OBJECTIVE: To look for gene polymorphism loci influencing valproic acid interindividual differences, thus to provide support for treating epilepsy patients with valproic acid. METHODS: Through the KEGG Database, genes and their loci influencing valproic acid pharmacokinetics and pharmacodynamics were inquired from the perspective of pathway: literature was searched about valproic acid-related gene polymorphisms: the FastSNP was used to estimate the risk of the genes found from KEGG Database and literature: the dbSNP database was used to find the distribution of the gene loci with higher risk in Chinese and then to select the loci for the experimental study. RESULTS: The related gene inquired from the perspective of pathway were ABAT, CACNA1I, CACNA1H, CACNA1G, CDY2B, CDY1B, CDY1, CDY2A, CYP2C9, and CYP3A4. Through literature search and bioinformatics methods, 29 influencing loci on valproic acid were identified, including rs1641021, rs1731017, and rs1057910, and so on. CONCLUSION: From this bioinformatics research, the gene polymorphism loci affecting valproic acid interindividual difference are successfully screened. This study provides genetics basis for individual treatments of epileptic patients.

Medicine, Chinese Traditional ; methods

OBJECTIVETo investigate the clinical application of free superficial iliac circumflex artery skin flaps, as well as the management of donor site defects.

METHODS17 free superficial iliac circumflex artery skin flaps were applied for the traumatic defects or deformities on face, neck, foot, hand, ankle and lower leg, respectively. The donor site defects were closed directly or covered by paraumbilical island flaps.

RESULTSThe 17 flap size ranged from 5 cm x 3 cm to 19 cm x 14 cm. 16 flaps survived completely except 1 flap with partial necrosis, which was closed by free skin graft. The donor site defects were closed directly in 10 cases, and covered by paraumbilical island flaps in 7 flaps without no flap necrosis. The abdomen had a good appearance.

CONCLUSIONSGood appearance can be achieved with free superficial iliac circumflex artery skin flaps for the defects on face, neck, foot, hand, ankle and lower leg. Paraumbilical island flap can be used for the donor site defects.

Arteries ; Foot ; Free Tissue Flaps ; blood supply ; transplantation ; Humans ; Reconstructive Surgical Procedures ; Skin ; Skin Transplantation ; Transplant Donor Site ; surgery ; Wounds and Injuries ; surgery

Many schools of academic doctrines have emerged throughout the development history of traditional Chinese medicine (TCM) due to geographic, time, Shicheng (mentor-apprentice system) and academic diversities. Classic TCM School, Classic Formula School and Febrile Disorder School, though all lacking a clearly demonstrable or continuous Shicheng relationship, are nevertheless so classified because of their consistency in reference to the classic TCM works. Each of the Four Famous Masters of Jin and Yuan Dynasties had its distinctively different academic doctrine, resulting in the establishment of individually integrated academic schools. The emergence of the Warming and Tonifying School in late Yuan and early Ming Dynasties was realized as a means to rectify the ill effects of the cool and cold medications prevalent at the time. On the other hand, the advent of the Warm Disease School and the rise of the Confluence School embodied the close relationship carried by TCM academic schools to contemporary historical background. Looking at this development history, it is evident that the development of TCM academic schools could flourish only if it allows dissenting, yet mutually tolerant, opinions. In present medical environment where TCM and Western medicine are of equal importance, Classic TCM Schools, TCM Modernization Schools and Integrative Medicine Schools should all receive emphasis to foster development.
Academies and Institutes ; Medicine, Chinese Traditional ; Schools, Health Occupations ; classification ; Textbooks as Topic

Objective To calculate the electric field intensity and transmembrane voltage of spherical cells and ellipsoi -dal red blood cells ( RBC) in an extremely low frequency electromagnetic field .Through this calculation , we can provide reference to the search for interaction targets and mechanics between the extremely low frequency electromagnetic field and organisms.Methods The Finite Element Method was used in the numerical computation for the spherical cell model and the ellipsoidal RBC model .Results The electric field intensity of the two types of cells on the cellular membrane was both significantly higher than the applied electric field strength , and the values of the induced field strength and transmembrane voltage varied with the direction of the electric field periodically .Conclusion The cell shape and direction of the applied electric field are not the main determinants of the cellular membrane electric field intensity and the transmembrane voltage compared with electromagnetic parameters .The distribution of the electric field intensity and transmembrane voltage are re-lated to the direction of the applied electric field.

