At present,transplantation has been the predominant way to solve most of the end-stage diseases,ensued by the use of immunosuppressive drugs.Since the immunosuppressive drugs have narrow therapeutic index,the blood drug concentration is needed to mornior.Pharmacogenetics is one subject which focuses on the interaction between gene and the metabolism of the drug,providing great help for designing the regime of achieving the target drug concentration.Meanwhile,it facilitates the realization of individual therapy.This review thus focuses on the latest advancement on the pharmacogenetics of those immunosupprressants,hoping to provide help for the treatment.

Objective To evaluate 99Tcm-MIBI imaging in patients with hyperparathyroidism and its correlation with serum intact PTH level. Methods Seventy patients with suspicious hyperparathyroidism underwent 99Tcm-MIBI imaging and serum intact PTH measurement. Abnormal increased uptake lesion appeared at early phase and even more clearly at delayed phase was considered as the positive by 99Tcm-MIBI imaging. A cut-off value of PTH ＞ 88 ng/L was taken as the criteria for hyperparathyroidism diagnosis. The diagnostic efficacy of 99Tcm-MIBI imaging combined with serum PTH measurement was assessed according to post-surgical histopathology or clinical follow-up. For those operated patients, Pearson correlation coefficient between serum PTH and the gland volume was calculated. Results Hyperparathyroidism was confirmed in 38 patients by histopathology (n = 36) or follow-up (n = 2). The overall diagnostic accuracy of 99Tcm-MIBI imaging was 90.0% (63/70), in which the accuracy was 80.0% (12/15) for patients with normal serum PTH and 92.7% (51/55) for those with elevated serum PTH. False positive 99Tcm-MIBI imaging were found in 3 patients with normal serum PTH. The diagnostic accuracy of abnormally high serum PTH combined with 99Tcm-MIBI imaging was 94.3% (66/70). There was a positive correlation between serum PTH level and the volume of pathologic parathyroid glands (r = 0.782, P ＜ 0.001 ). Conclusions Serum PTH measurement may help to improve the diagnostic accuracy of 99Tcm-MIBI imaging in patients with hyperparathyroidism.

Objective To investigate the drug resistance genes of extended-spectrum beta- lactamase-producing bacteria in 49 strains.Methods Extended-spectrum ?-lactamase -producing strains were detected by the disc diffusion test.The techniques of polymerase chain reaction,sequence analysis, pulsed-field gel electrophoresis were used to analyze the genotype and homology of extended-spectrum ?- lactamase-producing strains.Results The incidence of ESBL-producing strains from E.coli,K pneumoniae,K oxytoca,was 20% in 2000,and 40% in 2003.Among the 49 ESBLs producers the most common genotype was CTX-M-14( n=33).The others were CTX-M-3,CTX-M-9,CTX-M-12,CTX-M-15, CTX-M-24 and SHVSa.Both two CTX-M subtypes,CTX-M-3 and CTX-M-14,were detected in one strain. However,4 ESBL-producing strains confirmed by phenotype remained untyped.The results showed that the ESBLs producers were not closely related,except for two strains of E.coli and two strains of K.pneumoniae which were homgenic respectively.Concolusions The incidence of ESBL-producing strains increases with years.The most common genotype of ESBLs is CTX-M.There is no evidence for epidemiologic spread of ESBL-producers by pulsed-field gel electrophoresis.

Objective To study the role of Mycoplasma genitalium(Mg)infection in chronic non- bacterial prostatitis.Methods Culture and two PCR systems were performed on prostatic secretion specimens from 487 patients with chronic non-bacterial prostatitis and 75 health men in Changchun regions. Results positive rate of Mg in the prostatic secretion from the 487 patients was 7.39% (36/487);In the controls,the positive rate of Mg was 1.33%(1/75).The differences between the two groups were statistically significant (X~2=3.88,P

Breast Neoplasms ; metabolism ; pathology ; Cytokines ; metabolism ; Female ; Fluorescent Antibody Technique ; Humans ; Microscopy, Fluorescence ; Paraffin Embedding ; Proliferating Cell Nuclear Antigen ; metabolism ; Quantum Dots ; Receptor, ErbB-2 ; metabolism ; Receptors, Estrogen ; metabolism ; Stomach Neoplasms ; immunology ; pathology

