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Objective: To investigate the clinical and pathological features of primary gastric (gastrointestinal)-type mucoglandular lesions of the endometrium. Methods: Eight cases of primary gastric (gastrointestinal)-type mucoglandular lesions of endometrium diagnosed between 2014 to 2022 were retrieved from pathology archives of the Obstetrics and Gynecology Hospital Affiliated to Fudan University, Shanghai, China. The clinical history, pathological sections and follow-ups were analyzed. Results: The eight patients ranged in age from 35 to 67 years, with an average age of 55.5 years. Seven patients were examined for high-risk human papillary virus (HPV) before operation. Only one of them was positive for high-risk HPV52. No cervical mucinous lesions were found in any of the patients. Two cases were invasive gastric (gastrointestinal)-type adenocarcinoma, 2 cases were benign gastric (gastrointestinal)-type mucinous metaplasia, and the other 4 cases were atypical gastric (gastrointestinal)-type mucinous gland hyperplasia. Microscopically, tumor cells showed mucous epithelium with gastrointestinal differentiation. Immunophenotyping showed that MUC6 was diffusely or focally positive in 5 cases, CK20 and CDX2 were positive in 3 cases. And p16 was negative or focally positive in 5 cases and strongly positive in 1 case. ER was expressed in both benign and atypical lesions, and weakly positive or negative in the invasive adenocarcinoma. p53 showed mutant expression in one case and wild-type expression in the rest. HPV in situ hybridization was negative. Conclusions: Primary gastric (gastrointestinal)-type mucoglandular lesions of the endometrium show various forms of gastrointestinal differentiation, which are high-risk HPV independent. Morphology combined with immunohistochemistry is helpful for the diagnosis, which can only be made on exclusion of cervical gastrointestinal glandular lesion, gastrointestinal metastatic carcinoma and the mucinous subtype of endometrioid carcinoma.
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Female , Humans , Middle Aged , Adult , Aged , Uterine Cervical Neoplasms/pathology , Papillomavirus Infections , China , Adenocarcinoma/pathology , Endometrium/pathology , Gastrointestinal Neoplasms/pathology , Biomarkers, Tumor/analysisABSTRACT
Abstract Spleen tyrosine kinase (SYK) is not only a key kinase in the B-cell receptor (BCR) signaling pathway, but also a critical component of other signal transduction pathways such as Fc receptor, complement receptor and integrin. Abnormal activation of SYK closely related to the occurrence and development of hematological malignancies, thus targeting SYK has become a research hotspot. Several SYK inhibitors including Fostamatinib, Entospletinib and Cerdulatinib were being evaluated in clincal trials. As a second generation SYK inhibitor, Entospletinib has achieved good efficacy in lymphoid and myeloid hematologic tumors. Furthermore, Entospletinib can significantly relieve hematopoietic stem cell transplantation(HCT) related graft versus host disease (GVHD). In this review the role of SYK inhibitors in treatment of hematological malignancies is summarized brifely.
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Humans , Graft vs Host Disease , Hematologic Neoplasms , Protein Kinase Inhibitors , Spleen , Syk KinaseABSTRACT
Abstract In recent years, development of the targeted drugs according to the biological characteristics of tumors have provided more treatment options for tumor patients. It was found that the overactivation or abnormality of B cell receptor (BCR) signal pathway closely related to the occurrence and development of various B cell tumors, such as chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL). As a key kinase in the BCR pathway, BTK inhibitors have obvious anti-tumor effect when its activity is being inhibitered. Currently, BTK inhibitors developed include the first-generation Ibrutinib and the second-generation Acalabrutinib, which can be targeted at the inhibition of BTK and its downstream signaling pathway, and have important therapeutic value for a variety of B-cell tumors, such as CLL and partial non-Hodgkin's lymphoma (NHL). However, its side effects and drug-resistance also gradually emerged, effective drug combination therapy has shown a certain clinical activity. This reviews summarizes briefly the mechanism and status of BTK inhibitors in the treatment of various B-cell tumors.
