1.Risk factor analysis of acute kidney injury after orthotopic liver transplantation
Chun ZHANG ; Ting LIN ; Jingyao ZHANG ; Xiaogang ZHANG ; Zheng WANG ; Xuemin LIU ; Bo WANG ; Liang YU ; Yi LYU ; Chang LIU
Chinese Journal of Digestive Surgery 2018;17(5):488-496
Objective To investigate the risk factors and prognosis of acute kidney injury (AKI) after orthotopic liver transplantation (OLT).Methods The retrospective case-control study was conducted.The clinical data of 127 patients who underwent OLT in the First Affiliated Hospital of Xi'an Jiaotong University from January 2013 to December 2015 were collected.Of 127 patients,24 were complicated with postoperative AKI,including 17 in grade 1,5 in grade 2 and 2 in grade 3,and 103 were not complicated with AKI.AKI after OLT was treated according to the diagnostic criteria of AKI from 2012 guidelines of Kidney Disease:Improving Global Outcomes (KDIGO).Observation indicators:(1) risk factors analysis affecting AKI after OLT;(2) comparison of postoperative recovery in patients with different AKI grade;(3) follow-up and survival situations.Follow-up using outpatient examination and telephone interview was performed up to July 2017.Measurement data with nornal distribution were represented as x±-s,and measurement data with skewed distribution were described as M (range).Univariate analysis was done using the t test and rank sum test.Comparisons of count data and univariate analysis were done using chi-square test or Fisher exact probability.Multivariate analysis was done using the logistic regression model.The survival rate and curve were respectively calculated and drawn by the KaplanMeier method,and Log-rank test was used for survival analysis.Results (1) Risk factors analysis affecting AKI after OLT:results of univariate analysis showed that age,combined hypertension,preoperative Child-Pugh score,preoperative model for end-stage liver disease score (MELD),preoperative hemoglobin,preoperative serum albumin,preoperative blood urea nitrogen,preoperative glomerular filtration rate,preoperative prothrombin time,operation time,inferior vena cava occlusion time,duration of anhepatic phase,volume of intraoperative blood loss,total volume of intraoperative blood transfusion,volumes of intraoperative plasma and red blood cells transfusion,duration of postoperative ICU stay,use time of postoperative vasoactive drugs,time of postoperative mechanical ventilation,cases with postoperative infection,body mass index of donor and donor liver cold-ischemia time were related factors affecting occurrence of AKI after OLT (t =4.154,x2 =8.482,t =5.129,3.694,1.294,9.223,5.418,Z=4.287,t=2.105,5.168,8.182,10.042,Z=1.074,0.664,6.274,3.712,1.289,t=1.056,x2 =10.617,t=2.447,3.371,1.476,P<0.05).Results of multivariate analysis showed that age,preoperative MELD score,preoperative serum albumin,volume of intraoperative blood loss and donor liver cold-ischemia time were independent factors affecting occurrence of AKI after OLT [odds ratio (OR) =0.812,0.866,1.392,1.001,0.516,95% confidence interval:0.717-0.919,0.751-0.997,1.104-1.755,1.000-1.001,0.282-0.944,P<0.05].(2) Comparison of postoperative recovery in patients with different AKI grade:cases with complete recovery,partial recovery and chronic renal failure were respectively 14,3,0 in 17 patients with grade 1 of AKI and 3,2,0 in 5 patients with grade 2 of AKI and 0,1,1 in 2 patients with grade 3 of AKI,with a statistically significant difference (x2=14.140,P<0.05).(3) Follow-up and survival situations:127 patients were followed up for 9-44 months,with a median of 23 months.The 1-year overall survival rate of 127 patients was 95.3%.During the follow-up,22 patients died,including 9 with multiple organ failure,8 with primary disease recurrence and 5 with respiratory complication.The median overall survival time after OLT was 36 months in 24 patients with AKI and 40 months in 103 patients without AKI,with no statistically significant difference (x2=3.033,P>0.05).Conclusion Age,preoperative MELD score,preoperative serum albumin,volume of intraoperative blood loss and donor liver cold-ischemia time are independent factors affecting occurrence of AKI after OLT,and there is better recovery in patients with grade 1 of AKI.
