To collect small molecule drugs and their drug target data such as enzymes, ion channels, G-protein-coupled receptors and nuclear receptors from KEGG database as the training sets, in order to establish drug-target interaction models based on the random forest algorithm. The accuracies of the models were evaluated by the 10-fold cross-validation test, showing that the predicted success rates of the four drug target models were 71.34%, 67.08%, 73.17% and 67.83%, respectively. The models were adopted to predict the targets of 26 chemical components and establish the compound-target-disease network. The results were well verified by literatures. The models established in this paper are highly accurate, and can be used to discover potential targets in other traditional Chinese medicine ingredients.
Algorithms ; Drugs, Chinese Herbal ; pharmacology ; Gene Regulatory Networks ; drug effects ; Humans ; Ligusticum ; chemistry ; Molecular Targeted Therapy ; Rhizome ; chemistry

OBJECTIVETo compare the effect of reinforcing Shen method (RSM) and activating blood method (ABM) in treating osteoarthritis (OA) at the molecular level.

METHODSThe physical and chemical characteristics of components from respective recipes of RSM and ABM, and network features of component-target interaction network were analyzed by computer simulation methods including chemical space, molecular docking, and biological network, etc.

RESULTSThe chemical components of RSM and ABM were scarcely scattered with larger overlapping. Among established networks, the distribution of network features was partially similar in RSM and ABM. The average target number correlated with each component was 1.86 in RSM and 2.11 in ABM respectively. Each average target number was respectively correlated with 4.46 compounds and 3.93 compounds, reflecting multi-component and multi-target actions.

CONCLUSIONComputer simulation could intuitively trace out similarities and differences of two different methods and their interaction with targets, which revealed that the compatibility of RSM and ABM could have broader protein targets and potential synergism at the molecular level.

Computer Simulation ; Drugs, Chinese Herbal ; administration & dosage ; therapeutic use ; Humans ; Osteoarthritis ; drug therapy ; Phytotherapy ; methods

Background Bulbar conjunctiva tissue appears to be thinning,elasticity declined,tension reduced and fascia atrophied in conjunctivochalasis.Histopathological examination of conjunctivochalasis shows decrease of elastic fibers and melt of collagen fibers.But there are fewer studies on the ultrastructure of conjunctiva of conjunctivochalasis up to now.Objective This study was to investigate the ultrastructure change of conjunctiva tissue in conjunctivochalasis.Methods Five loose conjunctiva samples of conjunctivochalasis and 5 normal conjunctival tissue samples were collected and ultra-microstructure changes of these samples were observed under the transmission electron microscope.Results The number of fibroblasts in conjunctivochalasis lamina was progressively decreased.The shape of fibroblasts was long and fusiform.Somatic synapse was slim.Nucleus-cytoplasm ratio was increased.Disorder,scattered and broken of the collagen fibril were seen,and some areas were dissolved or lacunae.Normal conjunctival fibroblasts were oval or polygonal,with wieners and long somatic synapse,and intercellular matrix was full of collagen fibril and dense arranged fibers.Fibroblasts in fascia of eonjunctivochalasis were linear,and collagen fibril was seriously defected.Fascia fibroblasts of normal bulbar conjunctiva were spindleshaped and bigger than conjunctivochalasis fibroblasts.There were full of collagen fibrils in intercellular matrix.Conclusions The collagen fibril is decreased and fibroblast cells are degenerated in lamina and fascia of conjunctivochalasis.

Objective Compare the three kind of criteria in evaluating the incidences of postop-erative cognitive dysfunction in non-cardiac surgery.Methods Four hundred and sixty one non-cardiac surgery patients were randomly enrolled in this study group and two hundred forty four non-surgery patients as control group.Patients??cognitive state was measured on preoperative and postoperative 1 and 3 d by mini-mental state examination(MMSE).POCD was assessed by patients??education level, one standard deviation and Z-score scale,respectively.Results On the first and third day after sur-gery,Z-score scale assess POCD result showed the highest relevance ratio and 95%CI as well as the lowest education level.The education scale showed the lowest incidence of POCD.Education level criteria was positive on postoperative 1 and 3 day,while one case on postoperative 1 day and four cases on postoperative 3 day were negative by Z-score scale.Conclusion The incidence of POCD in same pa-tients by three kind of criteria are different.The Z-score scale is recommended to evaluate the POCD in order to avoid misdiagnosis.

