ankylosing spondylitis by combining the sacroiliac joint resistance index and systemic immune-inflammation index
Yuhong OUYANG ; Jianxiong ZHENG ; Xing ZHANG ; Wenjiao KANG ; Qianqiong CHEN ; Haili SHEN
Chinese Journal of Rheumatology 2026;30(2):1-8
Objective:To construct a "local-systemic" dual-track prediction model integrating the resistance index (RI) score of bilateral sacroiliac joints and the systemic immune-inflammation index (SII), and to evaluate its predictive efficacy for the active stage of ankylosing spondylitis (AS).Methods:A total of 205 patients with ankylosing spondylitis (AS) from the Second Hospital of Lanzhou University between April 2022 and April 2025 were retrospectively enrolled and categorized into an active group ( n=113) and a remission group ( n=92). Hematological parameters and ultrasound data were collected. The resistance index (RI) of the synovial area in bilateral sacroiliac joints was measured by Doppler ultrasound and scored as follows: RI < 0.5: 3 points; RI 0.5~0.55: 2 points; RI > 0.55: 1 point; undetectable blood flow: 0 points. A total bilateral RI score (range 0 to 6) was calculated. The systemic immune-inflammation index (SII) was derived as (neutrophils× platelets)/lymphocytes. Normality was tested for all continuous variables; normally distributed data were compared using the t-test, while non-normally distributed data were analyzed with the Mann-Whitney U test. Categorical variables were compared using the χ2 test or analysis of variance.Variable selection was performed using Lasso regression, and a multivariate logistic regression model was developed to assess predictive performance. Results:The proportion of patients with a bilateral RI total score≥5 was significantly higher in the active group compared to the remission group (50 of 113, 44.3% vs 2 of 92, 2.2%, χ2=55.63, P<0.001). Multivariate logistic regression analysis, after adjustment for confounding variables, identified the SII [ OR(95% CI)=1.01(1.00, 1.01), P<0.001], bilateral RI total score [ OR(95% CI)=1.67(1.29, 2.26), P<0.001], erythrocyte sedimentation rate [ OR(95% CI)=1.19(1.11, 1.30), P<0.001], and mean corpuscular hemoglobin concentration [ OR(95% CI)=1.09(1.03, 1.17), P<0.001] as independent risk factors for active AS. Conversely, lymphocyte count [ OR(95% CI)=0.42(0.18, 0.92), P=0.030] and globulin [ OR(95% CI)=0.89(0.80, 0.99), P=0.040] were significantly associated with protective effects. The bilateral RI total score demonstrated the strongest predictive effect, with each 1-point increase associated with a 67% elevation in the risk of active disease. ROC curve analysis indicated that the area under the curve (AUC) for predicting whether AS is in the active disease phase was 0.94 for the combined model (SII+bilateral RI total score), compared with 0.93 for the SII-alone model and 0.92 for the bilateral RI total score-alone model, demonstrating superior predictive performance of the combined model (SII+bilateral RI total score). An online prediction tool has been developed based on the combined model. Conclusion:The dual-track prediction model, which integrates local joint hemodynamic characteristics and systemic immune-inflammatory status, facilitates a multidimensional assessment of the risk of active AS and provides an objective basis for early identification.
