BACKGROUND: Arsenic trioxide (ATO) is indicated as a broad-spectrum medicine for a variety of diseases, including cancer and cardiac disease. While the role of ATO in hepatic ischemia/reperfusion injury (HIRI) has not been reported. Thus, the purpose of this study was to identify the effects of ATO on HIRI. METHODS: In the present study, we established a 70% hepatic warm I/R injury and partial hepatectomy (30% resection) animal models in vivo and hepatocytes anoxia/reoxygenation (A/R) models in vitro with ATO pretreatment and further assessed liver function by histopathologic changes, enzyme-linked immunosorbent assay, cell counting kit-8, and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay. Small interfering RNA (siRNA) for extracellular signal-regulated kinase (ERK) 1/2 was transfected to evaluate the role of ERK1/2 pathway during HIRI, followed by ATO pretreatment. The dynamic process of autophagic flux and numbers of autophagosomes were detected by green fluorescent protein-monomeric red fluorescent protein-LC3 (GFP-mRFP-LC3) staining and transmission electron microscopy. RESULTS: A low dose of ATO (0.75 μmol/L in vitro and 1 mg/kg in vivo ) significantly reduced tissue necrosis, inflammatory infiltration, and hepatocyte apoptosis during the process of hepatic I/R. Meanwhile, ATO obviously promoted the ability of cell proliferation and liver regeneration. Mechanistically, in vitro  studies have shown that nontoxic concentrations of ATO can activate both ERK and phosphoinositide 3-kinase-serine/threonine kinase (PI3K-AKT) pathways and further induce autophagy. The hepatoprotective mechanism of ATO, at least in part, relies on the effects of ATO on the activation of autophagy, which is ERK-dependent. CONCLUSION Low, non-toxic doses of ATO can activate ERK/PI3K-AKT pathways and induce ERK-dependent autophagy in hepatocytes, protecting liver against I/R injury and accelerating hepatocyte regeneration after partial hepatectomy.
Animals ; Arsenic Trioxide ; Autophagy/physiology* ; Reperfusion Injury/prevention & control* ; Mice ; Male ; Proto-Oncogene Proteins c-akt/physiology* ; Arsenicals/therapeutic use* ; Oxides/therapeutic use* ; Liver/metabolism* ; Extracellular Signal-Regulated MAP Kinases/metabolism* ; Mice, Inbred C57BL

Objective The combined entropy weight technique for order preference by similarity to an ideal solution(TOPSIS)and rank sum ratio(RSR)methods were utilized to rate the protective performance of ice hockey helmets,and the effectiveness and influencing factors of the rating system,as well as the relationship between protective performance and purchase price were explored.Methods The linear acceleration data during impact drops of twenty-four ice hockey helmets were collected using a uniaxial accelerometer in a collision test machine after low and ambient temperature treatments.The protective performance of ice hockey helmets was rated using the STAR model combined with the entropy weight TOPSIS and RSR methods.One-way ANOVA or the Kruskal-Wallis H test was employed to assess the differences in protective performance among helmets across different grade groups.The correlation between different indicators was analyzed by Pearson's correlation coefficient.Results The comprehensive protective performance ratings of the CCM TACKS 310,IBX,BAUD,and WARRIORS COVERT RS PRO helmets were classified as poor,whereas the BAUER REAKT 150,HYPERLITE,and REAKT 200 helmets were rated as excellent.The remaining helmets were rated as moderate.There was a moderate to high positive correlation between the ambient temperature STAR(A)and Rowson's STAR values,the comprehensive Ti and low temperature Ti,the comprehensive T,and ambient temperature Ti(P＜0.05).The comprehensive Ti satisfied the homogeneity of variance(P＞0.05)and exhibited significant differences among groups(P＜0.05).Significant differences were found in the low temperature indicators among different groups(P＜0.05),and their weight coefficients ranked among the top three.The ambient temperature indicators were not affected by the protective performance grade(P＞0.05).A weak positive correlation existed between the comprehensive Ti and purchase price(P＜0.05).Conclusions According to the energy absorption test protocol,the combined entropy weight TOPSIS and RSR methods can efficiently rate the comprehensive protective performance of ice hockey helmets.The effectiveness of using low temperature indicators for the comprehensive evaluation and rating of ice hockey helmet protective performance is superior to that of ambient temperature indicators and purchase price.Consumers are advised not to use price as a criterion for evaluating the comprehensive protective performance of ice hockey helmets.

