Ferritinophagy-Mediated Hippocampus Ferroptosis is Involved in Cognitive Impairment in Immature Rats Induced by Hypoxia Combined with Propofol.

Propofol is a clinically common intravenous general anesthetic and is widely used for anesthesia induction, maintenance and intensive care unit (ICU) sedation in children. Hypoxemia is a common perioperative complication. In clinical work, we found that children with hypoxemia who received propofol anesthesia experienced significant postoperative cognitive changes. To explore the causes of this phenomenon, we conducted the study. In this study, our in vivo experiments found that immature rats exposed to hypoxia combined with propofol (HCWP) could develop cognitive impairment. We performed the RNA-seq analysis of its hippocampal tissues and found that autophagy and ferroptosis may play a role in our model. Next, we verified the participation of the two modes of death by detecting the expression of autophagy-related indexes Sequestosome 1 (SQSTM1) and Beclin1, and ferroptosis-related indicators Fe2+, reactive oxygen species (ROS) and glutathione peroxidase 4 (GPX4). Meanwhile, we found that ferrostatin-1 (Fer-1), an inhibitor of ferroptosis, could improve cognitive impairment in immature rats caused by HCWP. In addition, we found that nuclear receptor coactivator 4 (NCOA4)-mediated ferritinophagy, which acted as a key junction between autophagy and ferroptosis, was also involved. Finally, our in vitro experiments concluded that autophagy activation was an upstream factor in HCWP-induced hippocampus ferroptosis through the intervention of autophagy inhibitor 3-methyladenine (3-MA). Our study was expected to provide an attractive therapeutic target for cognitive impairment that occurred after HCWP exposures.

Fusobacterium nucleatum bacteremia complicated with intracranial Porphyromonas gingivalis and HSV-1 infection: a case report and literature review.

BACKGROUND: Fusobacterium nucleatum (F. nucleatum) belongs to the genus Fusobacterium, which is a gram-negative obligate anaerobic bacterium. Bacteremia associated with F. nucleatum is a serious complication, which is not common in clinic, especially when it is combined with other intracranial pathogenic microorganism infection. We reported for the first time a case of F. nucleatum bacteremia combined with intracranial Porphyromonas gingivalis (P. gingivalis) and herpes simplex virus type 1(HSV-1) infection. CASE PRESENTATION: A 60-year-old woman was admitted to our hospital with a headache for a week that worsened for 2 days. Combined with history, physical signs and examination, it was characterized as ischemic cerebrovascular disease (ICVD). F. nucleatum was detected in blood by matrix-assisted laser desorption/ionization time-offight mass spectrometry (MALDI-TOF-MS). Meanwhile, P. gingivalis and HSV-1 in cerebrospinal fluid (CSF) were identified by metagenome next generation sequencing (mNGS). After a quick diagnosis and a combination of antibiotics and antiviral treatment, the patient recovered and was discharged. CONCLUSION: To our knowledge, this is the first report of intracranial P. gingivalis and HSV-1 infection combined with F. nucleatum bacteremia.

The median effective concentration of ropivacaine for ultrasound-guided caudal block in children: a dose-finding study.