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Hepatic fibrosis refers to the pathological process of abnormal proliferation of connective tissue in the liver caused by various pathogenic factors. Hepatic fibrosis is observed in the whole process of liver injury repair and healing, and long-term chronic injury factors may induce the progression of hepatic fibrosis into liver cirrhosis. Epidemiological data show that there are 1.1805 million new cases of hepatitis B and 243 thousand cases of hepatitis C reported in 2017. Chronic viral hepatitis has brought heavy social and economic burden. Forkhead transcription factor (FOXO) belongs to the forkhead family and plays an important role in various cell life activities. Studies have shown that FOXO1/3 can regulate hepatic stellate cell activity through the TGFβ pathway and thus play an important role in hepatic fibrosis. This article reviews the research advances in the pathogenesis of hepatic fibrosis, the mechanism of action of FOXO1/3 in the regulation of hepatic fibrosis, and targeted therapy for FOXO1/3 (one of the sites for hepatic fibrosis).
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Objective: Microarray chip was used to detect the differentially expressed microRNA (miRNA) in kidney tissues of rats with kidney-Yang deficiency induced by adenine,and its significance was analyzed by bioinformatics method. Method: Rats with kidney-Yang deficiency were induced by intragastric administration of 150 mg·kg-1 adenine in model group, while rats in normal group were given the same amount of saline.Kidney tissues were taken for hematoxylin-eosin (HE) staining pathological sections after anesthesia and blood urea nitrogen (BUN), creatinine (SCr) in blood and 24-hour urinary protein (24U-TP) in urine were measured. μParaflo microfluidic chip technology was used to investigate differential expression miRNA in kidney tissues, and microarray results were verified by Real-time PCR. Bioinformatics database was used to analyze the target genes and functions of differential expression miRNAs. Result: Gene chip results showed that there were 50 differentially expressed microRNAs after modeling. Compared with control group, only 9 miRNAs were highly expressed in kidney tissues with significant difference were detected in model group. Compared with the normal group, the expression of rno-miR-21-5p, rno-let-7i-5p, rno-miR-146b-5p and rno-miR-15b-5p in model group increased significantly(PPPPPConclusion: This experiment found 4 miRNAs involved in the regulation of renal interstitial fibrosis (RIF) and 2miRNAs with unknown functions, which provided a new clue for further analysis of the regulatory network of kidney-yang deficiency.
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Epigenetic abnormalities play an important role in the pathogenesis of hematological malignancies, especially acute leukemia (AL). Similar to DNA methylation and histone modifications, RNA methylation is another important epigenetic modification. m6A methylation is one of the most prevalent and extensively studied RNA methylation. m6A methylation is involved in many biological and pathological process. Recent studies have found that m6A methylation is involved in the occurrence, development and drug-resistance of AL. This review focuses on the research progress of m6A methylation in AL.
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Humans , DNA Methylation , Epigenesis, Genetic , LeukemiaABSTRACT
Aim To construct a lentiviral vector for stable delivery of the connexin32 (Cx32) gene in human hepatocellular carcinoma cell line Huh7,and also to detect its effect on cell proliferation.Methods Human Cx32 gene sequence was obtained by whole gene synthesis and amplified by PCR,and was then inserted into LV5-GFP lentiviral vector to construct the recombinant plasmid LV5-GFP-hCx32.Following identified by restriction endonuclease digestion and DNA sequencing,this plasmid together with lentiviral package plasmid was transfected into 293T cells to produce the lentiviral particles,and the viral titer was assessed under fluorescent microscope.Targeted Huh7 cells were infected with the lentivirus (LV5-hCx32 and LV5-NC),and the infected cells after selection with puromycin were amplified and cultured.The expression and localization of Cx32 were detected by real-time RT-PCR,Western blot and immunofluorescence assay,respectively.The gap junction (GJ) function between adjacent cells was measured by dye transfer assay.The Huh7 cell proliferation capacity was determined by MTT and colony formation assays.Results The results of double enzyme digestion and DNA sequencing proved that the recombinant lentiviral vector LV5-GFP-hCx32 was successfully constructed.After packing in 293T cells,the recombinant lentivirus LV5-GFP-hCx32 with virus drops to 3 × 1011 TU · L-1 was obtained.Huh7 cells transiently infected with the lentivirus LV5-GFP-hCx32 remarkably over-expressed Cx32 at both mRNA and protein levels.Moreover,Cx32 expression was also significantly up-regulated in stably transfected Huh7 cells,and the presence of enhanced functional GJ in intact cells could be detected due to an increased amount of Cx32 protein along the plasma membrane at cell-cell contacts.Compared to LV5-NC group,the proliferation ability in Huh7 cells with recombinant Cx32 declined (P ＜ 0.05).Conclusions The lentiviral vector over-expressing Cx32 gene is successfully constructed,and can stably transfect Huh7 cells to yield sustained over-expression of exogenous Cx32 gene,thus eventually inhibits cell proliferation.