OBJECTIVE: To investigate the influence of chemokine like factor-1(CKLF-1) on the genesis and development of lupus nephritis. METHODS: Immunohistochemistry stain was employed on the 34 lupus nephridial tissues and 10 nephridial tissues of control group. And light microscopy was applied to observe the percentage of CKLF-1 positive cells of renal gromerulus and tubule. RESULTS: The percentages of CKLF-1 positive cells of renal gromerulus and tubule were 10.4%+/-1.5% and 48.9%+/-4.3% in the lupus nephritis group, and the percentages of control group were 4.6%+/-1.1% and 4.3%+/-0.9%. There was significant difference between 2 groups (P<0.01). And there was positive correlation between the percentage of CKLF-1 positive cells of renal gromerulus and tubule and lupus active index (r=0.74 and r=0.53, respectively, P<0.05). CONCLUSION CKLF-1 plays a role in the genesis and development of lupus nephritis.
Adult ; Chemokines ; biosynthesis ; Female ; Humans ; Immunohistochemistry ; Kidney ; chemistry ; pathology ; Lupus Nephritis ; metabolism ; pathology ; MARVEL Domain-Containing Proteins ; Male

In the research and development of new drugs, it is very important to investigate the in vitro metabolism of candidate drugs. Traditional models such as liver microsomes have many limitations, while the in vitro model of recombinant human drug metabolizing enzymes is considered as an important and useful approach because of its convenient access, stable activity and low cost. In this study, six major human UDP-glucuronosyltransferases (UGTs) genes (UGT1A1, 1A3, 1A4, 1A6, 1A9 and 2B7) were cloned from human liver cDNA and heterologously expressed in Saccharomyces cerevisiae and baculovirus-infected insect cell. UGT1A1, 1A3, 1A6 and 1A9 were successfully expressed in yeast and showed glucuronidation activity against a variety of different structural types of substrates, but their activities were low. All six UGTs were successfully expressed and exhibited significantly improved glucuronidation activity when Trichopolusia ni cells BTI-TN5B1-4 (High Five) were used as the host. The recombinant human UGTs expressed in insect cells can catalyze the glucuronidation of their specific substrates, and the glucuronidation products were synthesized at milligram-scale with yields of 13%-66% for the first time, of which the structures were identified via MS, ¹H NMR, and ¹³C NMR spectroscopic analysis. Above all, the recombinant human UGTs yeast and insect cell expression systems constructed in this study can be used for in vitro metabolism evaluation in the early stage of new drugs research and development, and also provide a new tool for the synthesis of glucuronide metabolites.

OBJECTIVETo study the serum proteome of rat endotoxemia treated by figwort root (FR).

METHODThe differences of serum proteome among rats treated with lipopolysaccharide (LPS), FR, LPS + FR and saline respectively were analyzed by two-dimensional electrophoresis (2DE) assay.

RESULTThe volumes of sixteen serum proteins (xPr) in LPS induced-endotoxemia group were greatly changed compared with those of the control group. Among them, the volumes of xPr 16, 19 were significantly decreased, and the volumes of xPr 1, 2, 3, 4, 5, 6, 7, 8, 9, 11, 12, 14, 18, 23 were significantly increased. When treated with FR, the volumes of xPr 1, 6, 7, 8, 9, 11, 12, 14, 18, 23 were significantly decreased, and the volumes of xPr 8, 9, 11, 12, 23, 14 were back to normal level. Two factors statistic analysis showed that FR had interaction with LPS for xPr 1, 5, 8, 10, 11, 12, 18, 19, 20, 21, 22, and FR might be the functional antagonist of LPS. We also observed that the volumes of xPr 10, 13, 15, 20, 21, 22 were found to change significantly only in FR treated group but not in LPS treated group or control group. Interestingly, the volume of xPr 13, 20, 21, 22 were increased and the volume of xPr 10, 15 were decreased.

CONCLUSIONThe molecular basis of therapeutic effect of FR on endotoxemia might be through the regulation of xPr 1, 6, 7, 8, 9, 11, 12, 14, 18, 23. We can use proteomic techniques to study the molecular mechanisms of diseases treated by functional Chinese herbs and the combination of different herbs is necessary for the treatment of endotoxemia, as FR can not regulated all the changed proteins induced by LPS.

Animals ; Blood Proteins ; metabolism ; Drugs, Chinese Herbal ; isolation & purification ; pharmacology ; Endotoxemia ; blood ; chemically induced ; Injections, Intravenous ; Lipopolysaccharides ; administration & dosage ; Male ; Plants, Medicinal ; chemistry ; Proteome ; analysis ; Rats ; Rats, Sprague-Dawley ; Scrophularia ; chemistry

AIMTo establish a method for cynomolgus monkey sperm cryopreservation in a chemically defined extender.

