Human knee joint as a research object, it has become an effective way to establish models of human knee joint. The types of human knee joint models are identified, and each type of model is simply introduced respectively. Focusing on the types of the kinematics and kinetics models of human knee joint on the basis of anatomy, the current research status is detailedly described and comprehensively analyzed at home and abroad correspondingly. Through in-depth study the various kinematics and kinetics models, and their advantages and limitations are discovered. The existing problems are summarized, solution and development trend are also proposed.

OBJECTIVE:To study curative effect of the combination of cyclosporine A,mycophenolate mofetil,anti-thymocyte globulin,interleukin-11 and short-term methotrexate as acute graft-versus-host disease(aGVHD) prophylaxis on HLA-matched unrelated donor or HLA-mismatched related donor allogenic peripheral blood stem cell transplantation(Allo-PBSCT).METHODS:Thirteen patients with haematological malignancies who underwent HLA-matched unrelated donor or HLA-mismatched related donor Allo-PBSCT with the combination of cyclosporine A as aGVHD prophylaxis at Haikou Municipal People's Hospital from September to November 2008 were selected,including 7 of unrelated donor,3 of haplotype transplantation,and 3 of 1-locus mismatched.The conditioning regimen was performed at 7 days prior to transplantation,with cyclosporine A 5-10 mg/(kg?d),12 hours per time with twice per day.From day 7 prior to transplantation,mycophenolic acid was intravenous drip once per day,then 2.5 mg/(kg?d) antithymocyte globulin at days 5-2 prior to transplantation,1.5 mg/d interleukin 11 was subcutaneous injected at day 2 prior to and 10 days after transplantation,followed by intravenous drip 15 mg/m2 amethopterin at day 1 and 10 mg/m2 at days 3,6,11 after transplantation.The drug doge was reduced and stopped gradually after 3-6 months,which could be prolonged for haplotype grafter.Recombinant human granulocyte colony-stimulating factor was injected subcutaneously at day 3 prior to transplantation,and PBSCT was collected at days 4 and 5 after medication,which was infused to patients with subclavian vein at the same day.In total(7.82-9.11)?108/kg mononuclearcell and(2.9-7.7)?106/kg CD34+ cells were infused.RESULTS:Hematopoiesis was rebuilt in all patients with 46.15%(6/13) aGVHD incidence rate,including 8 %(1/13) of Ⅲ-Ⅳ aGVHD.Up to April of 2009,all patients live and work as normal except one patient who can not visit public places.CONCLUSION:The combination of cyclosporine A,mycophenolate mofetil,anti-thymocyte globulin,interleukin-11 and short-term methotrexate is effective in the prevention of aGVHD.

Allotransplantation of peripheral blood-derived hemopoietic stem cells is the best therapy for acute leukemia. With increases of only-child families, sibling donors are decreasing. Moreover, the probability is low and time consuming is long to search a matched hemopoietic stem cell donor from the Chinese Marrow Donor Program. Haploidentical stem cell transplantation would bring a hope for donor resource. However, difficult transplantation and high incidence of graft versus host disease are two risks. Based on modified regimen and cyclosporine A+short-term amethopterin, mycophenolic acid, interleukin-11, anti-lymphocyte immunoglobulin and hemopoietic stem cells mobilized by recombinant human granulocyte colony-stimulating factor can prevent graft versus host disease. This therapy succeeded in two cases with no severe graft versus host disease.

Objective To analyse the effect of mobilization and collection's time of peripheral blood stem cells(PBSC) from 8 cases of healthy donors. Methods The 10 donors were studied by self-control design.The number of aphereses was two times every donors. Healthy donors received rhG-CSF according to two different PBSC collection starting time: group 1:PBSC collection was starts 2 hours(2 h) after the fourth day or the fifth day of rhG-CSF. group 2:PBSC collection was starts 4 hours(4 h) after the fourth day or the fifth day of rhG-CSF.(The first dose of rhG-CSF was given on day 1, considering day 0 as the day before starting mobilization). In this study we have compared with two groups of apheresis product. Results The MNC count was significantly higher for donors 4 h collection (groups 2) then 2 h. ( groups 1)(P

