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

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.

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 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.

Objective： The current study was designed to search into the detection of micrometastasis in peripheral blood in the patients with hepatocellular carcinoma(HCC)and its significance.Method： Peripheral blood samples were obtained from 65 patients with hepatocellular carcinoma, 21 non-HCC malignant tumors, 22 chronic hepatitis B or cirrhosis, and 21 cases of normal healthy volunteers. For identifying hepatocellular carcinoma cells in peripheral blood, the authors detected liver-specific alpha-fetoprotein(AFP) mRNA from total RNA extracted from whole blood by nested reverse transcription-polymerase chain reaction(Nested-RT-PCR). Results： AFP-mRNA was not detected in the normal healthy volunteers and the patient with non-HCC malignant tumors. The presence of AFP-mRNA in the patients with HCC (67.7％ ,44/65) was higher than those with chronic hepatitis B or cirrhosis ( 9.1％ ,2/22,P< 0.01). The detective rate of AFP-mRNA in the blood seemed to be correlated with the clinical stages of HCC, the presence of extrahepatic metastasis, and portal vein thrombosis. The positive AFP-mRNA in peripheral blood after treatment was correlated with the prognosis of the patients with HCC. AFP-mRNA was detected in 7 of 12 (58.3％) HCC patients with low level of serum AFP (< 25 μg/L). Conclusions： The presence of AFP-mRNA in peripheral blood may be an indicator of malignant or benign hepatocytes, which might predicate hematogenous spreading metastasis of tumor cells in the patients with HCC, it might be a valuable marker for predicting metastasis and recurrence of HCC, and it might play a supplementary role in the diagnosis of HCC with negative or low level of serum AFP.

OBJECTIVETo study the effects of polysaccharides of cultured Cryptoporus volvatus(CVPS) on airway hyperresponsiveness of ovalbumin-sensitized rats and to evaluate their mechanisms.

METHODSPolysaccharides A, B (5mg/kg, 20mg/kg) and ketotifen(5mg/kg) or vehicle(same volume of saline) were administrated orally for 10 days in ovalbumin -sensitized rats, methacholine bronchial provocation tests were performed to determine airway hyperresponsiveness. Bronchoalveolar lavage fluid (BALF) and peritoneal lavage fluid were prepared after the animals were challenged by nebulized antigen. The differential white cell count in BALF,and the degranulated mast cell count as well as differential white cell count in peritoneal lavage fluid were performed.

RESULTPolysaccharides markedly inhibited the increased lung resistance and the decreased lung compliance induced by antigen challenge,significantly reduced total cell counts and absolute eosinophil counts in BALF(P<0.05); polysaccharides B was more effective than polysaccharides A. They also inhibited recruitment of inflammatory cells in peritoneal lavage fluid and inhibited the allergen-induced mast cell degranulation.

CONCLUSIONPolysaccharides of CVPS inhibit airway hyperresponsiveness by stabilizing mast cell membranes and reducing infiltration and chemotaxis of eosinophils and may be developed as a potential anti-asthmatic drug.

Animals ; Anti-Asthmatic Agents ; pharmacology ; Bronchial Hyperreactivity ; drug therapy ; Bronchoalveolar Lavage Fluid ; cytology ; Cell Degranulation ; drug effects ; Male ; Mast Cells ; drug effects ; physiology ; Ovalbumin ; immunology ; Polyporaceae ; chemistry ; Polysaccharides ; pharmacology ; Rats ; Rats, Sprague-Dawley

BACKGROUNDVascular hyporeactivity, which occurs in the terminal stage of hemorrhagic shock, is believed to be critical for treating hemorrhagic shock. The present study was designed to examine whether the CB1 cannabinoid receptor (CB1R) was involved in the development of vascular hyporeactivity in rats suffering from hemorrhagic shock.

METHODSSixteen animals were randomly divided into two groups (n = 8 in each group): sham-operated (Sham) and hemorrhagic shock (HS) groups. Hemorrhagic shock was induced by bleeding. The mean arterial pressure (MAP) was reduced to and stabilized at (25 +/- 5) mmHg for 2 hours. The vascular reactivity was determined by the response of MAP to norepinephrine (NE). In later experiments another twelve animals were used in which the changes of CB1R mRNA and protein in aorta and superior mesenteric artery (SMA) were analyzed by RT-PCR and Western blotting. In addition, we investigated the effects of a CB1R antagonist on the vascular hyporeactivity and survival rates in rats with hemorrhagic shock. Survival rates were analyzed by the Fisher's exact probability test. The MAP response was analyzed by one-way analysis of variance (ANOVA).

RESULTSVascular hyporeactivity developed in all animals suffering from hemorrhagic shock. The expression of CB1R mRNA and protein in aorta and 2 - 3 branches of the SMA were significantly increased in the HS group after the development of vascular hyporeactivity when compared to those in Sham group. When SR141716A or AM251 was administered, the MAP response to NE was (41.75 +/- 4.08) mmHg or (44.78 +/- 1.80) mmHg respectively, which was higher than that in saline groups with (4.31 +/- 0.36) mmHg (P < 0.01). We also showed an increased 4-hour survival rate in the SR141716A or AM251-treated group with 20% or 30%, but with a statistically significant difference present between the AM251-treated and saline groups (P < 0.05).

CONCLUSIONSCB1R is involved in vascular hyporeactivity resulting from hemorrhagic shock in rats, and CB1R antagonist may be useful in treating patients with traumatic, hemorrhagic shock who need field-rescue or initial treatment.

Animals ; Blotting, Western ; Gene Expression Regulation ; drug effects ; Hypotension ; metabolism ; Male ; Piperidines ; pharmacology ; Pyrazoles ; pharmacology ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Receptor, Cannabinoid, CB1 ; antagonists & inhibitors ; genetics ; metabolism ; physiology ; Reverse Transcriptase Polymerase Chain Reaction ; Shock, Hemorrhagic ; metabolism ; mortality ; Survival Rate