Drugs are exogenous compounds for human bodies, and will be metabolized by many enzymes after administration. CYP450 enzyme, as a major metabolic enzyme, is an important phase I drug metabolizing enzyme. In human bodies, about 75% of drug metabolism is conducted by CYP450 enzymes, and CYP450 enzymes is the key factor for drug interactions between traditional Chinese medicine( TCM) -TCM, TCM-medicine and other drug combination. In order to make clear the interaction between metabolic enzymes and TCM metabolism, we generally chose the enzymatic activity as an evaluation index. That is to say, the enhancement or reduction of CYP450 enzyme activity was used to infer the inducing or inhibitory effect of active ingredients and extracts of traditional Chinese medicine on enzymes. At present, the common method for measuring metabolic enzyme activity is Cocktail probe drugs, and it is the key to select the suitable probe substrates. This is of great significance for study drug's absorption, distribution, metabolism and excretion (ADME) process in organisms. The study focuses on the interaction between TCMs, active ingredients, herbal extracts, cocktail probe substrates as well as CYP450 enzymes, in order to guide future studies.
Animals ; Cytochrome P-450 Enzyme Inhibitors ; metabolism ; pharmacology ; Cytochrome P-450 Enzyme System ; chemistry ; metabolism ; Drugs, Chinese Herbal ; metabolism ; pharmacology ; Enzyme Activation ; drug effects ; Enzyme Activators ; metabolism ; pharmacology ; Humans

Renal transplant (RT) recipients have a high risk of developing cardiovascular diseases.However,the effects of renal transplantation on the development of arteriosclerosis have been controversial.The carotid intima-media thickness (CIMT) and diameter (CD) are important indicators of vascular remodeling and arteriosclerosis.In this study,31 patients with hemodialysis (HD),31 RT recipients and 84 age-and gender-matched control subjects were enrolled.Their CIMT and CD were measured by ultrasonic radiofrequency tracking,and the linear regression models and Z test were used to identify the progression of arteriosclerosis and the risk factors.Compared with HD group,RT group had significantly lower CIMT and CD.CIMT was found to be associated with age,body weight,resistance index and diastolic velocity,while CD was associated significantly with age,body weight,pulsatility index,end diastolic velocity and diastolic blood pressure (DBP),respectively.The correlation curves between CIMT and age showed the slopes of curves were decreased successively in control,RT and HD groups,and the curves between CD and age showed the slopes were decreased in order of RT ＞ control ＞ HD groups.It was concluded that CIMT and CD were significantly correlated with age in RT and moderately with age in HD patients.RT could reduce the progress of arteriosclerosis in patients with end-stage renal disease.

To carry out the secretive expression of human laminin alpha4 chain LG4-5 module (hLNalpha4LG4-5), recombinant expression plasmid pPICZalphaA-LG45 was constructed by inserting of hLNalpha4LG4-5 cDNA into yeast expression vector pPICZaA. The hLNalpha4LG4-5 protein was expressed in GS115 Pichia yeast strain after induced by methanol, and purified target protein can obviously promote the expansion and adhesion of 293 cells.
Cell Line ; Genetic Vectors ; Humans ; Laminin ; biosynthesis ; genetics ; Pichia ; genetics ; metabolism ; Plasmids ; genetics ; Recombinant Fusion Proteins ; biosynthesis ; genetics ; isolation & purification

Objective To explore the association of C20orf54 gene rs3746804 position single nucleotide polymorphism and susceptibility to esophageal squamous cell carcinoma (ESCC).Methods Purification of genomic DNA from whole blood was used the Maxwell(R) 16 System.rs3746804 in C20ort54 was detected by direct sequencing in 434 ESCC patients from Changzhi (Shanxi province) and Linzhou (Henan province) and 554 healthy controls from Changzhi,Linzhou and including immigrators from Linzhou to Changzhi.Results For rs3746804,the genotypic frequencies of CT(37.5％ vs 51.0％,37.5％ vs 52.0％),CC (44.2％ vs 34.8％,44.2％ vs 33.0％) in Changzhi ESCC patients showed significant differences with healthy Changzhi controls and the healthy immigrator controls (all P ＜ 0.05),and the frequencies of TT(18.3％ vs 4.1％) and CC (44.2％ vs 54.6％) in Changzhi ESCC patients showed significant differences with Linzhou ESCC patients (all P ＜0.05).The genotypic frequencies of TT (4.1％ vs 15.0％),CT (41.2％ vs 52.0％) and CC(54.6％ vs 33.0％) showed significant differences between Linzhou ESCC patients and the healthy immigrator controls (all P ＜ 0.05),and the frequencies of TT (4.1％ vs 14.1％) and CC (54.6％ vs 34.8％) showed significant differences between Linzhou ESCC patients and Changzhi healthy controls (all P ＜ 0.01).Meanwhile,there were significant differences between ESCC patients (including Changzhi and Linzhou ESCC patients) and healthy controls (including the healthy Changzhi,Linzhou and immigrator controls) in genotypic frequencies of CT(39.2％ vs 48.7％) and CC (48.8％ vs 38.2％) (all P ＜ 0.01).CT and CT + TT genotype could decrease the risk of ESCC compared with the CC genotype (OR =0.630,95％ CI0.481-0.826 ; OR =0.654,95％ CI 0.507-0.844).Conclusion There is a closed relationship between SNP rs3746804 in C20orf54 and susceptibility to ESCC.

