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 investigate the prevalence and characters of residual physical symptoms in Chinese depressive patients after acute treatment and the influence on the quality of life and social function.Methods In the multi-centers cross-sectional study,1 503 adult depressive outpatients,from 11 hospitals,who had been treated by antidepressants for 8-12 weeks with significant improvement of at least 50％ by Self-rating Visual Analog Scale were involved.The group with residual physical symptoms could be differentiated by Brief 16-Item Quick Inventory of Depressive Symptomatology Self-Report (QIDS-SR16) ＞5,while the QIDS-SR16 of remission group was ≤5.The QIDS-SR16,Patient Health Questionnaire-15 (PHQ-15),Quality of Life Enjoyment and Satisfaction Questionnaire-Short Form (Q-LES-Q-SF) and Sheehan Disability Scale (SDS) were used to assess the depressive symptoms,physical symptoms and social function.Results 49.8％ (748/1 503) patients had residual physical symptoms (PHQ-15＞4).The most common physical symptoms (PHQ-15≥1) were feeling tired or having low energy (56.3％,846/1 503),trouble sleeping (50.6％,760/1 503),headache(43.6％,655 / 1 503),constipation,loose stools or diarrhea(41.3％,620/1 503),feeling heart pound or race (37.6％,565/1 503),dizziness (34.0％,511/ 1 503),nausea,gas or indigestion (33.6％,505/1 503),etc.The 75.7％ (555/733) of the physical symptoms (PHQ-15＞4) in residual group was significantly higher than the 25.1％ (193/770;x2=385.38,P＜0.01) in remission group.The differences on social function (t=2.77-10.47) and life quality (t=3.04-11.41) between two groups were significant (P＜0.01).Generalized linear regression analysis showed that gender (female),present history of first episode were related to better social function,and the factors related to both social function and quality of life included residual depressive symptoms,residual physical symptoms of different severity,comorbid medical conditions,age,duration of antidepressant treatment for this episode.Conclusion The rate of residual physical symptoms is higher in patients with major depression who responded to acute phase treatment.The more severe the residual physical symptoms,the worse the quality of life and social function.It suggests that physical symptoms be focused in order to achieve clinical recovery.

Objective To investigate the prevalence and characters of residual physical symptoms in Chinese depressive patients after acute treatment and the influence on the quality of life and social function.Methods In the multi-centers cross-sectional study,1 503 adult depressive outpatients,from 11 hospitals,who had been treated by antidepressants for 8-12 weeks with significant improvement of at least 50％ by Self-rating Visual Analog Scale were involved.The group with residual physical symptoms could be differentiated by Brief 16-Item Quick Inventory of Depressive Symptomatology Self-Report (QIDS-SR16) ＞5,while the QIDS-SR16 of remission group was ≤5.The QIDS-SR16,Patient Health Questionnaire-15 (PHQ-15),Quality of Life Enjoyment and Satisfaction Questionnaire-Short Form (Q-LES-Q-SF) and Sheehan Disability Scale (SDS) were used to assess the depressive symptoms,physical symptoms and social function.Results 49.8％ (748/1 503) patients had residual physical symptoms (PHQ-15＞4).The most common physical symptoms (PHQ-15≥1) were feeling tired or having low energy (56.3％,846/1 503),trouble sleeping (50.6％,760/1 503),headache(43.6％,655 / 1 503),constipation,loose stools or diarrhea(41.3％,620/1 503),feeling heart pound or race (37.6％,565/1 503),dizziness (34.0％,511/ 1 503),nausea,gas or indigestion (33.6％,505/1 503),etc.The 75.7％ (555/733) of the physical symptoms (PHQ-15＞4) in residual group was significantly higher than the 25.1％ (193/770;x2=385.38,P＜0.01) in remission group.The differences on social function (t=2.77-10.47) and life quality (t=3.04-11.41) between two groups were significant (P＜0.01).Generalized linear regression analysis showed that gender (female),present history of first episode were related to better social function,and the factors related to both social function and quality of life included residual depressive symptoms,residual physical symptoms of different severity,comorbid medical conditions,age,duration of antidepressant treatment for this episode.Conclusion The rate of residual physical symptoms is higher in patients with major depression who responded to acute phase treatment.The more severe the residual physical symptoms,the worse the quality of life and social function.It suggests that physical symptoms be focused in order to achieve clinical recovery.

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.

Objective To assess the type and prevalence of residual symptoms in Chinese depressive patients after acute phase treatment and the impact on the quality of life and social function. Method It was a nationwide, multi-center survey. A total of 11 sites participated and 1503 outpatients with major depressive disorder who subjectively self-reported a least 50%improvement after 8-12 weeks of antidepressants treatment were included in this study. Brief 16-Item Quick Inventory of Depressive Symptomatology Self-Report (QIDS-SR16), Patient Health Questionnaire-15 (PHQ-15), Quality of Life Enjoyment and Satisfaction Questionnaire-Short Form (Q-LES-Q-SF) and Sheehan Disability Scale (SDS) were used to assess the symptoms and function. Results Altogether 48.8%(733/1503) of patients who self-reported an improvement after acute-phase treatment still presented with residual symptoms (QIDS-SR16>5). The most common residual symptoms (QIDS-SR16≥1) were poor concentration/decision making (82.4%, 604/733), low energy (79.7%, 584/733), loss of interest (75.2%, 551/733), sad mood (72.4%, 531/733) and mid-nocturnal insomnia (72.3%, 530/733). The patients with severe residual symptoms had higher PHQ-15 total score (t=-10.55,P<0.01), lower Q-LES-Q-SF score (t=10.20,P=0.010) and higher SDS score (t=-13.22,P<0.01). Conclusion The great majority of patients who self-report an improvement after acute phase antidepressant treatment may still have residual symptoms. The severity of residual symptoms is associated with significant function impairment and poor life satisfaction.

Objective To assess the type and prevalence of residual symptoms in Chinese depressive patients after acute phase treatment and the impact on the quality of life and social function. Method It was a nationwide, multi-center survey. A total of 11 sites participated and 1503 outpatients with major depressive disorder who subjectively self-reported a least 50%improvement after 8-12 weeks of antidepressants treatment were included in this study. Brief 16-Item Quick Inventory of Depressive Symptomatology Self-Report (QIDS-SR16), Patient Health Questionnaire-15 (PHQ-15), Quality of Life Enjoyment and Satisfaction Questionnaire-Short Form (Q-LES-Q-SF) and Sheehan Disability Scale (SDS) were used to assess the symptoms and function. Results Altogether 48.8%(733/1503) of patients who self-reported an improvement after acute-phase treatment still presented with residual symptoms (QIDS-SR16>5). The most common residual symptoms (QIDS-SR16≥1) were poor concentration/decision making (82.4%, 604/733), low energy (79.7%, 584/733), loss of interest (75.2%, 551/733), sad mood (72.4%, 531/733) and mid-nocturnal insomnia (72.3%, 530/733). The patients with severe residual symptoms had higher PHQ-15 total score (t=-10.55,P<0.01), lower Q-LES-Q-SF score (t=10.20,P=0.010) and higher SDS score (t=-13.22,P<0.01). Conclusion The great majority of patients who self-report an improvement after acute phase antidepressant treatment may still have residual symptoms. The severity of residual symptoms is associated with significant function impairment and poor life satisfaction.

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.