Drug metabolism will change significantly during inflammation, including the reduction of expression and activity of many drug metabolizing enzymes and transporters. Body would release a series of inflammatory cytokines which can regulate drug metabolizing enzymes. Recent studies have revealed that drug transporters are also regulated by the cytokines with obvious species difference. Mechanism studies show that several transcription factors play important roles during the signal pathways of regulation. This review focuses on the progress in the regulation of drug transporters during inflammation.

EGFR testing has become the consensus before epidermal growth factor-tyrosine kinase inhibitorrs (EGFR-TKIs) treatment in non-small cell lung cancer(NSCLC) patients.Malignant pleural effusion is the common clinical manifestation in NSCLC patients,and EGFR testing by using different methods in pleural effusion cells and free nucleic acids has good prospect for predicting the efficacy of EGFR-TKIs.

Objective To observe the effects of puerarin on the expression of glycogen synthase kinase- 3 (GSK- 3) in the skeletal muscle of rats with insulin resistance induced by high fat and sucrose diets. Methods 30 Wistar rats were randomly divided into three groups: normal group, model group and puerarin group, 10 rats in each group. The model group and puerarin group were fed with the high fat and sucrose diets for 4 weeks. Then puerarin group was treated with puerarin by abdominal injection (100 mg/kg) for 6 weeks. At the end of the experiment, GSK- 3 content was detected by Western blot analysis. Body weight, serum triglyceride and cholesterol levels, fasting plasma glucose and serum insulin concentrations were measured regularly and insulin sensitivity index was also computed as well. Results The outcome of Western blot analysis showed that the expression of GSK- 3 in the skeletal muscle of the model group increased by 70.20 % (P

Objective To investigate the role of nuclear factor-kappa B (NF-κB)signaling pathway in propofol-induced suppression of up-regulation of inducible nitric oxide synthase (iNOS) gene expression in LPSstimulated RAW264.7 cells.Methods RAW264.7 cells were purchased from cell bank of Chinese Academy of Sciences and cultured in DMEM culture medium containing 10％ fetal bovine serum.The cells were seeded in 6 cm diameter dishes (3 ml/dish) or in 6-well plates (2 ml/well) with a density of 5 × 105/ml and randomly divided into 3 groups ( n =18): normal control group (group C),group LPS (group L)and group LPS + propofol (group LP).The cells were incubated with LPS 1 μg/ml in groups L and LP.Propofol 50μmol/L was added to the culture medium at 2 h before LPS in group LP.Cells were harvested at 30 min after being stimulated with LPS.Phosphorylation of IκB kinase(p-IKK) and NF-κB activity were detected by Western blot.The expression of iNOS mRNA was determined after 6 h exposure of the cells to LPS.Results LPS significantly up-regulated the expression of p-IKK and iNOS mRNA and increased NF-κB activity in group L as compared with group C.Propofol pretreatment significantly attenuated the effects of LPS on p-IKK,iNOS mRNA expression and NF-κB activity.Conclusion NF-κB signaling pathway is involved in the propofol-induced suppression of up-regulation of iNOS mRNA expression in LPS-stimulated RAW264.7 cells.

Objective To investigate MR imaging features of femoral marrow in treated ?-thalassemia major.Methods MR imaging of the proximal femoral marrow was performed in 35 cases of ?-thalassemia major and 45 age-and sex-matched normal children as control.Coronal images of femoral marrow with the techniques of spin echo and fast field echo(FFE)were obtained.On T_1-weighted imaging the red and yellow femoral marrow were judged and marrow distribution was classified into five groups.The hemosiderosis of marrow was judged on the basis of signal intensity of marrow on FFE imaging.The marrow distribution classification and the hemosiderosis on MR imaging were correlated with clinical features.Results On FFE,marrow hemosiderosis occurred in 15 patients with a marked hypo-intensity signal and was related to the age(P=0.032).On T_1-weighted imaging,the femoral marrow in 35 patients was classified as groupⅢand IV,while the marrow distribution was groupⅠorⅡin all normal children,there was statistically significant difference(P

