Objective To study artificial lumbar intervertebral disc three-dimensional finite element model and its stress state. Methods The three-dimensional finite element models of artificial lumbar intervertebral disc were established by finite element software MSC. MARK. While L4-5 motion segment from young healthy cadaver was created to give the models biomaterial characters. The vertebral disc of L4-5 was replaced by artificial lumbar intervertebral disc to make a model of an artificial disc replacement. Results After three-dimensional finite element models with biomaterial characters of artificial lumbar intervertebral disc and L4-5 motion segment had been created, the stress distribution of artificial lumbar intervertebral disc showed some characteristics as follows:1)The stress exerted in the center of polyethylene slide core and end plates is biggest in all motion states, the next exists at the deviated site while the polyethylene slide core set in motion. 2)The upper surface of polyethylene slide core and end plates bear 2-3 times stress as much as that of the lower surface. 3)The biggest stress exists in the center of polyethylene slide core and end plates during compression in all motion states. Conclusion Establishment of three-dimensional finite element models of artificial lumbar intervertebral disc and analysis of its stress are feasible. The results are reliable.

BACKGROUND: Presently-used artificial intervertebral disk is different greatly from the normal physiological intervertebral disk in structure, material and biological properties and so on. Therefore, stress conduction at corresponding spinal section will have a certain change after the implantation of artificial intervertebral disk.OBJECTIVE: To investigate the stress distribution in small joints of normal intervertebral disk group, vertebral extirpation group and artificial lumbar intervertebral disk group with three-dimensional element method in order to discuss exploratorily the influence of the implantation of artificial lumbar intervertebral disk on the stress distribution in small joints.DESIGN: Observative and comparison experiment.SETTING: Orthopedic Department, Third Affiliated Hospital and Second Affiliated Hospital, Sun Yat-sen University; Biomechanical Laboratory in Southern Medical University.PARTICIPANTS: Spinal specimen collected from the healthy people who died in accidenct without any spinal illness (donated by their family member) was used to establish three kinds of three-dimensional element models of normal intervertebral disk, artificial intervertebral disk and vertebral extirpation as experimental subjects.METHODS: Finite element MSC.MARK software was used to establish normal intervertebral disk model with height of 10.00 mm, cross sectional area of 1300.00 mm2, and vertebral pulp cross sectional area of 495.8 mm2;in the model of vertebral pulp extirpation,the intrinsic pressure of vertebral pulp was zero; and in the three dimensional models of artificial lumbar intervertebral disk and L4-5 movement segment , the small joints were about 10.53 mm high with width of 13.37 mm and auricular area of 135 mm2.Then lumbar movement was simulated for the study of the stress distribution in small joint.MAIN OUTCOME MEASURES: Comparison of the stress in small joints under 6 kinds of states in the above three kinds of intervertebral disk movement model.RESULTS:In vertebral pulp extirpation group, the stress was proved to be the highest at superior edge, posterior middle part, lower edge and anterior middle part of small joints under anteflexion, backward extension, compression, lateroflexion and revolving states, moreover, small joint stress in artificial lumbar intervertebral disk was higher than that in normal intervertebral disk, but obviously lower than that in vertebral pulp extirpation group;however, the small joint of the middle part of artificial lumbar intervertebral disk bore the highest stress under revolving states.CONCLUSION: In contrast with vertebral pulp extirpation group, the small joint stress could be reduced after the implantant of artificial lumbar intervertebral disk, but was still higher than that of normal lumbar intervertebral disk group and the anti-verticity in artificial lumbar intervertebral disk group was markedly lower than that of normal lumbar intervertebral disk group and vertebral pulp ablation group, thus indicating that although presently-used artificial lumbar intervertebral disk possesses most of mechanical functions of normal lumbar intervertebral disk, but is still different from true lumbar intervertebral disk.

