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.

The central nervous system is susceptible to the modulation of various neurophysiological processes by the cytochrome P450 enzyme(CYP),which plays a crucial role in the metabolism of neurosteroids.The antiepileptic drug phenytoin(PHT)has been observed to induce neuronal side effects in patients,which could be attributed to its induction of CYP expression and testosterone(TES)metabolism in the hip-pocampus.While pregnane X receptor(PXR)is widely known for its regulatory function of CYPs in the liver,we have discovered that the treatment of mice with pregnenolone 16α-carbonitrile(PCN),a PXR agonist,has differential effects on CYP expression in the liver and hippocampus.Specifically,the PCN treatment resulted in the induction of cytochrome P450,family 3,subfamily a,polypeptide 11(CYP3A11),and CYP2B10 expression in the liver,while suppressing their expression in the hippocampus.Func-tionally,the PCN treatment protected mice from PHT-induced hippocampal nerve injury,which was accompanied by the inhibition of TES metabolism in the hippocampus.Mechanistically,we found that the inhibition of hippocampal CYP expression and attenuation of PHT-induced neurotoxicity by PCN were glucocorticoid receptor dependent,rather than PXR independent,as demonstrated by genetic and pharmacological models.In conclusion,our study provides evidence that PCN can negatively regulate hippocampal CYP expression and attenuate PHT-induced hippocampal neurotoxicity independently of PXR.Our findings suggest that glucocorticoids may be a potential therapeutic strategy for managing the neuronal side effects of PHT.

Objective: To investigate the effects of circulating exosomes derived from oral cancer patients on the proliferation, migration and invasion of tongue cancer CAL27 cells. Methods: Circulating exosomes were isolated from the peripheral blood of 20 oral cancer patients using gradient centrifugation. The characteristics of the exosome was studied by transmission electron microscope (TEM) and Western blot. After treatment with circulating exosomes, CAL27 cell proliferation was evaluated with MTT assay, migration was observed by cell wound scratch assay and the invasion of CAL27 cells was tested by Transwell assay. CAL27 cell bearing nude mice were used to estimate the effect of circulating exosome on CAL27 cell proliferation and metastasis in vivo. Results: The proliferation, migration and invasion of CAL27 cells were enhanced by circulating exosomes from oral cancer patients. In vivo study showed that the tumorigenesis and metastasis of CAL27 cells were enhanced by circulating exosomes. Conclusion: Circulating exosomes from oral cancer patients can promote the proliferation, migration, invasion and metastasis of CAL27 cells.

Objective To explore nursing professional degree graduates' understanding and expetance of advanced practice nurses (APN), reflect on the process of clinical practice teaching, and provide a reference for APN traning by interviewing nursing graduates for their experience of clinical roles. Methods Using the phenomenological method of qualitative research, a semi-structured interview was conducted among 20 individuals, including nursing professional degree graduates who were practiced in clinical for 3 months, instructors and clinical lecturers. The Colaizzi seven-step analysis method is used to repeatedly read, analyze, encode, classify, and refine the interview materials, and summarize the theme ideas. Results After encoding, analyzing and condensing the data, we obtained four themes in APN and their supervisors' training and understanding of APN roles. Theme 1: Combined development of reseatch and clinical abilities, and attention was paid to specialty abilities; theme 2: their overall quality and clinical thinking should be enhanced;theme 3: their professional quality and confidence should be improved; theme 4: a harmonious medical working environment should be built, and policy support should be enhanced. Conclusions Starting from clinical actualities, learning clinical practice experience, exploring nursing students and their supervisors' understanding and expetance of APN, and discussing the problems and causes in current clinical practice training may provide a reference for nursing educators to improve the clinical teaching practice model for APNs.

Objective To investigate the motivation of non-medical students choosing Medical Humanistic Care curriculum and their cognition of medical humanistic care, so as to provide reference for the popularization of medical humanistic care knowledge. Methods A total of 10 non-medical students were selected by purposive sampling method for semi-structured interviews. The research data was analyze and refine the theme by phenomenological research method. Results Motivation of taking the course and medical humanities cognition were refined, which consisted of seven aspects, including learning to care others, interest in medical science, attention on the doctor-patient relationship ,the influence of family, doctor benevolence, mutual understanding between doctors and patients, and hard working with regret. Conclusions From the perspective of non-medical majors, teachers should tap their thirst for medical humanistic care, expand their medical knowledge and enhance their humanistic care ability.