ObjectiveTo study the relationship between plasma riboflavin levels and esophageal squamous cell carcinoma.Methods We detected and compared plasma concentrations of riboflavin in patients with esophageal squamous cell carcinoma (ESCC) and immigrants of Linzhou living in Changzhi.Plasma riboflavin levels were quantified in 445 ESCC patients,689 healthy control subjects and 347 immigrants of Linzhou living in Changzhi by using enzyme-linked immunosorbent assay.ResultsThe plasma riboflavin levels in patients with ESCC were significantly lower than those in the healthy controls and immigrants of Linzhou living in Changzhi [ (731.69 ± 330.67 ) μg/L vs ( 1090.43 ± 445.08 ) μg/L,(731.69 ± 330.67) μg/L vs ( 897.58 ± 177.78) μg/L,respectively,all P ＜ 0.05 ],and the plasma riboflavin levels of the healthy controls were higher than those in the immigrants of Linzhou living in Changzhi (P ＜ 0.05).ConclusionPatients with ESCC have decreased plasma riboflavin levels as compared with the healthy controls and immigrants of Linzhou living in Changzhi,there exists a lack of riboflavin in ESCC patients,but the specific mechanism needs further study.

To carry out the secretive expression of human 67 kD laminin receptor (67LR), recombinant expression plasmid pPIC9K-67LR was constructed by inserting of 67LR cDNA into yeast expression vector pPIC9K. The 67LR protein was expressed in Pichia pastoris after induced by methanol, and about 12.56 mg electrophoresis purity 67LR could be obtained after the purification of 1L culture using affinity chromatograph column. In vitro competitive binding assay showed that target protein has an excellent biological activity. The successful expression of 67LR has placed a solid foundation for the research on structure and functions of 67LR.
Genetic Vectors ; Humans ; Pichia ; genetics ; metabolism ; Plasmids ; genetics ; Receptors, Laminin ; biosynthesis ; genetics ; Recombinant Proteins ; biosynthesis ; genetics ; metabolism

At present, treatment for chronic radial head dislocation mainly focus on open reduction, and conservative treatment is invalid. While the surgical procedure generally applies to extend ulnar, short radial, reset radial head. Repair or reconstruction of annular ligament is the focus of study. For the dysfunction, radial head resection served as the final choice. Early diagnosis is the key to the treatment of chronic radial head dislocation. While ulnar or radial osteotomy and non-reconstruction of annular ligament is still the main trend of today.
Humans ; Joint Dislocations ; surgery ; Ligaments, Articular ; surgery ; Radius ; injuries ; surgery

Objective To explore the effective management of inpatients' fall so as to reduce the incidence of inpatients fall.Methods To use the feedforward control of the theories and methods,set up management group to prevent inpatients' fall,conducted specialized training,developed standardized nursing processes,three quality control was carried out in the process of nursing.Results After training,the pass rate of nurses' knowledge about the prevention of inpatients' fall was 92.16％ which was significantly higher than 66.67 ％ before the training ( x2 =20.2681,P ＜ 0.01 ),and the pass rate of patients and families' knowledge of fall prevention was increased from 63.03％ to 85.73％ after training ( x2 =76.8791,P ＜ 0.01 ).After the control,1348 patients without one case of fall,patient satisfaction was significantly improved from original 96.2％ to now 99.6％.Conclusions The feedforward control is effective means to prevent the inpatients' fall and improve the quality of security care.