Objective To investigate the effectiveness of ilioischial plating through modified Stoppa and iliac fossa approaches for complex acetabular fractures. Methods A consecutive series of 40 patients with complex acetabular fracture were treated operatively from January 2014 to February 2015. Of them, 20 were treated through modified Stoppa plus iliac fossa approaches as an experimental group ( including 12 males and 8 females with a mean age of 46. 8 ± 10. 3 years ) . The anterior column was stabilized with a recon-struction plate for the iliac wing along the iliopectineal line to the pubis in all cases. The posterior column was fixed with a newly developed ilioischial plate running from the ilium to the ischial ramus. The other 20 patients ( 10 males and 10 females with a mean age of 45. 6 ± 11. 7 years ) served as a control group, treated with a reconstruction plate for the conventional posterior column fixation through the Kocher-Langenbeck approach. The 2 groups were compared in terms of operative time, intraoperative blood loss, reduction and functional recovery of the hip. Results The 40 patients obtained an average follow-up of 18 months ( from 8 to 24 months ) . The experimental group reported significantly shorter operation time ( 2. 1 ± 0. 7 hours ) and signifi-cantly less intraoperative bleeding ( 320. 8 ± 100. 4 mL ) than the control group ( 2. 9 ± 0. 6 hours and 621. 6 ± 118. 7 mL, respectively ) ( P <0. 05 ) . According to modified Matta's criteria for reduction, the experimental group had 15 excellent, 3 good, one fair and one poor cases ( giving an excellent to good rate of 90％) while the control group had 17 excellent, one good, one fair and one poor cases ( giving an excellent to good rate of 90％) . According to the modified Merle d'Aubigné and Postel scoring for the functional recovery of the af-fected hip at the final follow-ups, the experimental group had 14 excellent, 3 good, 2 fair and one poor cases ( giving an excellent to good rate of 85％) while the control group had 12 excellent, 4 good, 3 fair and one poor cases (giving an excellent to good rate of 80％). There were no significant differences between the 2 groups in the above comparisons ( P> 0. 05 ) . There were no significant differences in the MOS item short form health survey score and postoperative complication rate between the experimental group and the control group. Conclu-sion Ilioischial plating through modified Stoppa and iliac fossa approaches has advantages of reliable fixa-tion, limited invasion, less intraoperative blood loss and fewer complications for complex acetabular fractures.

Objective To investigate the efficacy differences of different doses of cyclophosphamide(CTX)among subcategories of diffuse proliferative lupus nephritis(LN). Methods Clinical data of 133 LN patients diagnosed by renal biopsy with class IV or class IV +V who were treated with corticosteroid plus CTX were analyzed retrospectively. The baseline Scr, 24 h urine protein, CTX dosages and prognosis were compared among different dosages for each subcategory. Results The average cumulative dose of CTX within 6 months was(11.1 4.1)g. The high dose group was >12 g, the medium dose group was >6-12 g and the low dose group was ≤6 g. Compared to low dose group, high dose CTX increased the remission rate of class Ⅳ +Ⅴ(67% vs 40%, P=0.314)and chronic renal lesion(43% vs 0%, P=0.212), but such enhancement was not obvious in class Ⅳ(Ⅳ-S: 67% vs 50%, P=0.548, Ⅳ-G: 65% vs 70%, P= 0.560). Difference of overall adverse reactions was not significant between high dose group and low dose group(51% vs 37% ,P=0.224). Conclusion Corticosteroid plus high dose CTX may improve the remission rate of patients with class IV + V and chronic renal lesions.