2. Meta-analysis on safety and efficacy of dual antiplatelet therapy combining with proton pump inhibitors for patients after percutaneous coronary intervention
Qianqiu CHE ; Qiang WU ; Yubo LIANG ; Runmin SUN ; Qianwen LYU ; Junli MA ; Hao HU ; Xin LIN ; Guangli XU ; Shougang SUN ; Chun ZHANG ; Qiongying WANG ; Jing YU ; Feng BAI
Chinese Journal of Cardiology 2019;47(2):129-140
Objective:
To analyze the impact of dual antiplatelet (DAPT) therapy combining with or without proton pump inhibitors (PPI) on the main outcomes after percutaneous coronary intervention (PCI).
Methods:
The PubMed, EMBASE and Cochrane Library were searched for relevant literature and the references obtained from these sources were retrieved manually from inception till September 2017. Inclusion and exclusion criteria were established follow the Cochrane review standard. A total of 977 literatures were included, 193 duplicates were excluded, 74 reviews, case reports, letters and systematic reviews were excluded, 667 literatures were excluded after reading the title and abstract, 34 literatures were excluded due to non-randomized control studies and unrelated outcome indicators, and 9 literatures were finally included with a total of 16 589 patients. RevMan 5.3 software was used to compare the incidence of major adverse cardiovascular events (MACE), cardiogenic death, recurrent myocardial infarction, target vessel revascularization, all-cause death, stent thrombosis, stroke, gastrointestinal bleeding and gastrointestinal events in patients with DAPT combining with or without PPI after PCI.
Results:
MACE was observed in 8 out of the 9 included literatures, and the results showed that MACE occurred in 561 out of 6 282 patients receiving DAPT combining with PPI therapy and in 951 out of 9 632 patients using DAPT alone (
3.Perianal swabs surveillance cultures of Carbapenem-resistant Enterobacteriaceae(CRE) can be hints for CRE bloodstream infection in patients with hematological diseases.
Chun Hui XU ; Yang SU ; Yan Xia LYU ; Zhi Ying TIAN ; Fu Jun SUN ; Qing Song LIN ; Chuan WANG
Chinese Journal of Hematology 2018;39(12):1021-1025
Objective: To analyze the hints role of surveillance cultures of Carbapenem-resistant Enterobacteriaceae (CRE) by perianal swabs in patients with hematological diseases, and seek risk factors of CRE bloodstream infection. Methods: The resistance of CRE from 2 914 patients with hematological diseases who cultured perianal swabs, CRE bloodstream infection and risk factors were analyzed during January 2016 to December 2017. Results: In this study, perianal swabs from 2 914 patients with hematological diseases were cultured, 74 patients were CRE positive, and bloodstream infection with CRE was found in 13 of these patients. A total of 87 CRE strains were isolated (The same patient only keep the first one for the same location), including 31 Klebsiella pheuminiae, 43 Escherichia coli, 8 Enterobacter cloacae and 6 other Enterobacteriaceae. The resistance rates to piperacillin / tazobactam, imipenem, meropenam, amikacin, levofloxacin, tigecycline were 91.9%, 74.4%, 98.8%, 17.6%, 74.4% and 8.0%, respectively. Resistance to carbapenem, aminoglycoside, quinolones and tegacycline were highly consistent between two sites from 13 patients, whose both perianal swabs and blood were positive in CRE cultures. Febrile neutropenic time, digestive tract symptoms and perianal infection were independent risk factors for bloodstream infection in patients with perianal swabs positive results, the odds ratios (OR) were 1.10 (P=0.029), 1.13 (P=0.005) and 1.23 (P=0.016), respectively. Conclusion: Perianal swabs surveillance cultures of CRE can be hints for CRE bloodstream infection in patients with hematological diseases, and also can provide suggestions for antibiotics. Long time of febrile neutropenic, digestive tract symptoms and perianal infection can be the early warning for CRE bloodstream infections.
