The E3 ubiquitin ligase NEDD4-1 protects against acetaminophen-induced liver injury by targeting VDAC1 for degradation

Acetaminophen (APAP) overdose is a major cause of liver injury. Neural precursor cell expressed developmentally downregulated 4-1 (NEDD4-1) is an E3 ubiquitin ligase that has been implicated in the pathogenesis of numerous liver diseases; however, its role in APAP-induced liver injury (AILI) is unclear. Thus, this study aimed to investigate the role of NEDD4-1 in the pathogenesis of AILI. We found that NEDD4-1 was dramatically downregulated in response to APAP treatment in mouse livers and isolated mouse hepatocytes. Hepatocyte-specific NEDD4-1 knockout exacerbated APAP-induced mitochondrial damage and the resultant hepatocyte necrosis and liver injury, while hepatocyte-specific NEDD4-1 overexpression mitigated these pathological events both in vivo and in vitro. Additionally, hepatocyte NEDD4-1 deficiency led to marked accumulation of voltage-dependent anion channel 1 (VDAC1) and increased VDAC1 oligomerization. Furthermore, VDAC1 knockdown alleviated AILI and weakened the exacerbation of AILI caused by hepatocyte NEDD4-1 deficiency. Mechanistically, NEDD4-1 was found to interact with the PPTY motif of VDAC1 through its WW domain and regulate K48-linked ubiquitination and degradation of VDAC1. Our present study indicates that NEDD4-1 is a suppressor of AILI and functions by regulating the degradation of VDAC1.

Clinical efficacy and safety of paclitaxel or docetaxel combined with oxaliplatin or cisplatin and fluorouracil or tiggio in the treatment of advanced gastric cancer / 中国基层医药

Objective To compare the treatment effect and adverse reaction of oxaliplatin and tiggio and paclitaxel or docetaxel combined with oxaliplatin or cisplatin and fluorouracil or tiggio in the treatment of advanced gastric cancer.Methods From January 2015 to April 2018, 60 patients with advanced gastric cancer were selected from Department of Oncology of the First Affiliated Hospital of Anhui Medical University.The patients were randomly divided into two groups according to the principle of simple randomization,with 30 cases in each group.The control group was treated with oxaliplatin + tiggio.The observation group was given paclitaxel (or docetaxel) combined with oxaliplatin (or cisplatin) and fluorouracil.The incidence of adverse reactions(hematotoxicity and non-hematologic toxicity),the efficacy(CR,PR,SD,PD) of the two groups were compared.Results The RR level of the observation group was 66.7% ,which was significantly higher than 40.0% of the control group (χ2 =4.286,P<0.05).There were no statistically significant differences between the two groups in incidence of adverse reactions such as thrombo-cytopenia,impaired liver function, anemia, oral mucositis, nausea and vomiting and neurotoxicity ( all P >0.05). Conclusion Treatment of advanced gastric cancer with FLOT or DCF can improve efficacy without increasing side effects.

Clinical efficacy and safety of paclitaxel or docetaxel combined with oxaliplatin or cisplatin and fluorouracil or tiggio in the treatment of advanced gastric cancer / 中国基层医药

Objective@#To compare the treatment effect and adverse reaction of oxaliplatin and tiggio and paclitaxel or docetaxel combined with oxaliplatin or cisplatin and fluorouracil or tiggio in the treatment of advanced gastric cancer.@*Methods@#From January 2015 to April 2018, 60 patients with advanced gastric cancer were selected from Department of Oncology of the First Affiliated Hospital of Anhui Medical University.The patients were randomly divided into two groups according to the principle of simple randomization, with 30 cases in each group.The control group was treated with oxaliplatin + tiggio.The observation group was given paclitaxel (or docetaxel) combined with oxaliplatin (or cisplatin) and fluorouracil.The incidence of adverse reactions(hematotoxicity and non-hematologic toxicity), the efficacy(CR, PR, SD, PD) of the two groups were compared.@*Results@#The RR level of the observation group was 66.7%, which was significantly higher than 40.0% of the control group (χ2=4.286, P<0.05). There were no statistically significant differences between the two groups in incidence of adverse reactions such as thrombocytopenia, impaired liver function, anemia, oral mucositis, nausea and vomiting and neurotoxicity(all P>0.05).@*Conclusion@#Treatment of advanced gastric cancer with FLOT or DCF can improve efficacy without increasing side effects.