This study aims to evaluate the preventive effect of the exogenous protein chIFN-γ-chCD154 against Salmonella typhimurium(S.typhimurium)infection in White Leghorn chick-ens,and the potential mechanism.In this study,Escherichia coli was used to express the proteins chIFN-γ,chCD154 and chIFN-γ-chCD154.Before S.typhimurium infection,the White Leghorn chickens were pre-immunized via drinking water for three consecutive days,and infected with S.typhimurium by gavage.The results from Western blot,quantitative real-time PCR(qRT-PCR)analysis and histopathology analysis showed that compared to chIFN-γ and chCD154,chIFN-γ-chCD154 pre-treatment could synergistically increase the survival rate of infected chickens,reduce the bacterial load in the liver and cecum,and attenuate the pathological damage of liver and cecum.Moreover,chIFN-γ-chCD154 significantly decreased the mRNA expression of Toll-like receptor-4(TLR-4)and myeloid differentiation primary response gene 88(MyD88)in the cecum,and then inhibited the mRNA expression of NF-κB and pro-inflammatory cytokines(TNF-α and IL-6),and maintained the integrity of the intestinal tight junction proteins(zo-1,claudin-1,occlu-din).Compared with single protein pretreatment,chIFN-γ-chCD154 pretreatment significantly up-regulated the mRNA expression of the genes related to the vitamin D(VD)pathway(cyp27b1,VD receptor VDR,antimicrobial peptide AvBD7 and cathelicidin-b1)in S.typhimurium-infected peripheral blood mononuclear cells(PBMCs).The results of colony counting showed that the num-ber of S.typhimurium in the chIFN-γ-chCD154 group were the lowest.Also,chIFN-γ-chCD154 could up-regulate the relative abundance of beneficial bacteria such as Blautia,Ruminococcus,En-terococcus and Faecalibacterium,while down-regulate the relative abundance of harmful bacteria such as Staphylococcaceae in the cecum and improve the intestinal dysbiosis.In conclusion,chIFN-γ-chCD154 could activate the VD-antimicrobial peptide pathway and inhibit the TLR-4/MyD88/NF-κB inflammatory signaling pathway in S.typhimurium-infected chickens,which significantly improve the intestinal barrier function,reduce the inflammatory damage of liver and cecum,im-prove the structure of cecum microbial,promote the health of intestinal tract,and provide theoreti-cal basis for the development of chIFN-γ-chCD154 as a safe and effective alternative antibiotic.

Objective The combined entropy weight technique for order preference by similarity to an ideal solution(TOPSIS)and rank sum ratio(RSR)methods were utilized to rate the protective performance of ice hockey helmets,and the effectiveness and influencing factors of the rating system,as well as the relationship between protective performance and purchase price were explored.Methods The linear acceleration data during impact drops of twenty-four ice hockey helmets were collected using a uniaxial accelerometer in a collision test machine after low and ambient temperature treatments.The protective performance of ice hockey helmets was rated using the STAR model combined with the entropy weight TOPSIS and RSR methods.One-way ANOVA or the Kruskal-Wallis H test was employed to assess the differences in protective performance among helmets across different grade groups.The correlation between different indicators was analyzed by Pearson's correlation coefficient.Results The comprehensive protective performance ratings of the CCM TACKS 310,IBX,BAUD,and WARRIORS COVERT RS PRO helmets were classified as poor,whereas the BAUER REAKT 150,HYPERLITE,and REAKT 200 helmets were rated as excellent.The remaining helmets were rated as moderate.There was a moderate to high positive correlation between the ambient temperature STAR(A)and Rowson's STAR values,the comprehensive Ti and low temperature Ti,the comprehensive T,and ambient temperature Ti(P＜0.05).The comprehensive Ti satisfied the homogeneity of variance(P＞0.05)and exhibited significant differences among groups(P＜0.05).Significant differences were found in the low temperature indicators among different groups(P＜0.05),and their weight coefficients ranked among the top three.The ambient temperature indicators were not affected by the protective performance grade(P＞0.05).A weak positive correlation existed between the comprehensive Ti and purchase price(P＜0.05).Conclusions According to the energy absorption test protocol,the combined entropy weight TOPSIS and RSR methods can efficiently rate the comprehensive protective performance of ice hockey helmets.The effectiveness of using low temperature indicators for the comprehensive evaluation and rating of ice hockey helmet protective performance is superior to that of ambient temperature indicators and purchase price.Consumers are advised not to use price as a criterion for evaluating the comprehensive protective performance of ice hockey helmets.