Objective To investigate the clinicopathologic characteristics, classification and outcome in lupus nephritis(LN)patients with thrombotic microangiopathy(TMA). Methods LN patients with TMA proven by renal biopsy, from January 2000 to February 2009 in our hospital were enrolled. They were classified as poly-immunocomplex deposit group(n =35)and pauci-immunocomplex deposit group(n=25). Their clinicopathologic features and outcome were analyzed retrospectively. Results(l)The incidence of TMA in lupus nephritis was 9.2%(n=62), which presented severe hypertension, prominently elevated serum creatinine, anemia, thrombocytopenia, and was also the poorest prognosis of all the vascular lesion types. The incidence of death/end stage renal disease(ESRD)was 25.0%, with a mortality rate of 13.6%.(2)According to immunocomplex deposit in renal tissue, LN complicated with TMA could be classified as "poly immunocomplex deposit subtype" and "pauci-immunocomplex deposit subtype". The former presented better response to steroid and immunosuppressant therapy, in spite of more active clinicopathologic manifestations. The incidences of death/ESRD of poly subtype and pauci subtype were 8.8% and 32.0% respectively. Conclusions TMA presenting severe manifestations and the poorest prognosis is not rare in LN. LN with TMA may be classified as poly-immunocomplex deposit subtype and pauci-immunocomplex deposit subtype. This classification may be helpful in prognosis because the latter shows bad response to steroid-immunosuppressant therapy.

This study aims to investigate the function of two SNPs (rs8904C > T and rs696G >A) in 3' untranslated region (3'UTR) of NFKBIA gene by constructing luciferase reporter gene. A patient's genomic DNA with rs8904 CC and rs696 GA genotype was used as the PCR template. Full-length 3'UTR of NFKBIA gene was amplified by different primers. After sequencing validation, these fragments were inserted to the luciferase reporter vector, pGL3-promoter to construct recombinant plasmids containing four kinds of haplotypes, pGL3-rs8904C/rs696G, pGL3-rs8904C/rs696A, pGL3-rs8904T/rs696G and pGL3-rs8904T/rs696A. Then these plasmids were transfected into LS174T cells and the luciferase activity was detected. Compared with pGL3-vector transfected cells (negative control), the luciferase activity of the four kinds of recombinant plasmids was significantly decreased (P < 0.001). For rs696G > A, the luciferase activity of the recombinant plasmids containing A allele (pGL3-rs8904C/rs696A and pGL3-rs8904T/rs696A) was about 45.1% (P < 0.05) and 56.1% (P < 0.001) lower than those containing G allele (pGL3-rs8904C/rs696G and pGL3-rs8904T/rs696G), respectively. For rs8904C > T, there were no significant differences in the luciferase activity between the recombinant plasmids containing T allele and those with C allele. Together, the luciferase reporter gene vectors containing SNPs in NFKBIA gene 3'UTR were constructed successfully and rs696G > A could decrease the luciferase activity while rs8904C >T didn't have much effect on the luciferase activity.

Aim To develop an in vitro high throughput drug screening system based on reporter gene assay for identification of novel compounds with PXR, FXR and LXRα agonist activity. Methods The expressions of exogenous PXR, FXR and LXRαgene in HEK293, HepG2 and LS174T cells were examined by Real-Time quantity PCR. pSG5-hPXR and pGL3-XREM-CYP3A4, pEGFP-N3-hFXR and EcRE-TK-Luc, pCMX-FLAG-hLXRα and pGL3-XREM-CYP3A4 were cotransfected into cells and the optimal ratio of three plasmids was determined. The dose-response relationship between the positive drug and the fold induction was determined. The specificity of the model was ex-amined, and the repeatability was also determined by Z′ value. Results ① The PXR, FXR and LXRα mRNA expression in HEK293 cell is low among three different cells. ②reporter gene vector and expression plasmid ratio of 1∶ 1, 2∶ 1 and 2∶ 1 were proved to be suitable for highest relative luciferase activity for PXR, FXR or LXRα agonist screening model. ③ The relative luciferase activity was induced by Rif, CDCA or T0901317 in a dose-dependent manner. ④Only Rif, CDCA or T0901317 could significantly increase the relative luciferase activity in PXR,FXR or LXRα agonist screening model, no effect of other nuclear re-ceptors agonist was observed, and the values of Z′-factor for PXR, FXR and LXRαagonist screening model were 0. 58, 0. 66 and 0. 63, respectively. Conclusion An in vitro PXR, FXR and LXRα agonist high-throughput screening models are devel-oped with acceptable specificity and repeatability, and the mod-els can be used to screen PXR, FXR and LXRα agonist.