With the process of rapid mobilization,China is suffering from huge road tolls.The ethical issues related to road safety are also emerging.To provide recommendations for relevant public policies,we discussed several ethical issues in this article as follows.Human lives and health may not be traded off for the benefit of mobilization.The designers,regulators of road traffic system share responsibilities for road safety with users.The principle of equity needs to be embodied in the road traffic system.Therefore,it is necessary to increase investment in underdeveloped areas and enhance the protection of vulnerable road users.

Objective To compare and analyze gene expression patterns in rat model of nonalcoholic fatty liver disease (NAFLD).Methods Twelve male Sprague-Dawley rats were randomly given either general diet (control group) or a high-fat diet (model group) for 4 weeks.The histopathologic changes of the liver were observed and gene expression patterns were analyzed and compared by cDNA mieroarray.Results Hepatocellular steatosis and inflammatory infiltration were observed in model group after high-fat diet for 4 weeks.Fifty-one differential genes were found in model group,20 of which were up-regulated (sterol regulatory element binding factor 1,stearoyl-coenzyme A desaturase 1 and Bcl 2 modifying factor)and 31 were down-regulated (peroxisomal enoyl coenzyme A hydratase 1,heat shock 70 protein 1A and ATPase inhibitory factor 1). The up-regulating genes were involved in lipogenesis and cell apoptosis,while down-regulated genes were involved in fatty acid oxidation, protein modification and energy metabolism.Conclusions The differential expression of genes may involve in the pathogenesis of NAFLD.

Objective To explore the effect of Flavokawain B on the proliferation and apoptosis of acute T lymphoblastic leukemia(T -ALL)cells and its preliminary mechanism.Methods After the T -ALL cell lines CEM-C7(sensitive to glucocorticoids)and MOLT -4(resistant to glucocorticoids)cells were treated with different concentrations of Flavokawain B,the influence of Flavokawain B on the growth rate and doubling time of CEM-C7 and MOLT -4 cells was observed by 3 -(4,5 -dimethylthiazol -2 -yl)-5 -(3 -carboxymethoxyphenyl)-2 -(4 -sulfophenyl)-2H -tetrazolium(MTS)assay,and apoptosis was analyzed by using flow cytometry.Furthermore,Wes-tern blot assay was used to detect the expressions of Bim,Bcl -2 and cleaved Caspase -9.At last,the expressions of Bim and Bcl -2 in clinical T -ALL patient samples were also detected by using Western blot assay.Results MTS as-say showed that Flavokawain B significantly inhibited the cellular proliferation of T -ALL cell lines in a dose and time dependent manner(P <0.01 ).Flow cytometry findings revealed that Flavokawain B significantly induced the apoptosis of T -ALL cells in a dose -dependent manner(P <0.001 ).Western blot results indicated that Flavokawain B in-creased the expression of Bim and cleaved Caspase -9,and decreased the expression of Bcl -2 in T -ALL cell lines, which increased Bim and decreased Bcl -2 in clinical T -ALL patients samples,both in a dose -dependent manner. Conclusions Flavokawain B can inhibit the proliferation and induce the apoptosis of T -ALL cells by up -regulating the expression of Bim and down -regulating the expression of Bcl -2 and activating Caspase -9,whether resistant to glu-cocorticoids or not.

Objective To explore the influences of hierarchical management on working pressure and turnover intention in internal medicine nurses. Methods From January to December 2014, we investigated 53 internal medicine nurses working in Zhoushan Maternal and Child Health Hospital and the nurses were hierarchical management for one year. We compared their job satisfaction, working pressure and demission rate before and after the hierarchical management. Results After the management, the job satisfaction was improved from 90. 57% to 98. 07% (P<0. 05);the score of working pressure was reduced from (87. 9 ± 7. 3) to (65. 4 ± 6. 4) (t=9. 10,P<0. 05);the demission rate was declined to 1. 92% (P<0. 05). Conclusions Hierarchical management can improve internal medicine nurses′ job satisfaction, and reduce their working stress and demission rate.

