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

Abstract: Objective　To monitor and analyze the avian influenza virus contamination in the environment outside the poultry-related places in Guangxi, and to assess the risk of human infection with avian influenza viruses, so as to provide a scientific basis for the prevention and control of avian influenza in Guangxi. Methods　From 2021 to 2022, environmental samples from 5 kinds of poultry-related sites were collected monthly in 14 cities of Guangxi. The real-time fluorescent quantitative RT-PCR method was used to detect the nucleic acids of generic influenza A viruses, and H5, H7, and H9 subtypes of avian influenza virus. The detection results of avian influenza virus in the environment of the poultry-related sites in Guangxi were collected for retrospective analysis. SPSS 22.0 was used for data analysis, and the chi-square test was used to compare the rates. Results　From 2021 to 2022, a total of 5 960 environmental samples were collected in 14 cities, of which 3 918 were positive for influenza A virus nucleic acid, with a positive rate of 65.74%; Among the positive samples, 281 were positive for H5 subtype (7.17%), 2 508 were positive for H9 subtype (64.01%), 552 were positive for H5+H9 subtype (14.09%), 577 were positive for type A but not H5/H7/H9 (14.73%), and no subtype H7 was detected. The positive rate of influenza A in poultry-related environment samples was higher throughout the year in Guangxi; except for Wuzhou, which had a similar number of H5, H9, and A non-H5/H7/H9 subtypes, the H9 subtype was predominantly detected in other cities. There was significant variability in positive rates among different regions, with the highest being in Hezhou City (90.32%, 653/723) and the lowest in Yulin City (28.96%, 75/259). The positive rate of different specimen types ranged from 50.32% to 74.94%. There were statistically significant differences in the positive rates of samples from different types of samples (χ2=163.08, P<0.001), different months (χ2=172.69, P<0.001), different regions (χ2=498.86, P<0.001), different monitoring sites (χ2=370.01, P<0.001). Conclusions　There is severe contamination of avian influenza virus in the poultry-related environment in Guangxi, predominantly with the H9 and H5 subtypes. Therefore, the relevant authorities in Guangxi should strengthen the monitoring, management, and disinfection of poultry-related premises.

OBJECTIVETo study the inhibition of berberine (BBR) against ECV-304 apoptosis induced by Staphylococcus aureus (S. aureus).

METHODSECV-304 cells were pre-treated with 128 microg/mL BBR for 2 h and then S. aureus was added (1:100). The viability of cells was detected by MTT (3-4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. The morphological changes were observed by Hoechst 33258 staining. The protection of BBR for infected cells was detected by DNA Ladder.

RESULTSECV-304 cells' viability were not obviously affected by berberine. But S. aureus induced ECV-304 cells' viability could be significantly inhibited by pre-treatment of BBR (P < 0.05). Besides S. aureus-induced ECV-304 apoptosis could be reduced, with significantly lessened apoptotic body and unobvious DNA degradation.

CONCLUSIONBBR could significantly inhibit S. aureus induced ECV-304 apoptosis.

Apoptosis ; drug effects ; Berberine ; pharmacology ; Cell Line ; Human Umbilical Vein Endothelial Cells ; drug effects ; microbiology ; pathology ; Humans ; Staphylococcus aureus

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.

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 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.

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