No abstract

Postoperative cognitive dysfunction (POCD) is a severe neurological complication after anesthesia and surgery. However, there is still a lack of effective clinical pharmacotherapy due to its unclear pathogenesis. Caffeic acid phenethyl ester (CAPE), which is obtained from honeybee propolis and medicinal plants, shows powerful antioxidant, anti-inflammatory, and immunomodulating properties. In this study, we aimed to evaluate whether CAPE mitigated cognitive impairment following anesthesia and surgery and its potential underlying mechanisms in aged mice. Here, isoflurane anesthesia and tibial fracture surgery were used as the POCD model, and H2O2-induced BV2 cells were established as the microglial oxidative stress model. We revealed that CAPE pretreatment suppressed oxidative stress and promoted the switch of microglia from the M1 to the M2 type in the hippocampus, thereby ameliorating cognitive impairment caused by anesthesia and surgery. Further investigation indicated that CAPE pretreatment upregulated hippocampal Sirt6/Nrf2 expression after anesthesia and surgery. Moreover, mechanistic studies in BV2 cells demonstrated that the potent effects of CAPE pretreatment on reducing ROS generation and promoting protective polarization were attenuated by a specific Sirt6 inhibitor, OSS_128167. In summary, our findings opened a promising avenue for POCD prevention through CAPE pretreatment that enhanced the Sirt6/Nrf2 pathway to suppress oxidative stress as well as favor microglia protective polarization.

Our study aimed to evaluate the potential of prognostic nutritional index (PNI) and Brain natriuretic peptide (BNP) in predicting the prognosis of heart transplantation (HTx). We retrospectively investigated 489 patients undergoing HTx between 2015 and 2020 in our center. The relationship between preoperative index and prognosis was analyzed respectively, the optimal cut-off values for preoperative PNI and BNP level were evaluated with receiver operating curve analysis. Uni-variate analysis and multivariate analysis were used to compare baseline data (sex, age, diagnosis, etc.) of groups divided by the level of PNI and BNP. Propensity score matching (PSM) was applied to eliminate bias. We calculated the C-index from the prediction efficiency of PNI and BNP. During the period, 489 recipients undergoing HTx in our center were included according to the inclusion criteria; 383 (78.3%) males and 106 (21.7%) females were included in this study, with a median age of 47.57 years old. The ROC curve showed that the optimal cut-off values of each indicator were verified as 49.345 for PNI, and 4397.500 for BNP. The multivariate analyses indicated that PNI (p = 0.047), BNP (p = 0.024), age (p = 0.0023), and waiting time (p = 0.012) were risk factors for all-cause death after HTx. Propensity score matching generated 116 pairs based on PNI level and 126 pairs based on BNP level, and the results showed that OS (overall survival) was significantly correlated with PNI (n = 232, p = 0.0113) and BNP (n = 252, p = 0.0146). Our study implied that higher PNI and lower BNP level had direct correlation with better survival after HTx. Combining PNI and BNP together would be a potential clinical preoperative instrument to predict the survival of patients after HTx, especially in short-term survival.