Objective To prepare polyclonal antibodies of anti Nogo-66, the extracellular region of one central nervous system neurite regeneration inhibitor Nogo, which could be used to further identification and functional study of Nogo molecule.Methods Preparing rabbit anti rat Nogo-66 polyclonal antibodies with a purified Nogo-66 fusion protein expressed in E.coli system. Studying its specificity by Western-blot and immuno-histochemical techniques and identifying its biological activity in PC12 cells.Results The high titer (1∶[KG-*2]10 000) anti rat Nogo-66 polyclonal antibodies were obtained.This antibody could specifically recognize the Nogo protein expressed in E.coli system.Immuno-histochemical staining indicated that the Nogo was widely expressed in rat spinal cord neurons and oligodendrocytes.It could effectively block the neurite extensioninhibition of Nogo protein in PC12.Conclusion Successful preparation of anti rat Nogo polyclonal antibodies provides a useful tool in identification or further functional study of Nogo molecule.

OBJECTIVE： To investigate the relationship between ATP-binding cassette subfamily B member 1 （ABCB1） polymorphism and tacrolimus-related adverse drug reactions in renal transplant patients during perioperative period. METHODS： Totally 170 patients who underwent renal transplantation from Nov. 2014 to Mar. 2018 in our hospital as well as were tested for their ABCB1 C1236T （rs1128503）， ABCB1 G2677T/A （rs2032582） and ABCB1 C3435T （rs1045642） genotype were selected in this study. χ2 test was used to compare the incidence of tacrolimus-related ADR among patients with different genotypes. The related adverse reactions included digestive tract reaction， pulmonary infection， renal dysfunction， abnormal liver function， elevated blood sugar， elevated blood lipid and decreased white blood cells. Logistic regression model was used to analyze the unit point risk. The main haplotypes of the above genes were analyzed by PHASE software， and their correlation with tacrolimus-induced ADR was analyzed. RESULTS： Among 170 patients， 21 cases （12.3％） of CC type， 78 cases （45.9％） of CT type and 71 cases （41.8％） of TT type were detected by ABCB1 C1236T （rs1128503）. ABCB1 G2677T/A （rs2032582） test showed that 25 cases （14.7％） were GG type， 95 cases （55.9％） were GA+GT type and 50 cases （29.4％） were AA+AT+TT type. ABCB1 C3435T （rs1045642） test showed that 57 cases （33.5％） were CC type， 82 cases （48.2％） were CT type and 31 cases （18.3％） were TT type. There was no significant difference in the incidence of digestive tract reaction， pulmonary infection， renal dysfunction， elevated blood sugar， elevated blood lipid and decreased white blood cells among patients with different ABCB1 genotypes （P＞0.05）. However， there was significant difference in the incidence of abnormal liver function between ABCB1 C1236T （rs1128503） and ABCB1 C3435T （rs1045642） genotypes （P＜0.05）. There was no significant difference in the incidence of abnormal liver function among ABCB1 G2677T/A （rs2032582） genotypes （P＝0.069）， but P was lower than 0.1. Logistic regression analysis showed that ABCB1 C1236T （rs1128503） CC genotype [OR＝4.959， 95％CI （1.700， 14.468）， P＝0.003]， ABCB1 G2677T/A （rs2032582） GG genotype [OR＝3.500， 95％CI （1.164， 10.524）， P＝0.026] and ABCB1 C3435T （rs1045642） CC genotype [OR＝3.033， 95％CI （1.012， 9.095）， P＝0.048] were risk factors for tacrolimus-related abnormal liver function. ABCB1 CGC haplotype was the main haplotype. There was significant difference in the incidence of abnormal liver function caused by tacrolimus between ABCB1 CGC haplotype and non-ABCB1 CGC haplotype （P＝0.002）， and it was also a risk factor for tacrolimus-related liver dysfunction [OR＝3.173， 95％CI（1.512， 6.656）， P＝0.002]. CONCLUSIONS： The abnormal liver function of ABCB1 CGC haplotype kidney transplantation patients is more likely to occur when tacrolimus is administered during the perioperative period.

Drug-induced hyperglycemia/diabetes is a global issue. Some drugs induce hyperglycemia by activating the pregnane X receptor (PXR), but the mechanism is unclear. Here, we report that PXR activation induces hyperglycemia by impairing hepatic glucose metabolism due to inhibition of the hepatocyte nuclear factor 4-alpha (HNF4α)‒glucose transporter 2 (GLUT2) pathway. The PXR agonists atorvastatin and rifampicin significantly downregulated GLUT2 and HNF4α expression, and impaired glucose uptake and utilization in HepG2 cells. Overexpression of PXR downregulated GLUT2 and HNF4α expression, while silencing PXR upregulated HNF4α and GLUT2 expression. Silencing HNF4α decreased GLUT2 expression, while overexpressing HNF4α increased GLUT2 expression and glucose uptake. Silencing PXR or overexpressing HNF4α reversed the atorvastatin-induced decrease in GLUT2 expression and glucose uptake. In human primary hepatocytes, atorvastatin downregulated GLUT2 and HNF4α mRNA expression, which could be attenuated by silencing PXR. Silencing HNF4α downregulated GLUT2 mRNA expression. These findings were reproduced with mouse primary hepatocytes. Hnf4α plasmid increased Slc2a2 promoter activity. Hnf4α silencing or pregnenolone-16α-carbonitrile (PCN) suppressed the Slc2a2 promoter activity by decreasing HNF4α recruitment to the Slc2a2 promoter. Liver-specific Hnf4α deletion and PCN impaired glucose tolerance and hepatic glucose uptake, and decreased the expression of hepatic HNF4α and GLUT2. In conclusion, PXR activation impaired hepatic glucose metabolism partly by inhibiting the HNF4α‒GLUT2 pathway. These results highlight the molecular mechanisms by which PXR activators induce hyperglycemia/diabetes.