Alcoholic steatohepatitis (ASH) is a liver disease characterized by steatosis, inflammation, and necrosis of the liver tissue as a result of excessive alcohol consumption. Pregnane X receptor (PXR) is a xenobiotic nuclear receptor best known for its function in the transcriptional regulation of drug metabolism and disposition. Clinical reports suggested that the antibiotic rifampicin, a potent human PXR activator, is a contraindication in alcoholics, but the mechanism was unclear. In this study, we showed that the hepatic expression of fatty acid binding protein 4 (FABP4) was uniquely elevated in ASH patients and a mouse model of ASH. Pharmacological inhibiting FABP4 attenuated ASH in mice. Furthermore, treatment of mice with the mouse PXR agonist pregnenolon-16α-carbonitrile (PCN) induced the hepatic and circulating levels of FABP4 and exacerbated ASH in a PXR-dependent manner. Our mechanism study established FABP4 as a transcriptional target of PXR. Treatment with andrographolide, a natural compound and dual inhibitor of PXR and FABP4, alleviated mice from ASH. In summary, our results showed that the PXR-FABP4 gene regulatory axis plays an important role in the progression of ASH, which may have accounted for the contraindication of rifampicin in patients of alcoholic liver disease. Pharmacological inhibition of PXR and/or FABP4 may have its promise in the clinical management of ASH.

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.

ObjectiveTo evaluate the security and effectiveness of minimal invasive fixation with 3D fluoro-images navigation in the management of acetabular fractures.MethodsFrom August 2008 to December 2010,20 patients with acetabular fractures were treated with percutaneous screw fixation under the guidance of 3D fluoro-images based on navigation system after closed reduction.There were 9 males and 11 females,aged 26-54 years old(mean,37.1±1.2 years).Fractures were caused by traffic accident in 15cases,and falling from height in 5 cases.According to AO classification,there were 2 cases of A1.1 type,3 cases of A2.2 type,4 cases of A2.3 type,2 cases of A3.2 type,2 cases of A3.3 type,2 cases of B1.1 type,2 cases of B2.2 type,1 case of B3.1 type,1 case of C2.1 type,1 case of C2.3 type.The interval from injury to hospitalization was 2-46 h (mean,8.6±0.2 h).After 3-14 days of skeletal traction through tibial tubercle,the operation was performed.ResultsTotally 46 screws were fixed.The average time for surgery was(22.6 ±1.2) min per screw.Forty-five screws were placed correctly with a successful rate of 97.8％,only one screw was reinserted for deviation.All the screws were checked by the 3D fluoro-images that they were not in the joint space after fixation.The result was same with CT scan.No incision problem and implant failure occurred.All 20 patients were followed up 12 to 28 months with an average of (22.8±1.7) months.At last follow-up,fracture union was achieved in all patients with satisfactory screw fixation.ConclusionThe minimal invasive fixation with 3D fluoro-images navigation makes the surgery for the nondisplaced acetabular fracture more precise and time-saving,minimize the surgery injury,and improves clinical results without an increasing rate of complications.

Nuclear receptors pregnane X receptor (PXR) and constitutive androstane receptor (CAR) are originally characterized as transcription factors regulating many target genes. Recent works have revealed that these nuclear receptors play critical roles in regulating genes that encode drug metabolism enzymes and modulating hepatic energy metabolism, such as down-regulating gluconeogenesis, fatty acid oxidation, and ketogenesis, as well as up-regulating lipogenesis. Studies on PXR and CAR have important implication on drug-drug interaction (DDI) and potential disease treatment targets.

BACKGROUND:The treatment of displaced acetabular fractures consists of formal open reduction and internal fixation.However,extensile exposure can lead to a lot of complications Percutaneous screw fixation for acetabukar fractures can decrease these complications Recently developed fluoroscopic-based computerized navigation technology not only allows the surgeon to achieve maximum accuracy of screw fixation but also significantly reduce radiation exposure time.OBJECTIVE:To evaluate the clinical application of the fluoroscopic-based computerized navigation system for percutaneous screwing for acetabular fractures.METHODS:A total of 18 adult patients with 20 non-displaced and displaced acetabular fractures were treated with percutaneous screw fixation under the guidance of a fluoroscopy-based navigation system.All acetabular fractures were acetabular anterior column fractures and posterior column fractures,which were fixed by varied hollow screws Static muscle contraction and limited active and passive motion were performed at 2 days,and weight-bearing exercise was performed at 4 weeks after operation.The time of screw implantation,screw position deviation,screw biocompatibility,as well as adverse effect after screw implantation was observed.In addition.d'Aubigne and Postel scoring was used in follow-up.RESULTS AND CONCLUSION:A total of 30 acetabular screws were inserted.The average operation time for per screw was24.1 minutes from the image acquisition to wound closure.The average fluoroscopic time for per screw was 27.6 seconds.Compared to the final position of the screw,the average wire tip error was 1.5 mm and the average trajectory difference was2.25°.One patient sustained a transient femoral nerve palsy which was attribute to reduction clamp inserting from the use of the limited open reduction method rather than screw fixation itself and resolved 2 months after the operation.No evidence was noted of secondary displacement of the fragment or screw failure Using the rating system of d'Aubigne and Postel,13 patients had excellent results,4 patients had good results,and 1 patient had a fair result.The excellent to good rate was 94%All results demonstrated that percutaneous screw fixation of acetabular fractures with fluoroscopy-based navigation can produce excellent results in selected patients with non-displaced and displaced fracture amenable to closed or limited open reduction,which becomes a safe and effective alternative to traditional open reduction and internal fixation for the treatment of certain acetabular fractures.