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This study was aimed to investigate the protective effect and mechanism of β-asarone on the animal model of Alzheimer's disease(AD) which was induced by intracerebroventricular injection of Aβ₁₋₄₂ combined cerebral ischemia. One hundred and five rats were randomly divided into seven groups including sham-operated group, AD model group, β-asarone 10 mg•kg⁻¹ group, β-asarone 20 mg•kg⁻¹ group, β-asarone 30 mg•kg⁻¹ group, donepezil group(0.75 mg•kg⁻¹) and Ginkgo biloba extract group(24 mg•kg⁻¹). Rats' learning and memory abilities, cerebric regional blood flow, pathological changes in hippocampal CA1 region, the expression level of HIF-1α and serum CAT, SOD and MDA level were detected 4 weeks later. The results showed that the application of intracerebroventricular injection of Aβ₁₋₄₂ joint 2-VO could lead to rats' dysfunction of learning and memory, decrease in regional cerebral blood flow. Neurons in CA1 region were arranged in disorder, and amyloid deposition was increased. The number of cerebral cortical cells expressing HIF-1α was increased as well. The level of serum CAT and SOD decreased, while level of serum MDA increased. However these symptoms were improved by 20 mg•kg⁻¹ and 30 mg•kg⁻¹ β-asarone. The results indicated that β-asarone could effectively relieve the symptoms of the AD model induced by intracerebroventricular injection of Aβ₁₋₄₂ combined cerebral ischemia, and the potential mechanism might be that it could attenuate damage of MDA to the body by improving the level of CAT and SOD, meanwhile the level of HIF-1α decreased as the decline of hyperoxide which might attenuate its damage to neuron, so it finally achieved alleviating Alzheimer's disease.
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OBJECTIVE@#To discuss the expression of long noncoding RNA TUG1 (lncRNA-TUG1) in gastric carcinoma (GC) and its effects on the transferring and invading capacity of gastric carcinoma cells.@*METHODS@#Forty cases of carcinoma tissue and para-carcinoma tissue were selected from GC patients who underwent surgical removal in Zhejiang Provincial Hospital of Chinese Traditional Medicine and Wenzhou Central Hospital from January, 2013 to December, 2014; the expressing level of lncRNA-TUG1 in GC and para-C tissues was detected by applying the qRT-PCR technique. The correlation between lncRNA-TUG1 expression and patients' clinical data was classified and analyzed. SGC-7901 cells were transfected using lncRNA-TUG1 specific siRNA. Changes of the transferring and invading capacity of siRNA-transfected SGC-7901 cells were scratch-tested and transwell-detected. qRT-PCR was applied to detect the expression level of microRNA-144 after lncRNA-TUG1 was silenced. Changes of c-Met mRNA and protein expressions was detected by qRT-PCR and western-blot test.@*RESULTS@#The expression level of lncRNA-TUG1 in GC tissue was significant higher than that in para-C tissue (P < 0.05) and the high expression level of lncRNA-TUG1 in GC tissue was significantly correlated with tumor lymph nodes metastasis and advance TNM phasing (P < 0.05). The transferring and invading capacity of SGC-7901 cells was highly inhibited after being transfected by lncRNA-TUG1 specific siRNA (P < 0.05). The results of qRT-PCR and western-blot proved that the expression of microRNA-144 was significantly boosted and the expression level of c-Met mRNA and protein was inhibited after lncRNA-TUG1 was silenced (P < 0.05).@*CONCLUSIONS@#lncRNA-TUG1 shows an up-regulated expression in GC tissue and that bears a correlation with clinicopathological features of malignant tumor. lncRNA-TUG1 can promote the transferring and invading capacity of GC by inhibiting the pathway of microRNA-144/c-Met.
