In order to improve the efficiency of drug screening on serotonin transporter (SERT) inhibitors, a high-throughput screening (HTS) model is established in RBL-2H3 cells. The RBL-2H3 cells are very similar to the serotonin genetic neuro, in modulation of post-receptor mechanisms and transduction pathway of SERT reactivated. Depending on a fluorescence substrate ASP+ used in detection method of inhibitor rates, it's convenient, quick, accurate and effective, not making the environmental biohazard compared with radioactive experiments. Furthermore, biological screening model combined with computer aided virtual screening technique describing high-throughput virtual screening (HTVS). Bayesian classification method and molecular fingerprint similarity were applied to virtual screening technique, for screening compounds in compound library. Some compounds have been found, and then validated further by biological screening model. Combination of HTS and HTVS improves the efficiency of screening SERT inhibitors.
Animals ; Bayes Theorem ; Cell Line ; Drug Evaluation, Preclinical ; High-Throughput Screening Assays ; Models, Biological ; Rats ; Serotonin Plasma Membrane Transport Proteins ; metabolism ; Serotonin Uptake Inhibitors ; pharmacology

AlM: To investigate the effect of endocapsular phacoemulsification cataract extraction and intraocular lens (lOL) implantation with a 1. 8mm or 3. 0mm clear corneal incision on total root mean square ( RMS ) value of the cornea, corneal astigmatism, spherical aberration, coma, trefoil and tear film.
METHODS:ln a prospective study, 156 age- related patients ( 196 eyes ) were randomly distributed into two groups. 1. 8mm-group comprised 94 eyes that had a silicone lOL inserted through a 1. 8mm sutureless clear corneal incision, while, 3. 0mm- group comprised 102 eyes through a 3. 0mm clear corneal incision. Postoperatively, the changes in the total RMS value of the cornea, corneal astigmatism, spherical aberration, coma, trefoil and tear film at 1wk, 1 and 3mo were determined respectively.
RESULTS:ln both groups, postoperatively at 1wk,there were statistically significant differences ( P<0. 05 ) in the total RMS value of the cornea, corneal astigmatism, spherical aberration, coma, trefoil and tear film, while, there were statistically minimal differences ( P< 0. 05 ) between 1. 8mm-group and 3. 0mm-group at 1mo, but were not statistically significantly different ( P > 0. 05 ) between two groups at 3mo postoperative.
CONCLUSlON:This study confirms that incision size has strong impact on the corneal higher-order aberrations, especially, 3. 0mm incision caused significant differences in the total RMS value of cornea, corneal astigmatism, spherical aberration, coma, trefoil and tear film compared with 1. 8mm micro-incision, therefore, micro-incision is very beneficial for clinical use in phacoemulsification.

ObjectiveTo observe testis tissue changes of experimental cryptorchidism after orchiopexy in various-day-rats.MethodsSeventy-two Sprague-Dawley(SD) male rats were divided into 3 groups randomly and made artificial cryptorchidism:unilateral cryptorchidism group(n=24),bilateral cryptorchidism group(n=24)and sham operation group(n=24)at age 21-day-old.Intra-abdominal testicle was resetting in 2 weeks,at age 40 days and 60 days,the rats were sacrificed for detection tubular fertility index(TFI) and mean tubular diametar(MTD) with hematoxylin-eosine staining and germ cell apoptosis by terminal deoxynucleotidyl transferase mediated d-UTP nick end labeling(TUNEL) assay.ResultsThere were significant differences of MTD,TFI and apoptosis index(AI) between cryptorchidism and scrotal testes(P0.05).The AI of cryptorchidism testes of unilateral cryptorchidism group were significantly lower than that of bilateral cryptorchidism group in 40 days(P0.05).ConclusionsAI of artificial resetting testis is increased and contralateral descended testes in unila-teral cryptorchidism have various damage.It is to lighten that pathological damage of testes of cryptorchidism with prolongation of reset time.

The local field potentials (LFPs) underlying specific behavior were recorded and analyzed in this paper from primary motor cortex (M1) with several medium, such as the self-made single channel micro-electrodes, the system of multi-channels physiological signal acquisition and processing and so on. During the experiment, the specific behavior was divided into four periods according to the changes of the recorded LFPs and the changes of the specific behavior recorded simultaneously in rats. The four periods were named prophase of catching period, planning period, catching period and the completion period, respectively. Then several methods were used for the analysis of the LFPs by MATLAB, such as time domain analysis, power spectral distribution analysis and time-frequency analysis. The results suggested that the LFPs which were caused by different behavior from a large number of movement-related neurons of M1 during the specific behavior in the process of catching play an important part in the "code" guiding role in rats. The results demonstrat that the LFPs of M1 may provide a feasibility to discriminate the motor behavior of forelimb.
Animals ; Brain-Computer Interfaces ; Electrodes, Implanted ; Evoked Potentials, Motor ; physiology ; Feeding Behavior ; physiology ; Male ; Microelectrodes ; Motor Cortex ; physiology ; Rats ; Rats, Wistar

