Background and Aims NAFLD is a progressive disease without known effective drug treatments. Switch‐associated protein 70 (SWAP70) is a guanine nucleotide exchange factor that participates in the regulation of many cellular processes. However, the role of SWAP70 in NAFLD remains unclear. This study aimed to identify the function and mechanism of SWAP70 in NAFLD. Approach and Results The results showed that the expression of SWAP70 was significantly increased in mice and hepatocytes after metabolic stimulation. Overexpression of SWAP70 in hepatocytes suppressed lipid deposition and inflammation, and SWAP70 knockdown created the inverse effect. Using hepatocyte‐specific Swap70 knockout and overexpression mice fed a high‐fat, high‐cholesterol diet, we demonstrated that SWAP70 suppressed the progression of nonalcoholic steatohepatitis by inhibiting lipid accumulation, inflammatory response, and fibrosis. Mechanically, RNA sequencing analysis and immunoprecipitation assays revealed that SWAP70 inhibited the interaction between transforming growth factor β‐activated kinase 1 (TAK1) binding protein 1 and TAK1 and sequentially suppressed the phosphorylation of TAK1 and subsequent c‐Jun N‐terminal kinase/P38 signaling. Inhibition of TAK1 activation blocked hepatocyte lipid deposition and inflammation caused by SWAP70 knockdown. Conclusions SWAP70 is a protective molecule that can suppress the progression of NAFLD by inhibiting hepatic steatosis and inflammation. SWAP70 may be important for mitigating the progression of NAFLD.

Background Bladder cancer is one of the most common urological cancers all over the world, and NMIBC occupies almost 80% of recently diagnosed bladder cancer cases. Progress and recurrence of bladder cancer are the main problems during the disease. The level of TP53 mutation is obviously higher in the high stage than the lower. This meta‐analysis is to evaluate the potential diagnosis feature of TP53 mutation by the expression of TP53 mutation of Ta stage vs high stage in bladder cancer. Methods A systematic search of databases was conducted, and some relevant articles were selected. Next, the meta‐analysis was carried out according to the standard guidelines. Results There were seven researches in which 677 participants were selected at the basis of inclusion standard. TP53 mutation was associated highly with increased diagnosis of bladder cancer. We found that the high stage of bladder cancer has obviously higher level of TP53 mutation than the lower stage, and these patients of MIBC have higher expression of TP53 mutation compared with NMIBC. No significant publication bias has been observed in this meta‐analysis. The expression of TP53 mutation might be a diagnose‐related biomarker for lots of patients with bladder cancer. Conclusions The results of this meta‐analysis provided further evidences that the expression of TP53 mutation was associated with the diagnosis efficiency of advanced bladder cancer. Higher expression of TP53 mutation was observed in the high stage of bladder cancer or the MIBC, and lower expression of TP53 mutation in the Ta stage of bladder cancer or the NMIBC. The expression level of TP53 mutation was probably a critical diagnosed biomarker in advanced bladder cancer.

ObjectiveThis study analysed differences in the perceived patient safety climate among different working departments and job types in public general hospitals in China.DesignCross-sectional survey.SettingEighteen tertiary hospitals and 36 secondary hospitals from 10 areas in Shanghai, Hubei Province and Gansu Province, China.ParticipantsOverall, 4753 staff, including physicians, nurses, medical technicians and managers, were recruited from March to June 2015.Main outcome measureThe Patient Safety Climate in Healthcare Organisations (PSCHO) tool and the percentages of ‘problematic responses’ (PPRs) were used as outcome measures. Multivariable two-level random intercept models were applied in the analysis.ResultsA total of 4121 valid questionnaires were collected. Perceptions regarding the patient safety climate varied among departments and job types. Physicians responded with relatively more negative evaluations of ‘organisational resources for safety’, ‘unit recognition and support for safety efforts’, ‘psychological safety’, ‘problem responsiveness’ and overall safety climate. Paediatrics departments, intensive care units, emergency departments and clinical auxiliary departments require more attention. The PPRs for ‘fear of blame and punishment’ were universally significantly high, and the PPRs for ‘fear of shame’ and ‘provision of safe care’ were remarkably high, especially in some departments. Departmental differences across all dimensions and the overall safety climate primarily depended on job type.ConclusionsThe differences suggest that strategies and measures for improving the patient safety climate should be tailored by working department and job type.

AIM:To study the expression of human insulin gene in gastrointestinal tracts of diabetic rats. METHODS: pCMV.Ins, an expression plasmid of the human insulin gene, wrapped with chitosan nanoparticles, was transfected to the diabetic rats through lavage and coloclysis, respectively. Fasting blood glucose and plasma insulin levels were measured for 7 d. Reverse transcription polymerase chain reaction (RT-PCR) analysis and Western blot analysis were performed to confirm the expression of human insulin gene. RESULTS: Compared with the control group, the fasting blood glucose levels in the lavage and coloclysis groups were decreased significantly in 4 d (5.63 ± 0.48 mmol/L and 5.07 ± 0.37 mmol/L vs 22.12 ± 1.31 mmol/L, respectively, P < 0.01), while the plasma insulin levels were much higher (32.26 ± 1.81 μIU/mL and 32.79 ± 1.84 μIU/mL vs 14.23 ± 1.38 μIU/mL, respectively, P < 0.01). The human insulin gene mRNA and human insulin were only detected in the lavage and coloclysis groups. CONCLUSION: Human insulin gene wrapped with chitosan nanoparticles can be successfully transfected to rats through gastrointestinal tract, indicating that chitosan is a promising non-viral vector.

Ramelteon is the first medicine in human history that treat insomnia as a melatonin receptor agonist. Herein, we report an efficient three-step synthetic route to access it from commercially available 2,3-dihydrobenzofuran-4-amine, which represents as the shortest racemic synthesis to date with a 26 % overall yield. Key to the success is the application of the intermolecular Catellani-type alkylation and intramolecular redox-relay Heck cyclization cascade for preparation of the key indane-containing aldehyde. The unique primary amide-involved reductive amination of aldehyde is another feature of this route. New process of ramelteon can be developed based on this chemistry.[a] S.