Objective To investigate the effect of hypert riglyceridemia on vascular endothelial function. Methods With high-resolution ultrasound, flow and nitroglycerin-induced dilatation of the brachial artery were determined in thirty hypertriglyceridemic patients and thirty healthy subjects as controls. Serum lipid and plasma endothelin (ET) were determined. Results In patients with hypertriglyceridemia,flow-induced vasodilatation was much reduced compared with that in the control subjects[(2.7±2.0)% vs (15.0±8.0)%, P<0.001］.However, vasodilatation in response to nitroglycerin were similar in both groups［(15.0±5.0)% vs (16.8±9.0)%, P>0.05].Plasma ET level in the hypertriglyceridemic group was significantly higher than that in the control group［(106.22±19.16) μg/L vs (72.37±14.06) μg/L, P<0.001].ConclusionEndothelium-dependent vasodilatation was impaired in patients with hypertriglyceridemia.

Objective To assess the feasibility of using an automatic tube current modulation (ATCM)method to obtmn consistent image quality with reduced radiation dose for young children undergoing chest scans with a set of 64-slice spiral CT.Methods Fifry young children underwent chest scans on a GE 64-slice VCT with automatic tube current modulation.The noise index(NI)for this study group was set to 8 or 9 based on the proposed reference for pediatric chest imaging in our hospital.We compared image quality and radiation dose for the study group with the age-matched control group of 50 young children acquired with standard protocol of fixed-mAs(120 and 150 mAs for under 1 and above 1 year old,respectively).The volume CT dose index(CTDIvol)values were recorded for beth groups.Two experienced pediatric radiologists assessed image quality on a 5-point scale with 5 being the best.Scores greater than or equal to 3 were considered clinically acceptable.The degree of interobserver concordance was determined by Kappa statistics.Results The average objective image noise and CTDIvol for control group was(4.78±0.58)and(6.68±0.62)mGy,respectively.For the study group the mean value of objective mAs wag(41.6±11.6)(20-79 mAs)with mean CTDIvol of(2.34 4±0.71)mGy,and the use of ATCM produced mean noise of(7.84±0.66).The average CTDIvol with the use of NI of 8-9 was about 65% lower than that with the fixed mAs setting.The mean image quality score for the study group and control group was(3.46±0.40)and(4.65±0.46)respectively.All studies had acceptable image quality,and there was good inter-observer agreement in diagnostic acceptability(Kappa=0.474 and 0.536).Conclusion The automatic tube current modulation method could be used to obtain consistent image qualityfor young children undergoing 64-slice MSCT chest scans.With proper noise level setting(NI=8 or 9),one may obtmn clinically acceptable images with much reduced radiation dose.

AIM:To investigate the alterations of phospholamban(PLB)expression and cardiac sarcoplasmic reticulum(SR)Ca 2+-ATPase activity,and the change of cardiac function in rats with diabetes mellitus(DM).METHODS:The diabetes mellitus in male Wistar rats was induced by intraperitoneal injection of streptozotocin.The levels of PLB mRNA and PLB protein,the activity of SR Ca 2+-ATPase and the left ventricular hemodynamics parameters were measured 4 weeks,6 weeks and 8 weeks after DM was induced in rats,while the normal rats served as control group.RESULTS:There was no significant difference in PLB mRNA level and protein level between 4-week-DM rats and normal control rats.6-week-DM rats and 8-week-DM rats had markedly increased PLB mRNA and protein level compared with normal control rats.SR Ca 2+-ATPase activity was not significantly changed in 4-week-DM rats compared with normal control rats,and was markedly depressed in 6-week-DM rats and 8-week-DM rats.LVSP,LVEDP and ?dp/dt max were not significantly changed in 4-week-DM rats compared with normal control rats.In 6-week-DM rats and 8-week-DM rats,LVSP and ?dp/dt max were decreased,LVEDP was increased compared with normal control rats.CONCLUSION:The elevated levels of PLB mRNA and PLB protein contribute to SR Ca 2+-ATPase activity reduction,which leads to cardiac dysfunction in DM rats.