BACKGROUND: At present, there are very big differences in structure,material character and biological property between artificial intervertebral disc (AID) and normal physiological intervertebral disc.OBJECTIVE: Three-dimensional finite element method was used to observe and analysis the stress conduction of artificial lumbar intervertebral disc in lumbar motion segment.DESIGN: Single sample observation was designed.SETTING: Department of Orthopaedics, Third Affiliated Hospital, Sun Yat-sen University; Department of Orthopaedics, Second Affiliated Hospital, Sun Yat-sen University; Laboratory of Mechanics, Southern Medical UniversityPARTICIPANTS: It was to employ a vertebral sample without any spinal disorder of a healthy male died due to accidence and a finite element model of AID implantation in vertebral motion segment established with SB Charite Ⅲ AID.METHODS: According to industrial design chart of AID, finite element software MSC.MARK was utilized to establish three-dimensional model of artificial lumbar intervertebral disc. The corpus sample of motion segment of healthy lumbar vertebrae was collected and scanned with spiral CT machine and imaging documents were input in computer to preserve.Geometric model of L4-5 segment was established in three-dimensional coordinate system in ASC.MARK software. The intervertebral disc in L4-5 motion segment model was replaced by AID. It was to ensure the fixation of lower terminal lamina of L5 in the model. 4 Nm moment of force was exerted in anterior flexion, posterior extension, lateral bending and torsion on the sample successively. Finally, force of internodes representing AID was calculated and stress distribution was recorded.MAIN OUTCOME MEASURES: To observe stress distribution of anterior flexion, posterior extension, compression, lateral bending and rotation of AID.RESULTS: Finite element model of artificial lumbar intervertebral disc implanted lumbar motion segment that is in conformity with clinical practice was established. Stress distribution of AID was characterized as:er lamina was the maximum and that in the lower inclined part of slide of slide core and cover lamina was two or three times as same as that of sion, the stress in the center of slide core and cover lamina was the maximum.CONCLUSION: The finite element model of artificial lumbar intervertebral disc implanted lumbar motion segment established is in conformity with the structural character of practical artificial intervertebral disc in morphology, size and motion property, based on which, it is feasible to carry on the experiment on stress distribution of artificial intervertebral disc.

Chemical genetics is the science which takes the small molecular compounds as tools to solve the genetics problems or to disturb/adjust normal biological process so as to find out protein functions. Because the small molecules have the diverse chemical characters and the ability to identify the target proteins, they also can be filtrated on the basis of phenotype. So the methods of chemical genetics have been applied in almost all of the researches on biology and medicine. In this paper, the methods to acquire small molecular compounds are introduced. The enormous progress achieved in the field of combinatorial chemistry, which has allowed the rapid production of a large number of chemically diverse molecules, is an important prerequisite to make chemical libraries available to academic researchers. And the applications of the compounds in early embryo development, cell differentiation, on-set and course of disease are discussed, too. The application of small molecules has an enormous impact on our understanding of cell biology. There are many examples where small molecules, in combination with genetic screens, have facilitated the dissection of complex cellular processes.
Combinatorial Chemistry Techniques ; Genetic Techniques ; Genetics ; trends ; Humans ; Molecular Probe Techniques ; Small Molecule Libraries ; chemistry

Purpose: Molecular residual disease (MRD) is a promising biomarker in colorectal cancer (CRC) for prognosis and guiding treatment, while the whole-exome sequencing (WES) based tumor-informed assay is standard for evaluating MRD based on circulating tumor DNA (ctDNA). In this study, we assessed the feasibility of a fixed-panel for evaluating MRD in CRC. Materials and Methods: Seventy-five patients with resectable stage I-III CRC were enrolled. Tumor tissues obtained by surgery, and preoperative and postoperative day 7 blood samples were collected. The ctDNA was evaluated using the tumor-agnostic and tumor-informed fixed assays, as well as the WES-based and panel-based personalized assays in randomly selected patients. Results: The tumor-informed fixed assay had a higher preoperative positive rate than the tumor-agnostic assay (73.3% vs. 57.3%). The preoperative ctDNA status failed to predict disease-free survival (DFS) in either of the fixed assays, while the tumor-informed fixed assay-determined postoperative ctDNA positivity was significantly associated with worse DFS (hazard ratio [HR], 20.74; 95% confidence interval [CI], 7.19 to 59.83; p < 0.001), which was an independent predictor by multivariable analysis (HR, 28.57; 95% CI, 7.10 to 114.9; p < 0.001). Sub-cohort analysis indicated the WES-based personalized assay had the highest preoperative positive rate (95.1%). The two personalized assays and the tumor-informed fixed assay demonstrated same results in postoperative landmark (HR, 26.34; 95% CI, 6.01 to 115.57; p < 0.001), outperforming the tumor-agnostic fixed panel (HR, 3.04; 95% CI, 0.94 to 9.89; p=0.052). Conclusion Our study confirmed the prognostic value of the ctDNA positivity at postoperative day 7 by the tumor-informed fixed panel. The tumor-informed fixed panel may be a cost-effective method to evaluate MRD, which warrants further studies in future.