This study aims to evaluate the preventive effect of the exogenous protein chIFN-γ-chCD154 against Salmonella typhimurium(S.typhimurium)infection in White Leghorn chick-ens,and the potential mechanism.In this study,Escherichia coli was used to express the proteins chIFN-γ,chCD154 and chIFN-γ-chCD154.Before S.typhimurium infection,the White Leghorn chickens were pre-immunized via drinking water for three consecutive days,and infected with S.typhimurium by gavage.The results from Western blot,quantitative real-time PCR(qRT-PCR)analysis and histopathology analysis showed that compared to chIFN-γ and chCD154,chIFN-γ-chCD154 pre-treatment could synergistically increase the survival rate of infected chickens,reduce the bacterial load in the liver and cecum,and attenuate the pathological damage of liver and cecum.Moreover,chIFN-γ-chCD154 significantly decreased the mRNA expression of Toll-like receptor-4(TLR-4)and myeloid differentiation primary response gene 88(MyD88)in the cecum,and then inhibited the mRNA expression of NF-κB and pro-inflammatory cytokines(TNF-α and IL-6),and maintained the integrity of the intestinal tight junction proteins(zo-1,claudin-1,occlu-din).Compared with single protein pretreatment,chIFN-γ-chCD154 pretreatment significantly up-regulated the mRNA expression of the genes related to the vitamin D(VD)pathway(cyp27b1,VD receptor VDR,antimicrobial peptide AvBD7 and cathelicidin-b1)in S.typhimurium-infected peripheral blood mononuclear cells(PBMCs).The results of colony counting showed that the num-ber of S.typhimurium in the chIFN-γ-chCD154 group were the lowest.Also,chIFN-γ-chCD154 could up-regulate the relative abundance of beneficial bacteria such as Blautia,Ruminococcus,En-terococcus and Faecalibacterium,while down-regulate the relative abundance of harmful bacteria such as Staphylococcaceae in the cecum and improve the intestinal dysbiosis.In conclusion,chIFN-γ-chCD154 could activate the VD-antimicrobial peptide pathway and inhibit the TLR-4/MyD88/NF-κB inflammatory signaling pathway in S.typhimurium-infected chickens,which significantly improve the intestinal barrier function,reduce the inflammatory damage of liver and cecum,im-prove the structure of cecum microbial,promote the health of intestinal tract,and provide theoreti-cal basis for the development of chIFN-γ-chCD154 as a safe and effective alternative antibiotic.

Aiming at the practical problems of insufficient supply efficiency and low utilization rate of primary health services,it systematically reviewed the research status of residents'participation in the value co-creation of primary health services from the perspective of residents'active utilization.It explores the theoretical framework of realizing the value of primary health service based on residents'active utilization,and deeply analyzes its internal logic.Finally,it puts forward the concrete realization path,that is,multi-subject broadening the health information communication channel,optimizing the health service supply mode according to local conditions,constructing multi-dimensional trust mechanism between doctors and patients,and building a precise digital health management platform.

Aiming at the practical problems of insufficient supply efficiency and low utilization rate of primary health services,it systematically reviewed the research status of residents'participation in the value co-creation of primary health services from the perspective of residents'active utilization.It explores the theoretical framework of realizing the value of primary health service based on residents'active utilization,and deeply analyzes its internal logic.Finally,it puts forward the concrete realization path,that is,multi-subject broadening the health information communication channel,optimizing the health service supply mode according to local conditions,constructing multi-dimensional trust mechanism between doctors and patients,and building a precise digital health management platform.

Aiming at the practical problems of insufficient supply efficiency and low utilization rate of primary health services,it systematically reviewed the research status of residents'participation in the value co-creation of primary health services from the perspective of residents'active utilization.It explores the theoretical framework of realizing the value of primary health service based on residents'active utilization,and deeply analyzes its internal logic.Finally,it puts forward the concrete realization path,that is,multi-subject broadening the health information communication channel,optimizing the health service supply mode according to local conditions,constructing multi-dimensional trust mechanism between doctors and patients,and building a precise digital health management platform.

Aiming at the practical problems of insufficient supply efficiency and low utilization rate of primary health services,it systematically reviewed the research status of residents'participation in the value co-creation of primary health services from the perspective of residents'active utilization.It explores the theoretical framework of realizing the value of primary health service based on residents'active utilization,and deeply analyzes its internal logic.Finally,it puts forward the concrete realization path,that is,multi-subject broadening the health information communication channel,optimizing the health service supply mode according to local conditions,constructing multi-dimensional trust mechanism between doctors and patients,and building a precise digital health management platform.

Aiming at the practical problems of insufficient supply efficiency and low utilization rate of primary health services,it systematically reviewed the research status of residents'participation in the value co-creation of primary health services from the perspective of residents'active utilization.It explores the theoretical framework of realizing the value of primary health service based on residents'active utilization,and deeply analyzes its internal logic.Finally,it puts forward the concrete realization path,that is,multi-subject broadening the health information communication channel,optimizing the health service supply mode according to local conditions,constructing multi-dimensional trust mechanism between doctors and patients,and building a precise digital health management platform.