This study aimed to investigate the involved immunologic mechanism of pure total flavonoids from Citrus (PTFC) on the development of non-alcoholic steatohepatitis (NASH). C57BL/6 mice were fed with high .fat diet for 16 weeks to induce the NASH model, and from the 7th week three dosages (25, 50 and 100 mg x kg(-1) x d(-1)) of PTFC were administrated intragastric for 10 weeks respectively. Serum TG, CHOL, ALT, AST were determined by biochemical assay, histopathological changes of the liver tissue were observed by HE staining, expression of RORyt and Foxp3 mRNA of the liver tissue was detected by Real-time PCR, and serum IL-17, IL-6, IL-10 and IL-4 were determined by.Cytometric Beads Array. As a result, we find that after the administration of PTFC, the in- flammation of the liver tissue of NASH mice was attenuated, liver function was improved, and the expression of RORgammat mRNA was higher in the liver tissue while which was lower of Foxp3 mRNA, the level of proinflammatory cytokines IL-17 and IL-6 decreased and the level of suppressive cytokines IL-10 and IL-4 increased. These data show that PTFC protects the development of NASH through regulating the Th17/Treg balance and attenuating inflammation.
Animals ; Citrus ; chemistry ; Cytokines ; blood ; Flavonoids ; pharmacology ; Male ; Mice ; Mice, Inbred C57BL ; Non-alcoholic Fatty Liver Disease ; immunology ; prevention & control ; T-Lymphocytes, Regulatory ; drug effects ; Th17 Cells ; drug effects

OBJECTIVETo observe the effect of pure total flavonoids from Citrus (PTFC) on the hepatic fatty degeneration, inflammation, oxidative stress and SIRT1/PGC-1alpha expressions in mice with non-alcohol steatohepatitis (NASH), and discuss the action mechanism of PTFC on NASH.

METHODMice were given high-fat diet for 16 weeks to induce the NASH model. Since the seventh week after the model establishment, the mice were intervened with 100, 50 and 25 mg x kg(-1) x d(-1) PTFC for 10 weeks. The pathologic changes in hepatic tissues were observed with HE staining. The contents of TG, CHOL in hepatic tissue, as well as the levels of AST, ALT in serum were detected by using the biochemical process. The expression of SIRT1, PGC-1alpha and MnSOD mRNA in hepatic tissues were detected with Real-time PCR assay. SIRT1, PGC-1alpha protein and 8-OHdG expressions were determined with the immunohistochemical method. The SOD level in hepatic tissues was tested by the xanthine oxidase method. The MDA content in hepatic tissues was examined by the thiobarbituric acid method.

RESULTThe contents of TG, CHOL, NAFLD activity scores and ALT level in serum in hepatic tissues of mice in the model induced by fat-rich diet were obviously higher than that of the normal group (P < 0.010. The SIRT1, PGC-1alpha, MnSOD mRNA and protein expression in hepatic tissues were significantly lower than that of the normal group (P < 0.01). The expression of 8-OHdG and the content of MDA in hepatic tissues were obviously higher than that of the normal group (P < 0.01). After the intervention with different doses of PTFC, the NAFLD activity scores, the content of TG and the level of AST in serum were notably lower than that of the normal group (P < 0.01, P < 0.05); whereas the SIRT1, PGC-1alpha, MnSOD mRNA and protein expression were obviously higher than that of the normal group (P < 0.01, P < 0.05), with the significant decrease in the expression of 8-OHdG and the content of MDA (P < 0.01).

CONCLUSIONOxidative stress/lipid peroxidation enhancement in in NASH mice induced by high-fat diet may be related to the changes in SIRT1/PGC-1alpha signal transduction pathway. PTFC could enhance the anti-oxidant capacity in liver, relieve the damage of reactive oxygen during the fatty acid metabolic process, and prevent NASH from the occurrence and development by regulating the SIRT1/PGC-1alpha signal pathway.

Animals ; Citrus ; chemistry ; Fatty Liver ; drug therapy ; genetics ; metabolism ; Flavonoids ; chemistry ; pharmacology ; Inflammation ; drug therapy ; genetics ; metabolism ; Liver ; drug effects ; metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Non-alcoholic Fatty Liver Disease ; Oxidative Stress ; drug effects ; genetics ; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha ; Sirtuin 1 ; genetics ; metabolism ; Transcription Factors ; genetics ; metabolism