6.Analysis of follow-up and prognosis in pediatric rheumatic diseases associated with pulmonary embolism
Tong YUE ; Yuchun YAN ; Min KANG ; Jia ZHU ; Yingjie XU ; Dan ZHANG ; Ming LI ; Min WEN ; Feifei WU ; Jianming LAI
Chinese Journal of Pediatrics 2026;64(1):89-94
Objective:To explore the clinical characteristics, diagnosis and treatment strategies, and prognosis of pulmonary embolism (PE) complicating childhood rheumatic diseases.Methods:A retrospective case series study was performed on the demographic data, laboratory indicators, imaging features, treatment regimens, and follow-up data of 8 children with rheumatic diseases complicated by PE who were admitted to the Department of Rheumatology and Immunology, Capital Center for Children′s Health, Capital Medical University from January 2014 to October 2023.Results:Among the 8 children, there were 4 boys and 4 girls, with an age of 12.0 (7.5, 13.0) years. Among the primary diseases, there were 3 cases of systemic lupus erythematosus, 2 cases of Beh?et′s disease, 2 cases of Takayasu arteritis, and 1 case of antiphospholipid syndrome. All children developed PE during the active phase of the primary disease. PE was detected at the onset of the primary disease in 3 cases, and the median time from the diagnosis of the primary disease to the development of PE was 10.0 (6.0, 25.0) months in the remaining 5 cases. Fever was present in all 8 children, 4 cases were accompanied by chest tightness, dyspnea, etc., and 2 cases only presented with fever. Laboratory examinations revealed the following results: erythrocyte sedimentation rate was 42.0 (17.0, 78.0) mm/1 h, high-sensitivity C-reactive protein was 12.7 (2.6, 78.7) mg/L, white blood cell count was 9.6 (7.2, 18.7)×10 9/L; D-dimer was 2.3 (0.9, 6.2) mg/L; and hemoglobin was (109±16) g/L.Imaging examinations revealed that 5 cases had involvement of the bilateral lower pulmonary arteries, 5 cases had peripheral embolism, and 3 cases had central PE. Complications included 3 cases of deep vein thrombosis, 2 cases of intracranial venous sinus thrombosis, and 1 case of mild pulmonary hypertension.In terms of treatment, 7 cases received anticoagulation with heparin followed by warfarin. Immunomodulation was mainly based on glucocorticoids combined with immunosuppressants, and 4 cases were combined with biological agents. The follow-up time of 4.17 (1.75, 7.17) years, the time for complete absorption of PE was 10.5 (6.0, 18.0) months; all 8 children had no target events, with no recurrence or chronic thromboembolic pulmonary hypertension, and the pulmonary artery remodeling was good. Conclusions:PE complicating childhood rheumatic diseases is closely related to the activity of the primary disease. The clinical manifestations are insidious, with fever as the main symptom. Imaging examination is the key to diagnosis.Early adoption of heparin followed by warfarin anticoagulation and glucocorticoids combined with immunosuppressants and (or) biological agents to control the primary disease can achieve a favorable prognosis.
7.Cerium dioxide nanoparticles regulate expression of inflammatory factors in M1 macrophages and affect fibroblast co-culture system
Peisen XIE ; Zhenpeng GUAN ; Xianjie WEI ; Keshi ZHANG ; Qingyuan KANG ; Wentao XIAO ; Xiaoshuai GUO
Chinese Journal of Tissue Engineering Research 2026;30(2):375-383
BACKGROUND:Macrophage polarization plays a key role in chronic inflammatory joint diseases such as rheumatoid arthritis.Cerium dioxide(CeO2)nanoparticles have a wide range of biomedical applications such as modulating the local inflammatory microenvironment of tissues.OBJECTIVE:To investigate the role of CeO2 nanoparticles on macrophage polarization and inflammatory factor expression,as well as inflammatory modulation in a co-culture system of macrophages and fibroblasts.METHODS:(1)CeO2 nanoparticles were dispersed and observed morphologically by transmission electron microscopy.(2)Human leukemia monocytes(THP-1)were induced to differentiate and establish the M1 macrophage pro-inflammatory cell model of rheumatoid arthritis.The cells were divided into M0 group(undifferentiated macrophages),M1 group(successful macrophage modeling),CeO2 nanoparticle treatment group(M1 group with CeO2 nanoparticle treatment),and dexamethasone control group(M1 group with dexamethasone treatment)and incubated for 48 hours.The effects of CeO2 nanoparticles on the expression of inflammatory factors(endogenous nitric oxide synthase,CD86,CD80)in M1 macrophages and M1 macrophage phenotype(CD80,CD206)were detected by RT-qPCR,western blot assay,and flow cytometry.(3)A co-culture system of macrophages and fibroblasts was established,and CeO2 nanoparticles acted on the upper macrophages.The regulation of CeO2 nanoparticles on the expression of inflammatory factors(interleukin-6,tumor necrosis factor-α,cyclooxygenase-2,and endogenous nitric oxide synthase)of fibroblasts in the co-culture system was observed at the mRNA and protein levels.RESULTS AND CONCLUSION:(1)Transmission electron microscopy showed that the diameter of CeO2 nanoparticles was(19.5±2.0)nm.(2)Compared with the M0 group,the mRNA of endogenous nitric oxide synthase and CD86,and the protein expression of endogenous nitric oxide synthase and CD80 in the M1 group were upregulated.Compared with the M1 group,the mRNA expression of endogenous nitric oxide synthase and CD86,and the protein expression of endogenous nitric oxide synthase and CD80 in the CeO2 nanoparticle treatment group were downregulated.Flow cytometry showed that 20 nm CeO2 nanoparticles downregulated the number of M1 macrophages.(3)Compared with the M1 group,20 nm CeO2 nanoparticles downregulated the mRNA and protein expression of inflammatory factors(tumor necrosis factor α,interleukin 6,cyclooxygenase 2,and endogenous nitric oxide synthase)in the co-culture system HFL1 cells.(4)The results showed that 20 nm CeO2 nanoparticles can alleviate inflammation in the co-culture system by inhibiting the expression of pro-inflammatory factors in M1 macrophages,providing a new idea for the treatment of inflammatory diseases such as rheumatoid arthritis.