Study on Curriculum System Setting of "3+2" Cut-through Nursing Major at Undergraduate Stage / 中国医学伦理学

Objective:To construct the "3+2" counterpart cut-through sectional training nursing major un-dergraduate curriculum system, which is oriented by vocational competence. Methods: The preliminary draft of"3+2" nursing undergraduate curriculum setting was established base on the literature review and expert group in-terview, and the 25 experts was conducted two rounds of expert questionnaire consultation using Delphi method. Results:Experts' opinions tended to be consistent after two rounds of consultation, the expert authority coefficient was 0 . 92 , the coordination coefficient of Kendall was 0 . 44 in the second round of expert consultation and finally established 5 curriculum groups, including total 28 courses of public elementary courses, professional basic cour-ses, professional core courses, professional oriented courses and centralized practice courses. Conclusion: It should construct the"3+2" counterpart cut-through nursing major undergraduate curriculum system, which is o-riented by vocational competence, and achieve effective connection between the knowledge structure and the quality of the nursing students, in order to provide the reference for perfecting the curriculum system of vocational educa-tion in our country.

Systematic evaluation of patient safety culture assessment in nursing home / 中国实用护理杂志

Objective@#To focus on the patient′s safety culture management and related research of nursing home in China.@*Methods@#China National Knowledge Infrastructure (CNKI), China Biology Medicine disc (CBM), China Scientific Journal Database by VIP (VIP), Wanfang, PubMed, EBSCO and SpringerLink databases were searched by computer to find out all the literature about patient safety culture evaluation in nursing home. Two investigators independently screened, scrambled and cross-checked data according to inclusion and exclusion criteria.@*Results@#Finally 11 articles complied with the inclusion criteria, and conducted a descriptive study of patient safety culture assessments.@*Conclusions@#The evaluation of patient safety culture is conducive to the development of patient safety culture in nursing home. The study of patient safety culture in China′s nursing home is still in its infancy and needs to be further deepened.

IFN-γ induces overexpression of PD-L1 and epithelialmesenchymal transformation of breast cancer cells through activating ERK/Jak2-STAT signaling pathways / 生物工程学报

To investigate the effect of INF-γ on the expression of programmed death ligand 1 (PD-L1), epithelial-mesenchymal transition (EMT) and the potential mechanism in breast cancer cell line MDA-MB-231, the cells were treated with different concentrations of INF-γ. The expressions of proteins, including PD-L1, cell-migration-related proteins (E-cadherin, N-cadherin and vimentin), ERK, p-ERK, Jak2, and p-Jak2 were detected by Western blotting analysis and immunofluorescent staining assay. Cell migration was studied through cell wound healing assay and transwell assay. IFN-γ could up-regulate the expressions of PD-L1 in MDA-MB-231 cells. The cell migration rate was significantly increased after adding IFN-γ. The expression levels of vimentin and N-cadherin were increased whereas the expression of E-cadherin was decreased after adding IFN-γ. The expression levels of ERK, p-ERK, Jak2 and p-Jak2 were significantly increased and this phenomenon was inhibited when adding ERK inhibitor U0126 or Jak2 inhibitor AG490. These results demonstrate that IFN-γ could up-regulate the expression of PD-L1, promote cell migration and transmission, and facilitate epithelial-mesenchymal transformation of breast cancer cells and this process may be related with ERK and Jak2-STAT signaling pathways.

Preparation and identification of anti-human ICAM-1 scFv / 生物工程学报

To screen the specific anti-human intercellular adhesion molecule-1 (ICAM-1) single chain fragment variable (scFv) using phage display library technology and to identify its biological activity. P1 peptide was used as antigen, and the phage antibodies against human ICAM-1 antigen were panned by four binding-eluting-amplifying cycles using Tomlinson I+J phage display library. After four rounds of selective enrichment screening, the positive clones were determined by PCR, enzyme linked immunosorbent assay (ELISA)-based antigenic cross reaction and Dot blotting. Then the binding specificity and biological activity of purified scFv were identified by Western blotting, competitive ELISA and cell adhesion inhibition assay respectively. Furthermore, four positive clones were first panned through P1 peptide coated-ELISA assay, and then J-A1 was obtained and identified by PCR, ELISA-based antigenic cross reaction and Dot blotting, which could show a specific binding between P1 peptide and human ICAM-1 protein antigen. Subsequently, the purified scFv showed a satisfactory specificity and anti-adhesive activity in competitive ELISA and the cell adhesion inhibition assay. The specific anti-human ICAM-1 scFv was prepared successfully from Tomlinson I+J phage display library, which pave the way for further application of anti-human ICAM-1 scFv for inflammation diseases therapeutics.