Anti-Bacterial Agents
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Bacteremia
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Carbapenem-Resistant Enterobacteriaceae
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Carbapenems
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Enterobacteriaceae Infections
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Hematologic Diseases
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Humans
4.Correlation between chemokine CX3C ligand 1, CX3C chemokine receptor 1 and heart function grade, prognosis in patients with chronic heart failure
Chun YANG ; Lei LYU ; Yugang YIN ; Lin CHEN
Chinese Journal of Postgraduates of Medicine 2024;47(9):780-785
Objective:To analyze the correlation between chemokine CX3C ligand 1 (CX3CL1), CX3C chemokine receptor 1 (CX3CR1) and heart function grade, prognosis in patients with chronic heart failure (CHF).Methods:The clinical data of 200 patients with CHF from June 2021 to June 2023 in General Hospital of Eastern Theater of the Chinese People′s Liberation Army and Wuhan Asia Heart Hospital were retrospectively analyzed, and all patients received standardized treatment for heart failure. The baseline clinical data were recorded; the levels of CX3CL1 and CX3CR1 were detected by enzyme linked immunosorbent assay; the heart function grade was evaluated by New York Heart Association (NYHA) heart function grade method. The patients were followed up until December 2023, the patients were divided into poor prognosis group (all-cause death and readmission due to heart failure) and good prognosis group based on their prognosis. Pearson method was used for correlation analysis. Multivariate Logistic regression analysis was used to analyze the independent risk factors of poor prognosis in patients with CHF.Results:Among the 200 patients, NYHA heart function grade Ⅰ to Ⅱ was in 80 cases, Ⅲ to Ⅳ in 120 cases. The levels of CX3CL1 and CX3CR1 in patients with NYHA heart function grade Ⅲ to Ⅳ were significantly higher than those in patients with NYHA heart function grade Ⅰ to Ⅱ: (3.34 ± 0.45) mg/L vs. (2.45 ± 0.26) mg/L and (8.71 ± 0.92) mg/L vs. (2.53 ± 0.35) mg/L, and there were statistical differences ( t = 15.99 and 57.34, P<0.01). The proportion of age<60 years old, rate of coronary heart disease, CX3CL1, CX3CR1, body mass index and high-sensitivity C-reactive protein in poor prognosis group (40 cases) were significantly higher than those in good prognosis group (160 cases): 82.50% (33/40) vs. 10.62% (17/160), 90.00% (36/40) vs. 68.12% (109/160), (3.26 ± 0.77) mg/L vs. (2.25 ± 0.27) mg/L, (8.35 ± 2.01) mg/L vs. (2.48 ± 0.31) mg/L, (26.80 ± 3.55) kg/m 2 vs. (24.74 ± 2.76) kg/m 2 and (9.31 ± 2.19) mg/L vs. (3.58 ± 2.28) mg/L, the rate of smoking history and left ventricular ejection fraction were significantly lower than those in good prognosis group: 37.50% (15/40) vs. 46.88% (75/160) and (30.14 ± 5.77)% vs. (59.40 ± 6.58)%, and there were statistical differences ( P<0.01). Pearson correlation analysis result showed that the CX3CL1 and CX3CR1 were positively correlated with NYHA heart function grade ( r = 0.29 and 0.34, P<0.05), and negatively correlated with prognosis ( r = - 0.54 and - 0.36, P<0.05). Multivariate Logistic regression analysis result showed that the CX3CL1 and CX3CR1 were the independent risk factors of poor prognosis in patients with CHF ( OR = 2.110 and 1.566, 95% CI 0.445 to 3.125 and 0.270 to 3.455, P<0.01). Conclusions:The CX3CL1 and CX3CR1 are closely related to the heart function grade in patients with CHF. At the time of CHF patient admission, it may be considered to combine the two indicators for preliminary evaluation of and provide targeted interventions to improve prognosis.