8.Mitogen-activated protein kinase signaling pathway regulates the development of osteoarthritis:guiding targeted therapy with traditional Chinese medicine
Hao LI ; Hongcheng TAO ; Ping ZENG ; Jinfu LIU ; Qiang DING ; Chicheng NIU ; Kai HUANG ; Hongyu KANG
Chinese Journal of Tissue Engineering Research 2026;30(6):1476-1485
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.
9.Relationship between Alzheimer's disease and sarcopenia and body mass index:analysis of GWAS datasets for European populations
Qiwang HE ; Bo CHEN ; Fuchao LIANG ; Zewei KANG ; Yuan ZHOU ; Anxu JI ; Xialin TANG
Chinese Journal of Tissue Engineering Research 2026;30(4):1036-1046
BACKGROUND:Alzheimer's disease has been associated with sarcopenia,but a causal relationship has not been established.Exploring the causal relationship between the two most common disability-burdening diseases in the aging population-Alzheimer's disease and sarcopenia-and their potential mediating factors holds certain implications for further alleviating the healthcare costs and socioeconomic burden for older adults in China.OBJECTIVE:To explore the potential causal relationship between Alzheimer's disease and sarcopenia in the general population using a Mendelian randomization study and to explore the role of body mass index in this context.METHODS:Two-sample Mendelian randomization analysis based on published genome-wide association studies(GWAS)were used to infer causality,and univariate Mendelian randomization and mediation analyses were used in the study design.Through the Integrative Epidemiology Unit(IEU)database,ieu-b-2 was selected as the Alzheimer's disease dataset(sample size:63 926),ieu-b-4816 as the body mass index dataset(99 998),ebi-a-GCST90000027 as the appendicular lean mass dataset(244 730),ukb-b-7478 as the left hand grip strength dataset(461 026),ukb-b-10215 as the right hand grip strength dataset(461 089)and ukb-b-4711 as the walking pace dataset(459 915).Inverse-variance weighting was used as the primary analysis method,and the results were validated by pleiotropy and heterogeneity analysis.The Steiger Directionality Test was performed to validate the reasonableness of the causal direction.RESULTS AND CONCLUSION:(1)The Mendelian randomization analyses provided evidence that Alzheimer's disease predicted the risk of appendicular lean mass[odds ratio(OR)=1.009;95%confidence interval(Cl),1.001-1.017;P=0.023),and walking pace(OR=1.010;95%Cl,1.003-1.017;P=0.008).No correlation with hand grip strength was observed.(2)Alzheimer's disease was negatively correlated with body mass index(OR=0.893;95%Cl,0.811-0.984;P=0.022);body mass index was positively correlated with appendicular lean mass(OR=1.084;95%Cl,1.031-1.141;P=0.002)and negatively correlated with walking pace(OR=0.975;95%Cl,0.969-0.980;P<0.001).(3)Mediation analyses showed that the causal relationship between Alzheimer's disease and appendicular lean mass and walking pace was partially mediated by body mass index,with the proportion of mediations being 50.25%and 32.11%,respectively.(4)The results of this study suggest that based on large-scale population studies,genetic prediction of Alzheimer's disease is a potential risk factor for sarcopenia,in which body mass index plays an important mediating role.This suggests that in clinical practice,attention should be paid to the muscle condition of patients with Alzheimer's disease,and weight management should be implemented,as maintaining a body mass index within the normal high range may have a preventive effect on the occurrence of sarcopenia in patients with Alzheimer's disease.However,further research is needed to verify the applicability of this conclusion to other ethnic groups.This study utilized an international public database for analysis,providing a reference for research on the correlation between Alzheimer's disease and sarcopenia in the Chinese population.It also highlights the significant mediating role of body mass index,offering insights for further prevention and treatment of sarcopenia among Chinese individuals.