ObjectiveTo identify the pharmacodynamic substances for the anti-inflammatory and analgesic effects of Bupleuri Radix by structure-activity omics. MethodA mouse model of pain was established with formaldehyde to examine the anti-inflammatory and analgesic effects of saikosaponins in vivo. The core targets of the active components in Bupleurum Radix for the anti-inflammatory and analgesic effects were screened from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP）， Online Mendelian Inheritance in Man （OMIM）， and Search Tool for Recurring Instances of Neighbouring Genes （STRING）. The key core targets with high binding affinity were screened based on the comprehensive score in the molecular docking between different types of saikosaponins and core targets. The structure-activity relationship was discussed and analyzed based on the binding of compounds to pharmacodynamic targets. ResultSaikosaponins alleviated the foot swelling induced by formaldehyde and reduced the content of prostaglandin E₂ （PGE₂） in the mouse model， showcasing a significant inhibitory effect on the inflammatory pain caused by PGE₂. Nine components and 39 targets of saikosaponins， as well as 3 074 targets of anti-inflammatory and analgesic effects were screened out， and 22 common targets shared by saikosaponins and the effects were obtained as the direct targets. The protein-protein interaction （PPI） analysis showed that the main active components of Bupleurum Radix were saikosaponins a， b₁， b₂， b₃， c， d， e， f， and v， and the key targets were fms-related receptor tyrosine kinase 1 （FLT1）， kinase insert domain receptor （KDR）， fibroblast growth factor 2 （FGF2）， vascular endothelial growth factor A （VEGFA）， and signal transducer and activator of transcription 3 （STAT3）. Molecular docking between saikosaponins and the top 5 targets with high degrees in PPI network analysis revealed 25 highly active docks， including 6 docks with scores of 5-6 and 18 docks with scores above 6. ConclusionThis study adopted structural-activity omics to analyze the material basis for the anti-inflammatory and analgesic effects of Bupleuri Radix in vivo， providing new ideas and methods for identifying the pharmacodynamic substances in traditional Chinese medicine.

ObjectiveTo reveal the pharmacodynamic substances for the anti-inflammatory and analgesic effects of Glycyrrhizae Radix et Rhizoma by structure-activity omics. MethodOn the basis of the previous study about the screening of active components in vitro， this study explored the effects of flavonoids in Glycyrrhizae Radix et Rhizoma in vivo. The flavonoids in Glycyrrhizae Radix et Rhizoma and their direct targets for the anti-inflammatory and analgesic effects were obtained from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP）， PharmMapper， Swiss TargetPrediction， DisGeNET， and Online Mendelian Inheritance in Man （OMIM）. STRING and Cytoscape 3.7.2 were employed to establish the protein-protein interaction （PPI） network of key targets. Molecular docking was performed to simulate the binding of five targets with high degrees to flavonoids in Glycyrrhizae Radix et Rhizoma， on the basis of which the key core targets were selected. The targets were used as a bridge to correlate the structures and effects of one or more classes of chemical components in Glycyrrhizae Radix et Rhizoma. According to the binding affinity between flavonoids with different structures in Glycyrrhizae Radix et Rhizoma and targets， the relationships between compound structures and core targets were discussed. ResultThe flavonoids in Glycyrrhizae Radix et Rhizoma reduced the content of prostaglandin E₂ （PGE₂） in the rat model of pain induced by formalin， demonstrating definite anti-inflammatory and analgesic effects. Sixty active compounds （flavonoids） with anti-inflammatory and analgesic effects of Glycyrrhizae Radix et Rhizoma were obtained. With the total score as the standard， prostaglandin-endoperoxide synthase 2 （PTGS2） and mitogen-activated protein kinase 3 （MAPK3） were selected as the key core targets of Glycyrrhizae Radix et Rhizoma for the anti-inflammatory and analgesic effects. Except that flavones showed selectivity of binding to MAPK3， the other flavonoids of Glycyrrhizae Radix et Rhizoma showed strong binding to PTGS2 and MAPK3， and the structures containing glycoside fragments showed stronger binding affinity to the targets. The introduction of chain olefins in the ring of chalcones facilitated the binding to the targets. The isopentenyl fragment in flavonols may cause the difference in binding affinity. The parallel combination of a ring into pyran ring in flavanes was not conducive to the binding to the target. The electric charge， liposolubility， and steric hindrance of the substituent group on the B ring of isoflavones directly affected the binding affinity. ConclusionThis study adopts structure-activity omics to analyze the material basis for the anti-inflammatory and analgesic effects of Glycyrrhizae Radix et Rhizoma. Structure-activity omics provides new ideas and methods for predicting the pharmacodynamic substances of traditional Chinese medicine.

The complex chemical composition and limited research ideas of traditional Chinese medicine （TCM） have led to the unclear material basis and mechanism of the medicinal effects， which is a common problem hindering the modernization of TCM in China. The introduction of computer virtual technology has provided a new perspective for TCM research. In this study， we established the research method of structure-activity omics to study the relationships between the structures and effects of different compounds in TCM based on the chemical structures of TCM components and to analyze and predict the material basis and multitarget synergistic mechanism of TCM. Furthermore， a structure-activity omics study was carried out with the anti-inflammatory and analgesic effects of Qizhi Weitong granules as an example. This study provides support for screening the pharmacodynamic components and analyzing the active ingredients of TCM and gives insights into the research on the material basis and mechanism of compound efficacy and the development of lead compounds of TCM， thus promoting the modern research and the innovative development of TCM.