Purpose: Molecular residual disease (MRD) is a promising biomarker in colorectal cancer (CRC) for prognosis and guiding treatment, while the whole-exome sequencing (WES) based tumor-informed assay is standard for evaluating MRD based on circulating tumor DNA (ctDNA). In this study, we assessed the feasibility of a fixed-panel for evaluating MRD in CRC. Materials and Methods: Seventy-five patients with resectable stage I-III CRC were enrolled. Tumor tissues obtained by surgery, and preoperative and postoperative day 7 blood samples were collected. The ctDNA was evaluated using the tumor-agnostic and tumor-informed fixed assays, as well as the WES-based and panel-based personalized assays in randomly selected patients. Results: The tumor-informed fixed assay had a higher preoperative positive rate than the tumor-agnostic assay (73.3% vs. 57.3%). The preoperative ctDNA status failed to predict disease-free survival (DFS) in either of the fixed assays, while the tumor-informed fixed assay-determined postoperative ctDNA positivity was significantly associated with worse DFS (hazard ratio [HR], 20.74; 95% confidence interval [CI], 7.19 to 59.83; p < 0.001), which was an independent predictor by multivariable analysis (HR, 28.57; 95% CI, 7.10 to 114.9; p < 0.001). Sub-cohort analysis indicated the WES-based personalized assay had the highest preoperative positive rate (95.1%). The two personalized assays and the tumor-informed fixed assay demonstrated same results in postoperative landmark (HR, 26.34; 95% CI, 6.01 to 115.57; p < 0.001), outperforming the tumor-agnostic fixed panel (HR, 3.04; 95% CI, 0.94 to 9.89; p=0.052). Conclusion Our study confirmed the prognostic value of the ctDNA positivity at postoperative day 7 by the tumor-informed fixed panel. The tumor-informed fixed panel may be a cost-effective method to evaluate MRD, which warrants further studies in future.

Purpose: Molecular residual disease (MRD) is a promising biomarker in colorectal cancer (CRC) for prognosis and guiding treatment, while the whole-exome sequencing (WES) based tumor-informed assay is standard for evaluating MRD based on circulating tumor DNA (ctDNA). In this study, we assessed the feasibility of a fixed-panel for evaluating MRD in CRC. Materials and Methods: Seventy-five patients with resectable stage I-III CRC were enrolled. Tumor tissues obtained by surgery, and preoperative and postoperative day 7 blood samples were collected. The ctDNA was evaluated using the tumor-agnostic and tumor-informed fixed assays, as well as the WES-based and panel-based personalized assays in randomly selected patients. Results: The tumor-informed fixed assay had a higher preoperative positive rate than the tumor-agnostic assay (73.3% vs. 57.3%). The preoperative ctDNA status failed to predict disease-free survival (DFS) in either of the fixed assays, while the tumor-informed fixed assay-determined postoperative ctDNA positivity was significantly associated with worse DFS (hazard ratio [HR], 20.74; 95% confidence interval [CI], 7.19 to 59.83; p < 0.001), which was an independent predictor by multivariable analysis (HR, 28.57; 95% CI, 7.10 to 114.9; p < 0.001). Sub-cohort analysis indicated the WES-based personalized assay had the highest preoperative positive rate (95.1%). The two personalized assays and the tumor-informed fixed assay demonstrated same results in postoperative landmark (HR, 26.34; 95% CI, 6.01 to 115.57; p < 0.001), outperforming the tumor-agnostic fixed panel (HR, 3.04; 95% CI, 0.94 to 9.89; p=0.052). Conclusion Our study confirmed the prognostic value of the ctDNA positivity at postoperative day 7 by the tumor-informed fixed panel. The tumor-informed fixed panel may be a cost-effective method to evaluate MRD, which warrants further studies in future.

Purpose: Molecular residual disease (MRD) is a promising biomarker in colorectal cancer (CRC) for prognosis and guiding treatment, while the whole-exome sequencing (WES) based tumor-informed assay is standard for evaluating MRD based on circulating tumor DNA (ctDNA). In this study, we assessed the feasibility of a fixed-panel for evaluating MRD in CRC. Materials and Methods: Seventy-five patients with resectable stage I-III CRC were enrolled. Tumor tissues obtained by surgery, and preoperative and postoperative day 7 blood samples were collected. The ctDNA was evaluated using the tumor-agnostic and tumor-informed fixed assays, as well as the WES-based and panel-based personalized assays in randomly selected patients. Results: The tumor-informed fixed assay had a higher preoperative positive rate than the tumor-agnostic assay (73.3% vs. 57.3%). The preoperative ctDNA status failed to predict disease-free survival (DFS) in either of the fixed assays, while the tumor-informed fixed assay-determined postoperative ctDNA positivity was significantly associated with worse DFS (hazard ratio [HR], 20.74; 95% confidence interval [CI], 7.19 to 59.83; p < 0.001), which was an independent predictor by multivariable analysis (HR, 28.57; 95% CI, 7.10 to 114.9; p < 0.001). Sub-cohort analysis indicated the WES-based personalized assay had the highest preoperative positive rate (95.1%). The two personalized assays and the tumor-informed fixed assay demonstrated same results in postoperative landmark (HR, 26.34; 95% CI, 6.01 to 115.57; p < 0.001), outperforming the tumor-agnostic fixed panel (HR, 3.04; 95% CI, 0.94 to 9.89; p=0.052). Conclusion Our study confirmed the prognostic value of the ctDNA positivity at postoperative day 7 by the tumor-informed fixed panel. The tumor-informed fixed panel may be a cost-effective method to evaluate MRD, which warrants further studies in future.