Mitochondria are morphologically dynamic organelles which undergo fission and fusion processes. Our previous study found that arterial constriction was always accompanied by increased mitochondrial fission in smooth muscle cells, whereas inhibition of mitochondrial fission in smooth muscle cells was associated with arterial relaxation. Here, we used the typical vasorelaxants, verapamil and phentolamine, to further confirm the coupling between arterial constriction and mitochondrial fission in rat aorta. Results showed that phentolamine but not verapamil induced vasorelaxation in phenylephrine (PE)-induced rat thoracic aorta constriction. Verapamil, but not phentolamine, induced vasorelaxation in high K(KPSS)-induced rat thoracic aorta constriction. Pre-treatment with phentolamine prevented PE- but not KPSS-induced aorta constriction and pre-treatment with verapamil prevented both PE- and KPSS-induced aorta constriction. Transmission electron microscopy (TEM) results showed that verapamil but not phentolamine inhibited KPSS-induced excessive mitochondrial fission in aortic smooth muscle cells, and verapamil prevented both PE- and KPSS-induced excessive mitochondrial fission in aortic smooth muscle cells. Verapamil inhibited KPSS-induced excessive mitochondrial fission in cultured vascular smooth muscle cells (A10). These results further demonstrate that arterial relaxation is coupled to inhibition of mitochondrial fission in arterial smooth muscle cells.

Objective To investigate the experience and needs of caregivers of patients with hematopoietic stem cell transplantion (HSCT) , in order to provide the basis for targeted intervention. Methods Using qualitative phenomenological research methods, semi- structured interviews of 10 caregivers of HSCT patients were conducted, then the data were summarized and analyzed. Results Four themes were extracted: heavy caregiving burden, adaptation to the caregiving role, professional support needs, humanistic care needs. Conclusions The medical staff should strengthen the health education on HSCT caregivers to improve their ability and their own health concerns, alleviate their psychological pressure, and mobilize social forces to reduce the burden of care.

Objective We tried to investigate the nutritional status and related factors in patients undergoing allogenetic hematopoietic stem cell transplantation.Methods A total of 75 patients were recruited from a class-three hospital in Suzhou.They were investigated with a basic information questionnaire and the Patient-Generated-Subjective Global Assessment (PG-SGA).The related factors influencing nutritional status were analyzed.Results The PAB level began to rise since conditioningregimen,and it rose to the highest level in the second week,then began to decline.The weight and the BMI had been declining in the four weeks since conditioning regimen.29.33％ of the patients were malnourished,the scored PG-SGA was (5.60±4.96),the percentage of patients with dietary problems was 33.3％ before conditioning regimen; 85.33％ of the patients were malnourished,the scored PG-SGA was (19.26±7.18),the percentage of patients with dietary problems was 93.2％ in the second week since conditioning regimen; 85.33％ of the patients were malnourished,the scored PG-SGA was (12.95±6.19),the percentage of patients with dietary problems was 75.8％ in the fourth week; Age is the main factor affecting the patients' albumin level in the second week.Conclusions The nutritional status of patients deteriorated and the percentage of patients with malnutrition increased during allogeneic hematopoietic stem cell transplantation.Clinical staff should pay attention to the assessment of nutritional status,and give a reasonable nutritional support when necessary.

Objective To measure osteoporosis knowledge,belief and self-efficacy of elderly patients with vertebral fracture,and to provide the basis for reducing the incidence of refracture.Methods Totally 72 patients were recruited from an upper first-class hospital in suzhou by using the convenience sampling method.They were measured with the self-designed general information questionnaire,Osteoporosis Knowledge Tests (OKT),Osteopomsis Health Belief scale (OHBS) and Osteoporosis Self-Efficacy Scale (OSES).Results The total score of knowledge was (1 1.06±6.71),the factor scores of risk factors,exercise and calcium intake were(4.13±2.82),(2.90±2.54),(4.04±2.54).The average score of OHBS was (141.82± 13.00).The total score of self-efficacy was (79.49±35.15).Conclusions Health education for elderly patients with vertebral fractures needs to be improved,and to reduce the occurrence of refracture according to different groups of targeted education.

Objective To evaluate immune function of patients with multiple myeloma ( MM) by detect the changes of the Treg cells in bone marrow of patients with MM .Methods Treg cells in peripheral blood and bone marrow of 45 patients with MM and 15 healthy controls were measured by flow cytometry .Results The per-centage of Treg cells in peripheral blood of MM was higher than that in healthy person ;The percentage of Treg cells in MM bone marrow was lower than that in healthy person ,and the extent was positively correlated with the level of β2-MG and ISS(P<0.05).Conclusion MM Patients display an abnormal level of CD 4 +CD25 +Treg cells,which may be an important mechanism of MM immune deficiency .