METHODSSemen samples were collected by electro-ejaculation from four sexually mature male cynomolgus monkeys. The spermatozoa were frozen in straws by liquid nitrogen vapor using egg-yolk-free Tes-Tris mTTE synthetic extender and glycerol as cryoprotectant. The effects of glycerol concentration (1 %, 3 %, 5 %, 10 % and 15 % [v/v]) and its equilibration time (10 min, 30 min, 60 min and 90 min) on post-thaw spermatozoa were examined by sperm motility and sperm head membrane integrity.

RESULTSThe post-thaw motility and head membrane integrity of spermatozoa were significantly higher (P0.05) for 5 % glycerol (42.95 +/- 2.55 and 50.39+/- 2.42, respectively) than those of the other groups (1%: 19.19 +/- 3.22 and 24.84 +/- 3.64; 3%: 34.23 +/- 3.43 and 41.37 +/- 3.42; 10%:15.68 +/- 2.36 and 21.39 +/- 3.14; 15%: 7.47 +/- 1.44 and 12.90 +/- 2.18). The parameters for 30 min equilibration(42.95 +/- 2.55 and 50.39 +/- 2.42) were better (P0.05) than those of the other groups (10 min: 31.33 +/- 3.06 and 38.98 +/- 3.31; 60 min: 32.49 +/- 3.86 and 40.01 +/- 4.18; 90 min: 31.16 +/- 3.66 and 38.30 +/- 3.78). Five percent glycerol and 30 min equilibration yielded the highest post-thaw sperm motility and head membrane integrity.

CONCLUSIONCynomolgus monkey spermatozoa can be successfully cryopreserved in a chemically defined extender, which is related to the concentration and the equilibration time of glycerol.

Animals ; Cryopreservation ; Cryoprotective Agents ; Glycerol ; chemistry ; Macaca fascicularis ; Male ; Semen Preservation ; Spermatozoa ; cytology

OBJECTIVETo research the effects of glycogen synthase kinase (GSK3β) overexpression and GSK3β inhibitor SB-216763 on the proliferation of hepatic oval cells in rats and its regulatory mechanisms by Wnt signaling pathway.

METHODSThe hepatic oval cells WBF-344 were divided into the blank control group, GSK3β over-expression group, DMSO control group and GSK3β inhibitor groups, while the inhibitor groups set up three concentration gradients, that was 1, 5, 10 µmol/L. Using the GSK3β over-expression lentivirus, which had been identified correctly, and SB-216763 dealt with the cells WBF-344. The cells morphology of each group was observed under the phase contrast inverted microscope, and the expression of fluorescence in the lentivirus-transfected group was observed under the fluorescent microscope. The proliferation of each group cells was tested by CCK8 kits. The cells' apoptosis was detected by AnnexinV-FITC/PI kits. The expression of GSK3β, β-catenin and cyclin D1 were detected by Western blot.

RESULTSThe cells of GSK3β over-expression group were fewer and obvious aging. However, in each inhibitor added group, the cells' division and proliferation was vigorous, and the condition was good. Moreover, the cells' proliferation was getting stronger with the concentration of SB-216763 increasing. A large number of green fluorescence was expressed in the lentivirus-transfected cells. The cells' proliferation in GSK3β over-expression group restrained (t = 7.178, P < 0.01, as compared with control), while the cells' proliferation was vigorous in inhibitor groups (F = 45.030, P < 0.01, as compared with control). Flow Cytometry showed that the cells apoptosis was significant in GSK3β over-expression group. Western blot showed that the expression of GSK3β was increased, while the expression of β-catenin and cyclin D1 was decreased in the over-expression group. The expression of GSK3β had no significant difference among the control group and inhibitor groups. However, the expression of β-catenin and cyclin D1 was significantly increased with the concentration of SB-216763 increasing.

CONCLUSIONSThe overexpression of GSK3β can inhibit the Wnt signaling pathway, thus restrain the cells' proliferation and promotes apoptosis. SB-216763 can activate the Wnt pathway, thus promotes cells' proliferation.

Animals ; Cell Line ; Cell Proliferation ; drug effects ; Cyclin D1 ; metabolism ; Glycogen Synthase Kinase 3 ; metabolism ; Glycogen Synthase Kinase 3 beta ; Glycogen Synthase Kinases ; metabolism ; Hepatocytes ; drug effects ; Indoles ; pharmacology ; Male ; Maleimides ; pharmacology ; Rats ; Transfection ; Wnt Signaling Pathway ; beta Catenin ; metabolism