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

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.

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.

Although immunotherapy has made a breakthrough in the treatment of cancer,the emergence of drug resistance has limited be-nefits in most patients,and reversing immunotherapy resistance remains a hotly debated and unresolved issue.The tumor microenviron-ment(TME)comprises a large number of T lymphocytes.During the biological processes of proliferation,activation,and the effect of tumor-infiltrating lymphocytes(TILs),TILs face severe local metabolic stress,resulting in metabolic reprogramming to meet the markedly increased energy demand and biosynthesis requirements.This process of adaptive changes in the metabolic pattern is closely related to the pheno-type and function of TILs,affecting immunotherapy efficacy and mediating immunotherapy resistance.In recent years,with the study of TIL metabolism and the search for specific metabolic regulatory points,targeting the TIL metabolic pathway could restore the tumor-killing func-tion and reverse immunotherapy resistance.This review explores the relationship between the metabolic reprogramming of TILs and im-mune resistance,and provides a new strategy for reversing immune resistance.