5.Expressions of matrix metalloproteinase 7 and secretory leukocyte protease inhibitor in papillary thyroid carcinoma and their significances
Feng GAO ; Guang-Rong LIN ; Li-Hang XING ; Sheng-Tao LI ; Peng ZHAO ; Chun-Hui LYU
Chinese Journal of Current Advances in General Surgery 2023;26(12):943-946
Objective:To investigate the expressions of matrix metalloproteinase 7(MMP7)and secretory leukocyte protease inhibitor(SLPI)in papillary thyroid carcinoma(PTC)and their signifi-cances.Methods:Based on the gene expression data of thyroid cancer in the tumor Genome Atlas(TCGA)database,a total of 567 samples were collected,including 509 cancer tissues and 58 normal tissues.The gene matrix data were extracted and sorted out.Two groups of differentially expressed genes were screened by using the R language edger package,and the potential key genes were screened by the mcode plug-in in Cytoscape.Select a key gene and mine closely related genes through the UALCAN database.Immunohistochemical SABC method was used to detect the ex-pressions of MMP7 and SLPI proteins in PTC tissues and their paracancerous tissues collected from 69 patients in Binzhou People's Hospital Affiliated to Shandong First Medical University from January 2020 to June 2021,and the association of expression levels of MMP7 and SLPI with the clinico-pathological factors of PTC patients was also analyzed.Results:Based on the data of TCGA database,1471 genes were obtained,of which 1000 were up-regulated and 471 were down-regu-lated.Through the mcode plug-in in Cytoscape,20 key genes were screened(MMP7,CCL18,CYR61,SPECC1,CRABP2,PLXNA3,KRT17,TMEM59L,RETN,SRF,ITGB4,PPL,PLEKHN1,RMI2,LCN6,SPX,NRIP1,ARHGEF28,SLC39A14,SNCA).Through the UALCAN database,the correlation between MMP7 and SLPI was retrieved(Pearson correlation coefficient was 0.5,P<0.05).The results of immunohistochemistry showed that the positive expression rates of MMP7 and SLPI proteins in PTC tissues were significantly higher than those in paracancerous tissues[82.6%(57/69)vs 29.0%(20/69),71.0%(49/69)vs 15.9%(11/69)],and the differences were statistically significant(x2 val-ues were 40.222 and 42.579,both P<0.01).The expressions of MMP7 and SLPI in PTC tissues were correlated with TNM stage,differentiation,extramembranous invasion and lymph node metastasis(all P<0.05).There was a positive correlation between MMP7 and SLPI proteins expressions in PTC(r=0.381,P=0.001).Conclusions:The interaction between MMP7 and SLPI proteins can be in-volved in the development and progression of PTC.
6.Radix Angelica Sinensis and Radix Astragalus ultrafiltration extract improves radiation-induced pulmonary fibrosis in rats by regulating NLRP3/caspase-1/GSDMD pyroptosis pathway
Chun-Zhen REN ; Jian-Fang YUAN ; Chun-Ling WANG ; Xiao-Dong ZHI ; Qi-Li ZHANG ; Qi-Lin CHEN ; Xin-Fang LYU ; Xiang GAO ; Xue WU ; Xin-Ke ZHAO ; Ying-Dong LI
Chinese Pharmacological Bulletin 2024;40(11):2124-2131
Aim To investigate the mechanism of py-roptosis mediated by the NLRP3/caspase-1/GSDMD signaling pathway and the intervention effect of Radix Angelica Sinensis and Radix Astragalus ultrafiltration extract(RAS-RA)in radiation-induced pulmonary fi-brosis.Methods Fifty Wistar rats were randomly di-vided into five groups,with ten rats in each group.Ex-cept for the blank control group,all other groups of rats were anesthetized and received a single dose of 40 Gy X-ray local chest radiation to establish a radiation-in-duced pulmonary fibrosis rat model.After radiation,the rats in the RAS-RA intervention groups were orally administered doses of 0.12,0.24 and 0.48 g·kg-1 once a day for 30 days.The average weight and lung index of the rats were observed after 30 days of contin-uous administration.Hydroxyproline(HYP)content in lung tissue was determined by hydrolysis method.The levels of IL-18 and IL-1 β in serum were detected by ELISA.Lung tissue pathological changes were ob-served by HE and Masson staining.Ultrastructural changes in lung tissue were observed by transmission e-lectron microscopy.The expression levels of NLRP3/caspase-1/GSDMD pyroptosis pathway-related proteins and fibrosis-related proteins in lung tissue were detec-ted by Western blot.Results Compared with the blank group,the HYP content in lung tissue and the levels of IL-18 and IL-1 β in serum significantly in-creased in the model group(P<0.01).HE and Mas-son staining showed inflammatory cell infiltration and collagen fiber deposition.Transmission electron mi-croscopy revealed increased damaged mitochondria,disordered arrangement,irregular morphology,shallow matrix,outer membrane rupture,mostly fractured and shortened cristae,mild expansion,increased electron density of individual mitochondrial matrix,mild sparse structure of lamellar bodies,partial disorder,unclear organelles,and characteristic changes of pyroptosis.Western blot analysis showed increased expression of caspase-1,GSDMD,NLRP3,CoL-Ⅰ,α-SMA,and CoL-Ⅲ proteins(P<0.01).Compared with the model group,the RAS-RA intervention group showed signifi-cant improvement in body mass index and lung index of rats,decreased levels of IL-18 and IL-1 β inflammatory factors(P<0.01),improved mitochondrial structure,reduced degree of fibrosis,and decreased expression of caspase-1,GSDMD,NLRP3,COL-Ⅰ,COL-Ⅲ,and α-SMA proteins in lung tissue(P<0.01).Conclusion RAS-RA has an inhibitory effect on radiation-in-duced pulmonary fibrosis,and its mechanism may be related to the inhibition of pyroptosis through the regu-lation of the NLRP3/caspase-1/GSDMD signaling pathway.