10.Finite element analysis of implants with different crown-to-implant ratios under different bone conditions
Zirui KANG ; Yang WU ; Hailong SONG ; Qiaoyun YANG ; Lixiang ZANG ; Dongliang XU
Chinese Journal of Tissue Engineering Research 2026;30(2):319-328
BACKGROUND:Clinical studies suggest that both bone quality and excessive crown-to-implant ratio are factors that affect the success rate of implant surgery,but there is no consensus on how large the crown-to-implant ratio under each bone quality will affect the prognosis of implant repair.OBJECTIVE:To analyze the stress and strain of bone tissue around implant restorations with different crown-to-implant ratios under different bone types after stress loading using three-dimensional finite element method.Combined with the Frost bone mechanics regulation system theory,the physiological limits of bone strain were observed for each bone type within a certain range of crown to implant ratios.METHODS:Cone beam CT data were selected from a patient to establish solid bone block models with four different bone types(class Ⅰ bone:cortical bone thickness 3 mm+dense cancellous bone,class Ⅱ bone:cortical bone thickness 2 mm+relatively dense cancellous bone,class Ⅲ bone:cortical bone thickness 1 mm+relatively low-density cancellous bone,class Ⅳ bone:cortical bone thickness 1 mm+low-density cancellous bone).Implant restorations with five different crown-to-implant ratios(1,1.5,2,2.5,and 3)were created on each bone block model,for a total of 20 models.Vertical and oblique forces were applied to the dental crown to observe the von Mises stress values,strains,and displacement of the cortical and cancellous bones,as well as the degree of implant displacement.RESULTS AND CONCLUSION:(1)In the class Ⅰ bone model,when the crown-to-implant ratio reached 3 under oblique loading,the cortical bone strain exceeded the physiological limit.In the class Ⅱ bone model,under oblique loading,when the crown-to-implant ratio reached 2.5,the cortical bone strain exceeded the physiological limit.In the class Ⅲ bone model,under oblique loading,cortical bone exceeded the physiological limit when the crown-to-implant ratio reached 2.5,while cancellous bone reached the critical physiological limit at 1.In the class Ⅳ bone model,under oblique loading,when the crown-to-implant ratio reached 1.5,2,2.5,and 3,the cortical bone strain exceeded the physiological limit.In the class Ⅳ bone model,all five crown-to-implant ratios of cancellous bone exceeded physiological limits.(2)Under vertical load,the cancellous bone strain exceeded the physiological limit when the crown-root ratio reached 1,2,2.5,and 3 in the class Ⅲ bone model,and when the cancellous bone strain of the five crown-root ratios in the class Ⅳ bone model exceeded the physiological limit.(3)Under oblique or vertical load,the implant displacement of the 20 groups of models did not exceed 100 μm.(4)From the perspective of biomechanics,when patients with insufficient bone height choose implant restoration,the crown-root ratio that class Ⅰ bone can tolerate is up to 2.5 times,the crown-root ratio that class Ⅱ bone can tolerate is up to 2 times,and the crown-root ratio that class Ⅲ and class Ⅳ bones can tolerate is up to 1 times due to excessive strain of cancellous bone;but the crown-root ratio that cortical bone in class Ⅲ bone can tolerate is up to 2 times.Whether class Ⅲ bone can tolerate implant restoration with a high crown-root ratio and whether cancellous bone can tolerate higher strains needs further study.

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