Objective To study the X-ray signs of forearm and leg in skeletal fluorosis and its diagnostic value,aim at finding the easy examination parts.Methods One thousand four hundred and forty subjects were examined using developed shield,darkroom and other portable dedicated device combined with a small X-ray machine.A total of 384 cases were diagnosed skeletal fluorosis.All patients were divided into different groups and the time,degree and range of X-ray to the forearm and calf elbow,knee,and long bone were compared.Results The X-ray change in the forearm elbow was earlier than that of the leg knee,and trabecular bone change was the earliest indicator,197 cases and 157 cases,respectively,and the difference was statistically significant (x2 =28.006,P ＜ 0.01).Membrane ossification of forearm backbone was earlier than that of the leg,and most of them were degree Ⅰ photos,213 cases and 126 cases respectively.The difference was statistically significant (x2 =17.626,P ＜ 0.01).The direction of the interosseous membrane ossification was from the forearm radius to the ulna,then to the fibula and tibia,and was accompanied by changes in the aggravation of forearm.A variety of indicators were observed,especially the membrane ossification in bone and joint trabecular bone and the long bone was the most active,and the forearm was more sensitive,obviously than that of the calf.Conclusion In the X-ray screening or detection of endemic fluorosis,the forearm radiography is a simple,economical,and effective diagnostic method.

Background Human leucocyte antigen (HLA)-B27-associated uveitis is one of the most common causes of non-infectious uveitis.T helper 17 (Th17) cells play an important role in human autoimmune diseases,but the pathology research on the production of Th17 cells in acute anterior uveitis patients positive for HLA-B27 was rarely reported.Objective The aim of this study was to investigate the expression and significance of the peripheral blood T helper cell subsets (Th1,Th2,Th17) in acute anterior uveitis patients positive for HLA-B27.Methods This study meets the criteria of the Helsinki Declaration.Informed consent was obtained from all the participants.A prospective cohort design was used in this study.Twenty-two patients with acute anterior uveitis positive for HLA-B27 were enrolled from Affiliated Second Hospital of Nanjing Medical University,and 16 normal healthy subjects with matched gender and age were enrolled as controls.The expression of interferon-γ (IFN-γ),interleukin-4 (IL-4) and IL-17 on lymphocytes (CD4+) in blood were assessed by flow cytometry,and immunoturbidimetry was used to detect the C reactive protein (CRP) level in blood.The degree of the severity of disease was evaluated by clinical scoring.The correlations between the percentage of IFN-γ+Th1,IL-4+Th2,or IL-17+Th17 with clinical factors and CRP were analyzed.Results The percentages of IFN-γ+Th1 and IL-17+Th17 in the peripheral blood were (23.11 ±9.69) ％ and (3.96±2.92) ％ in the patient group,showing a significant increase in comparison with (16.00±4.26)％ and (1.68±0.60) ％ in the control group (P=0.041,P=0.002).However,the IL-4+Th2 level was not significantly different between the patient group (0.33％ ±0.36％) and the control group (0.56％ ±0.34％) (P=0.122).No significant correlations were found between the percentage of IFN-γ+ Th1 with disease severity and CRP (r =0.197,P =0.500 ; r =0.253,P =0.383),between the percentage of IL-4+ Th2 with disease severity and CRP (r =0.068,P =0.817 ; r =0.439,P =0.116) as well as between the percentage of IL-17 + Th17 with CRP (r =0.226,P =0.436).However,a positive correlation was seen between the percentage of IL-17+ Th17 with disease severity (r =0.805,P =0.001).Conclusions IFN-γ and IL-17 in human CD4+T cells are significantly elevated in the blood of HLA-B27-related acute anterior uveitis patients.Disease severity is associated with the percentage of IL-17 +Th17,suggesting that Th1 cells together with Th17 cells participate in the pathogenesis of the disease and Th17 cells might play a dominant role in the disease.

