Deficiency of apoptosis-stimulating protein two of p53 promotes liver regeneration in mice by activating mammalian target of rapamycin.

Although liver regeneration has been intensively studied in various ways, the mechanisms underlying liver regeneration remain elusive. Apoptosis-stimulating protein two of p53 (ASPP2) was discovered as a binding partner of p53 and plays an important role in regulating cell apoptosis and growth. However, the role of ASPP2 in hepatocyte proliferation and liver regeneration has not been reported. The expression profile of ASPP2 was measured in a mouse model with 70% partial hepatectomy (PHX). Liver regeneration and hepatocyte proliferation were detected in wild-type (ASPP2+/+) and ASPP2 haploinsufficient (ASPP2+/-) mice with PHX. The mammalian target of rapamycin (mTOR) and autophagy pathways were analyzed in the ASPP2+/+ and ASPP2+/- mice with PHX. After rapamycin or 3-methyladenine (3-MA) treatment, hepatocyte proliferation and liver regeneration were analyzed in the ASPP2+/+ and ASPP2+/- mice with PHX. ASPP2 expression was shown to be upregulated at the early stage and downregulated at the late stage. Compared to the ASPP2+/+ mice, liver regeneration was enhanced in ASPP2+/- mice with 70% PHX. In addition, compared to the ASPP2+/+ mice, the mTORC1 pathway was significantly upregulated and the autophagic pathway was downregulated in ASPP2+/-mice with 70% PHX. Inhibition of the mTORC1 pathway significantly suppressed liver regeneration in ASPP2+/- mice with 70% PHX. In contrast, disruption of the autophagic pathway further enhanced liver regeneration in ASPP2+/- mice with 70% PHX. ASPP2 deficiency can promote liver regeneration through activating the mTORC1 pathway, which further regulates downstream molecules, such as those related to autophagy and p70S6K expression in mouse model post-PHX.

Role and importance of the expression of transcription factor FOXC2 in cervical cancer.

The aim of the present study was to investigate the relationship between the expression of transcription factor forkhead box C2 (FOXC2) and the clinical features of cervical cancer. A total of 66 patients with cervical cancer, 42 patients with cervical intraepithelial neoplasia (CIN) and 25 patients with cervical inflammation were enrolled. The positive expression rates and expression levels of mRNA of FOXC2, E-cadherin, N-cadherin, vascular endothelial growth factor (VEGF), stromal cell-derived factor-1 (SDF-1), Notch protein and lymphatic vessel endothelial hyaluronan receptor-1 (LYVE-1) in cervical tissues were detected using immunohistochemistry and RT-PCR. The positive expression rates and expression levels of mRNA of FOXC2, N-cadherin, VEGF, SDF-1, Notch and LYVE-1 in cervical cancer were significantly higher than those in CIN, and those in the inflammatory tissues were the lowest, while the positive expression rate of E-cadherin in cervical cancer was lower than that in CIN, and that in the inflammatory tissues was the highest (P<0.05). The positive expression rates of FOXC2, N-cadherin, VEGF, SDF-1, Notch and LYVE-1 in patients with cervical cancer [human papillomavirus (HPV) positive, squamous cell carcinoma, Stages III-IV, maximal diameter ≥3.8 cm and low differentiation] were increased, and the positive expression rate of E-cadherin was decreased (P<0.05). Correlation analysis revealed that FOXC2 was positively correlated with the positive expression rates of N-cadherin, VEGF, SDF-1, Notch and LYVE-1, and negatively correlated with E-cadherin (P<0.05). In conclusion, the high expression of FOXC2 is correlated with the HPV infection, pathological pattern, clinical stage, tumor diameter and differentiation grade of cervical cancer, which may be involved in the epithelial-mesenchymal transition, vascular and matrix formation, Notch signaling pathway and lymphangiogenesis.

Significant reduction of antibiotic consumption and patients' costs after an action plan in China, 2010-2014.

INTRODUCTION: On July 1, 2011, the Chinese government launched a national Action Plan for antibiotic stewardship targeting antibiotic misuse in public hospitals. The aim of this study was to evaluate the impacts of the Action Plan in terms of frequency and intensity of antibiotic utilization and patients costs in public general hospitals. METHODS: Administrative pharmacy data from July 2010 to June 2014 were sampled from 65 public general hospitals and divided into three segments: (1) July 2010 to June 2011 as the preparation period; (2) July 2011 to June 2012 as the intervention period; and (3) July 2012 to June 2014 as the assessment period. The outcome measures included (1) antibiotic prescribing rates; (2) intensity of antibiotic consumption; (3) patients costs; and (4) duration of peri-operative antibiotic treatment in clean surgeries of thyroidectomy, breast, hernia, and orthopedic procedures. Longitudinal and cross-sectional analyses were conducted. RESULTS: Longitudinal analyses showed significant trend changes in the frequency and intensity of antibiotic consumption, the patients' costs on antibiotics, and the duration of antibiotic treatment received by surgical patients undergoing the 4 clean procedures during the intervention period. Cross-sectional analyses showed that the antibiotic prescribing rates were reduced to 35.3% and 12.9% in inpatient and outpatient settings, that the intensity of antibiotic consumption was reduced to 35.9 DDD/100 bed-days, that patients' costs on antibiotics were reduced significantly, and that the duration of peri-operative antibiotic treatment received by surgical patients undergoing the 4 types of clean procedures decreased to less than 24 hour during the assessment period. CONCLUSION: The Action Plan, as a combination of managerial and professional strategies, was effective in reducing the frequency and intensity of antibiotic consumption, patients' costs on antibiotics, and the duration of peri-operative antibiotic treatment in the 4 clean surgeries.