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OBJECTIVE:To observe therapeutic efficacy and safety of Danshen chuanxiongqin injection combined with flunari-zine hydrochloride in the benign prevention and treatment of paroxysmal positional vertigo (BPPV) and lower extremity deep ve-nous thrombosis (DVT) in post-operative long-term bedridden patients with lower limb fractures. METHODS:300 post-operative long-term bedridden patients with lower limb fractures were selected and randomly divided into observation group and control group,with 150 cases in each group. Control group was given Flunarizine hydrochloride capsules orally 10 mg,qd;observation group was additionally given Danshen chuanxiongqin injection 10 ml+5% Glucose injection 250 ml,ivgtt,qd. The incidence of BPPV and DVT were observed in 2 groups after intervention,and the circumference of lower limb,blood coagulation indexes, blood rheology indexes and inflammatory factor were observed before and after intervention,and the incidence of ADR was com-pared. RESULTS:The incidence of BPPV and DVT in observation group were 18.0% and 16.7%,which were significantly lower than in control group(48.7% and 52.7%),with statistical significance(P0.05). CONCLUSIONS:Danshen chuanxiongqin injection combined with flunarizine hydrochloride is effective in the prevention of BPPV and DVT in long-term bed-ridden patients with lower limb fractures,with low incidence of ADR.
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Objective To discuss the expression of long noncoding RNA TUG1 (lncRNA-TUG1) in gastric carcinoma (GC) and its effects on the transferring and invading capacity of gastric carcinoma cells. Methods Forty cases of carcinoma tissue and para-carcinoma tissue were selected from GC patients who underwent surgical removal in Zhejiang Provincial Hospital of Chinese Traditional Medicine and Wenzhou Central Hospital from January, 2013 to December, 2014; the expressing level of lncRNA-TUG1 in GC and para-C tissues was detected by applying the qRT-PCR technique. The correlation between lncRNA-TUG1 expression and patients' clinical data was classified and analyzed. SGC-7901 cells were transfected using lncRNA-TUG1 specific siRNA. Changes of the transferring and invading capacity of siRNA-transfected SGC-7901 cells were scratch-tested and transwell-detected. qRT-PCR was applied to detect the expression level of microRNA-144 after lncRNA-TUG1 was silenced. Changes of c-Met mRNA and protein expressions was detected by qRT-PCR and western-blot test. Results The expression level of lncRNA-TUG1 in GC tissue was significant higher than that in para-C tissue (P < 0.05) and the high expression level of lncRNA-TUG1 in GC tissue was significantly correlated with tumor lymph nodes metastasis and advance TNM phasing (P < 0.05). The transferring and invading capacity of SGC-7901 cells was highly inhibited after being transfected by lncRNA-TUG1 specific siRNA (P < 0.05). The results of qRT-PCR and western-blot proved that the expression of microRNA-144 was significantly boosted and the expression level of c-Met mRNA and protein was inhibited after lncRNA-TUG1 was silenced (P < 0.05). Conclusions lncRNA-TUG1 shows an up-regulated expression in GC tissue and that bears a correlation with clinicopathological features of malignant tumor. lncRNA-TUG1 can promote the transferring and invading capacity of GC by inhibiting the pathway of microRNA-144/c-Met.