Myeloid-derived suppressor cells (MDSCs) play a crucial role in T cell dysfunction, which is related to poor outcome in patients with severe trauma. Cyclooxygenase-2 (Cox-2) contributes to immune disorder in trauma and infection via production of prostaglandin E2. However, the role of Cox-2 in the accumulation and function of MDSCs after traumatic stress has not been fully elucidated. In the present study, we treated murine trauma model with NS398, a selective Cox-2 inhibitor. Then the percentages of CD11b+/Gr-1+ cells, proliferation and apoptosis of CD4+ T cells were determined. Arginase activity and arginase-1 (Arg-1) protein expression of splenic CD11b+/Gr-1+ cells, and delayed-type hypersensitivity (DTH) response were analyzed. The results showed that Cox-2 blockade significantly decreased the percentages of CD11b+/Gr-1+ cells in the spleen and bone marrow 48 and 72 h after traumatic stress. NS398 inhibited arginase activity and down-regulated the Arg-1 expression of splenic CD11b+/Gr-1+ cells. Moreover, NS398 could promote proliferation and inhibit apoptosis of CD4+ T cells. It also restored DTH response of traumatic mice. Taken together, our data revealed that Cox-2 might play a pivotal role in the accumulation and function of MDSC after traumatic stress.

0.05); the levels of LL, LI, RRS in CBA group and CBA+IBT group were significantly lower than those in control group(P

OBJECTIVETo study the effect of dihydroartemisinin (DHA) combined irradiation on the apoptosis of human lung cancer GLC-82 cells and to study its mechanism.

METHODSThe growth inhibition rate of GLC-82 cells acted by different concentrations DHA was detected using MTT assay at 24, 48, and 72 h, respectively. Clone forming test was used. With multi-target single-hit model, the radiosensitization effect was assessed by calculating sensitizing enhancement ratio (SER).The effect of DHA combined irradiation on the apoptosis of GLC-82 cell cycle distribution and apoptosis were measured by flow cytometry. The protein expression of p53, p21, Bcl-2, and Bax were detected by Western blot.

RESULTSDifferent concentrations DHA (4, 8, 16, 32, 64, and 128 μg/mL) had cytotoxicity on GLC-82 cells. The IC50 for 24, 48, and 72 h was 38.25,20.58, and 10.36 μg/mL, respectively, in obvious dose- and time-dependent manner. The growth inhibition rate was more significantly increased than that of the blank control group (P < 0.01, P<0.05). DHA had sensitization enhancement effect on GLC-82 cells, with SER of 1.4. DHA combined irradiation could obviously change the structure of GLC-82 cells cell cycle and induce apoptosis (with the apoptosis rate of 21.5%), which was significantly different from that of the blank control group (P < 0.05). Western blot showed the expression of p53 and p21 protein could be increased by DHA combined irradiation, and the expression of Bcl-2 protein down-regulated (P <0.01, P <0. 05).

CONCLUSIONSDHA had stronger cytotoxicity and radiosensitization on GLC-82 cells. Its mechanisms might lie in making the arrest of GLC-82 cells' growth at G0/G1 phase, decreasing the ratio of cells at S phase, restoring the function of p53, decreasing the expression of Bcl-2 protein, and inducing apoptosis in GLC-82 cells.

Apoptosis ; drug effects ; Artemisinins ; pharmacology ; Cell Cycle ; drug effects ; Cell Proliferation ; drug effects ; Down-Regulation ; drug effects ; Flow Cytometry ; Humans ; Lung Neoplasms ; metabolism ; Neoplasm Proteins ; metabolism ; Radiation-Sensitizing Agents ; pharmacology ; Tumor Cells, Cultured ; bcl-2-Associated X Protein ; metabolism

Adult ; Female ; Humans ; Inhalation Exposure ; Male ; Middle Aged ; Paraquat ; poisoning