AIM:To investigate the effect of hydrogen sulfide(H2S)on ferroptosis and functional impairment induced by oxidized high-density lipoprotein(ox-HDL)in human umbilical vein endothelial cells(HUVECs),and to ex-plore its mechanisms.METHODS:The HUVECs were cultured in vitro and exposed to 200 mg/L ox-HDL,ferroptosis in-hibitor ferrostatin-1(Fer-1),protein kinase B(PKB/Akt)inhibitor MK-2206 2HCl(MK),Akt agonist SC79,and/or H2S for 24 h.Western blot was used to identify the relevant proteins.Intracellular levels of reactive oxygen species(ROS)were analyzed by flow cytometry and immunofluorescence staining.Intracellular iron was measured using an iron detection kit.The number of monocytes adhering to endothelial cells was counted using the monocyte adhesion assay.RESULTS:Compared with control group,acyl-CoA synthetase long-chain family member 4(ACSL4)protein expression in ox-HDL group was elevated by 1.45-fold(P<0.01),glutathione peroxidase 4(GPX4)protein expression was decreased by 29.79%(P<0.05),and ROS levels and iron ion content were elevated by 4.81-fold and 1.40-fold,respectively(P<0.01).The ratios of p-PI3K/PI3K and p-Akt/Akt were decreased by 45.65%and 41.68%,respectively(P<0.01),endo-thelial cell function-related protein IL-6,ICAM-1 and TNF-α expression was elevated 1.18-fold,1.24-fold and 1.41-fold(P<0.05),respectively,eNOS protein expression was decreased by 35.24%(P<0.01),and monocyte adhesion was ele-vated 3.43-fold(P<0.01).Compared with ox-HDL group,the endothelial cell iron death-related protein ACSL4 was de-creased by 22.32%(P<0.05),GPX4 was increased by 1.27-fold(P<0.01),and the p-Akt/Akt ratio was increased by 1.52-fold(P<0.01)in ox-HDL+H2S group.The fluorescence microscopy results showed that the ROS was decreased by 50.35%(P<0.01).The IL-6,ICAM-1 and TNF-α protein expression was decreased by 13.34%,9.83%and 13.46%(P<0.05),respectively,eNOS was elevated by 1.22-fold(P<0.01),and the number of monocyte adhesion was de-creased by 59.05%(P<0.01).Compared with ox-HDL group,GPX4 protein expression in ox-HDL+SC79 group was ele-vated by 1.49-fold(P<0.01),ACSL4 expression was decreased by 20.72%(P<0.05),and ROS and iron ions were de-creased by 59.31%and 23.85%(P<0.05),respectively.Compared with ox-HDL+H2S group,GPX4 protein expression was decreased by 21.28%,and ACSL4 protein expression was increased by 1.16-fold in ox-HDL+H2S+MK group(P<0.05).CONCLUSION:H2S activates Akt to inhibit ox-HDL-induced ferroptosis in HUVECs and alleviate their func-tional damage.

Objective:Acute kidney injury (AKI) is one of the common complications in critically ill septic patients, which is associated with increased risks of death, cardiovascular events, and chronic renal dysfunction. The duration of AKI and the renal function recovery status after AKI onset can affect the patient prognosis. Nevertheless, it remains controversial whether early recovery status after AKI is closely related to the prognosis in patients with sepsis-associated AKI (SA-AKI). In addition, early prediction of renal function recovery after AKI is beneficial to individualized treatment decision-making and prevention of severe complications, thus improving the prognosis. At present, there is limited clinical information on how to identify SA-AKI patients at high risk of unrecovered renal function at an early stage. The study aims to investigate the association between early recovery status after SA-AKI, identify risk factors for unrecovered renal function, and to improve patients ' quality of life.Methods:We retrospectively analyzed clinical data of septic patients who were admitted to the intensive care unit (ICU) and developed AKI within the first 48 hours after ICU admission in the Second Xiangya Hospital and the Third Xiangya Hospital of Central South University from January 2015 to March 2017. Sepsis was defined based on the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). AKI was diagnosed and staged according to the 2012 Kidney Disease:Improving Global Outcomes (KDIGO) guideline. SA-AKI patients were assigned into 3 groups including a complete recovery group, a partial recovery group, and an unrecovered group based on recovery status at Day 7 after the diagnosis of AKI. Patients ' baseline characteristics were collected, including demographics, comorbidities, clinical and laboratory examination information at ICU admission, and treatment within the first 24 hours. The primary outcome of the study was the composite of death and chronic dialysis at 90 days, and secondary outcomes included length of stay in the ICU, length of stay in the hospital, and persistent renal dysfunction. Multivariate regression analysis was performed to evaluate the prognostic value of early recovery status after AKI and to determine the risk factors for unrecovered renal function after AKI. Sensitivity analysis was conducted in patients who still stayed in hospital on Day 7 after AKI diagnosis, patients without premorbid chronic kidney disease, and patients with AKI Stage 2 to 3.Results:A total of 553 SA-AKI patients were enrolled, of whom 251 (45.4％), 73 (13.2％), and 229 (41.4％) were categorized as the complete recovery group, the partial recovery group, and the unrecovered group, respectively. Compared with the complete or partial recovery group, the unrecovered group had a higher incidence of 90-day mortality (unrecovered vs partial recovery or complete recovery: 64.2％ vs 26.0％ or 22.7％; P<0.001) and 90-day composite outcome (unrecovered vs partial recovery or complete recovery:65.1％vs 27.4％or 22.7％;P<0.001). The unrecovered group also had a shorter length of stay in the hospital and a larger proportion of progression into persistent renal dysfunction than the other 2 groups. After adjustment for potential confounders, patients in the unrecovered group were at an increased risk of 90-day mortality (HR=3.50, 95％ CI 2.47 to 4.96, P<0.001) and 90-day composite outcome (OR=5.55, 95％CI 3.43 to 8.98, P<0.001) when compared with patients in the complete recovery group, but patients in the partial recovery group had no significant difference (P>0.05). Male sex, congestive heart failure, pneumonia, respiratory rate>20 beats per minute, anemia, hyperbilirubinemia, need for mechanical ventilation, and AKI Stage 3 were identified as independent risk factors for unrecovered renal function after AKI. The sensitivity analysis further supported that unrecovered renal function after AKI remained an independent predictor for 90-day mortality and composite outcome in the subgroups. Conclusion:The early recovery status after AKI is closely associated with poor prognosis in critically ill patients with SA-AKI. Unrecovered renal function within the first 7 days after AKI diagnosis is an independent predictor for 90-day mortality and composite outcome. Male sex, congestive heart failure, pneumonia, tachypnea, anemia, hyperbilirubinemia, respiratory failure, and severe AKI are risk factors for unrecovered renal function after AKI. Therefore, timely assessment for the renal function in the early phase after AKI diagnosis is essential for SA-AKI patients. Furthermore, patients with unrecovered renal function after AKI need additional management in the hospital, including rigorous monitoring, avoidance of nephrotoxin, and continuous assessment for the renal function, and after discharge, including more frequent follow-up, regular outpatient consultation, and prevention of long-term adverse events.