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Diagnostic whole body scan (Dx-WBS) with 131I and serum Tg level are the main parameters to evaluate the effectiveness of thyroid remnant ablation in patients with DTC.Undetectable Tg and positive radioiodine uptake in the thyroid bed (Tg-/Dx-WBS+) may be found in some patients.However,the clinical significance is uncertain.A small amount of thyroidal remnant,a small DTC lesion,increased expression of NIS gene and autoimmune inflammation may all result in Tg-/Dx-WBS+.A wait-and-watch approach without rushing for high-dose radioiodine treatment might be a more reasonable approach for these patients.
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Objective To investigate and analyze the risk of dislocation failure after total hip arthroplasty (THA). Methods The optical motion capture system was used to obtain the kinematic data of the lower limbs during actions of daily living (ADLs) from normal people. The visual hip prosthesis motion analysis software was designed and developed to measure the maximum safe motion space of the hip prosthesis with different design parameters and judge the safety of the hip prosthesis by analyzing the relative motion relation between the cup and prosthetic stem. Results Based on the measured kinematics data, the motion analysis software could compare the range of motion of the natural joints and that after THA. Thus, the relationship between the dislocation of hip prosthesis and ADLs was obtained and the dislocation risk after THA was investigated. Conclusions There is a high risk when activities that require a high flexion motion are performed, especially for the kneeling and squatting activity.
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Objective To illustrate the influences of walking speed and road slope on lower limb motions by quantitative analysis on the changes of joint angles and muscle activation. Method Five walking speeds and three road slopes were selected from slow to fast according to the related measurement. The gaits of 15 young women were measured using the motion capture system and the EMG signals of 8 major muscles in lower limbs were collected simultaneously. The mean joint angles of hip, knee and ankle in sagittal plane at different speeds and different slopes were calculated. The subject whose data was closest to the mean value could be easily found. Results The joint angles of the subject’s hip, knee and ankle in sagittal plane at different speeds and different slopes in a gait cycle were presented and the activation curves of the 8 major muscles during lower limb movements were obtained. Conclusions In each gait cycle, the curves of joint angles and muscle activations varied little with 5 different speeds, while curves for 3 different road slopes only showed similar tendencies but with different peaks.
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Objective To obtain the statistical data from the range of motion in lower limb of the Chinese people during their stair ascent so as to provide references for the design of artificial joints with large range flexion. Methods Common staircase as an experimental device was designed, and motion capture system（Optotrak Certus, NDI）and 3D force plate（AMTI, Bertec）were used to establish a systematic method to measure the lower limb motion from 40 subjects during stair ascent. Results The variation of joint angle and range of motion in hip, knee and ankle joints for the 40 subjects in different directions within one cycle were obtained and calculated. The range of motion in hip, knee and ankle joints at the sagittal plane were -1.6°~66.7°, 0°~91.4°,-20.8°~22.4°, respectively. Conclusions During the movement of stair ascent, the range of motion at the sagittal plane in hip, knee and ankle joints reached the maximum, with the most flexion in hip and knee. Compared with the movement during walking and jogging on flat road, the range of motion in joints both in hip and knee at the sagittal plane were larger during stair ascent.