This research established an HPLC method for determination of six C-Glycoside flavones of warer-soluble total flavonoids from Isodon lophanthoides var. gerardianus (Benth.) H. Hara, and studied the antitumor activity of the warer-soluble total flavonoids. The HPLC system consisted of Kromasil 100-5 C18 (4.6 mm x 250 mm, 5 microm) column and a solution system of methanol, acetonitrile and 0.5% formic acid gradient elution at a flow rate of 0. 8 mL x min(-1) and the wavelength of detector was at 334 nm. The column temperature was 25 degrees C. The antitumor activity of water-soluble flavonoids was assayed using HepG2 cell as the tested cell. The linear ranges of vicenin II, vicenin III, isoschaftoside, schaftoside, vitexin, 6, 8-di-C-a-L-arabinosylapigenin were 0.25-2.53, 0.12-1.20, 0.37-3.69, 0.16-1.63, 0.19-1.92, 0.14-1.42 microg, respectively. The average recoveries (n = 6) were 99.6% (RSD 0.87%), 100.2% (RSD 2.0%), 99.6% (RSD 1.8%), 97.9% (RSD 1.5%), 98.8% (RSD 1.2%), 98.6% (RSD 1.2%), respectively. After exposure in 24, 48, 72 h, the total flavonoids showed inhibitory effect on the proliferation of HepG2 cells with IC50 as the evaluation index, the IC50 values of 1.89, 1.71, 1.51 g x L(-1), respectively. The method is quick, simple and accurate with good re- producibility, and can be used for determination of vicenin II, vicenin III, isoschaftoside, schaftoside, vitexin, 6, 8-di-C-a-L-arabino- sylapigenin in the warer-soluble total flavonoids from L lophanthoides var. gerardianus. The warer-soluble total flavonoids from L lophanthoides have inhibitory effect on the proliferation of HepG2 cells.
Antineoplastic Agents, Phytogenic ; analysis ; pharmacology ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Chromatography, High Pressure Liquid ; Drugs, Chinese Herbal ; analysis ; pharmacology ; Flavones ; analysis ; pharmacology ; Humans ; Isodon ; chemistry ; Monosaccharides ; analysis ; pharmacology

The emerging of network pharmacology and polypharmacology forces the scientists to recognize and explore new mechanisms of existing drugs. The drug target prediction can play a key significance on the elucidation of the molecular mechanism of drugs and drug reposition. In this paper, we systematically review the existing approaches to the prediction of biological targets of small molecule based on chemoinformatics, including ligand-based prediction, receptor-based prediction and data mining-based prediction. We also depict the strength of these methods as well as their applications, and put forward their developing direction.
Computational Biology ; Data Mining ; Drug Delivery Systems ; Drug Design ; Ligands

OBJECTIVETo investigate the effect of hypoxia on the expression of matrix metalloproteinase (MMP) and tissue inhibitors of matrix metalloproteinase (TIMP) in human periodontal ligament fibroblasts (HPDLF).

METHODSHPDLF were cultured in α-minima essential medium (α-MEM) and subcultured at confluence. In the hypoxic groups, cells were incubated in a humidified atmosphere of 1%O(2), 5%CO(2), 94%N(2) at 37°C for 12, 24 and 48 h, respectively. In the normoxic control group, cells were incubated under normoxic conditions of 20%O(2), 5%CO(2), 75%N(2). The mRNA expression of MMP and TIMP was measured using reverse transcription-polymerase chain reaction (RT-PCR). The data was analyzed by Student's t test, one-way ANOVA and LSD test with SPSS 13.0 software package.

RESULTSThe expression of MMP-2, TIMP-1 and TIMP-2 mRNA in the hypoxia groups was higher than that in control. The expression of MMP-2 mRNA in hypoxic groups showed a significantly increasing trend. There was significant difference between the hypoxic group and the normoxic control group in the expression of MMP-2 mRNA in HPDLF (P < 0.01). The expression of TIMP-1, TIMP-2 mRNA in hypoxic groups of 12 h was momentarily increased. There was significant difference between the hypoxic 12 h group and the normoxic control group in the expression of TIMP-1, TIMP-2 mRNA in HPDLF (P < 0.05). However, with prolonged hypoxia time, the expression of TIMP-1, TIMP-2 mRNA in hypoxic groups showed a significantly declining trend, there were significant differences between the hypoxic 12, 24 and 48 h group and the normoxic control group in the expression of TIMP-2 mRNA in HPDLF (P < 0.05). The expression of MMP-1 mRNA in hypoxic groups of 12 h was momentarily decreased and then increased after 24 h of hypoxia. There were significant differences between the hypoxic 48 h group and the normoxic control group in the expression of MMP-1 mRNA in HPDLF (P < 0.05). There were significant differences between the hypoxic 12 h group and the normoxic control group in the ratio of MMP-1/TIMP-1 mRNA (P < 0.05). The ratio of MMP-2/TIMP-2 mRNA in the hypoxia group significantly increased compared with normoxic group. There were significant differences between the hypoxic group and the normoxic control group in the ratio of MMP-2/TIMP-2 mRNA (P < 0.05).