7.New situation and new strategies——research and development and internationalization of new drugs and health products of traditional Chinese medicine
Ning JIANG ; Chun-Hui QI ; Liang CAO ; Lan-Ying CHEN ; Jin-Hui GU ; Yong KANG ; Inkyeom KIM ; Xiao-Yuan LIAN ; Yin LU ; Gui-Yuan LYU ; Ke NIE ; Yun QI ; SCHINI-KERTH VALÉRIE ; SPEDDING MICHAEL ; WAINWRIGHT CHERRY ; Yue-Hua WANG ; Wei XIAO ; Yong YANG ; Lin-Zhong YU ; Dan-Shen ZHANG ; Yong-He ZHANG ; Wen-Xia ZHOU ; Guan-Hua DU ; Yong-Xiang ZHANG
Chinese Journal of Pharmacology and Toxicology 2018;32(1):1-50
The 2017 China (Lianyungang) International Medical Technology Conference was held in Lianyungang,Jiangsu Province during November 15-17,2017.During this conference,the Division for Traditional Chinese Medicine and Natural Products Pharmacology of Chinese Pharmacological Society (CNPHARS) and Jiangsu Kanion Pharmaceutical Co. Ltd.jointly held the Forum on R&D and Interna-tionalization of New Drugs and Health Products of Traditional Chinese Medicine.The forum was co-chaired by Professor ZHANG Yong-xiang, President of CNPHARS, Chair of Division for Traditional Chinese Medicine and Natural Products Pharmacology of CNPHARS,and Chair of the Natural Product Section of Inter-national Union of Basic&Clinical Pharmacology(IUPHAR), Professor DU Guan-hua,former President of CNPHARS and Vice-Chair of Division for Traditional Chinese Medicine and Natural Products Pharmacology of CNPHARS,and Dr.XIAO Wei,Chairman of the Board of Jiangsu Kanion Pharmaceutical Co. Ltd. And Vice-Chair of Division for Traditional Chinese Medicine and Natural Products Pharmacology of CNPHARS. More than 70 scholars attended the forum, including four foreign experts [Michael SPEDDING, Secretary-General of IUPHAR; Professor Valérie B. SCHINI-KERTH, Vice-Chair of the Natural Product Section of IUPHAR; Professor Cherry WAINWRGHT, Director of Centre for Natural Product Drugs of Robert Gordon University; Professor InKyeom KIM, Director of the Korean Society of Pharmacology], members of the Division for Traditional Chinese Medicine and Natural Products Pharmacology of CNPHARS and leading researchers at Jiangsu Kanion Pharmaceutical Co.,Ltd.GU Jin-hui,Director of the Division of National Science and Technology Major Project for Drug Innovation,Department of Health Science,Technology and Education,National Health and Family Planning Commission of the People's Republic of China was also invited to attend the forum. Representatives discussed the R&D and internationalization of new drugs and health products of traditional Chinese medicine.The summary of views and advice of some experts was published here for the purpose of promoting domestic and overseas academic exchange, and playing an active role in improving the level of R&D and internationalization of new drugs and health products of traditional Chinese medicine in China.
8.A novel dammarane-type saponin from Gynostemma pentaphyllum and its neuroprotective effect.
