Recent studies have suggested that transplant of hiPS-CMs is a promising approach for treating heart failure. However, the optimally clinical benefits have been hampered by the immature nature of the hiPS-CMs, and the hiPS-CMs-secreted proteins contributing to the repair of cardiomyocytes remain largely unidentified. Here, we established a saponin + compound optimally induced system to generate hiPS-CMs with stable functional attributes in vitro and transplanted in heart failure mice. Our study showed enhanced therapeutic effects of optimally induced hiPS-CMs by attenuating cardiac remodeling and dysfunction, these beneficial effects were concomitant with reduced cardiomyocytes death and increased angiogenesis. Moreover, the optimally induced hiPS-CMs could gathering to the injured heart and secret an abundant PDGF-BB. The reparative effect of the optimally induced hiPS-CMs in the hypoxia-injured HCMs was mimicked by PDGF-BB but inhibited by PDGF-BB neutralizing antibody, which was accompanied by the changed expression of p-PI3K and p-Akt proteins. It is highly possible that the PI3K/Akt pathway is regulated by the PDGF-BB secreted from the compound induced hiPS-CMs to achieve a longer lasting myocardial repair effect compared with the standard induced hiPS-CMs. Taken together, our data strongly implicate that the compound induced hiPS-CMs promote the recovery of injured hearts via paracrine action. In this process, the paracrine factor PDGF-BB derived from the compound induced hiPS-CMs reduces isoproterenol-induced adverse cardiac remodeling, which is associated with improved cardiac function, and these effects are mediated by the PI3K/Akt pathway, suggesting that the optimally induced hiPS-CMs may serve as a new promising cell therapy for clinical applications.

BACKGROUND:Hyperkalemia is a serious complication in cirrhotic patients. However, the clinical characteristics, risk factors, and its impact on the outcomes in acute-on-chronic liver failure (ACLF) patients remain unclear.METHODS:We retrospectively recruited 650 ACLF patients in this study. The risk factors associated with hyperkalemia and its relationship with 90-day mortality were analyzed using multivariable regression models.RESULTS:Among 650 patients with ACLF, 12.2% (79/650) had hyperkalemia during hospitalization. Higher admission serum potassium levels and the presence of acute kidney injury (AKI) were independent risk factors for hyperkalemia. The prevalence rates of hyperkalemia in patients with and without AKI were 23.6% and 4.6%, respectively (P<0.001). Hyperkalemia was a predictor of mortality in AKI and non-AKI patients. The 90-day mortality rates in non-AKI patients with and without hyperkalemia were 44.4% and 24.7%, respectively (P<0.001), and in AKI patients with and without hyperkalemia were 80.3% and 56.6%, respectively (P<0.001). Hepatic encephalopathy (HE), gastrointestinal bleeding, AKI, hyperkalemia, elevated total bilirubin (TBIL) and international normalized ratio (INR) values, and higher Model for End-Stage Liver Disease (MELD) and chronic liver failure-sequential organ failure assessment (CLIF-SOFA) scores were independent risk factors for predicting the 90-day mortality in ACLF patients.CONCLUSIONS:Hyperkalemia increases the 90-day mortality in ACLF patients; hyperkalemia is associated with AKI. Patients with both AKI and hyperkalemia had the worst outcome.

Systemic inflammatory responses are associated with the development and progression of liver failure. Neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR), prognostic nutritional index (PNI), red cell distribution width (RDW), RDW-to platelet ratio (RPR), mean platelet volume (MPV), and MPV-to platelet ratio (MPR) are markers of systemic inflammation. This study aimed to evaluate the prognostic values of these inflammatory markers in patients with hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF). 203 HBV-ACLF patients, 79 cirrhosis patients (LC), 63 chronic hepatitis B (CHB), and 81 healthy subjects (HS) participated in this cohort study. Complete blood counts and biochemical examinations were obtained after overnight fasting. Multivariate analyses of 90-day outcome predictors were analyzed by Cox regression models. Survival probability curves were calculated by the Kaplan Meier method. The levels of NLR, MLR, RDW, MPV, RPR, and MPR were significantly higher and PNI was lower in patients with liver failure at presentation compared to those in LC, CHB, and HS (P<.001). In acute-on-chronic liver failure (ACLF) patients, NLR and MLR were higher in nonsurvivors than in survivors (P<.001), while other inflammatory markers showed no difference. ROC curve analyses showed that NLR combined with MLR had the highest AUC for identified poor outcome, followed by NLR, chronic liver failuresequential organ failure assessment (CLIF-SOFA), MLR, model for end-stage liver disease (MELD), Child-Turcotte-Pugh (CTP) and TBIL. Multivariate analyses showed that TBIL, NLR, CTP, MELD, and CLIF-SOFA were independent predictors for 90-day mortality. Combination of NLR and MLR are more accurate prognostic markers for predicting poor outcome than either marker alone in ACLF patients. And this combination is superior to the CLIF-SOFA, MELD, CTP score, and TBIL in terms of prognostic ability.