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<p><b>OBJECTIVE</b>To observe the effect of astragaloside on oxidative low-density lipoprotein (Ox-LDL) mediated oxidative damage of endothelial progenitor cells (EPCs).</p><p><b>METHODS</b>Peripheral blood mononuclear cells(PBMCs) were isolated by Ficoll density gradient centrifugation, and EPCs were identified by flow cytometry. Adherent cells were collected after seven-day incubation and randomly divided into the normal control group, the Ox-LDL group (as the model group, at the dose of 100 microg/mL), the low, middle, and high astragaloside groups (with 100 microg/mL Ox-LDL plus 2, 10, and 50 microg/mL astragaloside). Twenty-four h later, the proliferation and adhesion capabilities of EPCs were observed using MTT colorimetry and the adhesion capability detection. Levels of superoxide dismutase (SOD) and malonaldehyde (MDA) in the cell supernate of each group were determined.</p><p><b>RESULTS</b>After Ox-LDL damage, the proliferative and adhesive capacities of EPCs were significantly injured (53 +/- 8 vs 42 +/- 6, 0.49 +/- 0.12 vs 0.37 +/- 0.02, both P<0.05). The SOD content obviously decreased (21.95 +/- 1.43 vs 14.76 +/- 3.99, P<0.01), the MDA content obviously increased (3.72 +/- 0.30 vs 5.57 +/- 0.64, P<0.01). After intervened by astragaloside for 24 h, the proliferative and adhesive capacities of EPCs were significantly improved. The SOD contents of astragaloside intervention groups were obviously improved and the MDA content obviously lowered.</p><p><b>CONCLUSIONS</b>Astragaloside showed significant protection on Ox-LDL damaged EPCs. Its mechanism might be correlated with antioxidative damage.</p>
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Humans , Cells, Cultured , Endothelial Cells , Cell Biology , Metabolism , Leukocytes, Mononuclear , Metabolism , Lipoproteins, LDL , Metabolism , Malondialdehyde , Metabolism , Oxidation-Reduction , Oxidative Stress , Saponins , Pharmacology , Stem Cells , Cell Biology , Metabolism , Triterpenes , PharmacologyABSTRACT
Objective In order to avoid potential injuries imposed to human body, it can be feasible to use the musculoskeletal models which can be reconstructed from the cadaver color cryosection (CCC) images, computerized tomography (CT) images, magnetic resonance (MR) images or other images to analyze the dynamic properties of muscles in vivo during human movement. Methods We reconstruct the lower limb musculoskeletal model and define the uniform joint coordinate system (JCS) on the model and the subject. The coordinate transformation of the muscle attachment points both on the model and the subject is described in detail. Results The length and the moment arm of the biceps femoris (short head) during knee flexion are calculated and analyzed. Conclusion This method plays an important role in improving the kinematics and dynamic simulation and the muscle force estimation.
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Objective To study the effect of reasonable jogging speed on body shape and walking gait to make people acquire graceful posture through jogging. Method Five jogging speeds were selected according to related measurements. Kinematical data of subjects (15 young women volunteers) in jogging were measured by the motion capture system, while the EMG signals of 8 major muscles in lower limb were collected simultaneously. The mean angles of hip, knee and ankle joints in sagittal plane at different speeds were calculated. The subject whose data was closest to the mean value was chosen as the research subject and analyze the kinematical data. Results The angles of the subject's hip, knee and ankle joints in sagittal plane at different speeds in a gait cycle were presented, and activation curves of her 8 major muscles were obtained during lower limb movements. Relationships between the jogging speed, jogging stage, muscle activation and joint angle were described by the scoring method. Conclusions The range of joint angle and maximum of muscle activation don't change with jogging speed monotonously. The study provides a reference for young women to choose their own jogging speed.
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Objective In order to avoid potential injuries imposed to human body,it could be feasible to use the musculoskeletal models which can be reconstructed from the cadaver color cryosection(CCC)images,computerized tomography(CT)images,magnetic resonance(MR)images or other images to analyze the dynamic properties of muscles in vivo during human movement.Mothod We reconstruct the lower limb musculoskeletal model and define the uniform ioint coordinate system(JCS)on the model and the subject.The coordinate transformation of the muscle attachment points both on the model and the subject is described in detail.Results The length and the moment arm of the biceps femoris(short head)during knee flexion are calculated and analyzed.Conclusion This method plays an important role in improving the kinematics and dynamic simulation and the muscle force estimation.
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Objective In order to avoid potential injuries imposed to human body,it could be feasible to use the musculoskeletal models which can be reconstructed from the cadaver color cryosection(CCC)images,computerized tomography(CT)images,magnetic resonance(MR)images or other images to analyze the dynamic properties of muscles in vivo during human movement.Mothod We reconstruct the lower limb musculoskeletal model and define the uniform ioint coordinate system(JCS)on the model and the subject.The coordinate transformation of the muscle attachment points both on the model and the subject is described in detail.Results The length and the moment arm of the biceps femoris(short head)during knee flexion are calculated and analyzed.Conclusion This method plays an important role in improving the kinematics and dynamic simulation and the muscle force estimation.