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

Ischemic stroke (IS) is a globally life-threatening disease. Presently, few therapeutic medicines are available for treating IS, and rt-PA is the only drug approved by the US Food and Drug Administration (FDA) in the US. In fact, many agents showing excellent neuroprotection but no blood flow-improving activity in animals have not achieved ideal clinical efficacy, while thrombolytic drugs only improving blood flow without neuroprotection have limited their wider application. To address these challenges and meet the huge unmet clinical need, we have designed and identified a novel compound AAPB with dual effects of neuroprotection and cerebral blood flow improvement. AAPB significantly reduced cerebral infarction and neural function deficit in tMCAO rats, pMCAO rats, and IS rhesus monkeys, as well as displayed exceptional safety profiles and excellent pharmacokinetic properties in rats and dogs. AAPB has now entered phase I of clinical trials fighting IS in China.

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.