CONCLUSIONSHypoxia could change the expression of MMP and TIMP mRNA and other relevant growth factors and also lead to the imbalance of MMP-2/TIMP-2 mRNA expression. It is suggested that the imbalance of MMP-2/TIMP-2 expression may be closely correlated with the occurrence and development of periodontal disease and play an important role in the process of periodontal tissue destruction in periodontitis.

Adolescent ; Cell Hypoxia ; Cells, Cultured ; Fibroblasts ; cytology ; metabolism ; Humans ; Matrix Metalloproteinase 1 ; genetics ; metabolism ; Matrix Metalloproteinase 2 ; genetics ; metabolism ; Periodontal Ligament ; cytology ; RNA, Messenger ; metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Tissue Inhibitor of Metalloproteinase-1 ; genetics ; metabolism ; Tissue Inhibitor of Metalloproteinase-2 ; genetics ; metabolism

To analyze the genetic characteristics of echovirus 6 (E6) isolated from meningitis and encephalitis cases in Shandong Province, China, we collected cerebrospinal fluid samples from meningitis and encephalitis cases in Shandong Province from 2007 to 2012 for virus isolation. Viral RNAs were extracted from positive isolates, and complete VP1 coding regions were amplified by RT-PCR and sequenced. Homology comparison and phylogenetic analysis were performed. Six isolates were identified as E6 by microneutralization assay and molecular typing. The homology analysis showed that the six isolates had 78. 6%-99. 8% nucleotide and 95. 5%-100. 0% amino acid identities with each other, as well as 76. 9%-78. 4% nucleotide and 92. 3%-95. 1% amino acid identities with the prototype strain (D' Amori). The phylogenetic analysis based on the integrated VP1 sequences indicated that all Shandong E6 isolates could be separated into four clusters, designated as A, B, C, and D. The six E6 isolates belonged to clusters A, B, and D. Our study reveals high genetic differences between Shandong E6 isolates and suggests different transmission lineages of E6 co-circulated in Shandong Province.
Amino Acid Sequence ; Child ; Child, Preschool ; China ; epidemiology ; Echovirus 6, Human ; classification ; genetics ; isolation & purification ; Encephalitis ; epidemiology ; virology ; Female ; Genetic Variation ; Humans ; Infant ; Male ; Meningitis ; epidemiology ; virology ; Molecular Sequence Data ; Phylogeny ; Sequence Alignment ; Viral Proteins ; chemistry ; genetics

Objective To study the expression of cyclooxygenase-2(COX-2) and survivin in children with acute leukemia(AL) and its significance.Method The expression of COX-2 and survivin were determined by immunohistochemical SABC assay.Results The expression rate of COX-2 and survivin were 52.4%(22/42 cases)and 45.2%(19/42 cases)in AL,and the expression rate of COX-2 and survivin were 46.9%(15/32 cases)and 40.6%(13/32 cases)and in acute lymphonate leukemia(ALL),both of them were higher than those in control group(Pa0.05).The positive rate of COX-2 was 84%(16/19 cases)in 19 cases with survivin positive expression,and the negative rate of COX-2 was 85%(17/20 cases)in 20 cases with survivin negative expression,and there was positive correlation between COX-2 expression and survivin expression(r=0.579 P

Objective: To evaluate the efficacy and safety of mesenchymal stem cells in allogeneic hematopoietic stem cell transplantation for patients with refractory severe aplastic anemia (R-SAA) . Method: The clinical data of 25 R-SAA patients receiving co-transplantation of mesenchymal stem cells combined with peripheral blood stem cells from sibling donors (10 cases) and unrelated donors (15 cases) from March 2010 to July 2018 in Zhengzhou University Affiliated Tumor Hospital were retrospectively analyzed. Antithymocyte globulin (ATG) treatment was ineffective/relapsed in 11 cases, and cyclosporine (CsA) treatment ineffective/relapsed in 14 cases. Results: There were 13 male and 12 female among these patients. One patient had a primary graft failure, one patient had a poorly engraftment of platelets, and the remaining 23 patients achieved hematopoietic engraftment. The median time of granulocyte engraftment was 12.5 (10-23) days and 15 (11-25) days for megakaryocyte. Incidences of grade Ⅰ/Ⅱ acute graft-versus-host disease (aGVHD) and chronic graft-versus-host disease (cGVHD) were 37.5% (9/24) and 21.7% (5/23) , respectively. There was no severe GVHD and no severe complications that related to transplantation. 21 of 25 (84%) patients were alive with a median follow-up of 22.9 (1.6-107.8) months. The 5-year overall survival rate after transplantation was (83.6±7.5) %. Conclusion The combination of mesenchymal stem cells is reliable and safe in the treatment of R-SAA in peripheral blood stem cell transplantation of unrelated donors and sibling donors, which could significantly reduce the incidence of GVHD and severe transplantation-related complications.