PURPOSE: To determine the 50% minimum effective concentration (MEC50) and the 95% effective concentration (MEC95) of ropivacaine for ultrasound-guided caudal block during hypospadias repair surgery of pediatric patients. METHODS: Children were enrolled with the American Society of Anesthesiologists (ASA) physical status I-II undergoing elective hypospadias repair surgery. Children were grouped into two age groups: toddlerhood (1-3 years old) and preschool (3-6 years old). We measured The MEC50 using Dixon's up-and-down method. The first children received the caudal block with 1.0 mL/kg of 0.15% ropivacaine. We determined each subsequent patient's concentration based on the previous patient's response and adjusted the concentration in intervals of 0.015%. Meanwhile, the probit regression analysis obtains 95% effective concentration (MEC95). In addition, we recorded the general condition, adverse events, and postoperative pain of each child. RESULTS: 46 children undergoing elective hypospadias repair surgery were included in this study, 22 in the toddlerhood group and 24 in the preschool group. Of the total number of patients, the caudal block was successful in 25 (54%) and failed in 21 (46%). The MEC50 of 1 ml/kg ropivacaine was 0.102% (95% CI 0.099%, 0.138%) in the toddlerhood group and 0.129% (95% CI 0.124%, 0.138%) in the preschool group. The MEC95 of 1 ml/kg ropivacaine was 0.148% (95% CI 0.131%, 0.149%) in the toddlerhood group and 0.162% (95% CI 0.134%, 0.164%) in the preschool group. Our results showed that ropivacaine concentration was statistically different between preschool children and toddlers (P < 0.001). None of the adverse events occurred. CONCLUSIONS: This study showed that children in the preschool group required higher concentrations of ropivacaine than children in the toddler group during ultrasound-guided sacral block combined with non-intubated general anesthesia. At the same time, this method of anesthesia is safe and effective for children undergoing surgery for hypospadias.

Establishment and Validation of a Blood Test-based Nomogram to Diagnose Patients with AFP-negative HCC.

BACKGROUND: Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer death worldwide. Alpha-protein (AFP) is the most widely used blood biomarker for HCC. However, elevated serum AFP is only observed in part of HCC. AIMS: This study aimed to develop an efficient nomogram model to distinguish patients with alpha- protein-negative HCC and liver cirrhosis. OBJECTIVES: A total of 1130 patients (508 HCC patients + 622 cirrhosis patients) were enrolled in the training cohort. A total of 244 HCC patients and 246 cirrhosis patients were enrolled in the validation cohort. METHODS: A total of 41 parameters about blood tests were analyzed with logistic regression. The nomogram was based on independent factors and validated both internally and externally. RESULTS: Independent factors were eosinophils %, hemoglobin concentration distribution width, fibrinogen, platelet counts, total bile acid, and mitochondria aspartate aminotransferase. The calibration curve for the probability of HCC showed good agreement between prediction by nomogram and actual observation. The concordance index was 0.851. In the validation cohort, the nomogram distinguished HCC from liver cirrhosis with an area under the curve of receiver operating characteristic of 0.754. CONCLUSION: This proposed nomogram was an accurate and useful method to distinguish patients with AFP-negative HCC from liver cirrhosis.

HE4-based nomogram for predicting overall survival in patients with idiopathic pulmonary fibrosis: construction and validation.

Idiopathic pulmonary fibrosis (IPF) is a life-threatening interstitial lung disease. Identifying biomarkers for early diagnosis is of great clinical importance. The epididymis protein 4 (HE4) is important in the process of inflammation and fibrosis in the epididymis. Its prognostic value in IPF, however, has not been studied. The mRNA and protein levels of HE4 were used to determine the prognostic value in different patient cohorts. In this study, prognostic nomograms were generated based on the results of the cox regression analysis. We identified the HE4 protein level increased in IPF patients, but not the HE4 gene expression. The increased expression of HE4 correlated positively with a poor prognosis for patients with IPF. The HR and 95% CI were 2.62 (1.61-4.24) (p < 0.001) in the training set. We constructed a model based on the risk-score = 0.16222182 * HE4 + 0/0.37580659/1.05003609 (for GAP index 0-3/4-5/6-8) + (- 1.1183375). In both training and validation sets, high-risk patients had poor prognoses (HR: 3.49, 95%CI 2.10-5.80, p = 0.001) and higher likelihood of dying (HR: 6.00, 95%CI 2.04-17.67, p = 0.001). Analyses of calibration curves and decision curves suggest that the method is effective in predicting outcomes. Furthermore, a similar formulation was used in a protein-based model based on HE4 that also showed prognostic value when applied to IPF patients. Accordingly, HE4 is an independent poor prognosis factor, and it has the potential to predict IPF patient survival.