OBJECTIVETo study the effect of human alpha-mannosidase Man2c1 transgene on tumor growth and metastasis in mice.

METHODSHepatoma cell H22 or squamous epithelial carcinoma cell S180 was subcutaneously inoculated into the right armpit of mice (wild type mice and 28#, 35#, and 54# transgenic mice). Tumor size was measured every week. Mice were sacrificed on day 9 or 10 and then the tumors were exercised and weighted. Tumors and lungs were fixed in formaldehyde and sectioned. The sections were stained with hematoxylin/eosin and examined under microscope. The red blood cells in spleen were destroyed by Tris-NH4Cl. Natural killer (NK) cell activity was detected with Yac-1 cell as target.

RESULTSH22 and S180 tumors grew faster in all the three transgenic mice (28#, 35#, and 54#) than in wild type mice. The average size and weight of tumors between the transgenic mice and wild type mice were significantly different (P<0.05). Most tumors in the transgenic mice invaded the surrounding tissues. In contrast, nearly all the tumors in wild type mice were capsulized. Three of 10 28# transgenic mice, 5 of 10 35# transgenic mice, 3 of 10 54# transgenic mice, and 1 of 10 wild type mice showed lung metastasis of H22 tumor. Two of 6 28# transgenic mice, 3 of 6 35# transgenic mice, 1 of 6 54# transgenic mice, and 0 of 6 wild type mice showed lung metastasis of S180 tumor. No difference of NK activity in spleen cells was observed between the transgenic mice and wild type mice.

CONCLUSIONShMan2c1 transgene promotes growth, invasion, and metastasis of transplanted H22 and S180 tumors in mice. hMan2cl transgene does not affect NK activity in splenocytes.

Animals ; Cell Line, Tumor ; Humans ; Killer Cells, Natural ; immunology ; Lung Neoplasms ; secondary ; Mannosidases ; genetics ; Mice ; Mice, Transgenic ; Neoplasm Invasiveness ; Neoplasm Transplantation ; Neoplasms, Experimental ; immunology ; metabolism ; pathology ; Spleen ; immunology ; Transgenes

BACKGROUNDThe relationship between signal transduction and tumors has become one of the foci in cancer research. Signal transducer and activator of the transcription 6 (STAT6) signaling pathway is found to be activated in some cancer cells. But the function of the pathway in cancer cells is unknown. This study was undertaken to investigate the effect of the Stat6 signaling pathway on apoptosis in human colon cancer cells (HT-29 cells) and the possible mechanism of Stat6 by RNA interference techniques.

METHODSFour eukaryotic expression plasmid vectors of short hairpin RNA (shRNA) specific for the STAT6 gene were designed and generated by molecular biological technology. The plasmid vectors were transfected into HT-29 cells by cation liposomes to block the Stat6 signaling pathway. The expressions of STAT6 mRNA and phosph-Stat6 protein were detected by the reverse transcriptase polymerase chain reaction (RT-PCR) method and flow cytometry respectively to screen the most effective shRNA at 72 hours after transfection. The apoptosis condition of the cells in which the expression of the STAT6 gene had been interfered was analyzed by flow cytometry and confocal microscopy. Both mRNA and protein expression of B cell lymphoma-2 (Bcl-2) and Bax were detected by RT-PCR and western blotting.

RESULTSTwo effective eukaryotic expression plasmid vectors of shRNA specific for the STAT6 gene were generated successfully. One can reduce the expression of the STAT6 gene by 82.4% and the other by 56.8% (P < 0.01). The apoptotic rate of colon cancer cells in which STAT6 gene expression had been interfered was significantly higher than that in controlled colon cancer cells (P < 0.01). In the cells in which the Stat6 signaling pathway was blocked, the levels of mRNA and protein Bcl-2 were significantly decreased, whereas those of Bax were significantly increased (P < 0.01).

CONCLUSIONSThe Stat6 signaling pathway can inhibit apoptosis in human colon cancer cells. The subsequent disorder of Bcl-2/Bax expression may play an important part in that process. The STAT6 gene may serve as a potential target in cancer therapy.

Apoptosis ; Gene Silencing ; HT29 Cells ; Humans ; Plasmids ; Proto-Oncogene Proteins c-bcl-2 ; analysis ; genetics ; RNA, Messenger ; analysis ; RNA, Small Interfering ; pharmacology ; STAT6 Transcription Factor ; antagonists & inhibitors ; genetics ; Signal Transduction ; bcl-2-Associated X Protein ; analysis ; genetics