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.

Pregnane X receptor (PXR, NR1I2) is a prototypical member of the nuclear receptor superfamily. PXR can be activated by both endobiotics and xenobiotics. As a key xenobiotic receptor, the cellular function of PXR is mostly exerted by its binding to the regulatory gene sequences in a ligand-dependent manner. Classical downstream target genes of PXR participate in xenobiotic responses, such as detoxification, metabolism and inflammation. Emerging evidence also implicates PXR signaling in the processes of apoptosis, cell cycle arrest, proliferation, angiogenesis and oxidative stress, which are closely related to cancer. Here, we discussed, in addition to the characterization of PXR , the biological function and regulatory mechanism of PXR signaling in cancer, and its potential for the targeted prevention and therapeutics.

Objective To evaluate the clinical and esophageal dynamics characteristics, and initial treatment effect of patients with untreated achalasia using high resolution manometry. Methods From January 2012 to June 2016, patients newly diagnosed with achalasia were retrospectively recruited. Clinical information, endoscopy and X-ray findings, manometric variables and treatment outcomes were collected and compared among manometric subtypes. Results Among 133 patients with achalasia, 32 ( 24. 0%) were classified as type Ⅰ, 84 ( 63. 2%) as typeⅡ and 17 ( 12. 8%) as typeⅢ. Compared with the typeⅢ, the symptom of regurgitation was more common in the types I and typeⅡachalasia patients ( P=0. 020) . While compared with the type Ⅰ, the score of chest pain was higher in the patients with type Ⅱ and type Ⅲ ( P=0. 006) , as well as the basal lower esophageal sphincter pressure ( P=0. 015, P=0. 023 for type Ⅱ and type Ⅲ, respectively) . Integrated relaxation pressure was similar among the 3 subtypes ( P=0. 158) . Forty-five and 47 patients received pneumatic dilation ( PD ) and peroral endoscopic myotomy ( POEM ) respectively, and all of the patients were followed-up for at least 6 months. The success rate was higher in the POEM group than that of the PD group in all the 3 manometric subtypes, but only the difference between POEM and PD in the type Ⅲ was statistically significant ( 90. 0% VS 40. 0%, P = 0. 041 ) . Conclusion The clinical characteristics and treatment response are different among the 3 achalasia subtypes. Patients with type Ⅲ achalasia are probably the best candidates for POEM.

Objectiv e To investigate the correlation between ( CAG) n repeat polymorphism of androgen receptor(AR)geneandmalebreastcancer.Methods 40casesofmalebreastcancerand40controlswerecol-lected.DNA was extracted from peripheral blood and the AR gene CAG coding exon sequences for PCR amplifica -tion,sequencing and calculated the number of CAG repeats frquency .χ2 test and Logistic regression analysis were used assess the AR gene CAG repeat length frequency affect the number of male breast cancer risk .Results There was statistically significant difference in male breast cancer cases and controls the number of CAG repeat length frequency.Man for whom the(CAG)n≥22 repeat sequence had 3.52 times risk of male breast compared (CAG)n≤22(OR=3.52,P=0.036).Conclusion AR gene CAG repeat length is a predictor of the frequency of male breast cancer risk .Longer CAG repeats can increase the risk of male breast cancer .

to be resistant to antibiotics.