Retrospective analysis was performed on 1 child with silent inactivation (SI) of asparaginase (ASNas) who was diagnosed with acute lymphoblastic leukemia (ALL) and treated in the First Affiliated Hospital, Sun Yat-Sen University in October 2019.The patient was a 9 years and 3 months old boy who was diagnosed as ALL accompanied with late bone marrow relapse.After pegylated Escherichia coli-Asparaginase (PEG-ASNase) was given, he did not have the expected treatment-related adverse reactions, including hyperammonemia, hypofibrinogenemia, and the low activation of antithrombin Ⅲ (ATⅢ). The plasma asparagine (ASN) concentration failed to meet the depletion criteria and the ASNase activity was 64.5 U/L.Therefore, the SI of ASNase was confirmed.Erwinase was used to replace PEG-ASNase, the lowest level of ATⅢ was 33%, and the lowest level of fibrinogen was 1.20 g/L.Hyperammonemia and decreased ASN were also observed, and the ASNase activity was 1 813.0 U/L.All the above suggested that when, SI occurred, the replacement by Erwinase was effective.The ASNase activity should be monitored in ALL patients who were treated with ASNase.Monitoring the treatment-related adverse reactions such as hyperammonia and coagulation disorders closely has important implications to the SI of ASNase when the detection of ASNase activity was unavailable.

Objective:Endoplasmic reticulum stress(ERS)was used as the research emphasis to further investigate the mechanisms of apoptosis of FLT3-ITD-mutated leukemia cells and decreased expression of FLT3-ITD mutated protein induced by all-trans retinoic acid(ATRA).Methods:FLT3-ITD-mutated leukemia cell lines(MV4-11 and MOLM13)were treated with ATRA. Flow cytometry was conducted to assess cell apoptosis. Real-time fluorescent quantitative PCR(RT-qPCR)and Western blot were used to detect the expression of ERS-related and autophagy-related genes and protein, respectively.Results:A low-dose ATRA further increased FLT3-ITD cells and ERS levels. ATRA acted on the ERS-related PERK/eif2ɑ signaling pathway and continued to increase the ERS of FLT3-ITD cells, resulting in an upregulation of apoptotic gene CHOP expression. After the treatment with ATRA, FLT3-ITD protein in FLT3-ITD cells was decreased. Of the two main ERS-related protein degradation pathways, ER-associated degradation(ERAD)and ER-activated autophagy(ERAA), the expression of ERAD-related protein ATF6 in FLT3-ITD cells was not significantly changed on ATRA, whereas the expression of ERAA-related proteins Atg7 and Atg5 were significantly increased.Conclusions:ATRA further raises the ERS level of FLT3-ITD cells continuously by activating the ERS-related PERK/eif2ɑ signal pathway and induces FLT3-ITD protein autophagy degradation through ERAA pathway, which induces apoptosis of FLT3-ITD-mutated leukemia cells. These results provide preliminary evidence on the use of ATRA in the treatment of refractory leukemia with FLT3-ITD.

Purpose/Significance To solve the problem that regional clinical research data are difficult to integrate efficiently,and to promote"Chinese evidence"and"Chinese protocol"in the global clinical research community.Method/Process Based on the standard-ization theory,the data standardization system is proposed,and the construction and application methods of the regional clinical research data platform are explored with the integration of multi-center clinical research data as the starting point.Result/Conclusion The theo-retical framework of the regional clinical research data platform has been preliminarily established,and the clinical research capabilities of tertiary hospitals in Shanghai have been significantly improved.

The glymphatic system plays a pivotal role in maintaining cerebral homeostasis. Chronic cerebral hypoperfusion, arising from small vessel disease or carotid stenosis, results in cerebrometabolic disturbances ultimately manifesting in white matter injury and cognitive dysfunction. However, whether the glymphatic system serves as a potential therapeutic target for white matter injury and cognitive decline during hypoperfusion remains unknown. Here, we established a mouse model of chronic cerebral hypoperfusion via bilateral common carotid artery stenosis. We found that the hypoperfusion model was associated with significant white matter injury and initial cognitive impairment in conjunction with impaired glymphatic system function. The glymphatic dysfunction was associated with altered cerebral perfusion and loss of aquaporin 4 polarization. Treatment of digoxin rescued changes in glymphatic transport, white matter structure, and cognitive function. Suppression of glymphatic functions by treatment with the AQP4 inhibitor TGN-020 abolished this protective effect of digoxin from hypoperfusion injury. Our research yields new insight into the relationship between hemodynamics, glymphatic transport, white matter injury, and cognitive changes after chronic cerebral hypoperfusion.
Animals ; Brain Ischemia ; Carotid Stenosis/drug therapy* ; Cognitive Dysfunction/etiology* ; Digoxin ; Disease Models, Animal ; Mice ; Mice, Inbred C57BL ; White Matter