Hui LIU ; Shao-Fang XING ; Wei-Ye CUI ; Ma-Li ZU ; Chun-Lin LYU ; Xiang-Lan PIAO
China Journal of Chinese Materia Medica 2021;46(2):380-387
One new and two known dammarane-type saponins were isolated from the leaves of Gynostemma pentaphyllum using various chromatographic methods. Their structures were identified by HR-ESI-MS,~( 1)H-NMR, ~(13)C-NMR, 2 D-NMR spectra as 2α,3β,12β,20,24(S)-tetrahdroxydammar-25-en-3-O-[β-D-glucopyranosyl(1→2)-β-D-glucopyranosyl]-20-O-β-D-xylopyranosyl(1→6)-β-D-glucopyranoside(1, a new compound, namely gypenoside J5) and 2α,3β,12β,20,24(R)-tetrahdroxydammar-25-en-3-O-[β-D-glucopyranosyl(1→2)-β-D-glucopyranosyl]-20-O-β-D-xylopyranosyl(1→6)-β-D-glucopyranoside(2) and 2α,3β,12β,20-tetrahydroxy-25-hydroperoxy-dammar-23-en-3-O-[β-D-glucopyranosyl(1→2)][β-D-glucopyranosyl]-20-O-[β-D-xylopyranosyl(1→6)]-β-D-glucopy-ranoside(3), respectively. Compounds 1 and 2 were a pair of C-24 epimers. All compounds showed weak cytotoxicity agxinst H1299, HepG2, PC-3, SH-SY5 Y cancer cell lines. However, they exerted protective effect against SH-SY5 Y cellular damage induced by H_2O_2 dose-dependently, of which compound 1 displayed the strongest antioxidant effect. The present study suggested that G. pentaphyllum has antioxidative potential and the saponins from G. pentaphyllum are considered as the active compounds with neuroprotecitve effect.
Gynostemma
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Molecular Structure
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Neuroprotective Agents/pharmacology*
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Saponins/pharmacology*
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Triterpenes/pharmacology*
9.Study of microscopic effects of low-intensity pulsed ultrasound on bone lacunar-canalicular system
Jia-Ming WANG ; Xiao-Guang ZHANG ; Xuan LI ; Lin-Wei LYU ; Chun-Qiu ZHANG
Chinese Medical Equipment Journal 2023;44(11):27-33
Objective To explore the microscopic effects of low-intensity pulsed ultrasound(LIPUS)on bone lacunar-canalicular system(LCS).Methods Three consecutive bone cells from the real bone tissue were selected and used to build a LCS model with SolidWorks software,then the LCS model was imported into finite element analysis software COMSOL.LIPUS irradiation was performed on the top of the LCS model to analyze the distribution of the acoustic and thermal fields of the model under different conditions.Results After ultrasonic irradiation of the LCS model,the farther away from the ultrasonic incidence surface,the lower the acoustic field sound pressure was,and the distribution of the sound pressure inside the model had left-right symmetry;the acoustic field sound pressure inside the LCS model increased with the enhancement of the excitation sound pressure;the closer to the ultrasound focusing region,the denser the temperature contours.Conclusion The distribution laws of acoustic and thermal fields within the LCS are revealed from a microscopic point of view,and theoretical references are provided for LIPUS experiments and treatment.[Chinese Medical Equipment Journal,2023,44(11):27-33]
10.Design and finite element analysis of experimental device for simulating interface micro motion of bone trabecular prosthesis
Guang-Hui SHI ; Xiao-Guang ZHANG ; Xuan LI ; Lin-Wei LYU ; Chun-Qiu ZHANG
Chinese Medical Equipment Journal 2024;45(1):25-30
Objective To design an experimental device for simulating the interface micro motion of bone trabecular prosthesis and carry out the finite element analysis.Methods The experimental device was composed of a screw-in cylinder with threads,a flexible hinge,a micro-motion rod,a trabecular prosthesis,a connecting rod and a fixation post.A model of the experimental device was constructed with SolidWorks software,and then imported into ABAQUS software to establish a finite element model.An axial displacement load was applied to the femur to analyze the effects of the position of the flexible hinge,the gap between the prosthesis and the femur and the length of the connecting rod on the micro motion.Results The interface micro motion produced by the experimental device increased with the distance of the flexible hinge from the lower end of the screwed-in cylinder;the gap between the prosthesis and the femur did not affect the interface micro motion when the gap was not lower than 20 μm;the interface micro motion rose with the length of the connecting rod.Conclusion The experimental device can accurately simulate the micro motion of different bone trabecular prosthesis interfaces,and can be used for studying the effect of the interface micro motion on osseointegration.[Chinese Medical Equipment Journal,2024,45(1):25-30]