ObjectiveTo explain the anti-inflammatory and analgesic effects of Corydalis Rhizoma by the means of structure-activity omics. MethodOn the basis of the previous in vitro screening study， we studied the in vivo efficacy of the alkaloids in Corydalis Rhizoma. With the targets as a bridge， the structures of chemical components in Corydalis Rhizoma were connected with the efficacy. The molecular docking of the alkaloids in Corydalis Rhizoma with the targets of inflammation and pain was carried out. According to the docking scores and the differences in the structural nucleus of Corydalis Rhizoma alkaloids， a study of structure-activity omics was carried out to summarize the rules of their connection. ResultThe alkaloids in Corydalis Rhizoma had good anti-inflammatory and analgesic effects in vivo， involving 53 chemical components and 73 targets. There were 3 074 targets associated with inflammation and pain， and 42 targets of direct action were shared by the chemical components and the disease. The protein-protein interaction （PPI） and molecular docking analysis predicted that the main active components of Corydalis Rhizoma were tetrahydropalmatine and palmatine， and the core targets were prostaglandin endoperoxide synthase 2 （PTGS2）， glutamate receptor metabotropic 5 （GRM5）， estrogen receptor 1 （ESR1）， solute carrier family 6 member 4 （SLC6A4）， and fusion oncoproteins （FOS）. According to the differences of mother nucleus， the 53 alkaloid components of Corydalis Rhizoma were classified into 8 categories， including protoberberine， berberine， and aporphine， which had high binding affinities with PTGS2， GRM5 and other targets. The relationship between the structures of Corydalis Rhizoma alkaloids and docking scores in each group showed the same law. In protoberberine， appropriate substituents with hydroxyl， alkoxy or methyl groups on the A and D rings of the parent ring were conducive to enhancing the binding activities with the two targets. In berberine， the structure containing a methyl group on position 13 had strong binding affinities with the two targets. It is hypothesized that the methyl fragment changes the binding mode between the component structure and amino acid residues， which greatly improves the binding affinity. ConclusionThis study employs the method of structure-activity omics to analyze the material basis for the anti-inflammatory and analgesic effects of alkaloids in Corydalis Rhizoma， and the structure-activity omics provides new ideas for revealing the pharmacodynamic substances of traditional Chinese medicine.

ObjectiveTo explain the pharmacodynamic substances of Aurantii Fructus flavonoids that exert anti-inflammatory and analgesic effects using a structure-activity omics approach. MethodOn the basis of the previous in vitro pharmacological screening conducted by the research team， an in vivo pharmacological study of Aurantii Fructus flavonoids was carried out. Core targets of the anti-inflammatory and analgesic active components of flavonoids of Aurantii Fructus were identified using various network databases， including the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP）， the Online Mendelian Inheritance in Man （OMIM）， and the Search Tool for the Retrieval of Interacting Genes/Proteins （STRING）. Computer-aided virtual screening technology was used to dock different types of Aurantii Fructus flavonoids with core targets. The key core targets with high binding activity were selected based on the comprehensive scores of each target and the active structures. Using these targets as bridges， the structures of one or more types of chemical components in Aurantii Fructus were closely linked to pharmacological effects. The structure-activity relationship between the clear pharmacodynamic compounds and their effects was explored through the binding patterns of various structures with pharmacodynamic targets. ResultAurantii Fructus flavonoids demonstrated significant anti-inflammatory and analgesic effects on dextran sulfate sodium （DSS）-induced colitis in mice， which could improve symptoms and significantly reduce the levels of inflammatory factors interleukin-6 （IL-6） and interleukin-1β （IL-1β）（P<0.05）. Twelve active components of Aurantii Fructus flavonoids were identified and categorized into nine dihydroflavonoids and three flavonoids based on their structures of the parent nuclei. Through Venn analysis， 167 anti-inflammatory and analgesic targets for Aurantii Fructus were identified. Based on degree value and molecular docking comprehensive scores， prostaglandin-endoperoxide synthase 2（PTGS2） and mitogen-activated protein kinase 3（MAPK3） were selected for further structural analysis. Structural analysis revealed that components containing glycoside structures exhibited higher binding activity with anti-inflammatory and analgesic targets. ConclusionThis study utilized a structure-activity omics approach based on in vivo pharmacodynamic experiments to analyze the material basis of the anti-inflammatory and analgesic effects of Aurantii Fructus flavonoids. The structure-activity omics approach provides new ideas and methods for elucidating the pharmacodynamic substances of Chinese medicine.