Iron overload is strongly associated with heart disease. Ferroptosis is a new form of regulated cell death indicated in cardiac ischemia-reperfusion (I/R) injury. However, the specific molecular mechanism of myocardial injury caused by iron overload in the heart is still unclear, and the involvement of ferroptosis in iron overload-induced myocardial injury is not fully understood. In this study, we observed that ferroptosis participated in developing of iron overload and I/R-induced cardiomyopathy. Mechanistically, we discovered that Parkin inhibited iron overload-induced ferroptosis in cardiomyocytes by promoting the ubiquitination of long-chain acyl-CoA synthetase 4 (ACSL4), a crucial protein involved in ferroptosis-related lipid metabolism pathways. Additionally, we identified p53 as a transcription factor that transcriptionally suppressed Parkin expression in iron-overloaded cardiomyocytes, thereby regulating iron overload-induced ferroptosis. In animal studies, cardiac-specific Parkin knockout mice (Myh6-CreER ^T2 /Parkin ^fl/fl ) fed a high-iron diet presented more severe myocardial damage, and the high iron levels exacerbated myocardial I/R injury. However, the ferroptosis inhibitor Fer-1 significantly suppressed iron overload-induced ferroptosis and myocardial I/R injury. Moreover, Parkin effectively protected against impaired mitochondrial function and prevented iron overload-induced mitochondrial lipid peroxidation. These findings unveil a novel regulatory pathway involving p53-Parkin-ACSL4 in heart disease by inhibiting of ferroptosis.

Objective:To investigate the infection spectrum revealed by metagenomics high-throughput next-generation sequencing (mNGS), and to provide a reference for infection diagnosis after allogeneic hematopoietic stem cell transplantation (allo-HSCT).Methods:A total of 64 patients who developed systemic or local infection symptoms after allo-HSCT in Hebei Yanda Lu Daopei Hospital from January 2018 to November 2018 were enrolled. Gene sequences of pathogenic microorganisms in blood, cerebrospinal fluid and bronchoalveolar fluid specimens were detected by using mNGS. The pathogenic microorganisms or suspected pathogens were determined based on the clinical manifestations of patients.Results:There were 97 samples of mNGS detection for 64 patients who underwent allo-HSCT. The most common gram-positive bacteria were staphylococcus haemolyticus (19 times) and staphylococcus (14 times), and the most common gram-negative bacterium was acinetobacter baumannii (8 times). The most common viruses were cytomegalovirus, EB virus and Torque teno virus (35, 22 and 23 times, respectively), and the most common fungi were malassezia globus (14 times) and candida parapsilosis (8 times). There were 3 mycobacterium tuberculosis complexes detected in 3 patients with acute myeloid leukemia who received allo-HSCT. Mycoplasma orale was detected in one patient's sputum, and none parasite was detected.Conclusion:mNGS can comprehensively reveal the infection spectrum of hematologic diseases after allo-HSCT, especially for pathogenic microorganisms that are rare or difficult to cultivate, and it can effectively help the diagnosis of clinically infectious pathogens.

OBJECTIVE： To observe improvement effects of fingolimod on middle cerebral artery occlusion/reperfusion （MCAO/R） injury model rats. METHODS： Male SD rats were randomly divided into sham operation group， model group and fingolimod low-dose， medium-dose and high-dose groups （0.5， 1， 2 mg/kg）， with 8 rats in each group. Except for sham operation group， MCAO/R injury model was induced by suture-occluded method in other groups. Administration groups were given relevant medicine intragastrically after reperfusion [1 h after reperfusion （1st day）， 22.5 h after reperfusion （2nd day）， and then every 24 h until 142.5 h of reperfusion （7th day）]. Sham operation group and model group were given constant volume of normal saline intragastrically， once a day， for consecutive 7 d. The scores of neurological deficit and balance beam test， the times of memory error [work memory error （WME）， reference memory error （RME） and total error] were recorded in each group. The contents of serum inflammatory cytokines （IL-6， IL-8， IL-10， TNF-α） were determined by ELISA， and triphenyl tetrazolium chloride staining method was used to detect the rate of cerebral infarction. RESULTS： Compared with sham operation group， neurological deficit scores （at different time points of 1st-7th day after administration）， balance beam test scores （2nd， 4th， 7th day after administration）， times of memory error （2nd， 4th， 7th day after administration）， the contents of serum inflammatory cytokines and the rate of cerebral infarction were increased significantly in model group （P＜0.05 or P＜0.01）. Compared with model group， neurological deficit scores （low-dose group at different time points of 3rd-7th day， medium-dose and high-dose groups at different time points of 2nd-7th day after administration）， balance beam test scores （low-dose group at 7th day， medium-dose group at 4th and 7th day， high-dose group at 2nd， 4th， 7th day）， RME times and total error times （low-dose group at 4th and 7th day， medium-dose group and high-dose group at 2nd， 4th， 7th day after administration）， WME times （administrations groups at 7th day after administration）， serum contents of IL-6， IL-8 and IL-10 （administrations groups）， serum contents of TNF-α （medium-dose and high-does groups） and cerebral infarction rate （medium-dose and high-dose groups） were all decreased significantly （P＜0.05 or P＜0.01）. CONCLUSIONS： Intragastric administration of fingolimod can significantly reduce neurological deficit score， balance beam test score and the times of memory error in MCAO/R injury model rats， and has a protective effect on cerebral tissue and memory function. These effects may be related to the down-regulation of inflammatory cytokines such as IL-6 and TNF-α by fingolimod.

Objective to provide the evidence for inducing the SAP model in rats with proper concentration of sodium taurocholate.Methods 60 SD rats were divided into sham operated group, group of 1.5% in concentration, group of 3.5% in concentration and group of 5% in concentration randomly, while the SAP model was induced by the sodium taurocholate concentration of 1.5%,3.5% and 5% with the method of retrograde injection into the biliopancreatic duct.To calculate the mortality of different groups, measure the serum amylase, tumor necrosis factor -α(TNF -α) and interleukin -6 (IL -6),and to observe the pancreatic pathological scores of HE staining in rats.Results The mortality in group of 5% in concentration has a significant ascending compared with group of 1.5% in concentration, while the serum amylase, tumor necrosis factor -α(TNF -α) , interleukin -6( IL -6), pathological score of hemorrhage and acinar necrosis in group of 5% in concentration have a significant ascending compared with group of 1.5% in concentration and group of 3.5% in concentration.Conclusions A better SAP model may be induced by sodium taurocholate with the concentration of 5% by the method of retrograde injection into the biliopancreatic duct, which may accord with the physiological and pathological manifestation of SAP.